CODEINE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R EFERENCES
J AMES N. P ARKER , M.D. AND P HILIP M. P ARKER , P H .D., E DITORS
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ICON Health Publications ICON Group International, Inc. 4370 La Jolla Village Drive, 4th Floor San Diego, CA 92122 USA Copyright ©2003 by ICON Group International, Inc. Copyright ©2003 by ICON Group International, Inc. All rights reserved. This book is protected by copyright. No part of it may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without written permission from the publisher. Printed in the United States of America. Last digit indicates print number: 10 9 8 7 6 4 5 3 2 1
Publisher, Health Care: Philip Parker, Ph.D. Editor(s): James Parker, M.D., Philip Parker, Ph.D. Publisher's note: The ideas, procedures, and suggestions contained in this book are not intended for the diagnosis or treatment of a health problem. As new medical or scientific information becomes available from academic and clinical research, recommended treatments and drug therapies may undergo changes. The authors, editors, and publisher have attempted to make the information in this book up to date and accurate in accord with accepted standards at the time of publication. The authors, editors, and publisher are not responsible for errors or omissions or for consequences from application of the book, and make no warranty, expressed or implied, in regard to the contents of this book. Any practice described in this book should be applied by the reader in accordance with professional standards of care used in regard to the unique circumstances that may apply in each situation. The reader is advised to always check product information (package inserts) for changes and new information regarding dosage and contraindications before prescribing any drug or pharmacological product. Caution is especially urged when using new or infrequently ordered drugs, herbal remedies, vitamins and supplements, alternative therapies, complementary therapies and medicines, and integrative medical treatments. Cataloging-in-Publication Data Parker, James N., 1961Parker, Philip M., 1960Codeine: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-83831-3 1. Codeine-Popular works. I. Title.
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Disclaimer This publication is not intended to be used for the diagnosis or treatment of a health problem. It is sold with the understanding that the publisher, editors, and authors are not engaging in the rendering of medical, psychological, financial, legal, or other professional services. References to any entity, product, service, or source of information that may be contained in this publication should not be considered an endorsement, either direct or implied, by the publisher, editors, or authors. ICON Group International, Inc., the editors, and the authors are not responsible for the content of any Web pages or publications referenced in this publication.
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Acknowledgements The collective knowledge generated from academic and applied research summarized in various references has been critical in the creation of this book which is best viewed as a comprehensive compilation and collection of information prepared by various official agencies which produce publications on codeine. Books in this series draw from various agencies and institutions associated with the United States Department of Health and Human Services, and in particular, the Office of the Secretary of Health and Human Services (OS), the Administration for Children and Families (ACF), the Administration on Aging (AOA), the Agency for Healthcare Research and Quality (AHRQ), the Agency for Toxic Substances and Disease Registry (ATSDR), the Centers for Disease Control and Prevention (CDC), the Food and Drug Administration (FDA), the Healthcare Financing Administration (HCFA), the Health Resources and Services Administration (HRSA), the Indian Health Service (IHS), the institutions of the National Institutes of Health (NIH), the Program Support Center (PSC), and the Substance Abuse and Mental Health Services Administration (SAMHSA). In addition to these sources, information gathered from the National Library of Medicine, the United States Patent Office, the European Union, and their related organizations has been invaluable in the creation of this book. Some of the work represented was financially supported by the Research and Development Committee at INSEAD. This support is gratefully acknowledged. Finally, special thanks are owed to Tiffany Freeman for her excellent editorial support.
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About the Editors James N. Parker, M.D. Dr. James N. Parker received his Bachelor of Science degree in Psychobiology from the University of California, Riverside and his M.D. from the University of California, San Diego. In addition to authoring numerous research publications, he has lectured at various academic institutions. Dr. Parker is the medical editor for health books by ICON Health Publications. Philip M. Parker, Ph.D. Philip M. Parker is the Eli Lilly Chair Professor of Innovation, Business and Society at INSEAD (Fontainebleau, France and Singapore). Dr. Parker has also been Professor at the University of California, San Diego and has taught courses at Harvard University, the Hong Kong University of Science and Technology, the Massachusetts Institute of Technology, Stanford University, and UCLA. Dr. Parker is the associate editor for ICON Health Publications.
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About ICON Health Publications To discover more about ICON Health Publications, simply check with your preferred online booksellers, including Barnes & Noble.com and Amazon.com which currently carry all of our titles. Or, feel free to contact us directly for bulk purchases or institutional discounts: ICON Group International, Inc. 4370 La Jolla Village Drive, Fourth Floor San Diego, CA 92122 USA Fax: 858-546-4341 Web site: www.icongrouponline.com/health
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Table of Contents FORWARD .......................................................................................................................................... 1 CHAPTER 1. STUDIES ON CODEINE ................................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Codeine.......................................................................................... 5 E-Journals: PubMed Central ....................................................................................................... 18 The National Library of Medicine: PubMed ................................................................................ 19 CHAPTER 2. NUTRITION AND CODEINE ......................................................................................... 63 Overview...................................................................................................................................... 63 Finding Nutrition Studies on Codeine ........................................................................................ 63 Federal Resources on Nutrition ................................................................................................... 68 Additional Web Resources ........................................................................................................... 69 CHAPTER 3. ALTERNATIVE MEDICINE AND CODEINE ................................................................... 71 Overview...................................................................................................................................... 71 National Center for Complementary and Alternative Medicine.................................................. 71 Additional Web Resources ........................................................................................................... 75 General References ....................................................................................................................... 78 CHAPTER 4. PATENTS ON CODEINE ................................................................................................ 79 Overview...................................................................................................................................... 79 Patents on Codeine....................................................................................................................... 79 Patent Applications on Codeine................................................................................................. 104 Keeping Current ........................................................................................................................ 107 CHAPTER 5. BOOKS ON CODEINE.................................................................................................. 109 Overview.................................................................................................................................... 109 Book Summaries: Online Booksellers......................................................................................... 109 The National Library of Medicine Book Index ........................................................................... 109 Chapters on Codeine .................................................................................................................. 110 CHAPTER 6. MULTIMEDIA ON CODEINE ....................................................................................... 113 Overview.................................................................................................................................... 113 Video Recordings ....................................................................................................................... 113 CHAPTER 7. PERIODICALS AND NEWS ON CODEINE .................................................................... 115 Overview.................................................................................................................................... 115 News Services and Press Releases.............................................................................................. 115 Newsletter Articles .................................................................................................................... 117 Academic Periodicals covering Codeine ..................................................................................... 118 CHAPTER 8. RESEARCHING MEDICATIONS ................................................................................... 119 Overview.................................................................................................................................... 119 U.S. Pharmacopeia..................................................................................................................... 119 Commercial Databases ............................................................................................................... 120 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 125 Overview.................................................................................................................................... 125 NIH Guidelines.......................................................................................................................... 125 NIH Databases........................................................................................................................... 127 Other Commercial Databases..................................................................................................... 129 APPENDIX B. PATIENT RESOURCES ............................................................................................... 131 Overview.................................................................................................................................... 131 Patient Guideline Sources.......................................................................................................... 131 Finding Associations.................................................................................................................. 134 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 137 Overview.................................................................................................................................... 137 Preparation................................................................................................................................. 137
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Finding a Local Medical Library................................................................................................ 137 Medical Libraries in the U.S. and Canada ................................................................................. 137 ONLINE GLOSSARIES................................................................................................................ 143 Online Dictionary Directories ................................................................................................... 144 CODEINE DICTIONARY ............................................................................................................ 147 INDEX .............................................................................................................................................. 207
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FORWARD In March 2001, the National Institutes of Health issued the following warning: "The number of Web sites offering health-related resources grows every day. Many sites provide valuable information, while others may have information that is unreliable or misleading."1 Furthermore, because of the rapid increase in Internet-based information, many hours can be wasted searching, selecting, and printing. Since only the smallest fraction of information dealing with codeine is indexed in search engines, such as www.google.com or others, a non-systematic approach to Internet research can be not only time consuming, but also incomplete. This book was created for medical professionals, students, and members of the general public who want to know as much as possible about codeine, using the most advanced research tools available and spending the least amount of time doing so. In addition to offering a structured and comprehensive bibliography, the pages that follow will tell you where and how to find reliable information covering virtually all topics related to codeine, from the essentials to the most advanced areas of research. Public, academic, government, and peer-reviewed research studies are emphasized. Various abstracts are reproduced to give you some of the latest official information available to date on codeine. Abundant guidance is given on how to obtain free-of-charge primary research results via the Internet. While this book focuses on the field of medicine, when some sources provide access to non-medical information relating to codeine, these are noted in the text. E-book and electronic versions of this book are fully interactive with each of the Internet sites mentioned (clicking on a hyperlink automatically opens your browser to the site indicated). If you are using the hard copy version of this book, you can access a cited Web site by typing the provided Web address directly into your Internet browser. You may find it useful to refer to synonyms or related terms when accessing these Internet databases. NOTE: At the time of publication, the Web addresses were functional. However, some links may fail due to URL address changes, which is a common occurrence on the Internet. For readers unfamiliar with the Internet, detailed instructions are offered on how to access electronic resources. For readers unfamiliar with medical terminology, a comprehensive glossary is provided. For readers without access to Internet resources, a directory of medical libraries, that have or can locate references cited here, is given. We hope these resources will prove useful to the widest possible audience seeking information on codeine. The Editors
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From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.
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CHAPTER 1. STUDIES ON CODEINE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on codeine.
The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and codeine, you will need to use the advanced search options. First, go to http://chid.nih.gov/index.html. From there, select the “Detailed Search” option (or go directly to that page with the following hyperlink: http://chid.nih.gov/detail/detail.html). The trick in extracting studies is found in the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Journal Article.” At the top of the search form, select the number of records you would like to see (we recommend 100) and check the box to display “whole records.” We recommend that you type “codeine” (or synonyms) into the “For these words:” box. Consider using the option “anywhere in record” to make your search as broad as possible. If you want to limit the search to only a particular field, such as the title of the journal, then select this option in the “Search in these fields” drop box. The following is what you can expect from this type of search: •
Analgesic Nephropathy Source: New England Journal of Medicine. 338(7): 446-452. February 12, 1998. Summary: Classic analgesic nephropathy (kidney disease resulting using painkillers) is a slowly progressive disease resulting from the daily use over many years of mixtures containing at least two antipyretic analgesics and usually caffeine or codeine (or both), which may lead to psychological dependence. The nephropathy is characterized by renal papillary necrosis and chronic interstitial nephritis, with an insidious progression to renal failure. This review article examines classic analgesic nephropathy and the role of habitual analgesic use in the progression of chronic renal disease and the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on the kidney. The disease can be accurately diagnosed at any stage by CT scanning without contrast medium, even in the absence of reliable information on previous analgesic use. The withdrawal of phenacetin
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from the market, a move hypothesized to end analgesic nephropathy, did not completely eradicate the problem. Indeed, there is experimental, pharmacologic, and epidemiologic evidence that other analgesic mixtures (including aspirin and acetaminophen) that do not contain phenacetin are also nephrotoxic and produce the classic renal lesions of the disease. The association between chronic renal failure from any cause and excess analgesic use reported in three case-control studies does not establish cause and effect. Well-designed studies are needed to define the nephrotoxicity of analgesics in patients with renal disease. In the meantime, these patients should be advised that acetaminophen should be the nonnarcotic analgesic of choice for intermittent use. Prolonged, regular use of NSAIDs should be discouraged in all patients, and if such use is necessary, renal function should be carefully monitored. 2 figures. 2 tables. 39 references. •
Guide to the Treatment of GI Motility Disorders Source: Drug Therapy. 21(12): 15-16, 21, 25-26, 28. December 1991. Summary: Disorders of gastrointestinal (GI) motility result from disturbances of extrinsic neural control, enteric nervous system, or smooth muscle; rarely, changes in the hormonal system results in alterations in GI transit. This article presents a guide to the treatment of GI motility disorders, focusing on the restoration of propulsion in the affected segments to normal. The author covers 5 groups of prokinetic agents: cholinergic agonists and anticholinesterases, substituted benzamides, dopamine antagonists, 5-HT3 antagonists, and motilinomemetic agents. The author briefly considers pharmacotherapy that retards GI transit. Drugs discussed in the article include bethanechol, cisapride, codeine, domperidone, erythromycin, loperamide, metoclopramide, neostigmine, octreotide, ondansetron, and pyridostigmine. 1 figure. 2 tables. 35 references.
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Oral Management of the Patient with End-Stage Liver Disease and the Liver Transplant Patient Source: Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology, and Endodontics. 86(1): 55-64. July 1998. Contact: Available from Mosby, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146-3318. (800) 453-4351 or (314) 453-4351. Summary: This article addresses the oral management of the patient with end stage liver disease and the liver transplant patient. The authors emphasize that the patient with end stage liver disease, who is in need of a liver transplant, should have a pretransplant dental evaluation. Such a patient faces lifelong immunosuppression with an increased risk of infection. The article discusses both the need for control of oral diseases before liver transplantation and guidelines for oral care in the immediately postoperative and long term transplant patient. Specific indications for antibiotic prophylaxis and antibiotic regimens are presented; in addition, the adverse reactions and side effects of immunosuppressant drugs are discussed. The authors review pertinent drug interactions related to the dental management of patients with end stage liver disease, and present specific management recommendations. Specific drugs covered include cyclosporine, FK 506, prednisone, monoclonal antibody (OKT3), azathioprine, antilymphocyte globulin (ATG), morphine, codeine, nonsteroidal antiinflammatory drugs (NSAIDs), sedatives and anxiolytic drugs, local anesthetics, barbiturates, and propofol. 5 tables. 95 references. (AA-M).
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Fibromyalgia Syndrome: Is There Any Effective Therapy? Source: Consultant. 1279-1285; June 1996. Summary: This journal article for health professionals addresses the concerns that physicians most often have about the treatment of fibromyalgia syndrome (FMS). A variety of nonpharmacologic and pharmacologic therapies are available for patients with FMS. An empathetic attitude on the physician's part is particularly important. Mildly symptomatic patients usually respond well to patient education; physical therapy; an exercise program; simple analgesics; and, in some cases, low doses of a tricyclic antidepressant, cyclobenzaprine, or trazodone. Patients with severe symptoms usually require higher doses of these drugs or combined therapy with a tricyclic agent and a selective serotonin reuptake inhibitor. Valuable adjunctive therapies include cognitive behavior therapy, which may be particularly beneficial in patients with poor coping skills, and the injection of tender points with lidocaine or a mixture of lidocaine and triamcinolone diacetate. Recalcitrant symptoms or an acute flare-up may require a short course of acetaminophen with low-dose codeine. 14 references, 2 figures, and 3 tables. (AA-M).
Federally Funded Research on Codeine The U.S. Government supports a variety of research studies relating to codeine. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to codeine. For most of the studies, the agencies reporting into CRISP provide summaries or abstracts. As opposed to clinical trial research using patients, many federally funded studies use animals or simulated models to explore codeine. The following is typical of the type of information found when searching the CRISP database for codeine: •
Project Title: ANALGESIA OF SC-65872, OXYCODONE/ACETAMINOPHEN, OR IBUPR Principal Investigator & Institution: Brennan, Timothy J.; Associate Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001 Summary: This study is designed to compare the analgesic efficacy and safety of orally administered SC-65872, a novel compound that exhibits potent anti-inflammatory and analgesic activity via selective inhibition of one form of the enzyme cyclooxygenase, to oxycodone/acetaminophen, ibuprofen and placebo in patients with moderate to severe pain after general surgery.
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Healthcare projects are funded by the National Institutes of Health (NIH), Substance Abuse and Mental Health Services (SAMHSA), Health Resources and Services Administration (HRSA), Food and Drug Administration (FDA), Centers for Disease Control and Prevention (CDCP), Agency for Healthcare Research and Quality (AHRQ), and Office of Assistant Secretary of Health (OASH).
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Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BEHAVIORAL EFFECTS OF OPIOIDS IN VOLUNTEERS Principal Investigator & Institution: Zacny, James P.; Associate Professor; Anesthesia and Critical Care; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 15-MAR-1995; Project End 29-FEB-2004 Summary: Until recently, little attention had been paid to characterizing behavioral effects of opioids in normal volunteers (i.e., volunteers with no history of drug or alcohol dependence) using the rigorous testing methodologies that had been employed in the studies with abusers. For the past three years, we have employed an abuse liability/behavioral toxicology testing methodology to examine the effects of a number of different opioids that are typically given to patients for postoperative pain. This application will have four series of studies that are logical continuations of studies from the previous grant period. In the first series of studies, we will focus on opioids that are typically given to patients who are recovering from outpatient surgery. These patients might be at home or at work, engaging in different activities that may or may not be adversely affected by the opioids. It is vitally important to understand the behavioral toxicology of these opioids, yet rigorous toxicology studies (employing multiple measures of behavior and examining a range of doses that might be used by patients) have not been conducted to date. Therefore, we plan to continue our opioid characterization studies in normal volunteers, focusing on four oral drugs commonly used in outpatient settings: hydrocodone, oxycodone, propoxyphene, and tramadol. In the second series of studies, we will follow up on a study from the previous granting period in which some of morphine's subjective effects were attenuated by a painful stimulus. In four studies, we will use a cumulative dosing procedure recently developed in our laboratory to examine the degree to which a painful stimulus modulates the subjective and psychomotor effects of morphine, meperidine, butorphanol and nalbuphine. We will study different opioids at different doses and at different levels of painful stimulation in order to better understand how pain, which frequently accompanies opioid administration in patients, modulates behavioral effects of opioids. In the third series of studies, we will again follow up on a previous study from our laboratory in which we demonstrated that a painful stimulus modulated the reinforcing effects of an opioid, fentanyl. We propose to utilize a patient controlled analgesia (PCA) methodology to examine the degree to which four different opioids- morphine, meperidine, nalbuphine and butorphanol- maintain self-administration, and the degree to which self-administration is modulated by a painful stimulus. In the fourth series of studies, the effects of psychomotor stimulants alone and in combination with an opioid will be examined. Psychomotor stimulants are often given as adjuncts to opioids in patients suffering from chronic malignant pain to offset the sedating and impairing effects of high-dose opioid therapy. We will study buprenorphine in combination with three psychomotor stimulants- d-amphetamine, methylphenidate, and pemoline- to determine the relative pharmacodynamic profiles and which combination(s) produces the most analgesia with the least degree of troublesome side effects (including marked sedation and psychomotor/cognitive impairment). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: BIOBEHAVIORAL ACTIONS OF PARTIAL MU AGONISTS Principal Investigator & Institution: Picker, Mitchell J.; Psychology; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001; Project Start 01-JUL-1996; Project End 30-NOV-2003
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Summary: (Adapted from the Investigator's Abstract): In view of the many undesirable actions of morphine and other opium derivatives, considerable research efforts has been devoted to developing drugs that retain morphine's analgesic efficacy but are less likely to result in abuse and physical dependence. As class of drugs that was developed specifically for these reasons are the partial u (opioid) agonists. Unlike full u agonists (e.g. morphine), partial u agonists require activation of a relatively large fraction of the total pool in order to produce a behavioral or physiological response. A consequence of this unique pharmacological action is that responsiveness to these drugs can be used as an extremely sensitive model to study the factors (e.g. gender, genetics) that contribute to individual differences in drug sensitivity as well as individual vulnerability to drug abuse. There is ample evidence indicating that both inbred and outbred strains of rats display profound differences in their responsiveness to the antinociceptive effects of partial u agonists. In may instances, these differences are as large or larger than those observed in divergent lines of rodents selected for low and high sensitivity to a particular opioid effect. For our first specific aim we are proposing to determine if partial u agonists can be used to evaluate the genetic (rat strains) determinants of the reinforcing effects of opioids and the development of tolerance to their antinociceptive effects. A final goal will be to determine if the mechanism underlying strain-specific sensitivity to opioids is related to the intrinsic efficacy of opioids at the u receptor. There is an emerging body of clinical evidence indicating that human males and females differ in their responsiveness to the antinociceptive effects of opioids and it has been postulated that these differences are most pronounced with partial u agonists and opioids with activity at the k receptor site. For our second specific aim we are proposing to evaluate gender differences in the antinociceptive effects of partial u and k agonists, determine if gender differences are apparent at the spinal and supraspinal levels, and provide a quantitative comparison of the intrinsic efficacy of selected u agonists in males and females of rat strains known for their differential sensitivity to the antinociceptive effects of opioids. Recent clinical studies indicate that chronic opioid treatment* does not produce adequate levels of analgesia in female patients and that females differ from males in terms of the maximum dosage of opioids required during chronic treatment. For our third specific aim we are proposing to determine if there are gender differences in responsiveness to chronic opioid challenge and thus in the extent that tolerance develops to opioid-induced antinociception. As chronic opioid treatment has a profound effect on the activity of partial u agonists, responsiveness to these opioids should provide an extremely sensitive index of gender differences. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: BRAINSTEM NEURAL NETWORKS AND AIRWAY DEFENSIVE REFLEXES Principal Investigator & Institution: Shannon, Roger; Physiology and Biophysics; University of South Florida 4202 E Fowler Ave Tampa, Fl 33620 Timing: Fiscal Year 2001; Project Start 01-DEC-1993; Project End 30-NOV-2002 Summary: The goal of this research is to define the functional organization and internal operations of the brainstem network through which airway defensive reflex motor patterns are generated and modulated. Many-neuron recording technology and spike train analysis methods (i.e., cross-correlation, gravity) will be used to determine parallel and sequential neuronal responses during fictive cough and the laryngeal expiration reflex, and the define concurrent functional interactions among physiologically characterized neurons in several brainstem regions. The plausibility of network models derived from this approach will be tested with computer simulations. Fictive cough and
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the expiration reflex will be evoked by mechanical stimulation of the intrathoracic trachea and larynx, respectively, in decerebrated, paralyzed, ventilated cats. Hypothesis I. Botzinger/ventral respiratory group (BOT/VRG) network interactions produce the cough patterns that are relayed to spinal respiratory motoneurons. Hypothesis II. Laryngeal motoneuron activity during cough is controlled by BOT/VRG propriobulbar neurons. Hypothesis III. Cough receptors activate neurons in the caudal nucleus tractus solitarius (NTS) which distribute information concurrently to neurons in the dorsal respiratory group (DRG), and pontine respiratory group (PRG). Hypothesis IV. Functional connectivity among PRG neurons contribute to their respiratory modulation, and are similar to interactions among rhythm/pattern generating BOT/VRG neurons. Hypothesis V. The PRG modulates the BOT/VRG generated cough motor pattern through divergent actions of specific neurons uon the and raphe nuclei. Hypothesis VI. The raphe neuronal network is modulated during cough by inputs from NTS, PRG, and BOT/VRG. Hypothesis VII. The raphe neuronal network modulates the cough motor pattern through actions on the BOT/VRG. Other Parallel Studies: In the course of the planned experiments, we will also examine brainstem mechanisms that generate laryngeal expiration reflex motor patterns. Airway defensive reflexes are essential for the day-to-day survival of individuals with and without lung disease; they can also exacerbate other pathological conditions. These studies will contribute basic information that could be useful for future development of more effective therapeutic interventions for disorders involving these reflexes. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: CHANGES IN HOMICIDE AND DRUG OVERDOSE IN NEW YORK CITY Principal Investigator & Institution: Tardiff, Kenneth J.; Professor; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 30-SEP-1990; Project End 30-JUN-2007 Summary: (provided by applicant): We are applying for a continuation grant for the study of changes in homicide and accidental fatal drug overdoses. Continuing our long term collaboration with the New York City Medical Examiner, we will collect and analyze data from 2000 to 2006 on an estimated 30,000 fatal injuries, which added to our data base of 40,000 fatalities over 10 years, will allow us to analyze 70,000 fatalities over a 17 year period from 1990-2006. Our data set is unique in that it contains information on types of fatal injuries, time and place of injury and death, characteristics and residence of the victim, and toxicology results for a wide range of illicit drugs and alcohol. This will enable us to extend our surveillance of homicide and overdose mortality in NYC and to test etiologic hypotheses regarding these two causes of death. Our aims are: 1) To determine the incidence, temporal trends, and correlates of homicide, accidental drug overdoses and other fatal accidents with a focus on identifying the emerging role of newer drugs such as ecstasy and oxycodone. 2) To determine neighborhood-level determinants of homicide (e.g., drug use, policing, concentrated disadvantages) and to assess how they are related to changes in the frequency of homicide over timw and place. 3) To determine the association between individual drug use, age of decedents, neighborhood factors (e.g., economic disadvantage, level of illicit drug use), and the risk of becoming a homicide case using fatal accidents as controls. 4) To determine neighborhood-level determinants of drug overdose and to assess how these are related to changes in fatal drug overdose over time and place. There have been significant changes in the use of illicit drugs, the frequency of homicide and of fatal drug overdoses in NYC over the past decade. Although there are many theories as to why these changes
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have occurred, few scientific studies have been able to address the key hypotheses regarding these changes. Some of the questions that can be addressed in this proposal include: Have arrests for "quality of life" crimes restored public order and lowered the frequency of homicide ad changed drug-dealing? Has individual use of certain illicit drugs increased the risk for homicide and fatal drug overdose? We intend our findings to be helpful to public health and law enforcement practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DEVELOPMENT OF SCP-1/OPIOID COMBINATIONS FOR PAIN Principal Investigator & Institution: Narducy, Kenneth Wayne.; President; St. Charles Pharmaceuticals 2020 Gravier St New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-SEP-2003; Project End 31-MAR-2004 Summary: (provided by applicant): Combinations of acetaminophen with opioids (i.e., hydrocodone, codeine) are frequently prescribed for acute and chronic pain management. Combinations of analgesics with different mechanisms of action enhance analgesic efficacy while reducing the dose-dependent adverse effects of the individual components. Acetaminophen is a relatively safe, commonly used over-the-counter analgesic and antipyretic drug; however, ingestion of large doses can cause hepatotoxicity. Moreover, the analgesic tolerance, which evolves with repeated administration of opioid-containing combinations, is compensated by increasing the acetaminophen/opioid doses. This, in turn, increases the risk of acetaminophen-induced hepatic complications. Clearly physicians and patients will prefer analgesic combinations that have the fewest side effects and that provide a safer and more efficacious treatment for pain. The research in this SBIR project will optimize combinations of opioids and non-opioids with SCP-1. SCP-1 is the lead compound from St. Charles Pharmaceuticals's series of new proprietary derivatives of acetaminophen. SCP-1 has high analgesic activity but is free from antipyretic activity and hepatotoxicity. During phase I, we will use isobolographic analysis to demonstrate the feasibility of creating optimal doses within the combinations to obtain the synergistic effects with equal or higher efficacy and better safety profile than acetaminophen and opioid combination. We will determine the combinations that display the best onset and duration of analgesia and define their safety profiles by using GPT/GOT plasma activity and glutathione content in the liver and kidney. During Phase II, we will further characterize these SCP-1/opioid combinations looking for those combinations that are not antipyretics and are thus relevant to the treatment of post-surgical pain. Also the lead SCP-1 combinations will be evaluated for analgesia in other pain models such as chronic constriction injury and herpetic pain and we will undertake some of the preclinical studies using the selected combinations. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISCRIMINATIVE STIMULUS EFFECTS OF OPIOID WITHDRAWAL Principal Investigator & Institution: France, Charles P.; Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2001; Project Start 01-MAY-1995; Project End 31-MAY-2003 Summary: Despite the availability of several, effective pharmacotherapies, opioid abuse continues to pose a major public health problem worldwide. Currently available pharmacotherapies are effective in only some patients and the need continues for new and better treatments for opioid abuse. Prior research under this grant developed discrimination procedures for studying opioid dependence and withdrawal. Studies in
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this application will use those, and other, procedures to examine the development of dependence to novel opioids and to test hypotheses regarding drug interactions and the possible attenuation of dependence and withdrawal. Specific Aim I will determine whether opioid or non-opioid tolerance or dependence develops during treatment with the novel fentanyl derivative mirfentanil. Specific Aim II will examine the role of P450 enzymes in the morphine-like effects of codeine and oxycodone and determine whether other drugs (N-methyl-D-aspartate antagonists [NMDA] and nitric oxide synthase [NOS] inhibitors) modify opioid tolerance and dependence. These studies will compare methadone and its stereo isomers because these opioids also have effects at NMDA receptors. Upon completion of a study on LAAM dependence and withdrawal, studies under Specific Aim III will test the hypothesis that variations among mu opioids in their effects on receptor internalization and G-protein coupling will be expressed as differences in tolerance and dependence. Naltrexone will be established as a discriminative stimulus in untreated monkeys (Specific Aim IV) to begin a characterization of behavioral effects that might be important to the therapeutic utility of these drugs (e.g., alcohol abuse). Specific Aim V will use pigeons to study efficacy and selectivity differences among opioids and also to determine whether hypothesized interactions between different opioid receptors has functional consequences for drug dependence and withdrawal. The procedures developed under this grant provide a unique set of conditions for evaluating the effects of other drugs on behaviors related to and predictive of the subjective effects of withdrawal in humans. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: DISPOSITION OF CODEINE IN HAIR & SALIVA: EFFECT OF GENDER & HAIR COLOR Principal Investigator & Institution: Rollins, Douglas E.; University of Utah 200 S University St Salt Lake City, Ut 84112 Timing: Fiscal Year 2001 Summary: Hair and saliva are being proposed as alternatives to testing urine and blood for detecting drug use. The objectives of this project are to determine the effect of hair color and gender on the incorporation of codeine and ofloxacin into human hair, and to determine the saliva concentration of codeine. Thirty-seven subjects have been entered into the study. The analysis of ofloxacin in hair has been completed in thirty-five subjects. Subjects with black hair had the highest concentration of drug in the hair sampled, and patients with red hair had the lowest. Patients with blond or brown hair had intermediate values. These preliminary data suggest that there is an effect of hair color on the distribution of ofloxacin into hair. Additional volunteers with dark-colored hair are now being recruited, and ofloxacin concentration will be measured in plasma and hair of these subjects. Measures of codeine concentration in plasma, urine, hair, and saliva of all subjects enrolled is under way. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: DISTINCTION AMONG EIGHT OPIATE DRUGS IN URINE BY GAS CHROMATOGRAPHIC Principal Investigator & Institution: Nowatzke, William; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001 Summary: Opiates are commonly abused substances, and forensic urine drug-testing for them involves an immunoassay screen and gas chromatographic/mass spectrometric
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(GC/MS) confirmation. There are also medical reasons to test urine for opiates, and confirmation procedures other than GC/MS are often used for medical drug-testing which are more compatible with the demands of clinical services and which identify a wider range of opiates than those in standard forensic batteries. One such procedure involves thin-layer chromatographic (TLC) analysis of opiate derivatives and can distinguish eight clinically encountered opiates, including morphine, acetylmorphine, hydromorphone, oxymorphone, codeine, dihydrocodeine, hydrocodone, and oxycodone. Medical drug-testing results are sometimes challenged by patients, causing physicians to request additional confirmation of the identified opiates. To our knowledge, no previous report examines all opiates specified above in a single GC/MS pr ocedure, but we find that they can be distinguished by GC/MS analyses of trimethylsilyl (TMS) ether derivatives, the mass spectra of which contain prominent molecular ions. Inclusion of deuterium-labeled internal standards permits quantitation of each of the eight opiates in urine. The GC/MS assay is linear over a concentration range which spans the TLC cutoff level, and coefficients of variation of 10% or less at concentrations below the TLC cutoff are achieved by for all opiates specified above except for oxymorphone and oxycodone, which exhibit coefficients of variation of 1819%. This procedure has proved useful as a third-stage identification step for medical drug-testing specimens in which results from prior immunoassay and TLC analyses were challenged. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FACTORS INFLUENCING COCAINE USE IN HUMANS Principal Investigator & Institution: Higgins, Stephen T.; Professor; Psychiatry; University of Vermont & St Agric College 340 Waterman Building Burlington, Vt 05405 Timing: Fiscal Year 2001; Project Start 01-FEB-1993; Project End 30-JUN-2002 Summary: This is a continuation application for a project examining the influence of other drug use on human cocaine use using a laboratory model. The prior project focused on the influence of non-prescription drug use (i.e., alcohol, caffeine, marijuana, and nicotine) and the proposed project will focus on the influence of prescription drug use (i.e., psychomotor stimulants, sedative hypnotics, and opioid analgesics). Understanding the influence of such other drug use on the probability of cocaine use is essential to the development of effective clinical strategies for managing polydrug abuse in cocaine treatment clinics, and could also prove useful to the development of effective pharmacotherapies for cocaine abuse. Laboratory models are important due to the rigorous experimental control they afford and their lower costs compared to clinical trials. In our laboratory model, volunteers participate in a series of experimental sessions in which they make exclusive choices between doses of intranasal cocaine and varying amounts of money. In studies completed to date (l) cocaine use varied as an orderly function of monetary value, demonstrating experimental control over drug use; (2) acute alcohol, but not caffeine, pretreatment increased preference for cocaine over the alternative monetary option, suggesting the model has pharmacological sensitivity and selectivity; and (3) these laboratory findings were concordant with evidence from clinic studies with cocaine-dependent patients, supporting the generalizability of these observations to treatment settings. Six studies are proposed for the next funding period. All examine the acute effects of prescription drugs that are commonly used and abused by cocaine abusers. The specific drugs proposed for study are damphetamine, methylphenidate, pentobarbital, triazolam, codeine, and buprenorphine. These studies wTh provide important new information on (l) how use of these drugs alters preference for cocaine versus alternative, non-drug reinforcers, (2) possible differences between
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drugs in how they affect cocaine use, and (3) the utility of laboratory models for addressing clinically important issues. Additionally, by examining non-prescription (prior application) and prescription (this application) drugs, this project will contribute a comprehensive experimental analysis of the influence of commonly used drugs on human cocaine use. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: FUNCTIONAL EFFECTS OF ALLELIC VARIATION IN HUMAN CYP2D6 Principal Investigator & Institution: Haining, Robert L.; Assistant Professor; Basic Pharmaceutical Sciences; West Virginia University P. O. Box 6845 Morgantown, Wv 265066845 Timing: Fiscal Year 2001; Project Start 01-MAY-1999; Project End 30-APR-2004 Summary: The long term aim of the present proposal is to understand the role of human cytochrome P-450 2D6 in the protection from, or predisposition to neurological disease. CYP2D6 is polymorphically expressed in human liver, lung and brain, with over 17 distinct alleles described in the literature, eight of which encode for non-null variants. CYP2D6 plays a key role in the metabolism of many important psychoactive drugs, such as the activation of codeine to morphine, and is known to detoxify MPTP, a thermal breakdown product of 'street heroin' which causes Parkinsonian symptoms in susceptible individuals. Therefore, it is important to know the intrinsic metabolic capability of individual variants of 2D6 in these critical bioactivation and detoxification pathways. Using computer-derived homology models we should be able to rationalize the effects of specific mutations on the ability to bind substrates and inhibitors and the ability to interact with essential cofactors. With the advent of rapid genotyping, it may be possible to predict the outcome of exposure by individuals possessing minor allelic variants toward important environmental agents. The specific aims of the present proposal are: 1. Creation of cDNAs corresponding to each of the naturally occuring nonnull allelic variants of CYP2D6 followed by expression in and purification from an insect cell culture system. Only those proteins that have the capability to bind heme and CO will be carried forth. 2. Characterization of P450 enzymatic activity of each variant toward important substrates of CYP2D6 including MPTP, fluoxetine, codeine and dextromethorphan and rationalization of allelic variability data with homology models for 2D6. Our hypothesis is that different allelic variants of CYP2D6 will show substrate dependent changes in the metabolic clearance (kcat/Km) of these psychoactive substrates. In addition, we believe that isoforms of 2D6 which affect active site serine and threonine residues will show altered partition ratio of dextromethorphan Odemethylated to N-demethylated metabolites. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: FUSED POLYCYCLIC AMINES VIA DOUBLE ANNULATION Principal Investigator & Institution: Grossman, Robert B.; Associate Professor; Chemistry; University of Kentucky 109 Kinkead Hall Lexington, Ky 40506 Timing: Fiscal Year 2001; Project Start 05-JUN-2001; Project End 31-MAY-2005 Summary: (Principal Investigator's Abstract) We have discovered a novel two-step route to cis- and trans-fused bicyclic amines with multiple substitution and functionality. A double Michael reaction between a tethered carbon diacid and an alkynone gives a cyclopentane, cyclohexane, or piperidine ring with pendant functionality. A piperidine, pyrroline, or cyclohexane ring is then trans-annulated or a piperidine ring is then cis-
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annulated onto the first ring to give an azabicyclic compound with multiple functionality and well-defined stereochemistry. Protecting groups are not required for these highly chemo-, regio-, and stereoselective reactions, despite the densely functionalized nature of the intermediates. The method is distinguished from existing ones by its wide scope and by the highly substituted and functionalized nature of the products, which have heretofore been available only with difficulty. Our specific aims are to expand the scope of the double annulation route to bicyclic amines, including, trans-perhydroisoquinolines, trans-perhydroindoles, and cis-perhydroisoquinolines, and to apply it to the synthesis of biologically active molecules. We will prepare a series of tethered diacids and alkynones and explore the kinds of structures we can create, paying special attention to the preparation of rigid, cyclic alpha- and beta-amino acids. Our route to trans-perhydroisoquinolines will be used to prepare yohimbine, an alpha2adrenoceptor antagonist, corynanthine an alpha1-adrenoceptor antagonist, and codeine, a mu-opioid receptor agonist, by unique and efficient routes that are amenable to the preparation of bioactive analogs. The yohimbine and corynanthine analogs will be tested for alpha-adrenoceptor antagonist activity. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HOME CARE MANAGEMENT OF PEDIATRIC PAIN Principal Investigator & Institution: Sutters, Kimberly A.; Physiological Nursing; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001; Project Start 01-JUN-2000; Project End 29-FEB-2004 Summary: The pediatric surgery outpatient population has grown extensively in recent years. Tonsillectomy, one of the most prevalent ambulatory surgeries in children, has been associated with a substantial degree of postoperative morbidity, with inadequate pain control cited as a major concern. Therefore, this randomized clinical trial will compare the effectiveness of a structured pain management program (i.e. that combines routine parent postoperative education, with around the clock (ATC) dosing of analgesics and nurse coaching, that is targeted at decreasing barriers to effective pain control in the home), with either standard care (i.e. routine parent postoperative education) and "as needed" analgesic dosing, or standard care and ATC dosing. Patients (N = 300) will be recruited from a large ambulatory surgery program and will be randomized to one of three treatment groups. Parents in the standard care groups will receive routine postoperative education and will be told to administer pain medication to their children every 4 hours "as needed" (Group A), or every 4 hours ATC (Group B). Parents in the structured pain management group (Group C) will receive and educational session that includes standard postoperative instructions and pain management education targeted at increasing knowledge and decreasing barriers to effective pain management as part of a coaching intervention, and will told to administer pain medication every four hours ATC. Parents in all three groups will receive follow-up phone calls on days 1 and 2 following surgery. In the standard care groups, the purpose of the phone calls will be to ascertain level of adherence with completion of the daily logs. Parents in the structured pain management group will receive coaching during the phone calls to include review of pain scores, child adherence to taking pain medicine, strategies for pain medication administration (as indicated), rationale for ATC dosing and instruction for ATC dosing, and potential side effects. Patients will be followed for three days and nights following tonsillectomy and parents will complete diaries in the morning and in the evening. The major outcome variables for this study are: pain intensity scores with and without swallowing, analgesic consumption, oral intake of fluids, negative behaviors and side effects.
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Patients and parents in all pain management groups will have and end of study interview to describe their experiences with the program. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: HYPERALGESIA IN METHADONE PATIENTS: CAN IT BE TREATED? Principal Investigator & Institution: Compton, Margaret A.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: MODULATION OF G PROTEIN COUPLED RECEPTOR FUNCTION Principal Investigator & Institution: Childers, Steven R.; Professor; Wake Forest University 2240 Reynolda Rd Winston-Salem, Nc 27106 Timing: Fiscal Year 2002; Project Start 15-FEB-2002; Project End 31-JAN-2007 Summary: Opioid agonists like morphine, codeine and meperidine remain the most commonly used and effective treatment for chronic pain conditions. Despite the fact that chronic opioid treatment can produce high levels of tolerance and physical dependence.
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Mechanisms of tolerance and dependence for in brain are not well understood, but it is clear that chronic opioid treatment produces significant receptor desensitization in specific brain regions. Moreover, pain itself, as well as concurrent treatment with drugs like adenosine and alpha2- adrenergic agonists, alter the sensitivity of patients to opioid treatment. Opioid receptors (including mu, delta and kappa types), as well as adenosine A1 and alpha2-adrenergic receptors, are G-protein-coupled receptors, and their ability to activate signal transduction systems can be determined by the ability of agonists to stimulate [35S]GTPgammaS binding in both membranes and section autoradiography. This project will examine regulation of several receptor/G-protein interactions in rat spinal cord, using models of drug treatment, self-administration and chronic pain developed by other Center components. First, after determining the acute efficacies of opioid and adenosine A1 agonists in activating G-proteins in spinal cord, the ability of chronic drug exposure to produce receptor desensitization will be examined in both spinal cord membranes and by autoradiography. These treatments will include chronic intrathecal opioid administration to desensitize opioid receptor-activated G-proteins, and chronic intrathecal administration of adenosine and clonidine to desensitize agonist-stimulated incorporation of [32P]AAGTP into specific G-protein subunits. Second, various receptor-activated G-protein activities will be determined in both brains ans spinal cords from spinal nerve ligated rats to determine whether chronic pain and hypersensitivity affect receptor/G-protein coupling. These studies will also determine how chronic pain states modulate basal levels and activities of G-proteins in spinal cord. Third, the ability of NMDA antagonists and protein kinase C inhibitors to modulate receptor desensitization will be tested after chronic intrathecal administration of drugs. Information from this project will help design studies in the Clinical Core to test the use of opioid agonists of differing efficacies in treating chronic pain. Moreover, these studies will provide information to minimize tolerance in long-term drug treatment of chronic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: NOVEL DRUG COMBINATIONS FOR TREATING PAIN IN THE ELDERLY Principal Investigator & Institution: Vaccarino, Anthony L.; St. Charles Pharmaceuticals 2020 Gravier St New Orleans, La 70112 Timing: Fiscal Year 2003; Project Start 01-APR-2003; Project End 30-SEP-2003 Summary: (provided by applicant): Combination analgesics, including acetaminophen with opioids, are used extensively for pain management in the elderly (and others). This is, in part, because these combinations can produce analgesia that is additive or synergistic, and the adverse effects produced by the combinations can be less than those produced by equianalgesic doses of either component alone. Even so, the acetaminophen in these combinations can cause hepatotoxicity after ingestion of large doses or from chronic use, particularly in the elderly or when liver function is compromised. The opioid dosages need to be escalated in response to the tolerance that is developed from chronic use, increasing the occurrence of adverse side effects in the elderly. We have been exploring a series of new and proprietary derivatives of acetaminophen, in which the lead compound (SCP-1) has good oral efficacy in both young and aged animals, and produces little, if any, hepatotoxicity. This Phase I SBIR project explores the feasibility that combinations of SCP-1 + codeine can have synergistic effects comparable to or better than acetaminophen + codeine combinations, but with reduced side effects, in models of acute and chronic pain management using young and old animals. It will also determine (in both young and old animals) the
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development of tolerance and dependence after chronic dosing, as well as hepatotoxicity after chronic and acute dosing. If the SCP-1 with codeine is shown to be more efficacious and/or less toxic than acetaminophen with codeine, further drug development will be proposed under a Phase II SBIR with eventual clinical trials in elderly patients who require management of acute or chronic pain. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: PRECRIPTION OPIOID EFFECTS IN DRUG AND NON-DRUG ABUSERS Principal Investigator & Institution: Comer, Sandra D.; Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-MAY-2008 Summary: (provided by investigator): Prescription opioid abuse is becoming an increasingly widespread and serious public health concern. The 2001 National Household Survey on Drug Abuse report revealed that the number of first-time users of prescription opioid medications for non-medical reasons reached 2.0 million in the year 2000, a number that has quintupled since 1984, and the 2002 Drug Abuse Warning Network (DAWN) report showed that the number of emergency department mentions of several prescription opioid medications more than doubled between 1994 and 2001. Despite these trends, little experimental research has been directed towards understanding who may be abusing these medications, and under what conditions. The current application will examine the reinforcing, subjective, performance, and physiological effects of two commonly prescribed opioid medications (oxycodone, codeine) in two separate studies. Because it is not clear who is abusing prescription opioids, the medication effects will be compared in drug abusers and non-drug abusers. And because it is not clear under what conditions these medications are used, the effects of oxycodone and codeine will be examined in the presence and absence of experimentally-induced pain. For each study, one between- [drug use history (drug abusers, non-drug abusers)] and two within-subjects variables [pain condition (pain, no pain); medication dose (placebo, low, high dose)] will be examined. Because previous studies have shown sex differences in response to opioid medications, we will attempt to enroll equivalent numbers of men and women in each study so that we can conduct exploratory analyses of sex differences in response to oxycodone and codeine. The results of these studies will yield important information about who may be abusing prescription opioid medications, and will provide a better understanding of several important variables that may influence the propensity to abuse these medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
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Project Title: REGULATION TRANSDUCTION
OF
MU
OPIOID
RECEPTOR
SIGNAL
Principal Investigator & Institution: Murrin, Leonard C.; Pharmacology; University of Nebraska Medical Center Omaha, Ne 681987835 Timing: Fiscal Year 2003; Project Start 30-SEP-2003; Project End 01-SEP-2005 Summary: (provided by applicant): Mu opioid receptors (MOR) play a major role in many functions, including pain pathways, the respiratory system, control of GI activity, the limbic (emotional) system and the reward system. They are the target of clinically important drugs, such as morphine and codeine. Our understanding of how MOR function is regulated is incomplete. In preliminary studies, we discovered dramatic changes in the function of MOR during the development of rat brain, changes far greater
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than any we have seen studying other neurotransmitter systems. This suggested that this developmental paradigm would provide novel and interesting information about regulation of function within this system, information relevant not only to development but also to MOR function in adult animals. Based upon our preliminary data, we hypothesize that the dramatic changes in organization and maturation of the MOR in developing striatum are governed and regulated by changes in the expression of other proteins interacting with MOR. Specific Aim 1 is to examine the role of G protein expression on the development of MOR function. These studies include analysis of the developmental expression of the G protein subtypes with which MOR interact, analysis of which specific G protein subtypes interact with MOR at several stages during development, and how these interactions change quantitatively. Specific Aim 2 is to examine the interaction of MOR with other proteins, which may play a role in regulating MOR functional activity. These studies initially focus on the interaction of MOR with RanBPM, a protein initially identified by yeast two-hybrid screen as interacting with the MOR C-terminal tail. Our preliminary data support this hypothesis, indicating RanBPM modulates the signal transduction functions of MOR. This aim examines this interaction in detail, analyzes which domains of these two proteins are important for the interaction, and investigates the role of RanBPM in the changes in MOR function found during development. We think these studies will provide important information about what regulates MOR function during development and that these results also will provide insight into MOR function in the mature animal. Further understanding of the regulation of MOR function is relevant not only to development but to clinical situations involving drugs interacting with MOR, such as pain, diarrhea and drug dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •
Project Title: REGULATION OF THE COUGH REFLEX Principal Investigator & Institution: Bolser, Donald C.; Physiological Sciences; University of Florida Gainesville, Fl 32611 Timing: Fiscal Year 2003; Project Start 01-MAY-2003; Project End 30-APR-2007 Summary: (provided by applicant): Cough is the most common reason why sick patients visit physicians in the US. The long-range goal of this research is to delineate the neurogenic mechanisms by which cough is produced and regulated. The central hypothesis of this research is that the cough motor pattern is produced by an assembly of components that includes a novel regulatory element responsible for controlling the behavior of a reconfigured respiratory pattern generator. Moreover, the novel regulatory components that control laryngeal and tracheobronchial cough are not identical. The rationale for the proposed research is that once the functional organization of the brainstem cough pattern generation system is established, the mechanisms responsible for the production of pathological cough can be identified. The specific aims of the project are: 1) Determine the role of modulation of the expiratory phase in the regulation of the tracheobronchial and laryngeal cough motor patterns, 2) Determine the functional organization of the central regulatory system for tracheobronchial and laryngeal cough, 3) Determine the role of brainstem expiratory motor pathways in the antitussive-sensitive regulatory system for tracheobronchial cough, 4) Determine the role of spinal expiratory motor pathways in the antitussivesensitive regulatory system for cough. In the first aim, key regulatory mechanisms controlling the frequency and magnitude of repetitive tracheobronchial and laryngeal cough will be determined by altering of the excitability of each. Our preliminary data suggest a) that the frequency of repetitive coughing is primarily controlled by modulation of the duration of the latter part of the cough expiratory phase, and b) that
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separate regulatory mechanisms are responsible for the control of the frequency and intensity of repetitive coughing. In support of the second aim, preliminary findings suggest differential sensitivity of tracheobronchial and laryngeal cough to antitussive drugs and thus divergent central regulatory mechanisms for each. In the third aim, we test a model that predicts the presence of a tracheobronchial cough gating mechanism that is presynaptic to medullary and spinal expiratory motor pathways. This gating mechanism is sensitive to antitussive drugs. The sensitivity of rostral and caudal medullary expiratory neurons to antitussive drugs will be determined during breathing and cough to differentiate between inhibition or disfacilitation of these neurons by these compounds. In the fourth aim, antitussive drugs will be delivered intrathecally while monitoring expiratory motor drive during cough to determine the role of spinal pathways in the suppression of expiratory motor discharge. The results of these experiments will provide an important test of the proposed functional organization of the cough pattern generator. Furthermore, this project will test the proposed roles of medullary and spinal cellular elements that contribute to the generation and control of expiratory motor discharge during cough. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen
E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “codeine” (or synonyms) into the search box. This search gives you access to fulltext articles. The following is a sample of items found for codeine in the PubMed Central database: •
Diclofenac does not interact with codeine metabolism in vivo: A study in healthy volunteers. by Ammon S, Marx C, Behrens C, Hofmann U, Murdter T, Griese EU, Mikus G.; 2002; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=101395
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Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial. by Peter EA, Janssen PA, Grange CS, Douglas MJ.; 2001 Oct 30; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81582
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Prolonged erections produced by dihydrocodeine and sildenafil. by Goldmeier D, Lamba H.; 2002 Jun 29; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=116609
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Using evidence from different sources: an example using paracetamol 1000 mg plus codeine 60 mg. by Smith LA, Moore RA, McQuay HJ, Gavaghan D.; 2001; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=32200
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Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.
With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print.
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The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with codeine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “codeine” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for codeine (hyperlinks lead to article summaries): •
A comparison of etodolac (Ultradol) with acetaminophen plus codeine (Tylenol #3) in controlling post-surgical pain in vasectomy patients. Author(s): Casey R, Zadra J, Khonsari H. Source: Current Medical Research and Opinion. 1997; 13(10): 555-63. Erratum In: Curr Med Res Opin 1997; 14(1): 63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9327190&dopt=Abstract
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A comparison of ketorolac tromethamine and acetaminophen codeine in the management of acute apical periodontitis. Author(s): Sadeghein A, Shahidi N, Dehpour AR. Source: Journal of Endodontics. 1999 April; 25(4): 257-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10425951&dopt=Abstract
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A comparison of rectal and intramuscular codeine phosphate in children following neurosurgery. Author(s): McEwan A, Sigston PE, Andrews KA, Hack HA, Jenkins AM, May L, Llewelyn N, MacKersie A. Source: Paediatric Anaesthesia. 2000; 10(2): 189-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10736083&dopt=Abstract
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A comparison of the effects of intravenous tramadol, codeine, and morphine on gastric emptying in human volunteers. Author(s): Crighton IM, Martin PH, Hobbs GJ, Cobby TF, Fletcher AJ, Stewart PD. Source: Anesthesia and Analgesia. 1998 August; 87(2): 445-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706948&dopt=Abstract
6
PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.
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A double-blind comparison of orally administered ciramadol and codeine for relief of postoperative pain. Author(s): Graf DF, Pandit SK, Kothary SP, Freeland GR. Source: Journal of Clinical Pharmacology. 1985 November-December; 25(8): 590-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3908500&dopt=Abstract
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A double-blind placebo-controlled comparison of three ibuprofen/codeine combinations and aspirin. Author(s): Frame JW, Fisher SE, Pickvance NJ, Skene AM. Source: The British Journal of Oral & Maxillofacial Surgery. 1986 April; 24(2): 122-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2941056&dopt=Abstract
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A new source of drug-induced acute pancreatitis: codeine. Author(s): Hastier P, Buckley MJ, Peten EP, Demuth N, Dumas R, Demarquay JF, Caroli-Bosc FX, Delmont JP. Source: The American Journal of Gastroenterology. 2000 November; 95(11): 3295-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11095359&dopt=Abstract
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A practical approach to determine cutoff concentrations for opiate testing with simultaneous detection of codeine, morphine, and 6-acetylmorphine in urine. Author(s): Paul BD, Shimomura ET, Smith ML. Source: Clinical Chemistry. 1999 April; 45(4): 510-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10102911&dopt=Abstract
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A rapid GC-MS method for the determination of dihydrocodeine, codeine, norcodeine, morphine, normorphine and 6-MAM in urine. Author(s): Meadway C, George S, Braithwaite R. Source: Forensic Science International. 2002 June 25; 127(1-2): 136-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12098538&dopt=Abstract
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Abuse of codeine-containing cough syrups: a report from India. Author(s): Mattoo SK, Basu D, Sharma A, Balaji M, Malhotra A. Source: Addiction (Abingdon, England). 1997 December; 92(12): 1783-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9581010&dopt=Abstract
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Acetaminophen versus acetaminophen with codeine after pediatric tonsillectomy. Author(s): Moir MS, Bair E, Shinnick P, Messner A. Source: The Laryngoscope. 2000 November; 110(11): 1824-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11081593&dopt=Abstract
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Acetaminophen-codeine combination induced acute pancreatitis. Author(s): Renkes P, Trechot P. Source: Pancreas. 1998 May; 16(4): 556-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9598820&dopt=Abstract
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Acetaminophen-codeine combinations for rheumatic disorders. Author(s): Bannwarth B, Latreyte P, Lequen L, Dehais J. Source: Rev Rhum Engl Ed. 1997 June; 64(6): 359-61. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9513606&dopt=Abstract
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Acetylcodeine as a marker of illicit heroin in human hair: method validation and results of a pilot study. Author(s): Girod C, Staub C. Source: Journal of Analytical Toxicology. 2001 March; 25(2): 106-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300501&dopt=Abstract
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Acetylcodeine as a urinary marker to differentiate the use of street heroin and pharmaceutical heroin. Author(s): Brenneisen R, Hasler F, Wursch D. Source: Journal of Analytical Toxicology. 2002 November-December; 26(8): 561-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12501913&dopt=Abstract
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Alcohol consumption in heroin users, methadone-substituted and codeinesubstituted patients--frequency and correlates of use. Author(s): Backmund M, Schutz CG, Meyer K, Eichenlaub D, Soyka M. Source: European Addiction Research. 2003 January; 9(1): 45-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12566797&dopt=Abstract
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Allergic urticarial rash from oral codeine. Author(s): de Groot AC, Conemans J. Source: Contact Dermatitis. 1986 April; 14(4): 209-14. Erratum In: Contact Dermatitis 1986 September; 15(3): 194. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2941218&dopt=Abstract
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An evaluation of the role of ROC plots in the prediction of heroin use from total codeine and total morphine concentrations in urine. Author(s): O'Neal CL, Poklis A. Source: Journal of Analytical Toxicology. 1998 October; 22(6): 487-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9788524&dopt=Abstract
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Analgesia after intracranial surgery: a double-blind, prospective comparison of codeine and tramadol. Author(s): Jeffrey HM, Charlton P, Mellor DJ, Moss E, Vucevic M. Source: British Journal of Anaesthesia. 1999 August; 83(2): 245-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618937&dopt=Abstract
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Analgesia following arthroscopic surgery: comparison of diflunisal and acetaminophen with codeine. Author(s): Fulkerson JP, Folcik MA. Source: Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 1986; 2(2): 108-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3730061&dopt=Abstract
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Analgesic effect of an aspirin-codeine-butalbital-caffeine combination and an acetaminophen-codeine combination in postoperative oral surgery pain. Author(s): Forbes JA, Jones KF, Smith WK, Gongloff CM. Source: Pharmacotherapy. 1986 September-October; 6(5): 240-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3540875&dopt=Abstract
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Analgesic effect of naproxen sodium, codeine, a naproxen-codeine combination and aspirin on the postoperative pain of oral surgery. Author(s): Forbes JA, Keller CK, Smith JW, Zeleznock JR, Sevelius H, Beaver WT. Source: Pharmacotherapy. 1986 September-October; 6(5): 211-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3540871&dopt=Abstract
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Analgesic efficacy of ibuprofen alone and in combination with codeine or caffeine in post-surgical pain: a meta-analysis. Author(s): Po AL, Zhang WY. Source: European Journal of Clinical Pharmacology. 1998 January; 53(5): 303-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9516027&dopt=Abstract
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Analysis of apoptosis signaling pathway in human cancer cells by codeinone, a synthetic derivative of codeine. Author(s): Hitosugi N, Nagasaka H, Sakagami H, Matsumoto I, Kawase M. Source: Anticancer Res. 2003 May-June; 23(3B): 2569-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12894543&dopt=Abstract
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Analysis of cocaine, benzoylecgonine, codeine, and morphine in hair by supercritical fluid extraction with carbon dioxide modified with methanol. Author(s): Brewer WE, Galipo RC, Sellers KW, Morgan SL. Source: Analytical Chemistry. 2001 June 1; 73(11): 2371-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11403274&dopt=Abstract
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Analysis of codeine, dihydrocodeine and their glucuronides in human urine by electrokinetic capillary immunoassays and capillary electrophoresis-ion trap mass spectrometry. Author(s): Wey AB, Caslavska J, Thormann W. Source: J Chromatogr A. 2000 October 20; 895(1-2): 133-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11105855&dopt=Abstract
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Analysis of morphine and codeine in samples adulterated with Stealth. Author(s): Cody JT, Valtier S, Kuhlman J. Source: Journal of Analytical Toxicology. 2001 October; 25(7): 572-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11599602&dopt=Abstract
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Analysis of the analgesic efficacy of acetaminophen 1000 mg, codeine phosphate 60 mg, and the combination of acetaminophen 1000 mg and codeine phosphate 60 mg in the relief of postoperative pain. Author(s): Gertzbein SD, Tile M, McMurty RY, Kellam JF, Hunter GA, Keith RG, Harsanyi Z, Luffman J. Source: Pharmacotherapy. 1986 May-June; 6(3): 104-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3737440&dopt=Abstract
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Assessment of Fiorinal with Codeine in the treatment of tension headache. Author(s): Friedman AP. Source: Clinical Therapeutics. 1986; 8(6): 703-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3791366&dopt=Abstract
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Assessment of the antitussive efficacy of codeine in cough associated with common cold. Author(s): Freestone C, Eccles R. Source: The Journal of Pharmacy and Pharmacology. 1997 October; 49(10): 1045-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9364418&dopt=Abstract
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Bioactivation of the narcotic drug codeine in human liver is mediated by the polymorphic monooxygenase catalyzing debrisoquine 4-hydroxylation (cytochrome P-450 dbl/bufI). Author(s): Dayer P, Desmeules J, Leemann T, Striberni R. Source: Biochemical and Biophysical Research Communications. 1988 April 15; 152(1): 411-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3358767&dopt=Abstract
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Bioavailability study of fosfosal and codeine administered alone or in combination. Author(s): Ramis J, Gich I, Torrent J, Mis R, Jane F, Forn J. Source: Int J Clin Pharmacol Ther Toxicol. 1989 July; 27(7): 352-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2777424&dopt=Abstract
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Characteristics of dependent and nondependent regular users of codeine. Author(s): Sproule BA, Busto UE, Somer G, Romach MK, Sellers EM. Source: Journal of Clinical Psychopharmacology. 1999 August; 19(4): 367-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440466&dopt=Abstract
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Codeine analgesia is due to codeine-6-glucuronide, not morphine. Author(s): Vree TB, van Dongen RT, Koopman-Kimenai PM. Source: Int J Clin Pract. 2000 July-August; 54(6): 395-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092114&dopt=Abstract
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Codeine and clinical impairment in samples in which morphine is not detected. Author(s): Bachs L, Skurtveit S, Morland J. Source: European Journal of Clinical Pharmacology. 2003 April; 58(12): 785-9. Epub 2003 March 01. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12698303&dopt=Abstract
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Codeine and oxycodone use in patients with chronic rheumatic disease pain. Author(s): Ytterberg SR, Mahowald ML, Woods SR. Source: Arthritis and Rheumatism. 1998 September; 41(9): 1603-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9751092&dopt=Abstract
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Codeine caused pruritic scarlatiniform exanthemata: patch test negative but positive to oral provocation test. Author(s): Mohrenschlager M, Glockner A, Jessberger B, Worret WI, Ollert M, Rakoski J, Ring J. Source: The British Journal of Dermatology. 2000 September; 143(3): 663-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10971360&dopt=Abstract
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Codeine concentration in hair after oral administration is dependent on melanin content. Author(s): Kronstrand R, Forstberg-Peterson S, Kagedal B, Ahlner J, Larson G. Source: Clinical Chemistry. 1999 September; 45(9): 1485-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10471651&dopt=Abstract
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Codeine dosage in renal failure. Author(s): Matzke GR, Chan GL, Abraham PA. Source: Clin Pharm. 1986 January; 5(1): 15-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3948481&dopt=Abstract
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Codeine for pruritus in primary billiary cirrhosis. Author(s): Zylicz Z, Krajnik M. Source: Lancet. 1999 March 6; 353(9155): 813. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10459971&dopt=Abstract
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Codeine in post-operative pain. Study of the influence of sparteine phenotype and serum concentrations of morphine and morphine-6-glucuronide. Author(s): Poulsen L, Riishede L, Brosen K, Clemensen S, Sindrup SH. Source: European Journal of Clinical Pharmacology. 1998 August; 54(6): 451-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9776433&dopt=Abstract
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Codeine ingestion and apparent life-threatening event in a neonate. Author(s): Tong TF, Ng KK. Source: Pediatrics International : Official Journal of the Japan Pediatric Society. 2001 October; 43(5): 517-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11737718&dopt=Abstract
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Codeine intoxication in the neonate. Author(s): Magnani B, Evans R. Source: Pediatrics. 1999 December; 104(6): E75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10586009&dopt=Abstract
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Codeine phosphate in children: time for re-evaluation? Author(s): Cunliffe M. Source: British Journal of Anaesthesia. 2001 March; 86(3): 329-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573519&dopt=Abstract
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Codeine phosphate in paediatric medicine. Author(s): William DG, Hatch DJ, Howard RF. Source: British Journal of Anaesthesia. 2001 March; 86(3): 413-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573533&dopt=Abstract
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Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain. Author(s): Palangio M, Damask MJ, Morris E, Doyle RT Jr, Jiang JG, Landau CJ, de Padova A. Source: Clinical Therapeutics. 2000 July; 22(7): 879-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10945514&dopt=Abstract
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Combining diclofenac with acetaminophen or acetaminophen-codeine after oral surgery: a randomized, double-blind single-dose study. Author(s): Breivik EK, Barkvoll P, Skovlund E. Source: Clinical Pharmacology and Therapeutics. 1999 December; 66(6): 625-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10613619&dopt=Abstract
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Comparative analysis of apoptosis-inducing activity of codeine and codeinone. Author(s): Hitosugi N, Hatsukari I, Ohno R, Hashimoto K, Mihara S, Mizukami S, Nakamura S, Sakagami H, Nagasaka H, Matsumoto I, Kawase M. Source: Anesthesiology. 2003 March; 98(3): 643-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12606908&dopt=Abstract
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Comparative bioavailability study of codeine and ibuprofen after administration of the two products alone or in association to 24 healthy volunteers. Author(s): Laneury JP, Duchene P, Hirt P, Delarue A, Gleizes S, Houin G, Molinier P. Source: Eur J Drug Metab Pharmacokinet. 1998 April-June; 23(2): 185-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9725479&dopt=Abstract
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Comparative disposition of codeine and pholcodine in man after single oral doses. Author(s): Findlay JW, Fowle AS, Butz RF, Jones EC, Weatherley BC, Welch RM, Posner J. Source: British Journal of Clinical Pharmacology. 1986 July; 22(1): 61-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3741728&dopt=Abstract
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Comparative study of flurbiprofen, zomepirac sodium, acetaminophen plus codeine, and acetaminophen for the relief of postsurgical dental pain. Author(s): Sunshine A, Marrero I, Olson N, McCormick N, Laska EM. Source: The American Journal of Medicine. 1986 March 24; 80(3A): 50-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3515924&dopt=Abstract
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Comparison of diflunisal and acetaminophen with codeine in the management of grade 2 ankle sprain. Author(s): Aghababian RV. Source: Clinical Therapeutics. 1986; 8(5): 520-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3094957&dopt=Abstract
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Comparison of diflunisal and acetaminophen with codeine in the treatment of initial or recurrent acute low back strain. Author(s): Brown FL Jr, Bodison S, Dixon J, Davis W, Nowoslawski J. Source: Clinical Therapeutics. 1986; 9 Suppl C: 52-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2951012&dopt=Abstract
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Comparison of diflunisal and acetaminophen with codeine in the treatment of mild to moderate pain due to strains and sprains. Author(s): Indelicato PA. Source: Clinical Therapeutics. 1986; 8(3): 269-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3521855&dopt=Abstract
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Comparison of morphine sulphate and codeine phosphate in children undergoing adenotonsillectomy. Author(s): Semple D, Russell S, Doyle E, Aldridge LM. Source: Paediatric Anaesthesia. 1999; 9(2): 135-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10189654&dopt=Abstract
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Comparison of the efficacy and tolerability of a paracetamol/codeine fixed-dose combination with tramadol in patients with refractory chronic back pain. Author(s): Muller FO, Odendaal CL, Muller FR, Raubenheimer J, Middle MV, Kummer M. Source: Arzneimittel-Forschung. 1998 June; 48(6): 675-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9689426&dopt=Abstract
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Concentration ratios of codeine-to-morphine in plasma after a single oral dose (100 mg) of codeine phosphate. Author(s): Kronstrand R, Jones AW. Source: Journal of Analytical Toxicology. 2001 September; 25(6): 486-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550826&dopt=Abstract
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Concentration ratios of morphine to codeine in blood of impaired drivers as evidence of heroin use and not medication with codeine. Author(s): Ceder G, Jones AW. Source: Clinical Chemistry. 2001 November; 47(11): 1980-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11673366&dopt=Abstract
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Concentrations of unconjugated morphine, codeine and 6-acetylmorphine in urine specimens from suspected drugged drivers. Author(s): Ceder G, Jones AW. Source: J Forensic Sci. 2002 March; 47(2): 366-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11908609&dopt=Abstract
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Contribution of dihydrocodeine and dihydromorphine to analgesia following dihydrocodeine administration in man: a PK-PD modelling analysis. Author(s): Webb JA, Rostami-Hodjegan A, Abdul-Manap R, Hofmann U, Mikus G, Kamali F. Source: British Journal of Clinical Pharmacology. 2001 July; 52(1): 35-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11453888&dopt=Abstract
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Correlation of saliva codeine concentrations with plasma concentrations after oral codeine administration. Author(s): O'Neal CL, Crouch DJ, Rollins DE, Fatah A, Cheever ML. Source: Journal of Analytical Toxicology. 1999 October; 23(6): 452-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517550&dopt=Abstract
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Cytochrome P450 2D6 and treatment of codeine dependence. Author(s): Romach MK, Otton SV, Somer G, Tyndale RF, Sellers EM. Source: Journal of Clinical Psychopharmacology. 2000 February; 20(1): 43-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10653207&dopt=Abstract
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Decreased skin reactivity to codeine in patients with the acquired immunodeficiency syndrome. Author(s): Simonart T, Parent D, Heenen M, Farber CM, Van Vooren JP. Source: Clinical Immunology and Immunopathology. 1996 October; 81(1): 12-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8808635&dopt=Abstract
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Detection of acetylcodeine in urine as an indicator of illicit heroin use: method validation and results of a pilot study. Author(s): Staub C, Marset M, Mino A, Mangin P. Source: Clinical Chemistry. 2001 February; 47(2): 301-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159779&dopt=Abstract
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Detection of codeine and phenobarbital in sweat collected with a sweat patch. Author(s): Kintz P, Tracqui A, Jamey C, Mangin P. Source: Journal of Analytical Toxicology. 1996 May-June; 20(3): 197-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8735203&dopt=Abstract
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Determination of codeine and its metabolite in human urine by CE with amperometric detection. Author(s): Zhou T, Yu H, Hu Q, Fang Y. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 August 22; 30(1): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12151061&dopt=Abstract
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Determination of codeine and metabolites in plasma and urine using ion-pair highperformance liquid chromatography. Author(s): Svensson JO, Yue QY, Sawe J. Source: Journal of Chromatography. B, Biomedical Applications. 1995 December 1; 674(1): 49-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8749251&dopt=Abstract
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Determination of codeine in human plasma by high-performance liquid chromatography with fluorescence detection. Author(s): Weingarten B, Wang HY, Roberts DM. Source: J Chromatogr A. 1995 April 7; 696(1): 83-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7735464&dopt=Abstract
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Determination of codeine in plasma and urine by reversed-phase high-performance liquid chromatography. Author(s): Stubbs RJ, Chiou R, Bayne WF. Source: Journal of Chromatography. 1986 April 25; 377: 447-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3711241&dopt=Abstract
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Determination of codeine in urine and drug formulations using a clay-modified screen-printed carbon electrode. Author(s): Shih Y, Zen JM, Yang HH. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 July 31; 29(5): 827-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12093515&dopt=Abstract
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Determination of morphine and codeine in plasma by HPLC following solid phase extraction. Author(s): Freiermuth M, Plasse JC. Source: Journal of Pharmaceutical and Biomedical Analysis. 1997 March; 15(6): 759-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9172101&dopt=Abstract
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Determination of morphine and its 3- and 6-glucuronides, codeine, codeineglucuronide and 6-monoacetylmorphine in body fluids by liquid chromatography atmospheric pressure chemical ionization mass spectrometry. Author(s): Bogusz MJ, Maier RD, Erkens M, Driessen S. Source: J Chromatogr B Biomed Sci Appl. 1997 December 5; 703(1-2): 115-27. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9448068&dopt=Abstract
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Determination of the dihydrocodeine metabolites, dihydromorphine and nordihydrocodeine, in hepatic microsomal incubations by high-performance liquid chromatography. Author(s): Kirkwood LC, Nation RL, Somogyi AA. Source: J Chromatogr B Biomed Sci Appl. 1997 November 7; 701(1): 129-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9389348&dopt=Abstract
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Different effects of inhibitors on the O- and N-demethylation of codeine in human liver microsomes. Author(s): Yue QY, Sawe J. Source: European Journal of Clinical Pharmacology. 1997; 52(1): 41-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9143866&dopt=Abstract
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Dihydrocodeine prescription. Author(s): Matthew I, Frame J. Source: British Dental Journal. 1998 March 28; 184(6): 266. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9581357&dopt=Abstract
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Dihydrocodeine removal. Author(s): Speechley JA, Hancock PA. Source: British Dental Journal. 1998 June 13; 184(11): 525. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9682541&dopt=Abstract
•
Dihydrocodeine to stay on dental practitioners' list. Author(s): Carruthers S. Source: British Dental Journal. 1998 September 26; 185(6): 264. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803026&dopt=Abstract
•
Dihydrocodeine: a drug allergy diagnosed by patch testing. Author(s): Cooper SM, Shaw S. Source: Contact Dermatitis. 2000 May; 42(5): 307-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10789869&dopt=Abstract
•
Dihydrocodeine: a new opioid substrate for the polymorphic CYP2D6 in humans. Author(s): Fromm MF, Hofmann U, Griese EU, Mikus G. Source: Clinical Pharmacology and Therapeutics. 1995 October; 58(4): 374-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7586928&dopt=Abstract
•
Dihydrocodeine: a useful tool in the detoxification of methadone-maintained patients. Author(s): Banbery J, Wolff K, Raistrick D. Source: Journal of Substance Abuse Treatment. 2000 October; 19(3): 301-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11027902&dopt=Abstract
•
Dihydrocodeine--drug of use or misuse? Author(s): Seymour A, Black M, Oliver JS, Jay J. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2001 May; 51(466): 404-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11360709&dopt=Abstract
•
Discrimination between urticaria-prone and other allergic patients by intradermal skin testing with codeine. Author(s): Cohen RW, Rosenstreich DL. Source: The Journal of Allergy and Clinical Immunology. 1986 June; 77(6): 802-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3711548&dopt=Abstract
Studies
31
•
Disposition of codeine in female human hair after multiple-dose administration. Author(s): Wilkins DG, Haughey HM, Krueger GG, Rollins DE. Source: Journal of Analytical Toxicology. 1995 October; 19(6): 492-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8926744&dopt=Abstract
•
Distribution of codeine, morphine, and 6-acetylmorphine in vitreous humor. Author(s): Lin DL, Chen CY, Shaw KP, Havier R, Lin RL. Source: Journal of Analytical Toxicology. 1997 July-August; 21(4): 258-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9248941&dopt=Abstract
•
Do codeine and caffeine enhance the analgesic effect of aspirin?--A systematic overview. Author(s): Zhang WY, Po AL. Source: Journal of Clinical Pharmacy and Therapeutics. 1997 April; 22(2): 79-97. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9373807&dopt=Abstract
•
Dose-related effects of controlled release dihydrocodeine on oro-cecal transit and pupillary light reflex. A study in human volunteers. Author(s): Freye E, Baranowski J, Latasch L. Source: Arzneimittel-Forschung. 2001 January; 51(1): 60-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11215327&dopt=Abstract
•
Double blind randomized placebo control trial of controlled release codeine in the treatment of osteoarthritis of the hip or knee. Author(s): Peloso PM, Bellamy N, Bensen W, Thomson GT, Harsanyi Z, Babul N, Darke AC. Source: The Journal of Rheumatology. 2000 March; 27(3): 764-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10743822&dopt=Abstract
•
Double-blind comparison of an acetaminophen-codeine-caffeine combination in oral surgery pain. Author(s): Cooper SA, Erlichman MC, Mardirossian G. Source: Anesthesia Progress. 1986 May-June; 33(3): 139-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3461725&dopt=Abstract
•
Double-blind comparison of the analgesic potency of ciramadol, codeine and placebo against postsurgical pain in ambulant patients. Author(s): van Steenberghe D, Verbist D, Quirynen M, Thevissen E. Source: European Journal of Clinical Pharmacology. 1986; 31(3): 355-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3792434&dopt=Abstract
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Double-blind evaluation of short-term analgesic efficacy of orally administered diclofenac, diclofenac plus codeine, and diclofenac plus imipramine in chronic cancer pain. Author(s): Minotti V, De Angelis V, Righetti E, Celani MG, Rossetti R, Lupatelli M, Tonato M, Pisati R, Monza G, Fumi G, Del Favero A. Source: Pain. 1998 February; 74(2-3): 133-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9520227&dopt=Abstract
•
Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum. Author(s): Joseph RE Jr, Oyler JM, Wstadik AT, Ohuoha C, Cone EJ. Source: Journal of Analytical Toxicology. 1998 January-February; 22(1): 6-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9491963&dopt=Abstract
•
Drug testing with alternative matrices II. Mechanisms of cocaine and codeine deposition in hair. Author(s): Joseph RE Jr, Hold KM, Wilkins DG, Rollins DE, Cone EJ. Source: Journal of Analytical Toxicology. 1999 October; 23(6): 396-408. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517543&dopt=Abstract
•
Effect of an enteric-release formulation of naloxone on intestinal transit in volunteers taking codeine. Author(s): Hawkes ND, Richardson C, Evans BK, Rhodes J, Lewis SJ, Thomas GA. Source: Alimentary Pharmacology & Therapeutics. 2001 May; 15(5): 625-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11328255&dopt=Abstract
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Effect of codeine and oxazepam on afternoon cortisol secretion in men. Author(s): Garland EJ, Zis AP. Source: Psychoneuroendocrinology. 1989; 14(5): 397-402. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2813660&dopt=Abstract
•
Effect of codeine on gastrointestinal motility in relation to CYP2D6 phenotype. Author(s): Mikus G, Trausch B, Rodewald C, Hofmann U, Richter K, Gramatte T, Eichelbaum M. Source: Clinical Pharmacology and Therapeutics. 1997 April; 61(4): 459-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9129563&dopt=Abstract
•
Effect of codeine on oro-cecal transit time in Chinese healthy volunteers in comparison with Caucasian subjects. Author(s): Yue QY, Hasselstrom J, Svensson JO, Sawe J. Source: European Journal of Clinical Pharmacology. 1999 January; 54(11): 839-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10027657&dopt=Abstract
Studies
33
•
Effect of codeine on the sensations elicited by loaded breathing. Author(s): Supinski G, Dimarco A, Bark H, Chapman K, Clary S, Altose M. Source: Am Rev Respir Dis. 1990 June; 141(6): 1516-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2350094&dopt=Abstract
•
Effective treatment of narcolepsy with codeine in a patient receiving hemodialysis. Author(s): Benbadis SR. Source: Pharmacotherapy. 1996 May-June; 16(3): 463-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8726607&dopt=Abstract
•
Effects of dihydrocodeine on chemosensitivity and exercise tolerance in patients with chronic heart failure. Author(s): Chua TP, Harrington D, Ponikowski P, Webb-Peploe K, Poole-Wilson PA, Coats AJ. Source: Journal of the American College of Cardiology. 1997 January; 29(1): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8996307&dopt=Abstract
•
Effects of zolpidem, codeine phosphate and placebo on respiration. A double-blind, crossover study in volunteers. Author(s): Cohn MA. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1993 October; 9(4): 312-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8260124&dopt=Abstract
•
Efficacy and safety of levodropropizine and dihydrocodeine on nonproductive cough in primary and metastatic lung cancer. Author(s): Luporini G, Barni S, Marchi E, Daffonchio L. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1998 July; 12(1): 97-101. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9701421&dopt=Abstract
•
Efficacy and tolerance of lysine clonixinate versus paracetamol/codeine following inguinal hernioplasty. Author(s): de los Santos AR, Di Girolamo G, Marti ML. Source: Int J Tissue React. 1998; 20(2): 71-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9638504&dopt=Abstract
•
Efficacy of controlled-release codeine in chronic non-malignant pain: a randomized, placebo-controlled clinical trial. Author(s): Arkinstall W, Sandler A, Goughnour B, Babul N, Harsanyi Z, Darke AC. Source: Pain. 1995 August; 62(2): 169-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8545142&dopt=Abstract
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Efficacy of diflunisal versus acetaminophen with codeine in controlling mild to moderate pain after arthroscopy. Author(s): Indelicato PA. Source: Clinical Therapeutics. 1986; 8(2): 164-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3698062&dopt=Abstract
•
Efficacy of low dose combination analgesics: acetaminophen/codeine, aspirin/butalbital/caffeine/codeine, and placebo in oral surgery pain. Author(s): Desjardins PJ, Cooper SA, Finizio T. Source: Anesthesia Progress. 1986 May-June; 33(3): 143-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3461726&dopt=Abstract
•
Endogenous codeine and morphine in anorexia and bulimia nervosa. Author(s): Marrazzi MA, Luby ED, Kinzie J, Munjal ID, Spector S. Source: Life Sciences. 1997; 60(20): 1741-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9150413&dopt=Abstract
•
Endogenous codeine and morphine in poor and extensive metabolisers of the CYP2D6 (debrisoquine/sparteine) polymorphism. Author(s): Mikus G, Bochner F, Eichelbaum M, Horak P, Somogyi AA, Spector S. Source: The Journal of Pharmacology and Experimental Therapeutics. 1994 February; 268(2): 546-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8113966&dopt=Abstract
•
Evaluating codeine plus paracetamol for pain. Author(s): Kjaersgaard-Andersen P. Source: Nurs Times. 1991 April 17-23; 87(16): 52. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2020601&dopt=Abstract
•
Evaluation of a method for simultaneous quantification of codeine, dihydrocodeine, morphine, and 6-monoacetylmorphine in serum, blood, and postmortem blood. Author(s): Musshoff F, Daldrup T. Source: International Journal of Legal Medicine. 1993; 106(2): 107-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8217865&dopt=Abstract
•
Evaluation of a method for simultaneous quantification of codeine, ethylmorphine and morphine in blood. Author(s): Gjerde H, Fongen U, Gundersen H, Christophersen AS. Source: Forensic Science International. 1991 October; 51(1): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1752586&dopt=Abstract
Studies
35
•
Evaluation of a solid-phase extraction procedure for the simultaneous determination of morphine, 6-monoacetylmorphine, codeine and dihydrocodeine in plasma and whole blood by GC/MS. Author(s): Geier A, Bergemann D, von Meyer L. Source: International Journal of Legal Medicine. 1996; 109(2): 80-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8912052&dopt=Abstract
•
Evaluation of acetylcodeine as a specific marker of illicit heroin in human hair. Author(s): Kintz P, Jamey C, Cirimele V, Brenneisen R, Ludes B. Source: Journal of Analytical Toxicology. 1998 October; 22(6): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9788516&dopt=Abstract
•
Evaluation of analytical procedures for urinary codeine and morphine measurements. Author(s): Lin Z, Lafolie P, Beck O. Source: Journal of Analytical Toxicology. 1994 May-June; 18(3): 129-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8065120&dopt=Abstract
•
Evaluation of ketorolac (Toradol) with varying amounts of codeine for postoperative extraction pain control. Author(s): Garibaldi JA, Elder MF. Source: International Journal of Oral and Maxillofacial Surgery. 2002 June; 31(3): 276-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190134&dopt=Abstract
•
Evaluation of ketorolac, aspirin, and an acetaminophen-codeine combination in postoperative oral surgery pain. Author(s): Forbes JA, Butterworth GA, Burchfield WH, Beaver WT. Source: Pharmacotherapy. 1990; 10(6 ( Pt 2)): 77S-93S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2082317&dopt=Abstract
•
Evaluation of ketorolac, ibuprofen, acetaminophen, and an acetaminophen-codeine combination in postoperative oral surgery pain. Author(s): Forbes JA, Kehm CJ, Grodin CD, Beaver WT. Source: Pharmacotherapy. 1990; 10(6 ( Pt 2)): 94S-105S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2082318&dopt=Abstract
•
Evaluation of multicomponent fluorimetric analytical data by use of partial leastsquares calibration. Application to the determination of codeine and ephedrine in urine. Author(s): Bautista Jimenez RD, Jimenez Abizanda AI, Jimenez Moreno FJ, Arias Leon JJ. Source: Clinica Chimica Acta; International Journal of Clinical Chemistry. 1996 May 30; 249(1-2): 21-36. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8737589&dopt=Abstract
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Evaluation of two formulations of dihydrocodeine using patient-controlled analgesia. Author(s): Aitken HA, Clark EC, McArdle CS, Dimitri W, Kenny GN. Source: Anaesthesia. 1990 July; 45(7): 535-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2201224&dopt=Abstract
•
Evaluation of urinary dihydrocodeine excretion in human by gas chromatographymass spectrometry. Author(s): Balikova M, Maresova V, Habrdova V. Source: J Chromatogr B Biomed Sci Appl. 2001 March 5; 752(1): 179-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11254193&dopt=Abstract
•
Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150 mg diclofenac sodium in comparison with 60 mg codeine and placebo. Author(s): Stacher G, Steinringer H, Schneider S, Mittelbach G, Winklehner S, Gaupmann G. Source: British Journal of Clinical Pharmacology. 1986 January; 21(1): 35-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3947505&dopt=Abstract
•
Exploration of the metabolism of dihydrocodeine via determination of its metabolites in human urine using micellar electrokinetic capillary chromatography. Author(s): Hufschmid E, Theurillat R, Martin U, Thormann W. Source: Journal of Chromatography. B, Biomedical Applications. 1995 June 9; 668(1): 159-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7550973&dopt=Abstract
•
Extraction of benzoylecgonine (cocaine metabolite) and opiates (codeine and morphine) from urine samples using the Zymark RapidTrace. Author(s): Diamond FX, Vickery WE, de Kanel J. Source: Journal of Analytical Toxicology. 1996 November-December; 20(7): 587-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8934311&dopt=Abstract
•
Fatalities associated with an acute overdose of glutethimide (Doriden) and codeine. Author(s): Bender FH, Cooper JV, Dreyfus R. Source: Vet Hum Toxicol. 1988 August; 30(4): 332-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3176309&dopt=Abstract
•
Fever and urticaria to codeine. Author(s): Vidal C, Perez-Leiros P, Bugarin R, Armisen M. Source: Allergy. 2000 April; 55(4): 416-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10782540&dopt=Abstract
Studies
37
•
Fibrin formation during ongoing cutaneous allergic reactions: comparison of responses to antigen and codeine. Author(s): Atkins PC, von Allmen C, Moskovitz A, Valenzano M, Zweiman B. Source: The Journal of Allergy and Clinical Immunology. 1993 April; 91(4): 956-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7682581&dopt=Abstract
•
Fiorinal with Codeine in the management of tension headache: impact of placebo response. Author(s): Hwang DS, Mietlowski MJ, Friedman AP. Source: Clinical Therapeutics. 1987; 9(2): 201-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3552225&dopt=Abstract
•
Fiorinal with codeine in the treatment of tension headache--the contribution of components to the combination drug. Author(s): Friedman AP, Boyles WF, Elkind AH, Fillingim J, Ford RG, Gallagher RM, Hobbs D, Rapoport A, Richards BA, Sheftell FD, et al. Source: Clinical Therapeutics. 1988; 10(3): 303-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3078909&dopt=Abstract
•
Fixed drug eruption due to codeine. Author(s): Gonzalo-Garijo MA, Revenga-Arranz F. Source: The British Journal of Dermatology. 1996 September; 135(3): 498-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8949462&dopt=Abstract
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Flurbiprofen, aspirin, codeine, and placebo for postpartum uterine pain. Author(s): Bloomfield SS, Mitchell J, Cissell G, Barden TP. Source: The American Journal of Medicine. 1986 March 24; 80(3A): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3515927&dopt=Abstract
•
Forensic drug testing for opiates, III. Urinary excretion rates of morphine and codeine following codeine administration. Author(s): Cone EJ, Welch P, Paul BD, Mitchell JM. Source: Journal of Analytical Toxicology. 1991 July-August; 15(4): 161-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1943064&dopt=Abstract
•
Forensic drug testing for opiates. V. Urine testing for heroin, morphine, and codeine with commercial opiate immunoassays. Author(s): Cone EJ, Dickerson S, Paul BD, Mitchell JM. Source: Journal of Analytical Toxicology. 1993 May-June; 17(3): 156-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8336489&dopt=Abstract
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Formation of morphine from codeine in Chinese subjects of different CYP2D6 genotypes. Author(s): Tseng CY, Wang SL, Lai MD, Lai ML, Huang JD. Source: Clinical Pharmacology and Therapeutics. 1996 August; 60(2): 177-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8823235&dopt=Abstract
•
From codeine to transdermal fentanyl for cancer pain control: a safety and efficacy clinical trial. Author(s): Mystakidou K, Befon S, Kouskouni E, Gerolymatos K, Georgaki S, Tsilika E, Vlahos L. Source: Anticancer Res. 2001 May-June; 21(3C): 2225-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11501851&dopt=Abstract
•
Fully automated analytical method for codeine quantification in human plasma using on-line solid-phase extraction and high-performance liquid chromatography with ultraviolet detection. Author(s): Pascual JA, Sanagustin J. Source: J Chromatogr B Biomed Sci Appl. 1999 March 19; 724(2): 295-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10219671&dopt=Abstract
•
Gas chromatographic/mass spectrometric analysis of morphine and codeine in human urine of poppy seed eaters. Author(s): elSohly HN, Stanford DF, Jones AB, elSohly MA, Snyder H, Pedersen C. Source: J Forensic Sci. 1988 March; 33(2): 347-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3373154&dopt=Abstract
•
Gas chromatographic-mass spectrometric procedures used for the identification and determination of morphine, codeine and 6-monoacetylmorphine. Author(s): Wasels R, Belleville F. Source: J Chromatogr A. 1994 July 15; 674(1-2): 225-34. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8075772&dopt=Abstract
•
Gas chromatography with surface ionization detection: a highly sensitive method for determining underivatized codeine and dihydrocodeine in body fluids. Author(s): Seno H, Hattori H, Kurono S, Yamada T, Kumazawa T, Ishii A, Suzuki O. Source: Journal of Chromatography. B, Biomedical Applications. 1995 November 17; 673(2): 189-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8611952&dopt=Abstract
Studies
39
•
GC-MS confirmation of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone in urine. Author(s): Meatherall R. Source: Journal of Analytical Toxicology. 1999 May-June; 23(3): 177-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10369327&dopt=Abstract
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Generalized dermatitis due to codeine. Author(s): Rodriguez F, Fernandez L, Garcia-Abujeta JL, Maquiera E, Llaca HF, Jerez J. Source: Contact Dermatitis. 1995 February; 32(2): 120. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7758317&dopt=Abstract
•
Generalized eczema due to codeine. Author(s): Estrada JL, Puebla MJ, de Urbina JJ, Matilla B, Prieto MA, Gozalo F. Source: Contact Dermatitis. 2001 March; 44(3): 185. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11217996&dopt=Abstract
•
Genetic analysis of the interethnic difference between Chinese and Caucasians in the polymorphic metabolism of debrisoquine and codeine. Author(s): Johansson I, Yue QY, Dahl ML, Heim M, Sawe J, Bertilsson L, Meyer UA, Sjoqvist F, Ingelman-Sundberg M. Source: European Journal of Clinical Pharmacology. 1991; 40(6): 553-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1679392&dopt=Abstract
•
Glucuronidation of codeine and morphine in human liver and kidney microsomes: effect of inhibitors. Author(s): Yue Q, von Bahr C, Odar-Cederlof I, Sawe J. Source: Pharmacology & Toxicology. 1990 March; 66(3): 221-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2110360&dopt=Abstract
•
Glucuronidation of dihydrocodeine by human liver microsomes and the effect of inhibitors. Author(s): Kirkwood LC, Nation RL, Somogyi AA. Source: Clinical and Experimental Pharmacology & Physiology. 1998 March-April; 25(34): 266-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9590580&dopt=Abstract
•
Growth hormone replacement therapy induces codeine clearance. Author(s): Gil Berglund E, Johannsson G, Beck O, Bengtsson BA, Rane A. Source: European Journal of Clinical Investigation. 2002 July; 32(7): 507-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12153551&dopt=Abstract
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Codeine
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Hazards of codeine plus paracetamol compounds. Author(s): Wylie AS, Fraser AA. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 1994 August; 44(385): 376. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8068400&dopt=Abstract
•
Highly sensitive gas chromatographic-tandem mass spectrometric method for the determination of morphine and codeine in serum and urine in the femtomolar range. Author(s): Hofmann U, Seefried S, Schweizer E, Ebner T, Mikus G, Eichelbaum M. Source: J Chromatogr B Biomed Sci Appl. 1999 April 30; 727(1-2): 81-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10360425&dopt=Abstract
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High-performance liquid chromatographic determination of morphine, morphine-3glucuronide, morphine-6-glucuronide and codeine in biological samples using multiwavelength forward optical detection. Author(s): Chari G, Gulati A, Bhat R, Tebbett IR. Source: Journal of Chromatography. 1991 November 15; 571(1-2): 263-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1810955&dopt=Abstract
•
High-performance liquid chromatographic determination of morphine, morphine-3glucuronide, morphine-6-glucuronide and codeine in biological samples using multiwavelength forward optical detection: a reply. Author(s): Bogusz M. Source: Journal of Chromatography. 1992 August 7; 579(1): 189-90; Discussion 191-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1447348&dopt=Abstract
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Histamine release in intact human skin by monocyte chemoattractant factor-1, RANTES, macrophage inflammatory protein-1 alpha, stem cell factor, anti-IgE, and codeine as determined by an ex vivo skin microdialysis technique. Author(s): Petersen LJ, Brasso K, Pryds M, Skov PS. Source: The Journal of Allergy and Clinical Immunology. 1996 October; 98(4): 790-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8876555&dopt=Abstract
•
Human pharmacokinetic study of immediate-release (codeine phosphate) and sustained-release (codeine Contin) codeine. Author(s): Band CJ, Band PR, Deschamps M, Besner JG, Coldman AJ. Source: Journal of Clinical Pharmacology. 1994 September; 34(9): 938-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7983238&dopt=Abstract
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Hydrocodone versus codeine in acute musculoskeletal pain. Author(s): Turturro MA, Paris PM, Yealy DM, Menegazzi JJ. Source: Annals of Emergency Medicine. 1991 October; 20(10): 1100-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1928881&dopt=Abstract
Studies
41
•
Hydromorphone and hydrocodone interference in GC/MS assays for morphine and codeine. Author(s): Fenton J, Mummert J, Childers M. Source: Journal of Analytical Toxicology. 1994 May-June; 18(3): 159-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7520516&dopt=Abstract
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Hypoxaemia and hypotension after intravenous codeine phosphate. Author(s): Cox RG. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1994 December; 41(12): 1211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7532552&dopt=Abstract
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Ibuprofen plus codeine, ibuprofen, and placebo in a single- and multidose cross-over comparison for coxarthrosis pain. Author(s): Quiding H, Grimstad J, Rusten K, Stubhaug A, Bremnes J, Breivik H. Source: Pain. 1992 September; 50(3): 303-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1280802&dopt=Abstract
•
Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial. Author(s): Peter EA, Janssen PA, Grange CS, Douglas MJ. Source: Cmaj : Canadian Medical Association Journal = Journal De L'association Medicale Canadienne. 2001 October 30; 165(9): 1203-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11706909&dopt=Abstract
•
Identification of hydrocodone in human urine following controlled codeine administration. Author(s): Oyler JM, Cone EJ, Joseph RE Jr, Huestis MA. Source: Journal of Analytical Toxicology. 2000 October; 24(7): 530-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043655&dopt=Abstract
•
Impact of environmental and genetic factors on codeine analgesia. Author(s): Desmeules J, Gascon MP, Dayer P, Magistris M. Source: European Journal of Clinical Pharmacology. 1991; 41(1): 23-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1782973&dopt=Abstract
•
Impact of ethnic origin and quinidine coadministration on codeine's disposition and pharmacodynamic effects. Author(s): Caraco Y, Sheller J, Wood AJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 1999 July; 290(1): 413-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10381807&dopt=Abstract
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Impact of quinidine on plasma and cerebrospinal fluid concentrations of codeine and morphine after codeine intake. Author(s): Sindrup SH, Hofmann U, Asmussen J, Mikus G, Brosen K, Nielsen F, Ingwersen SH, Broen Christensen C. Source: European Journal of Clinical Pharmacology. 1996; 49(6): 503-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8706777&dopt=Abstract
•
Improved method for the simultaneous determination of morphine, codeine and dihydrocodeine in blood by high-performance liquid chromatography with electrochemical detection. Author(s): Bedford KR, White PC. Source: Journal of Chromatography. 1985 November 22; 347(3): 398-404. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4077940&dopt=Abstract
•
In vitro forecasting of drugs that may interfere with codeine bioactivation. Author(s): Dayer P, Desmeules J, Striberni R. Source: Eur J Drug Metab Pharmacokinet. 1992 April-June; 17(2): 115-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1425809&dopt=Abstract
•
In vitro interaction of codeine and diclofenac. Author(s): Ammon S, von Richter O, Hofmann U, Thon KP, Eichelbaum M, Mikus G. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2000 October; 28(10): 1149-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10997932&dopt=Abstract
•
Increased erythrocyte and protein binding of codeine in patients with sickle cell disease. Author(s): Mohammed SS, Christopher MM, Mehta P, Kedar A, Gross S, Derendorf H. Source: Journal of Pharmaceutical Sciences. 1993 November; 82(11): 1112-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8289123&dopt=Abstract
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Increased urinary morphine, codeine and tetrahydropapaveroline in parkinsonian patient undergoing L-3,4-dihydroxyphenylalanine therapy: a possible biosynthetic pathway of morphine from L-3,4-dihydroxyphenylalanine in humans. Author(s): Matsubara K, Fukushima S, Akane A, Kobayashi S, Shiono H. Source: The Journal of Pharmacology and Experimental Therapeutics. 1992 March; 260(3): 974-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1545408&dopt=Abstract
Studies
43
•
Indices and graphical approaches for the detection of interindividual and interethnic variations in codeine metabolism. Author(s): Yue QY, Iselius L, Sawe J. Source: British Journal of Clinical Pharmacology. 1997 September; 44(3): 239-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9296317&dopt=Abstract
•
Infants and young children metabolise codeine to morphine. A study after single and repeated rectal administration. Author(s): Quiding H, Olsson GL, Boreus LO, Bondesson U. Source: British Journal of Clinical Pharmacology. 1992 January; 33(1): 45-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1540490&dopt=Abstract
•
Influence of glutethimide on rat brain mononucleotides by sub-chronic codeine treatment. Author(s): Loghin F, Popa DS, Socaciu C. Source: Journal of Cellular and Molecular Medicine. 2001 October-December; 5(4): 40916. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067475&dopt=Abstract
•
Influence of hydrolysis procedures on the urinary concentrations of codeine and morphine in relation to doping analysis. Author(s): Delbeke FT, Debackere M. Source: Journal of Pharmaceutical and Biomedical Analysis. 1993 April-May; 11(4-5): 339-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8357870&dopt=Abstract
•
Information on codeine. Author(s): Bell G. Source: Anaesthesia. 2001 December; 56(12): 1214-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11766684&dopt=Abstract
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Inhibition of cytochrome P450 2D6 modifies codeine abuse liability. Author(s): Kathiramalainathan K, Kaplan HL, Romach MK, Busto UE, Li NY, Sawe J, Tyndale RF, Sellers EM. Source: Journal of Clinical Psychopharmacology. 2000 August; 20(4): 435-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10917405&dopt=Abstract
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Interindividual and interethnic differences in the demethylation and glucuronidation of codeine. Author(s): Yue QY, Svensson JO, Alm C, Sjoqvist F, Sawe J. Source: British Journal of Clinical Pharmacology. 1989 December; 28(6): 629-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2611085&dopt=Abstract
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Involvement of codeine in drug-related deaths. Author(s): Gerostamoulos J, Burke MP, Drummer OH. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 1996 December; 17(4): 327-35. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8947360&dopt=Abstract
•
Ketorolac versus acetaminophen-codeine in the emergency department treatment of acute low back pain. Author(s): Innes GD, Croskerry P, Worthington J, Beveridge R, Jones D. Source: The Journal of Emergency Medicine. 1998 July-August; 16(4): 549-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9696169&dopt=Abstract
•
Laboratory validation study of drug evaluation and classification program: alprazolam, d-amphetamine, codeine, and marijuana. Author(s): Heishman SJ, Singleton EG, Crouch DJ. Source: Journal of Analytical Toxicology. 1998 October; 22(6): 503-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9788526&dopt=Abstract
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Lack of effect of codeine in the treatment of cough associated with acute upper respiratory tract infection. Author(s): Eccles R, Morris S, Jawad M. Source: Journal of Clinical Pharmacy and Therapeutics. 1992 June; 17(3): 175-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1639879&dopt=Abstract
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Lack of effect of paracetamol on the pharmacokinetics and metabolism of codeine in man. Author(s): Somogyi A, Bochner F, Chen ZR. Source: European Journal of Clinical Pharmacology. 1991; 41(4): 379-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1804656&dopt=Abstract
•
Long-term codeine use is associated with depressive symptoms. Author(s): Romach MK, Sproule BA, Sellers EM, Somer G, Busto UE. Source: Journal of Clinical Psychopharmacology. 1999 August; 19(4): 373-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10440467&dopt=Abstract
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Lysine clonixinate vs. paracetamol/codeine in postepisiotomy pain. Author(s): De los Santos AR, Marti MI, Espinosa D, Di Girolamo G, Vinacur JC, Casadei A. Source: Acta Physiol Pharmacol Ther Latinoam. 1998; 48(1): 52-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9504193&dopt=Abstract
Studies
45
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Maintenance treatment of opiate addicts in Germany with medications containing codeine--results of a follow-up study. Author(s): Krausz M, Verthein U, Degkwitz P, Haasen C, Raschke P. Source: Addiction (Abingdon, England). 1998 August; 93(8): 1161-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9813897&dopt=Abstract
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Mania associated with codeine and paracetamol. Author(s): Orr KG, Mostert J, Castle DJ. Source: The Australian and New Zealand Journal of Psychiatry. 1998 August; 32(4): 5868. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9711376&dopt=Abstract
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Method for quantification of morphine and its 3- and 6- glucuronides, codeine, codeine glucuronide and 6-monoacetylmorphine in human blood by liquid chromatography-electrospray mass spectrometry for routine analysis in forensic toxicology. Author(s): Dienes-Nagy A, Rivier L, Giroud C, Augsburger M, Mangin P. Source: J Chromatogr A. 1999 August 27; 854(1-2): 109-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10497932&dopt=Abstract
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Microsomal codeine N-demethylation: cosegregation with cytochrome P4503A4 activity. Author(s): Caraco Y, Tateishi T, Guengerich FP, Wood AJ. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1996 July; 24(7): 761-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8818573&dopt=Abstract
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Misuse of dihydrocodeine tartrate (DF 118) among opiate addicts. Author(s): Swadi H, Wells B, Power R. Source: Bmj (Clinical Research Ed.). 1990 May 19; 300(6735): 1313. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2369664&dopt=Abstract
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Morphine and codeine are endogenous components of human cerebrospinal fluid. Author(s): Cardinale GJ, Donnerer J, Finck AD, Kantrowitz JD, Oka K, Spector S. Source: Life Sciences. 1987 January 19; 40(3): 301-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3796227&dopt=Abstract
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Multiple-dose safety study of ibuprofen/codeine and aspirin/codeine combinations. Author(s): Friedman H, Seckman C, Stubbs C, Oster H, Royer G. Source: Journal of Clinical Pharmacology. 1990 January; 30(1): 65-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2303583&dopt=Abstract
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Myocardial Infarction associated with methadone and/or dihydrocodeine. Author(s): Backmund M, Meyer K, Zwehl W, Nagengast O, Eichenlaub D. Source: European Addiction Research. 2001 March; 7(1): 37-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11316924&dopt=Abstract
•
Myth: codeine is a powerful and effective analgesic. Author(s): Arora S, Herbert ME. Source: The Western Journal of Medicine. 2001 June; 174(6): 428. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11381016&dopt=Abstract
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Myth: codeine is an effective cough suppressant for upper respiratory tract infections. Author(s): Herbert ME, Brewster GS. Source: The Western Journal of Medicine. 2000 October; 173(4): 283. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11018007&dopt=Abstract
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Neonatal abstinence syndrome due to codeine. Author(s): Khan K, Chang J. Source: Archives of Disease in Childhood. Fetal and Neonatal Edition. 1997 January; 76(1): F59-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9059191&dopt=Abstract
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No effect of preoperative paracetamol and codeine suppositories for pain after termination of pregnancies in general anaesthesia. Author(s): Dahl V, Fjellanger F, Raeder JC. Source: European Journal of Pain (London, England). 2000; 4(2): 211-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10957701&dopt=Abstract
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No pain relief from codeine.? An introduction to pharmacogenomics. Author(s): Fagerlund TH, Braaten O. Source: Acta Anaesthesiologica Scandinavica. 2001 February; 45(2): 140-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11167158&dopt=Abstract
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Obsessive-compulsive disorder in people that abuse codeine. Author(s): Senjo M. Source: Acta Psychiatrica Scandinavica. 1989 June; 79(6): 619-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2763855&dopt=Abstract
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Occupational dermatitis from thebaine and codeine. Author(s): Waclawski ER, Aldridge R. Source: Contact Dermatitis. 1995 July; 33(1): 51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7493464&dopt=Abstract
Studies
47
•
On the assessment of drug metabolism by assays of codeine and its main metabolites. Author(s): Haffen E, Paintaud G, Berard M, Masuyer C, Bechtel Y, Bechtel PR. Source: Therapeutic Drug Monitoring. 2000 June; 22(3): 258-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10850391&dopt=Abstract
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Opiate toxicity after self poisoning with aspirin and codeine. Author(s): Leslie PJ, Dyson EH, Proudfoot AT. Source: British Medical Journal (Clinical Research Ed.). 1986 January 11; 292(6513): 96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3002537&dopt=Abstract
•
Opioid analgesics and the risk of hip fracture in the elderly: codeine and propoxyphene. Author(s): Shorr RI, Griffin MR, Daugherty JR, Ray WA. Source: J Gerontol. 1992 July; 47(4): M111-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1624693&dopt=Abstract
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Optimizing the hydrolysis of codeine and morphine glucuronides in urine. Author(s): Hackett LP, Dusci LJ, Ilett KF, Chiswell GM. Source: Therapeutic Drug Monitoring. 2002 October; 24(5): 652-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12352938&dopt=Abstract
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Oral administration of codeine in the presence of ethanol: a pharmacokinetic study in man. Author(s): Bodd E, Beylich KM, Christophersen AS, Morland J. Source: Pharmacology & Toxicology. 1987 November; 61(5): 297-300. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3438223&dopt=Abstract
•
Oral ibuprofen versus paracetamol plus codeine for analgesia after ambulatory surgery. Author(s): Raeder JC, Steine S, Vatsgar TT. Source: Anesthesia and Analgesia. 2001 June; 92(6): 1470-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11375827&dopt=Abstract
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Over-the-counter codeine use in Iceland: the impact of increased access. Author(s): Almarsdottir AB, Grimsson A. Source: Scandinavian Journal of Public Health. 2000 December; 28(4): 270-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11228114&dopt=Abstract
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Pain following craniotomy: a preliminary study comparing PCA morphine with intramuscular codeine phosphate. Author(s): Stoneham MD, Cooper R, Quiney NF, Walters FJ. Source: Anaesthesia. 1996 December; 51(12): 1176-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9038464&dopt=Abstract
•
Pain management in dental practice: tramadol vs. codeine combinations. Author(s): Moore PA. Source: The Journal of the American Dental Association. 1999 July; 130(7): 1075-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10422401&dopt=Abstract
•
Pancreatitis induced by codeine: a case report with positive rechallenge. Author(s): Hastier P, Longo F, Buckley M, Chichmanian RM, Delmont JP. Source: Gut. 1997 November; 41(5): 705-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9414983&dopt=Abstract
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Paracetamol versus paracetamol-codeine in the treatment of post-operative dental pain: a randomized, double-blind, prospective trial. Author(s): Macleod AG, Ashford B, Voltz M, Williams B, Cramond T, Gorta L, Simpson JM. Source: Aust Dent J. 2002 June; 47(2): 147-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12139269&dopt=Abstract
•
Paracetamol with and without codeine in acute pain: a quantitative systematic review. Author(s): Moore A, Collins S, Carroll D, McQuay H. Source: Pain. 1997 April; 70(2-3): 193-201. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9150293&dopt=Abstract
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Paracetamol-codeine combinations versus paracetamol alone. Author(s): Li Wan Po A, Zhang WY. Source: Bmj (Clinical Research Ed.). 1996 November 9; 313(7066): 1209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8916778&dopt=Abstract
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Paracetamol-codeine combinations versus paracetamol alone. Actual size of increase needs to be measured. Author(s): Collins S, Moore A, McQuay H. Source: Bmj (Clinical Research Ed.). 1996 November 9; 313(7066): 1209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8916780&dopt=Abstract
Studies
49
•
Paracetamol-codeine combinations versus paracetamol alone. Intention to treat approach is not popular. Author(s): Skoglund LA. Source: Bmj (Clinical Research Ed.). 1996 November 9; 313(7066): 1209. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8916779&dopt=Abstract
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Parenteral codeine. Author(s): Semple TJ, Macintyre PE, Hooper M. Source: Anaesthesia. 1993 June; 48(6): 539-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8323008&dopt=Abstract
•
Patient-controlled analgesia (PCA) with codeine for postoperative pain relief in ten extensive metabolisers and one poor metaboliser of dextromethorphan. Author(s): Persson K, Sjostrom S, Sigurdardottir I, Molnar V, Hammarlund-Udenaes M, Rane A. Source: British Journal of Clinical Pharmacology. 1995 February; 39(2): 182-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7742159&dopt=Abstract
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Pattern of self-administered paracetamol and codeine analgesic consumption after mandibular third-molar surgery. Author(s): Berge TI. Source: Acta Odontologica Scandinavica. 1997 October; 55(5): 270-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9370023&dopt=Abstract
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Pentazocine and codeine: effects on human performance and mood and interactions with diazepam. Author(s): Saarialho-Kere U, Mattila MJ, Seppala T. Source: Med Biol. 1986; 64(5): 293-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3807445&dopt=Abstract
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Pharmacodynamic evaluation of codeine using tooth pulp evoked potentials. Author(s): Suri A, Kaltenbach ML, Grundy BL, Derendorf H. Source: Journal of Clinical Pharmacology. 1996 December; 36(12): 1126-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9013369&dopt=Abstract
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Pharmacogenetic determinants of codeine induction by rifampin: the impact on codeine's respiratory, psychomotor and miotic effects. Author(s): Caraco Y, Sheller J, Wood AJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 1997 April; 281(1): 330-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9103514&dopt=Abstract
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Pharmacogenetic determination of the effects of codeine and prediction of drug interactions. Author(s): Caraco Y, Sheller J, Wood AJ. Source: The Journal of Pharmacology and Experimental Therapeutics. 1996 September; 278(3): 1165-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8819499&dopt=Abstract
•
Pharmacogenetics of codeine metabolism in an urban population of children and its implications for analgesic reliability. Author(s): Williams DG, Patel A, Howard RF. Source: British Journal of Anaesthesia. 2002 December; 89(6): 839-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12453926&dopt=Abstract
•
Pharmacokinetic drug interactions of morphine, codeine, and their derivatives: theory and clinical reality, part I. Author(s): Armstrong SC, Cozza KL. Source: Psychosomatics. 2003 March-April; 44(2): 167-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12618536&dopt=Abstract
•
Pharmacokinetic evaluation of two ibuprofen-codeine combinations. Author(s): Kaltenbach ML, Mohammed SS, Mullersman G, Perrin JH, Derendorf H. Source: Int J Clin Pharmacol Ther. 1994 April; 32(4): 210-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8032582&dopt=Abstract
•
Pharmacokinetics and drug input characteristics for a diclofenac-codeine phosphate combination following oral and rectal administration. Author(s): Hanses A, Spahn-Langguth H, Meiss F, Mutschler E. Source: Arzneimittel-Forschung. 1996 January; 46(1): 57-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8821519&dopt=Abstract
•
Pharmacokinetics of dihydrocodeine and its active metabolite after single and multiple oral dosing. Author(s): Ammon S, Hofmann U, Griese EU, Gugeler N, Mikus G. Source: British Journal of Clinical Pharmacology. 1999 September; 48(3): 317-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10510141&dopt=Abstract
•
Phenacetin or two analgesic components plus caffeine/codeine? Author(s): Repges R. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1994; 9(12): 1839-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7708282&dopt=Abstract
Studies
51
•
Plasma and oral fluid pharmacokinetics and pharmacodynamics after oral codeine administration. Author(s): Kim I, Barnes AJ, Oyler JM, Schepers R, Joseph RE Jr, Cone EJ, Lafko D, Moolchan ET, Huestis MA. Source: Clinical Chemistry. 2002 September; 48(9): 1486-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12194925&dopt=Abstract
•
Plasma concentrations of codeine and its metabolite, morphine, after single and repeated oral administration. Author(s): Quiding H, Anderson P, Bondesson U, Boreus LO, Hynning PA. Source: European Journal of Clinical Pharmacology. 1986; 30(6): 673-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3770062&dopt=Abstract
•
Poppy seeds: differences in morphine and codeine content and variation in inter- and intra-individual excretion. Author(s): Pelders MG, Ros JJ. Source: J Forensic Sci. 1996 March; 41(2): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8871378&dopt=Abstract
•
Possible role of endogenous morphine and codeine on growth regulation of lung tissue. Author(s): Munjal ID, Minna JD, Manneckjee R, Bieck P, Spector S. Source: Life Sciences. 1995; 57(5): 517-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7623618&dopt=Abstract
•
Postmortem distribution of dihydrocodeine and metabolites in a fatal case of dihydrocodeine intoxication. Author(s): Skopp G, Klinder K, Potsch L, Zimmer G, Lutz R, Aderjan R, Mattern R. Source: Forensic Science International. 1998 July 20; 95(2): 99-107. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9722974&dopt=Abstract
•
Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients. Author(s): Backmund M, Meyer K, Eichenlaub D, Schutz CG. Source: Drug and Alcohol Dependence. 2001 October 1; 64(2): 173-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11543987&dopt=Abstract
•
Profound hypotension following intravenous codeine phosphate. Three case reports and some recommendations. Author(s): Parke TJ, Nandi PR, Bird KJ, Jewkes DA. Source: Anaesthesia. 1992 October; 47(10): 852-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1443476&dopt=Abstract
52
Codeine
•
Prolonged erections produced by dihydrocodeine and sildenafil. Author(s): Goldmeier D, Lamba H. Source: Bmj (Clinical Research Ed.). 2002 June 29; 324(7353): 1555. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12089093&dopt=Abstract
•
Prophylactic oral ibuprofen or ibuprofen-codeine versus placebo for postoperative pain after primary hip arthroplasty. Author(s): Dahl V, Raeder JC, Drosdal S, Wathne O, Brynildsrud J. Source: Acta Anaesthesiologica Scandinavica. 1995 April; 39(3): 323-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7793209&dopt=Abstract
•
Quantification of the O- and N-demethylated and the glucuronidated metabolites of codeine relative to the debrisoquine metabolic ratio in urine in ultrarapid, rapid, and poor debrisoquine hydroxylators. Author(s): Yue QY, Alm C, Svensson JO, Sawe J. Source: Therapeutic Drug Monitoring. 1997 October; 19(5): 539-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9357098&dopt=Abstract
•
Quantitation of morphine and codeine in human urine using high-filed asymmetric waveform ion mobility spectrometry (FAIMS) with mass spectrometric detection. Author(s): McCooeye MA, Ells B, Barnett DA, Purves RW, Guevremont R. Source: Journal of Analytical Toxicology. 2001 March; 25(2): 81-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11300511&dopt=Abstract
•
Quantitative determination of codeine and its major metabolites in human hair by gas chromatography-positive ion chemical ionization mass spectrometry: a clinical application. Author(s): Wilkins D, Rollins DE, Seaman J, Haughey H, Krueger G, Foltz R. Source: Journal of Analytical Toxicology. 1995 September; 19(5): 269-74. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7500611&dopt=Abstract
•
Quantitative, noninvasive assessment of antidiarrheal actions of codeine using an experimental model of diarrhea in man. Author(s): Barrow L, Steed KP, Spiller RC, Maskell NA, Brown JK, Watts PJ, Melia CD, Davies MC, Wilson CG. Source: Digestive Diseases and Sciences. 1993 June; 38(6): 996-1003. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8389688&dopt=Abstract
•
Quick onset of severe abdominal pain after codeine in an ultrarapid metabolizer of debrisoquine. Author(s): Dalen P, Frengell C, Dahl ML, Sjoqvist F. Source: Therapeutic Drug Monitoring. 1997 October; 19(5): 543-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9357099&dopt=Abstract
Studies
53
•
Randomized evaluation of controlled-release codeine and placebo in chronic cancer pain. Author(s): Dhaliwal HS, Sloan P, Arkinstall WW, Thirlwell MP, Babul N, Harsanyi Z, Darke AC. Source: Journal of Pain and Symptom Management. 1995 November; 10(8): 612-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8594122&dopt=Abstract
•
Rapid detection of dihydrocodeine by thermospray mass spectrometry. Author(s): Yoshida M, Akane A, Okii Y, Yoshimura S, Tokiyasu T, Watabiki T. Source: J Chromatogr B Biomed Sci Appl. 1998 October 23; 718(1): 55-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9832360&dopt=Abstract
•
Rash from oral codeine. Author(s): van Ketel WG. Source: Contact Dermatitis. 1986 September; 15(3): 195. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2946544&dopt=Abstract
•
Respiratory arrest precipitated by codeine in a child with chronic renal failure. Author(s): Talbott GA, Lynn AM, Levy FH, Zelikovic I. Source: Clinical Pediatrics. 1997 March; 36(3): 171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9078419&dopt=Abstract
•
Robotic method for the analysis of morphine and codeine in urine. Author(s): Vidal DL, Ting EJ, Perez SL, Taylor RW, Le SD. Source: J Forensic Sci. 1992 September; 37(5): 1283-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1402753&dopt=Abstract
•
Rofecoxib versus codeine/acetaminophen in postoperative dental pain: a doubleblind, randomized, placebo- and active comparator-controlled clinical trial. Author(s): Chang DJ, Fricke JR, Bird SR, Bohidar NR, Dobbins TW, Geba GP. Source: Clinical Therapeutics. 2001 September; 23(9): 1446-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589259&dopt=Abstract
•
Safe use of codeine in the recovering alcoholic or addict. Author(s): Stock CJ. Source: Dicp. 1991 January; 25(1): 49-53. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2008786&dopt=Abstract
54
Codeine
•
Safety, efficacy, and long-term results of a modified version of rapid opiate detoxification under general anaesthesia: a prospective study in methadone, heroin, codeine and morphine addicts. Author(s): Hensel M, Kox WJ. Source: Acta Anaesthesiologica Scandinavica. 2000 March; 44(3): 326-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10714849&dopt=Abstract
•
Saliva testing after single and chronic administration of dihydrocodeine. Author(s): Skopp G, Potsch L, Klinder K, Richter B, Aderjan R, Mattern R. Source: International Journal of Legal Medicine. 2001; 114(3): 133-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11296884&dopt=Abstract
•
Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation. Author(s): Eckhardt K, Li S, Ammon S, Schanzle G, Mikus G, Eichelbaum M. Source: Pain. 1998 May; 76(1-2): 27-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9696456&dopt=Abstract
•
Seizures with intravenous codeine phosphate. Author(s): Zolezzi M, Al Mohaimeed SA. Source: The Annals of Pharmacotherapy. 2001 October; 35(10): 1211-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11675848&dopt=Abstract
•
Simultaneous detection and quantitation of O6-monoacetylmorphine, morphine and codeine in urine by gas chromatography with nitrogen specific and/or flame ionization detection. Author(s): Vu-Duc T, Vernay A. Source: Biomedical Chromatography : Bmc. 1990 March; 4(2): 65-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2350600&dopt=Abstract
•
Simultaneous determination of 6-monoacetylmorphine, morphine and codeine in urine using high-performance liquid chromatography with combined ultraviolet and electrochemical detection. Author(s): Gerostamoulos J, Crump K, McIntyre IM, Drummer OH. Source: Journal of Chromatography. 1993 July 23; 617(1): 152-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8376530&dopt=Abstract
•
Simultaneous determination of acetylcodeine, monoacetylmorphine, and other opiates in urine by GC-MS. Author(s): O'Neal CL, Poklis A. Source: Journal of Analytical Toxicology. 1997 October; 21(6): 427-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9323521&dopt=Abstract
Studies
55
•
Simultaneous determination of codeine and chlorpheniramine in human plasma by capillary column gas chromatography. Author(s): Masumoto K, Tashiro Y, Matsumoto K, Yoshida A, Hirayama M, Hayashi S. Source: Journal of Chromatography. 1986 September 5; 381(2): 323-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3760090&dopt=Abstract
•
Simultaneous determination of codeine and its seven metabolites in plasma and urine by high-performance liquid chromatography with ultraviolet and electrochemical detection. Author(s): He H, Shay SD, Caraco Y, Wood M, Wood AJ. Source: J Chromatogr B Biomed Sci Appl. 1998 April 24; 708(1-2): 185-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9653961&dopt=Abstract
•
Simultaneous determination of codeine, norcodeine and morphine in biological fluids by high-performance liquid chromatography with fluorescence detection. Author(s): Chen ZR, Bochner F, Somogyi A. Source: Journal of Chromatography. 1989 July 21; 491(2): 367-78. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2808622&dopt=Abstract
•
Simultaneous determination of dihydrocodeine and dihydromorphine in serum by gas chromatography-tandem mass spectrometry. Author(s): Hofmann U, Fromm MF, Johnson S, Mikus G. Source: Journal of Chromatography. B, Biomedical Applications. 1995 January 6; 663(1): 59-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7704214&dopt=Abstract
•
Simultaneous determination of monoacetylmorphine, morphine, codeine, and other opiates by GC/MS. Author(s): Bowie LJ, Kirkpatrick PB. Source: Journal of Analytical Toxicology. 1989 November-December; 13(6): 326-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2607760&dopt=Abstract
•
Simultaneous determination of morphine and codeine in blood and bile using dual ultraviolet and fluorescence high-performance liquid chromatography. Author(s): Crump KL, McIntyre IM, Drummer OH. Source: Journal of Analytical Toxicology. 1994 July-August; 18(4): 208-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7967541&dopt=Abstract
56
Codeine
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Simultaneous identification and quantitation of codeine, morphine, hydrocodone, and hydromorphone in urine as trimethylsilyl and oxime derivatives by gas chromatography-mass spectrometry. Author(s): Broussard LA, Presley LC, Pittman T, Clouette R, Wimbish GH. Source: Clinical Chemistry. 1997 June; 43(6 Pt 1): 1029-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9191557&dopt=Abstract
•
Single dose dihydrocodeine for acute postoperative pain. Author(s): Edwards JE, McQuay HJ, Moore RA. Source: Cochrane Database Syst Rev. 2000; (4): Cd002760. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11034754&dopt=Abstract
•
Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain. Author(s): Moore A, Collins S, Carroll D, McQuay H, Edwards J. Source: Cochrane Database Syst Rev. 2000; (2): Cd001547. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10796810&dopt=Abstract
•
Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions. Author(s): Ziccardi VB, Desjardins PJ, Daly-DeJoy E, Seng GF. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 2000 June; 58(6): 622-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10847283&dopt=Abstract
•
Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Author(s): Moore RA, McQuay HJ. Source: Pain. 1997 February; 69(3): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9085303&dopt=Abstract
•
Skin prick test responses to codeine, histamine, and ragweed utilizing the Multitest device. Author(s): Lin RY, Erlich ER, Don PC. Source: Ann Allergy. 1990 September; 65(3): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2403228&dopt=Abstract
•
Skin reactivity to codeine and histamine during prolonged corticosteroid therapy. Author(s): Olson R, Karpink MH, Shelanski S, Atkins PC, Zweiman B. Source: The Journal of Allergy and Clinical Immunology. 1990 August; 86(2): 153-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2384646&dopt=Abstract
Studies
57
•
Skin testing with food, codeine, and histamine in exercise-induced anaphylaxis. Author(s): Lin RY, Barnard M. Source: Ann Allergy. 1993 June; 70(6): 475-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8507042&dopt=Abstract
•
Solitary rectal ulcer induced by excessive use of analgesic suppositories containing paracetamol, caffeine, and codeine. Author(s): Naumann MG, Hintze R, Karaus M. Source: The American Journal of Gastroenterology. 1998 December; 93(12): 2573-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9860430&dopt=Abstract
•
Stool water content and colonic drug absorption: contrasting effects of lactulose and codeine. Author(s): Hebden JM, Gilchrist PJ, Perkins AC, Wilson CG, Spiller RC. Source: Pharmaceutical Research. 1999 August; 16(8): 1254-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468028&dopt=Abstract
•
Storage temperature effect on the stability of morphine and codeine in urine. Author(s): Lin DL, Liu H, Chen CY. Source: Journal of Analytical Toxicology. 1995 September; 19(5): 275-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7500612&dopt=Abstract
•
Studies of the mechanism of angiotensin-converting enzyme (ACE) inhibitorassociated angioedema: the effect of an ACE inhibitor on cutaneous responses to bradykinin, codeine, and histamine. Author(s): Anderson MW, deShazo RD. Source: The Journal of Allergy and Clinical Immunology. 1990 May; 85(5): 856-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2185292&dopt=Abstract
•
Subjective, psychomotor, and analgesic effects of oral codeine and morphine in healthy volunteers. Author(s): Walker DJ, Zacny JP. Source: Psychopharmacology. 1998 November; 140(2): 191-201. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9860110&dopt=Abstract
•
Subtypes of codeine cough syrup abusers. Author(s): Mattoo SK, Basu D, Balaji M, Sharma A, Malhotra A. Source: Indian Journal of Medical Sciences. 1999 March; 53(3): 97-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10798008&dopt=Abstract
58
Codeine
•
Sweat testing for cocaine, codeine and metabolites by gas chromatography-mass spectrometry. Author(s): Huestis MA, Oyler JM, Cone EJ, Wstadik AT, Schoendorfer D, Joseph RE Jr. Source: J Chromatogr B Biomed Sci Appl. 1999 October 15; 733(1-2): 247-64. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10572984&dopt=Abstract
•
Symptomatic treatment of chronically recurring tension headache: a placebocontrolled, multicenter investigation of Fioricet and acetaminophen with codeine. Author(s): Friedman AP, DiSerio FJ. Source: Clinical Therapeutics. 1987; 10(1): 69-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3329967&dopt=Abstract
•
Tenoxicam and paracetamol-codeine combination after oral surgery: a prospective, randomized, double-blind, placebo-controlled study. Author(s): Merry AF, Swinburn PF, Middleton NG, Edwards JL, Calder MV. Source: British Journal of Anaesthesia. 1998 December; 81(6): 875-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10211012&dopt=Abstract
•
The analgesic effect of codeine as compared to imipramine in different human experimental pain models. Author(s): Enggaard TP, Poulsen L, Arendt-Nielsen L, Hansen SH, Bjornsdottir I, Gram LF, Sindrup SH. Source: Pain. 2001 May; 92(1-2): 277-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11323149&dopt=Abstract
•
The cholecystokinin antagonist proglumide enhances the analgesic effect of dihydrocodeine. Author(s): McCleane GJ. Source: The Clinical Journal of Pain. 2003 May-June; 19(3): 200-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12792559&dopt=Abstract
•
The detection of dihydrocodeine and its main metabolites in cases of fatal overdose. Author(s): Klinder K, Skopp G, Mattern R, Aderjan R. Source: International Journal of Legal Medicine. 1999; 112(3): 155-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10335876&dopt=Abstract
•
The detection of morphine and codeine in human teeth: an aid in the identification and study of human skeletal remains. Author(s): Cattaneo C, Gigli F, Lodi F, Grandi M. Source: J Forensic Odontostomatol. 2003 June; 21(1): 1-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12793124&dopt=Abstract
Studies
59
•
The disposition of cocaine and opiate analytes in hair and fingernails of humans following cocaine and codeine administration. Author(s): Ropero-Miller JD, Goldberger BA, Cone EJ, Joseph RE Jr. Source: Journal of Analytical Toxicology. 2000 October; 24(7): 496-508. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043652&dopt=Abstract
•
The effect of codeine in anti-cough syrup on morphine screen. Author(s): Hsu CL, Hung DZ, Yang DY. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2002 June; 65(6): 279-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12201569&dopt=Abstract
•
The effects of collection methods on oral fluid codeine concentrations. Author(s): O'Neal CL, Crouch DJ, Rollins DE, Fatah AA. Source: Journal of Analytical Toxicology. 2000 October; 24(7): 536-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043656&dopt=Abstract
•
The effects of the genetic absence and inhibition of CYP2D6 on the metabolism of codeine and its derivatives, hydrocodone and oxycodone. Author(s): Lurcott G. Source: Anesthesia Progress. 1998 Fall; 45(4): 154-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483388&dopt=Abstract
•
The prevalence of analgesics containing dextropropoxyphene or codeine in individuals suspected of driving under the influence of drugs. Author(s): Jonasson U, Jonasson B, Saldeen T, Thuen F. Source: Forensic Science International. 2000 August 14; 112(2-3): 163-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10940601&dopt=Abstract
•
The role of active metabolites in dihydrocodeine effects. Author(s): Schmidt H, Vormfelde SV, Walchner-Bonjean M, Klinder K, Freudenthaler S, Gleiter CH, Gundert-Remy U, Skopp G, Aderjan R, Fuhr U. Source: Int J Clin Pharmacol Ther. 2003 March; 41(3): 95-106. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665158&dopt=Abstract
•
The role of codeine phosphate premedication in fibre-optic bronchoscopy under insufficient local anaesthesia and midazolam sedation. Author(s): Tsunezuka Y, Sato H, Tsukioka T, Nakamura Y, Watanabe Y. Source: Respiratory Medicine. 1999 June; 93(6): 413-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10464824&dopt=Abstract
60
Codeine
•
The role of dihydrocodeine in causing death among drug users in the west of Scotland. Author(s): Seymour A, Black M, Jay J, Oliver JS. Source: Scott Med J. 2001 October; 46(5): 143-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11771494&dopt=Abstract
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The separation of codeine from nonprescription combination analgesic products. Author(s): Fleming GF, McElnay JC, Hughes CM. Source: Substance Use & Misuse. 2003 July; 38(9): 1217-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12908809&dopt=Abstract
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The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid. Author(s): Jones J, Tomlinson K, Moore C. Source: Journal of Analytical Toxicology. 2002 April; 26(3): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991534&dopt=Abstract
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Tramadol suppositories are less suitable for post-operative pain relief than rectal acetaminophen/codeine. Author(s): Pluim MA, Wegener JT, Rupreht J, Vulto AG. Source: European Journal of Anaesthesiology. 1999 July; 16(7): 473-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457880&dopt=Abstract
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Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial. Author(s): Mullican WS, Lacy JR; TRAMAP-ANAG-006 Study Group. Source: Clinical Therapeutics. 2001 September; 23(9): 1429-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589258&dopt=Abstract
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Transdermal fentanyl in opioid-naive cancer pain patients: an open trial using transdermal fentanyl for the treatment of chronic cancer pain in opioid-naive patients and a group using codeine. Author(s): Vielvoye-Kerkmeer AP, Mattern C, Uitendaal MP. Source: Journal of Pain and Symptom Management. 2000 March; 19(3): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10760623&dopt=Abstract
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Treatment of codeine dependence with inhibitors of cytochrome P450 2D6. Author(s): Fernandes LC, Kilicarslan T, Kaplan HL, Tyndale RF, Sellers EM, Romach MK. Source: Journal of Clinical Psychopharmacology. 2002 June; 22(3): 326-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12006904&dopt=Abstract
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Treatment of mild to moderate pain of acute soft tissue injury: diflunisal vs acetaminophen with codeine. Author(s): Muncie HL Jr, King DE, DeForge B. Source: The Journal of Family Practice. 1986 August; 23(2): 125-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2942630&dopt=Abstract
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Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects. Author(s): Wilder-Smith CH, Hill L, Spargo K, Kalla A. Source: Pain. 2001 March; 91(1-2): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11240075&dopt=Abstract
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Ultra rush bee venom immunotherapy does not reduce cutaneous weal responses to bee venom and codeine phosphate. Author(s): Jutel M, Skrbic D, Pichler WJ, Muller UR. Source: Clinical and Experimental Allergy : Journal of the British Society for Allergy and Clinical Immunology. 1995 December; 25(12): 1205-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8821301&dopt=Abstract
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Urinary concentrations of codeine and morphine after the administration of different codeine preparations in relation to doping analysis. Author(s): Delbeke FT, Debackere M. Source: Journal of Pharmaceutical and Biomedical Analysis. 1991; 9(10-12): 959-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1822219&dopt=Abstract
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Urinary concentrations of morphine and codeine after consumption of poppy seeds. Author(s): Thevis M, Opfermann G, Schanzer W. Source: Journal of Analytical Toxicology. 2003 January-February; 27(1): 53-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12587685&dopt=Abstract
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Urinary excretion of codeine and morphine following the administration of codeinecontaining cold syrup. Author(s): Chang BL, Huang MK. Source: Journal of Analytical Toxicology. 2000 March; 24(2): 133-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10732952&dopt=Abstract
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Urinary excretion of codeine, ethylmorphine, and their metabolites: relation to the CYP2D6 activity. Author(s): Hedenmalm K, Sundgren M, Granberg K, Spigset O, Dahlqvist R. Source: Therapeutic Drug Monitoring. 1997 December; 19(6): 643-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9421105&dopt=Abstract
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Urine and plasma pharmacokinetics of codeine in healthy volunteers: implications for drugs-of-abuse testing. Author(s): Lafolie P, Beck O, Lin Z, Albertioni F, Boreus L. Source: Journal of Analytical Toxicology. 1996 November-December; 20(7): 541-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8934303&dopt=Abstract
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Use of codeine analgesics in a general population. A Norwegian study of moderately strong analgesics. Author(s): Eggen AE, Andrew M. Source: European Journal of Clinical Pharmacology. 1994; 46(6): 491-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7995313&dopt=Abstract
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Utilisation of codeine and propoxyphene: geographic and demographic variations in prescribing, prescriber and recipient categories. Author(s): Henricson K, Carlsten A, Ranstam J, Rametsteiner G, Stenberg P, Wessling A, Melander A. Source: European Journal of Clinical Pharmacology. 1999 October; 55(8): 605-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10541780&dopt=Abstract
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CHAPTER 2. NUTRITION AND CODEINE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and codeine.
Finding Nutrition Studies on Codeine The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail:
[email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “codeine” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.
7
Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.
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The following information is typical of that found when using the “Full IBIDS Database” to search for “codeine” (or a synonym): •
A closer look at acetyl and pentafluoropropionyl derivatives for quantitative analysis of morphine and codeine by gas chromatography/mass spectrometry. Author(s): Marshfield Medical Center Laboratory, Wisconsin 54449-5795. Source: Grinstead, G F J-Anal-Toxicol. 1991 Nov-December; 15(6): 293-8 0146-4760
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A combination of acetylsalicylic acid and codeine phosphate versus acetylsalicylic acid as postoperative analgesics after mandibular third molar surgery. Source: Happonen, R P Oksala, E Ylipaavalniemi, P Proc-Finn-Dent-Soc. 1987; 83(1): 32-5 0355-4651
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A comparison of rectal and intramuscular codeine phosphate in children following neurosurgery. Author(s): Department of Anaesthetics, Great Ormond Street Hospital for Children NHS Trust,Great Ormond Street, London WC1N 3JH, UK. Source: McEwan, A Sigston, P E Andrews, K A Hack, H A Jenkins, A M May, L Llewelyn, N MacKersie, A Paediatr-Anaesth. 2000; 10(2): 189-93 1155-5645
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A fatality involving secobarbital, nitrazepam, and codeine. Author(s): Institute of Legal Medicine, Strasbourg, France. Source: Tracqui, A Kintz, P Mangin, P Lugnier, A A Chaumont, A J Am-J-Forensic-MedPathol. 1989 June; 10(2): 130-3 0195-7910
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Acetylcodeine as a marker of illicit heroin in human hair: method validation and results of a pilot study. Author(s): Institute of Forensic Medicine, Geneva, Switzerland. Source: Girod, C Staub, C J-Anal-Toxicol. 2001 March; 25(2): 106-11 0146-4760
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Acetylcodeine, an impurity of illicitly manufactured heroin, elicits convulsions, antinociception, and locomotor stimulation in mice. Author(s): Department of Pathology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA. Source: O'Neal, C L Poklis, A Lichtman, A H Drug-Alcohol-Depend. 2001 December 1; 65(1): 37-43 0376-8716
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Analgesic efficacy of ibuprofen alone and in combination with codeine or caffeine in post-surgical pain: a meta-analysis. Author(s): Centre for Evidence-Based Pharmacotherapy, Department of Pharmaceutical Sciences, The University of Nottingham, UK. Source: Po, A L Zhang, W Y Eur-J-Clin-Pharmacol. 1998 January; 53(5): 303-11 0031-6970
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Codeine concentrations in human samples in a case of fatal ingestion. Author(s): Institut de Medecine Legale, Strasbourg, France. Source: Kintz, P Tracqui, A Mangin, P Int-J-Legal-Med. 1991; 104(3): 177-8 0937-9827
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Codeine in post-operative pain. Study of the influence of sparteine phenotype and serum concentrations of morphine and morphine-6-glucuronide. Author(s): Department of Clinical Pharmacology, Odense University, Denmark. Source: Poulsen, L Riishede, L Brosen, K Clemensen, S Sindrup, S H Eur-J-ClinPharmacol. 1998 August; 54(6): 451-4 0031-6970
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Comparison of morphine sulphate and codeine phosphate in children undergoing adenotonsillectomy. Author(s): Department of Anaesthesia, Royal Hospital for Sick Children, Edinburgh, UK.
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Source: Semple, D Russell, S Doyle, E Aldridge, L M Paediatr-Anaesth. 1999; 9(2): 135-8 1155-5645 •
Determination of chlorpheniramine maleate, dihydrocodeine bitartrate and ephedrine hydrochloride in cough mixture by derivative and differential spectrometry. Author(s): Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, University of Alexandria, Egypt. Source: Korany, M A Bedair, M M el Gindy, A J-Pharm-Belg. 1990 Jul-August; 45(4): 2528 0047-2166
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Double-blind comparison of meclofenamate sodium plus codeine, meclofenamate sodium, codeine, and placebo for relief of pain following surgical removal of third molars. Author(s): Department of Oral and Maxillofacial Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298-0566. Source: Giglio, J A Laskin, D M J-Oral-Maxillofac-Surg. 1990 August; 48(8): 785-90 02782391
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Drug testing with alternative matrices I. Pharmacological effects and disposition of cocaine and codeine in plasma, sebum, and stratum corneum. Author(s): Addiction Research Center, Division of Intramural Research, National Institute on Drug Abuse, Baltimore, Maryland 21224, USA. Source: Joseph, R E Oyler, J M Wstadik, A T Ohuoha, C Cone, E J J-Anal-Toxicol. 1998 Jan-February; 22(1): 6-17 0146-4760
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Effect of codeine on oro-cecal transit time in Chinese healthy volunteers in comparison with Caucasian subjects. Author(s): Department of Clinical Pharmacology, Huddinge University Hospital, Karolinska Institute, Sweden. Source: Yue, Q Y Hasselstrom, J Svensson, J O Sawe, J Eur-J-Clin-Pharmacol. 1999 January; 54(11): 839-42 0031-6970
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Effects of codeine on the agitating force and gastrointestinal transit time in dogs, for use in drug absorption studies. Author(s): National Institute of Health Sciences, Tokyo, Japan. Source: Katori, N Aoyagi, N Kojima, S Biol-Pharm-Bull. 1998 April; 21(4): 418-20 09186158
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Effects of ephedrine and phenylpropanolamine on the antinociceptive effects of morphine and codeine in mice. Author(s): Department of Pharmacology, Faculty of Medicine, Chinese University of Hong Kong, Shatin, N.T. Source: Dambisya, Y M Wong, C L Chan, K Arch-Int-Pharmacodyn-Ther. 1990 NovDecember; 3085-12 0003-9780
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Effects of epinastine on the antitussive and rewarding effects of dihydrocodeine in mice. Author(s): Department of Pathophysiology & Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
[email protected] Source: Kamei, J Morita, K Ohsawa, M Onodera, K Methods-Find-Exp-Clin-Pharmacol. 1999 December; 21(10): 663-8 0379-0355
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Evaluation of acetylcodeine as a specific marker of illicit heroin in human hair. Author(s): Institut de Medecine Legale, Strasbourg, France. Source: Kintz, P Jamey, C Cirimele, V Brenneisen, R Ludes, B J-Anal-Toxicol. 1998 October; 22(6): 425-9 0146-4760
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Excessive grooming induced by the administration of codeine and morphine. Author(s): Department of Psychology, University Center at Binghamton, New York 13901. Source: Isaacson, R L Danks, A M Brakkee, J Schefman, K Gispen, W H Behav-NeuralBiol. 1988 July; 50(1): 37-45 0163-1047
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Excretion of codeine and morphine following ingestion of poppy seeds. Source: Struempler, R E J-Anal-Toxicol. 1987 May-June; 11(3): 97-9 0146-4760
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Glucuronidation of dihydrocodeine by human liver microsomes and the effect of inhibitors. Author(s): Centre for Pharmaceutical Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia. Source: Kirkwood, L C Nation, R L Somogyi, A A Clin-Exp-Pharmacol-Physiol. 1998 Mar-April; 25(3-4): 266-70 0305-1870
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Influence of glutethimide on rat brain mononucleotides by sub-chronic codeine treatment. Author(s): Department of Toxicology, University of Medicine and Pharmacy Iuliu Hatieganu, 13, Emil Isac, 3400 Cluj-Napoca, Romania.
[email protected] Source: Loghin, F Popa, D S Socaciu, C J-Cell-Mol-Med. 2001 Oct-December; 5(4): 409-16 1582-1838
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Ketorolac versus acetaminophen-codeine in the emergency department treatment of acute low back pain. Author(s): Royal Columbian Hospital, New Westminster, BC, Canada. Source: Innes, G D Croskerry, P Worthington, J Beveridge, R Jones, D J-Emerg-Med. 1998 Jul-August; 16(4): 549-56 0736-4679
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Laboratory validation study of drug evaluation and classification program: alprazolam, d-amphetamine, codeine, and marijuana. Author(s): National Institute on Drug Abuse, Division of Intramural Research, Baltimore, Maryland, USA.
[email protected] Source: Heishman, S J Singleton, E G Crouch, D J J-Anal-Toxicol. 1998 October; 22(6): 503-14 0146-4760
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Lysine clonixinate vs. paracetamol/codeine in postepisiotomy pain. Author(s): School of Medicine, Department of Medicine, Universidad de Buenos Aires, Argentina. Source: De los Santos, A R Marti, M I Espinosa, D Di Girolamo, G Vinacur, J C Casadei, A Acta-Physiol-Pharmacol-Ther-Latinoam. 1998; 48(1): 52-8 0327-6309
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Maintenance treatment of opiate addicts in Germany with medications containing codeine--results of a follow-up study. Author(s): Psychiatric Clinic, University Hospital Eppendorf, Hamburg, Germany. Source: Krausz, M Verthein, U Degkwitz, P Haasen, C Raschke, P Addiction. 1998 August; 93(8): 1161-7 0965-2140
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No effect of preoperative paracetamol and codeine suppositories for pain after termination of pregnancies in general anaesthesia. Author(s): Department of Anaesthesia, Baerum Hospital, Baerum Post, Norway.
[email protected] Source: Dahl, V Fjellanger, F Raeder, J C Eur-J-Pain. 2000; 4(2): 211-5 1090-3801
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On the assessment of drug metabolism by assays of codeine and its main metabolites. Author(s): Department of Clinical Pharmacology, University Hospital of Besancon, France.
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Source: Haffen, E Paintaud, G Berard, M Masuyer, C Bechtel, Y Bechtel, P R Ther-DrugMonit. 2000 June; 22(3): 258-65 0163-4356 •
Paracetamol versus paracetamol-codeine in the treatment of post-operative dental pain: a randomized, double-blind, prospective trial. Author(s): School of Dentistry, The University of Queensland, Brisbane.
[email protected] Source: Macleod, A G Ashford, B Voltz, M Williams, B Cramond, T Gorta, L Simpson, J M Aust-Dent-J. 2002 June; 47(2): 147-51 0045-0421
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Pharmacokinetics of codeine after parenteral and oral dosing in the rat. Author(s): Division of Pharmaceutical Science, School of Pharmacy, University of Missouri-Kansas City. Source: Shah, J Mason, W D Drug-Metab-Dispos. 1990 Sep-October; 18(5): 670-3 00909556
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Single dose paracetamol (acetaminophen), with and without codeine, for postoperative pain. Author(s): Cochrane Pain, Palliative and Supportive Care Group, Pain Research Unit, Churchill Hospital, Old Road, Oxford, UK, OX3 7LJ. Source: Moore, A Collins, S Carroll, D McQuay, H Edwards, J Cochrane-Database-SystRevolume 2000; (2): CD001547 1469-493X
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Single-dose vicoprofen compared with acetaminophen with codeine and placebo in patients with acute postoperative pain after third molar extractions. Author(s): University of Medicine and Dentistry of New Jersey, Department of Oral and Maxillofacial Surgery, Newark 07103-2400, USA.
[email protected] Source: Ziccardi, V B Desjardins, P J Daly DeJoy, E Seng, G F J-Oral-Maxillofac-Surg. 2000 June; 58(6): 622-8 0278-2391
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Slow release polymer-drug systems obtained by moisture promoted polyreactions. 1. Codeine resinate encapsulated in poly(alkyl alpha-cyanoacrylates). Author(s): Silesian Technical University, Department of Physical Chemistry and Technology of Polymers, Gliwice, Poland. Source: Lukaszczyk, J Urbas, P J-Microencapsul. 1998 Sep-October; 15(5): 609-20 02652048
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Testing human hair for drugs of abuse. I. Individual dose and time profiles of morphine and codeine in plasma, saliva, urine, and beard compared to drug-induced effects on pupils and behavior. Author(s): Addiction Research Center, National Institute on Drug Abuse, Baltimore, MD 21224. Source: Cone, E J J-Anal-Toxicol. 1990 Jan-February; 14(1): 1-7 0146-4760
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The acute effects of codeine on human aggressive and non-aggressive behavior. Author(s): Department of Psychiatry & Behavioral Science, University of Texas Mental Sciences Institute, University of Texas Medical School, Houston 77030. Source: Spiga, R Cherek, D R Roache, J D Cowan, K NIDA-Res-Monogr. 1989; 95479-80 1046-9516
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The detection of dihydrocodeine and its main metabolites in cases of fatal overdose. Author(s): Institut fur Rechtsmedizin und Verkehrsmedizin der Ruprecht-KarlsUniversitat, Heidelberg, Germany. Source: Klinder, K Skopp, G Mattern, R AderJanuary, R Int-J-Legal-Med. 1999; 112(3): 155-8 0937-9827
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The effect of ageing on the pharmacokinetics of dihydrocodeine. Author(s): Department of Medicine for the Elderly, University of Leicester, Leicester General Hospital, UK. Source: Davies, K N Castleden, C M McBurney, A Jagger, C Eur-J-Clin-Pharmacol. 1989; 37(4): 375-9 0031-6970
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The effects of codeine on human aggressive responding. Author(s): Department of Psychiatry and Behavioral Sciences, University of Texas Medical Schoo, Houston. Source: Spiga, R Cherek, D R Roache, J D Cowan, K A Int-Clin-Psychopharmacol. 1990 July; 5(3): 195-204 0268-1315
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The role of codeine phosphate premedication in fibre-optic bronchoscopy under insufficient local anaesthesia and midazolam sedation. Author(s): Department of Thoracic Surgery, Ishikawa Prefectural Central Hospital, Kanazawa, Japan.
[email protected] Source: Tsunezuka, Y Sato, H Tsukioka, T Nakamura, Y Watanabe, Y Respir-Med. 1999 June; 93(6): 413-5 0954-6111
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Therapeutic doses of codeine have no effect on acetaminophen clearance or metabolism. Author(s): Department of Medicine F, Gentofte University Hospital, Copenhagen, Denmark. Source: Sonne, J Poulsen, H E Loft, S Dossing, M Vollmer Larsen, A Simonsen, K Thyssen, H Lundstrom, K Eur-J-Clin-Pharmacol. 1988; 35(1): 109-11 0031-6970
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Thermolysis of O-allyl S-alkyl dithiocarbonates of codeine and isocodeine. Source: Fujii, I Koreyuki, M Kanematsu, K Chem-Pharm-Bull-(Tokyo). 1988 May; 36(5): 1750-7 0009-2363
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Urinary excretion of codeine and morphine following the administration of codeinecontaining cold syrup. Author(s): National Laboratories of Foods and Drugs, Department of Health, Taipei, Taiwan. Source: Chang, B L Huang, M K J-Anal-Toxicol. 2000 March; 24(2): 133-9 0146-4760
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Utilisation of codeine and propoxyphene: geographic and demographic variations in prescribing, prescriber and recipient categories. Author(s): Hospital Pharmacy, Malmo University Hospital, S-205 02 Malmo, Sweden. Source: Henricson, K Carlsten, A Ranstam, J Rametsteiner, G Stenberg, P Wessling, A Melander, A Eur-J-Clin-Pharmacol. 1999 October; 55(8): 605-11 0031-6970
Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •
healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0
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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov
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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov
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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/
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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/
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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/
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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/
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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/
Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats
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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html
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Google: http://directory.google.com/Top/Health/Nutrition/
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Healthnotes: http://www.healthnotes.com/
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Open Directory Project: http://dmoz.org/Health/Nutrition/
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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/
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WebMD®Health: http://my.webmd.com/nutrition
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
The following is a specific Web list relating to codeine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
Food and Diet Pain Source: Healthnotes, Inc.; www.healthnotes.com Sprains and Strains Source: Healthnotes, Inc.; www.healthnotes.com
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CHAPTER 3. ALTERNATIVE MEDICINE AND CODEINE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to codeine. At the conclusion of this chapter, we will provide additional sources.
National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to codeine and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “codeine” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to codeine: •
A randomized cross-over study of the efficacy of codeine phosphate versus Ispaghulahusk in patients with gynaecological cancer experiencing diarrhoea during pelvic radiotherapy. Author(s): Lodge N, Evans ML, Wilkins M, Blake PR, Fryatt I. Source: European Journal of Cancer Care. 1995 March; 4(1): 8-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7620654&dopt=Abstract
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Analgesic effects of dihydrocodeine and tramadol when administered either in the morning or evening. Author(s): Hummel T, Kraetsch HG, Lotsch J, Hepper M, Liefhold J, Kobal G. Source: Chronobiology International. 1995 February; 12(1): 62-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7750159&dopt=Abstract
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Biosynthetic conversion of thebaine to codeine and role of codeine methyl ether. Author(s): Brochmann-Hanssen E, Nielsen B, Aadahl G.
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Source: Journal of Pharmaceutical Sciences. 1967 September; 56(9): 1207-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6049719&dopt=Abstract •
Biosynthetic conversion of thebaine to codeine. Author(s): Parker HI, Blaschke G, Rapoport H. Source: Journal of the American Chemical Society. 1972 February 23; 94(4): 1276-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=5060270&dopt=Abstract
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Codeine and morphine in Papaver somniferum grown in a controlled environment. Author(s): Tookey HL, Spencer GF, Grove MD, Kwolek WF. Source: Planta Medica. 1976 December; 30(4): 331-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1005537&dopt=Abstract
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Codeinone as the intermediate in the biosynthetic conversion of thebaine to codeine. Author(s): Blaschke G, Parker HI, Rapoport H. Source: Journal of the American Chemical Society. 1967 March 15; 89(6): 1540-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6041360&dopt=Abstract
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Comparison of the effects of acupuncture and codeine on postoperative dental pain. Author(s): Sung YF, Kutner MH, Cerine FC, Frederickson EL. Source: Anesthesia and Analgesia. 1977 July-August; 56(4): 473-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=327853&dopt=Abstract
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Concentrations of morphine and codeine in serum and urine after ingestion of poppy seeds. Author(s): Hayes LW, Krasselt WG, Mueggler PA. Source: Clinical Chemistry. 1987 June; 33(6): 806-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3594820&dopt=Abstract
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Detection of morphine and codeine following consumption of poppy seeds. Author(s): Zebelman AM, Troyer BL, Randall GL, Batjer JD. Source: Journal of Analytical Toxicology. 1987 May-June; 11(3): 131-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3599919&dopt=Abstract
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Effect of codeine phosphate, Lomotil, and Isogel on iileostomy function. Author(s): Newton CR. Source: Gut. 1978 May; 19(5): 377-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=658767&dopt=Abstract
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Evaluation of 3'-azido-3'-deoxythymidine, morphine, and codeine as probe substrates for UDP-glucuronosyltransferase 2B7 (UGT2B7) in human liver microsomes: specificity and influence of the UGT2B7*2 polymorphism.
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Author(s): Court MH, Krishnaswamy S, Hao Q, Duan SX, Patten CJ, Von Moltke LL, Greenblatt DJ. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2003 September; 31(9): 1125-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920168&dopt=Abstract •
Excretion of codeine and morphine following ingestion of poppy seeds. Author(s): Struempler RE. Source: Journal of Analytical Toxicology. 1987 May-June; 11(3): 97-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3599922&dopt=Abstract
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Experimental pain induced by electrical and thermal stimulation of the skin in healthy man: sensitivity to 75 and 150 mg diclofenac sodium in comparison with 60 mg codeine and placebo. Author(s): Stacher G, Steinringer H, Schneider S, Mittelbach G, Winklehner S, Gaupmann G. Source: British Journal of Clinical Pharmacology. 1986 January; 21(1): 35-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3947505&dopt=Abstract
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Gas chromatographic/mass spectrometric analysis of morphine and codeine in human urine of poppy seed eaters. Author(s): elSohly HN, Stanford DF, Jones AB, elSohly MA, Snyder H, Pedersen C. Source: J Forensic Sci. 1988 March; 33(2): 347-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3373154&dopt=Abstract
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LC and LC-MS-MS analyses of undeclared codeine in antiasthmatic Chinese proprietary medicine. Author(s): Liu SY, Woo SO, Holmes MJ, Koh HL. Source: Journal of Pharmaceutical and Biomedical Analysis. 2000 April; 22(3): 481-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10766365&dopt=Abstract
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Microchemical investigation of medicinal plants. XI. Identification of morphine and codeine in opium using GC/MS. Author(s): Weber JM, Ma TS. Source: Mikrochim Acta. 1975; (4-5 Pt 2): 401-5. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1196153&dopt=Abstract
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Morphine and codeine in poppy seed. Author(s): Grove MD, Spencer GF, Wakeman MV, Tookey HL. Source: Journal of Agricultural and Food Chemistry. 1976 July-August; 24(4): 896-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=956551&dopt=Abstract
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Morphine, codeine and thebaine N-oxides [proceedings]. Author(s): Phillipson JD, Handa SS, El-Dabbas S. Source: The Journal of Pharmacy and Pharmacology. 1976 December; 28 Suppl: 70P. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12349&dopt=Abstract
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Poppy politics. The codeine (methylmorphine) connection. Author(s): Davis FA. Source: Clin Toxicol. 1978; 12(4): 505-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=657760&dopt=Abstract
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Poppy seeds: differences in morphine and codeine content and variation in inter- and intra-individual excretion. Author(s): Pelders MG, Ros JJ. Source: J Forensic Sci. 1996 March; 41(2): 209-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8871378&dopt=Abstract
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Potentiation of codeine analgesia by disodium edetate in albino rats. Author(s): Ahmed SS, Melgiri S, Abraham GJ. Source: Arch Int Pharmacodyn Ther. 1972 February; 195(2): 357-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4622668&dopt=Abstract
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Preliminary study of lupulin-dihydrocodeine in pain syndromes. Author(s): Miller J. Source: Curr Ther Res Clin Exp. 1967 February; 9(2): 85-8. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4962537&dopt=Abstract
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Stool water content and colonic drug absorption: contrasting effects of lactulose and codeine. Author(s): Hebden JM, Gilchrist PJ, Perkins AC, Wilson CG, Spiller RC. Source: Pharmaceutical Research. 1999 August; 16(8): 1254-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10468028&dopt=Abstract
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The analgesic properties of delta-9-tetrahydrocannabinol and codeine. Author(s): Noyes R Jr, Brunk SF, Avery DA, Canter AC. Source: Clinical Pharmacology and Therapeutics. 1975 July; 18(1): 84-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=50159&dopt=Abstract
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The effects of octreotide, soy polysaccharide, codeine and loperamide on nutrient, fluid and electrolyte absorption in the short-bowel syndrome. Author(s): Rodrigues CA, Lennard-Jones JE, Thompson DG, Farthing MJ.
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Source: Alimentary Pharmacology & Therapeutics. 1989 April; 3(2): 159-69. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2491467&dopt=Abstract •
TLC-UV densitometric and GC-MSD methods for simultaneous quantification of morphine and codeine in poppy capsules. Author(s): Popa DS, Oprean R, Curea E, Preda N. Source: Journal of Pharmaceutical and Biomedical Analysis. 1998 December; 18(4-5): 645-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9919965&dopt=Abstract
Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •
Alternative Medicine Foundation, Inc.: http://www.herbmed.org/
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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats
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Chinese Medicine: http://www.newcenturynutrition.com/
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drkoop.com®: http://www.drkoop.com/InteractiveMedicine/IndexC.html
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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm
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Google: http://directory.google.com/Top/Health/Alternative/
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Healthnotes: http://www.healthnotes.com/
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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine
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Open Directory Project: http://dmoz.org/Health/Alternative/
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HealthGate: http://www.tnp.com/
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WebMD®Health: http://my.webmd.com/drugs_and_herbs
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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html
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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/
The following is a specific Web list relating to codeine; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •
General Overview Anaphylaxis Source: Integrative Medicine Communications; www.drkoop.com Bronchitis Source: Healthnotes, Inc.; www.healthnotes.com
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Cough Source: Healthnotes, Inc.; www.healthnotes.com Crohn's Disease Source: Healthnotes, Inc.; www.healthnotes.com Diarrhea Source: Healthnotes, Inc.; www.healthnotes.com Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com Parasites Source: Healthnotes, Inc.; www.healthnotes.com Restless Legs Syndrome Source: Healthnotes, Inc.; www.healthnotes.com •
Herbs and Supplements Acetaminophen Source: Healthnotes, Inc.; www.healthnotes.com Amino Acid K Source: Integrative Medicine Communications; www.drkoop.com Aspirin Source: Healthnotes, Inc.; www.healthnotes.com Butalbital Source: Healthnotes, Inc.; www.healthnotes.com Caffeine Source: Healthnotes, Inc.; www.healthnotes.com Carisoprodol Source: Healthnotes, Inc.; www.healthnotes.com Codeine Source: Healthnotes, Inc.; www.healthnotes.com Empirin with Codeine Source: Healthnotes, Inc.; www.healthnotes.com Ephedra Alternative names: Ephedra sinensis, Ma huang Source: Integrative Medicine Communications; www.drkoop.com Ephedra Sinensis Source: Integrative Medicine Communications; www.drkoop.com
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Fiorinal Source: Healthnotes, Inc.; www.healthnotes.com GABA Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10027,00.html Green Tea Source: Healthnotes, Inc.; www.healthnotes.com Huperzine a Source: Prima Communications, Inc.www.personalhealthzone.com L-lysine Source: Integrative Medicine Communications; www.drkoop.com Lysine Alternative names: Amino Acid K, L-Lysine Source: Integrative Medicine Communications; www.drkoop.com Ma Huang Source: Integrative Medicine Communications; www.drkoop.com Phenergan Vc with Codeine Source: Healthnotes, Inc.; www.healthnotes.com Phenergan with Codeine Source: Healthnotes, Inc.; www.healthnotes.com Promethazine Source: Healthnotes, Inc.; www.healthnotes.com Robitussin AC Source: Healthnotes, Inc.; www.healthnotes.com Soma Compound with Codeine Source: Healthnotes, Inc.; www.healthnotes.com Sundew Alternative names: Drosera rotundifolia, Drosera ramentacea, Drosera intermedia, Drosera anglica Source: Healthnotes, Inc.; www.healthnotes.com Thuja Plicata Alternative names: Western Red Cedar Source: Alternative Medicine Foundation, Inc.; www.amfoundation.org Tylenol with Codeine Source: Healthnotes, Inc.; www.healthnotes.com
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Valerian Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10064,00.html Wild Cherry Source: Prima Communications, Inc.www.personalhealthzone.com
General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.
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CHAPTER 4. PATENTS ON CODEINE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “codeine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on codeine, we have not necessarily excluded non-medical patents in this bibliography.
Patents on Codeine By performing a patent search focusing on codeine, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We
8Adapted
from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.
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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on codeine: •
4A-Aryl-decahydroisoquinolines Inventor(s): Gless; Richard D. (Oakland, CA), Rapoport; Henry (Berkeley, CA), Weller; Dwight D. (Champaigne, IL) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 4,289,882 Date filed: September 5, 1978 Abstract: This invention relates to the production of 4a-aryldecahydroisoquinolines where the aryl group is selected as 3-methoxy phenyl and intermediates. These compounds are morphine analogs and show utility similar to the known morphine, codeine, and thebaine. Excerpt(s): Syntheses are presented of 4a-(3'-methoxyphenyl)decahydroisoquinolines with the carbocyclic ring functionalized so as to resemble the substitution pattern in ring C of the morphine alkaloids. A versatile synthesis was developed for the starting 4arylnipecotic acid which was then, via the methylene lactam rearrangement and intramolecular Michael reaction, stereospecifically converted to the 1,6dioxodecahydroisoquinoline, trans-1,6-dioxo-4a-(3'-methoxyphenyl)-2methyldecahydroisoquinoline (keto amide trans-9). Reduction gave ketone trans-36 [trans-4a-(3'-methoxyphenyl)-2-methyl-6-oxodecahydroisoquinoline], and selective functionalization at C-7 led to the key unsaturated ketal, trans-.DELTA.sup.7 -6,6dimethoxy-4a-(3'-methoxyphenyl)-2-methyl-octahydroisoquinoline (39). Hydrolysis yielded codeinone analog,.alpha.,.beta.-unsaturated ketone 40 [trans-.DELTA.sup.7 -4a(3'-methoxyphenyl)-2-methyl-6-oxooctahydroisoquinoline], reduction gave codeine analog.DELTA.sup.7 -allylic alcohol 7, and ether cleavage produced the morphine analog, trans-.DELTA.sup.7 -6.alpha.-hydroxy-4a.alpha.-(3'-hydroxyphenyl)-2methyloctahydroisoquinoli ne (6). Cis-fused analogs were obtained through 9 and ketal amide, 6,6-ethylenedioxy- 4a-(3'-methoxyphenyl)-2-methyl-1-oxodecahydroisoquinoline (34) or trans-.DELTA.sup.7 -4a-(3'-methoxy-phenyl)-2-methyl-6oxooctahydroisoquinoline (40) via isomerization at C-8a and were the predominant isomers at equilibrium. Alkali- or acid-catalyzed elimination of methanol from.DELTA.sup.7 -dimethyl ketal 39 produced mainly the thebaine analog,.DELTA.sup.6,.DELTA.sup.8(8a) -6-methoxy-4a-(3'-methoxyphenyl)-2methylhexahydroisoquinoline (8), which could be hydroxylated at C-8a with peracid to 14-hydroxycodeinone analogs,.DELTA.sup.7 -8a-hydroxy-4a-(3'-methoxyphenyl)-2methyl-6-oxooctahydroisoquinolines (57 and 58), but would not participate in DielsAlder cycloaddition with a variety of dienophiles. In an earlier article, Weller and Rapoport, J. of the Am. Chem. Soc., 98:6650 (1976), it was shown that trans- and cis-4aphenyldecahydroisoquinolines (2 and 3) could be prepared but the problem remained of the proper concordance of a different aryl fraction than phenyl as well as the concordance in the C ring, thus decahydroisoquinolines were necessary whose C rings would, with the exception of the C-5 oxygen bridge linkage, mimic the C rings of the hydrophenanthrene opium alkaloids. In order to prepare compounds which were pharmacologically consonant with natural compounds, the 4a-aryl moiety was chosen to be 3-methoxyphenyl. Thus, in the present system, decahydroisoquinolines 6, 7, 8 analogs of morphine, codeine, and thebaine 4 were prepared from a ketoamide, trans-
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1,6-dioxo-4a-(3'-methoxyphenyl)-2-methyldecahydroisoquinoline (trans-9). In addition, although trans-9 possesses the trans ring fusion, the present synthesis allows for both a trans- and cis- material, including the epimeric cis codeine analogs 10 and 11 (cis.DELTA.sup.7 -6.alpha.- and cis-.DELTA.sup. 7 -6.beta.-hydroxy-4a.alpha.-(3'methoxyphenyl)-2-methyloctahydroisoquinolin es). In the plan of the synthesis of the compounds, the synthesis of the keto amide above required the correct nipecotic ester and previous processes for the production of the nipecotates were unuseable. Web site: http://www.delphion.com/details?pn=US04289882__ •
Agents for the treatment of severe pain and preparation of said agents Inventor(s): Lohner; Manfred (Bonn, DE), Posselt; Klaus (Bonn, DE), Vogtle-Junkert; Ute (Alfter, DE), Wagener; Hans H. (Meckenheim, DE) Assignee(s): Dolorgiet Beteiligungs GmbH (St. Augustin, DE) Patent Number: 5,173,304 Date filed: August 14, 1990 Abstract: The agents for the treatment of conditions of severe pain, and especially of tumor pain and post-operative pain, consist of soft gelatin capsules containing from about 30 to about 50 parts by weight of ibuprofen and from about 1.5 to about 4 parts by weight of codeine and/or physiologically compatible salts thereof, partially dissolved and partially suspended in about 68.5 to about 46 parts by weight of polyoxyethylenepolyoxypropylene-diol or in a mixture comprising about 30 to about 76 parts by weight of polyoxyethylene-polyoxypropylenediol or polyethylene-glycol or polypropyleneglycol and from about 7 to about 40 parts by weight of a physiologically compatible surfactant. Excerpt(s): The present invention relates to agents for the treatment of conditions of severe pain, especially tumor pain and postoperative pain, and to a process for preparing said agents. From the EP-A-0 178 436 (Application No. 85 111 013.0) there have been known soft gelatin capsules containing ibuprofen and processes for preparing same. Said soft gelatin capsules have proven to be useful for alleviating acute pain with a rapid onset of action, since they rapidly release the active ingredient ibuprofen and, hence, create a good bioavailability of the active substance. Cooper et al. investigated the analgetic activity of combinations of ibuprofen and codeine and determined that codeine increases the analgetic activity of ibuprofen somewhat; however, this increase was so small that it has not been considered to be of sufficient statistical significance; cf. Pharmacotherapy 1982; 2:162-167. Web site: http://www.delphion.com/details?pn=US05173304__
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Analgesic composition containing a mixture of 6-chloro-.alpha.-methyl-carbazole-2acetic acid plus an opiate as the active agent Inventor(s): Baruth, Jr.; Herman W. (Wayne, NJ), Berger; Leo (Montclair, NJ), Corraz; Alfred J. (Wayne, NJ), Sepinwall; Jerry (Pine Brook, NJ) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,610,989 Date filed: July 31, 1985
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Abstract: A method of producing analgesia by administering an opiate alkaloid such as morphine, codeine, oxycodone or a pharmaceutically acceptable acid addition salt thereof together with a carbazole compound, 6-chloro-.alpha.-methyl-carbazole-2-acetic acid, or a salt thereof with a pharmaceutically acceptable base and composition therefor. Excerpt(s): Relief of pain is one of the important goals in medicine. One method for alleviating pain is administration of analgesic drugs which act to decrease the awareness of the sensation of pain by elevating the pain threshold. Opiate alkaloids, for example, morphine, codeine and oxycodone, are among the more potent analgesic drugs available in the treatment of pain. Although the primary action of opiate alkaloids is analgesia, there are serious side-effects associated with these compounds such as respiratory depression and addiction. In an effort to maintain the maximum analgesic effect of opiate alkaloids and to minimize the side effects of these compounds, there has been a search for a compound which would potentiate the action of the opiate alkaloid, and thereby, reduce the amount of opiate used. Web site: http://www.delphion.com/details?pn=US04610989__ •
Analgesic method Inventor(s): Hynes; Martin D. (Carmel, IN) Assignee(s): Eli Lilly and Company (Indianapolis, IN) Patent Number: 4,683,235 Date filed: July 25, 1986 Abstract: This invention provides a method of producing analgesia in mammals which comprises administering codeine and fluoxetine or norfluoxetine. Pharmaceutical formulations useful in this method are also provided. Excerpt(s): Fluoxetine [3-(4-trifluoromethylphenoxy)-N-methyl-3-phenylpropylamine] has been shown to be a highly specific inhibitor of serotonin uptake. See Fuller et al., J. Pharm. Exp. Ther., 193, 796 (1975) and Wong et al., id., 804 (1975). In addition, fluoxetine has been shown to possess analgesic properties when administered alone (U.S. Pat. No. 4,035,511) or when given with morphine (U.S. Pat. No. 4,083,982). Whether this latter activity is described as a synergistic effect or that of fluoxetine potentiating the morphine analgesic activity appears to depend upon the test system employed to demonstrate the analgesic activity. See Messing et al., Psychopharmacology Comm., 1, 511 (1975); Sugrue et al., J. Pharm. Pharmac., 28, 447 (1976); Larson et al., Life Sci., 21, 1807 (1977); and Hynes et al., Drug Dev. Res., 2, 33 (1982). Norfluoxetine [3-(4trifluoromethylphenoxy)-3-phenylpropylamine] is a metabolite of fluoxetine and is also known to block monoamine uptake, especially serotonin. See U.S. Pat. No. 4,313,896. It is desirable to find methods of causing analgesia which result in few, if any, adverse side effects to the patient. Thus, a method of potentiating the analgesic effect of analgesics, such as codeine, would enable one to employ less codeine to achieve the desired analgesic effect while limiting side effects normally associated with higher doses of the analgesic. Web site: http://www.delphion.com/details?pn=US04683235__
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Bacterial hydroxylation of codeine Inventor(s): Harder; Patricia A. (Wilmington, DE), Kunz; Daniel A. (Wilmington, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 4,798,792 Date filed: September 9, 1985 Abstract: A microbial process for converting codeine to 14-hydroxycodeine is provided. This process comprises aerobically culturing codeine with bacteria of the genus Streptomyces for at least about 3 days in a rich medium such as soybean flour medium. Excerpt(s): This invention relates to microbial processes for converting codeine to 14hydroxycodeine and more particularly to such processes by means of culturing codeine with bacteria of the genus Streptomyces. Codeine, morphine, and thebaine are natural alkaloid products of the opium poppy, Papaver somniferum. Thebaine is used to prepare a number of commercially important narcotic antagonists and agonist/antagonist analgesics by its chemical modification. Use of codeine and morphine as starting materials is also desirable but appropriate chemical routes for their use have not yet been perfected. A major requirement for the use of these three opium alkaloids for the production of some analgesics and/or narcotic antagonists is the addition of a hydroxyl group in the C-14 position. The present invention provides the first known microbial process for converting codeine to 14-hydroxycodeine with yields and efficiencies of conversion to make the process commercially feasible. Microbial conversions of alkaloids has been known for about 25 years. Tsuda et al., Microbial Transformation of Steroids and Alkaloids, 167-193, 1964, in the publication of the I. A. M. symposium on Microbiology, Institute of Applied Microbiology. (no. 6), University of Tokyo, disclose that 120 thebaine converting strains were selected from 1700 different bacterial and fungal strains tested for that ability. Most of the 120 strains were from the basidiomycetes, especially from the wood rot fungi Trametes sanguinea. Conversions of thebaine to 14-hydroxycodeinone and 14-hydroxycodeine were disclosed. Yields of the products depended on the nutrient solution used for cultivation of the organisms. Web site: http://www.delphion.com/details?pn=US04798792__
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Composition comprising a tramadol material and any of codeine, oxycodone or hydrocodone and their use Inventor(s): Raffa; Robert B. (Norristown, PA), Vaught; Jeffrey L. (Perkasie, PA) Assignee(s): McNeil Lab, Inc. (Spring House, PA) Patent Number: 5,468,744 Date filed: June 30, 1994 Abstract: This invention relates to compositions comprising a tramadol material selected from the group consisting of tramadol, its stereoisomers and its pharmaceutically acceptable salts and either codeine or oxycodone, and their use in treating pain. When the components, i.e., tramadol materials and either of codeine or oxycodone, of the composition are within certain ratios of pharmacological effects of the compositions are superaddditive (synergistic). Excerpt(s): This case is related to, but does not derive benefit under 35 U.S.C. 120 from application Ser. Nos. 07/974,863 and 07/974,865. U.S. Pat. No. 3,652,589 discloses a class of analgesic cycloalkanol-substituted phenol esters having a basic amine group in the
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cycloalkyl ring. The compound (1RS, 2RS) trans-2-[(dimethylamino)-methyl]-1-(3methoxyphenyl)cyclohexanol, commonly known as tramadol, is specifically disclosed therein. A series of articles pertaining to the pharmacology, toxicology and clinical studies of tramadol are found in Arzneim, Forsch (Drug Res.), 28(l), 114 (1978). Driessen et al., Arch. Pharmacol., 341, R104 (1990) disclose that tramadol produces its analgesic effect through a mechanism that is neither fully opioid-like nor non-opioid-like. The Abstracts of the VI th World Congress on Pain, Apr. 1-6 (1990) discloses that tramadol hydrochloride is an orally active pure agonist opioid analgesic. However, clinical experience indicates that tramadol lacks many of the typical-side effects of opioid agonists, e.g., respiratory depression (W. Vogel et al., Arzneim, Forsch, (Drug Res.), 28(l), 183 (1978)), constipation (I. Arend et al., Arzneim, Forsch, (Drug Res.), 28(l), 199 (1978)), tolerance (L. Flohe et al., Arzneim, Forsch, (Drug Res.), 28(l), 213 (1978)), and abuse liability (T. Yanagita, Arzneim, Forsch. (Drug Res.), 28(l), 158 (1978)). When given at a dose of 50 mg by rapid i.v. injection, tramadol may however, produce certain side effects unique to tramadol including hot flushes and sweating. Despite theses side effects, tramadol's combination of non-opioid and opioid activity makes tramadol a very unique drug. Tramadol is currently being marketed by Grunenthal GMBH in Germany as an analgesic. Opioids have for many years been used as analgesics to treat severe pain. However, they produce undesirable side effects which place limitations on their use. The side effect problems are well documented in the literature. See, Jaffe, J. in "Goodman and Gilman's The Pharmacological Basis of Therapeutics", 8th edition; Gilman et al.; Peragamon Press, New York, 1990; Chapter 22, pages 522-573, wherein it is disclosed that morphine and its congeners, e.g., codeine, hydrocodone and oxycodone, are opioid agonist analgesics that exhibit side effects such as respiratory depression, constipation, tolerance and abuse liability. Web site: http://www.delphion.com/details?pn=US05468744__ •
Facile synthesis of codeine precursors from thebaine Inventor(s): Baskin; Craig P. (Avenel, NJ), Dauben; William G. (Berkeley, CA), vanRiel; Herman C. H. A. (Alphen aan den Rijn, NL) Assignee(s): The United States of America as represented by the Department of Health (Washington, DC) Patent Number: 4,277,604 Date filed: January 25, 1980 Abstract: Thebaine is converted to a mixture of codeinone and neopinone in aqueous formic acid solution containing as catalyst a mercuric salt. Thebaine is converted to a neopinone ketal by irradiation in an alkanol or to a mixture of neopinone and codeinone in an acidic aqueous solution. Neopinone ketals, codeinone and neopinone can be converted to codeine. Excerpt(s): This invention is directed to synthesis, starting from thebaine, of neopinone dialkyl ketals, neopinone or codeinone, each of which is convertible to codeine by conventional processes. Codeine, widely used as a pain-killer and cough suppressant, has conventionally been prepared by methylation of morphine, which is also traditionally used as the raw material for the illicit drug heroin. Morphine is obtained by extraction of opium or poppy straw from the opium poppy (Papaver somniferum), of which commercial cultivation is illegal in the United States. Because no commercially viable total synthesis of codeine has been devised and because of the uncertainties of relying on foreign sources of intermediates for codeine, it is apparent that development
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of alternative routes to codeine using domestically available non-addictive intermediates is of considerable significance. Thebaine, a product isolated from the perennial poppy P. bracteatum, which does not produce morphine, would be an acceptable alternative to morphine as an intermediate for codeine. An additional advantage of using thebaine as an intermediate is that thebaine is not readily converted to morphine and thence to heroin. Moreover, the cultivation of P. bracteatum is not proscribed. Web site: http://www.delphion.com/details?pn=US04277604__ •
Ibuprofen-antitussive combinations Inventor(s): Sims; Robert T. (Holicong, PA), Slivka; William (Philadelphia, PA) Assignee(s): McNeil-PPC, Inc. (Fort Washington, PA), Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,164,398 Date filed: April 1, 1991 Abstract: This invention relates to pharmaceutical compositions for use in the treatment of pain and inflammation and the relief of cough and cold symptoms in a mammalian organism, said composition comprising:(i) an analgesically and anti-inflammatory effective amount of (S)-ibuprofen, or a salt thereof, substantially free of (R)-ibuprofen; and(ii) an antitussively effective amount of at least one antitussive agent selected from codeine, hydrocodone, caramiphen, carbetapentane, or dextromethorphan, or a therapeutically active stereoisomer thereof substantially free of its other stereoisomers and optionallyiii) a therapeutically effective amount of at least one expectorant selected from guaicolsulfonate, guaifenesin, guaiacol, or terpin;or a pharamceutically acceptable salt thereof. Excerpt(s): The non-steroidal anti-inflammatory drugs (NSAID) have been utilized in the treatment of pain/inflammation and have been disclosed as useful in the treatment, management and mitigation of cold symptoms and the pain associated therewith. Ibuprofen (2-(4-isobutylphenyl)propionic acid) is a well known and commonly employed NSAID. Recently, it has been found that a faster onset of pain relief and an enhanced analgesic response can be obtained by the utilization of the single enantiomer (S)-ibuprofen in comparison to racemic ibuprofen, (see for example U.S. Pat. No. 4,877,620). Antitussives (cough suppressants) are useful in relieving cough symptoms associated with cold and flu conditions. Expectorants are useful in relieving upper chest congestion associated with the common cold and flu. Web site: http://www.delphion.com/details?pn=US05164398__
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Inhibiting the development of tolerance to and/or dependence on a narcotic addictive substance Inventor(s): Lyle; John W. (Belmar, NJ), Mao; Jianren (Richmond, VA), Mayer; David J. (Richmond, VA), Price; Donald D. (Richmond, VA) Assignee(s): Virginia Commonwealth University Medical College (Richmond, VA) Patent Number: 5,321,012 Date filed: April 6, 1993
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Abstract: Nontoxic substances that block the N-methyl-D-aspartate (NMDA) receptor, e.g., a morphinan such as dextromethorphan or dextrorphan, or that block a major intracellular consequence of NMDA receptor activation, e.g., a ganglioside such as GM.sub.1 or GT.sub.1b, a phenothiazine such as trifluoperazine or a naphthalenesulfonamide such as N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, inhibit the development of tolerance to and/or dependence on addictive drugs, e.g., narcotic analgesics such as morphine, codeine, etc. Excerpt(s): This invention relates to a composition containing an addictive substance and a component which inhibits the development of tolerance to and/or dependence on the addictive substance. More particularly, the invention relates to a composition containing an addictive substance such as morphine or codeine and at least one nontoxic substance that blocks the N-methyl-D-aspartate (NMDA) receptor, e.g., a morphinan such as dextromethorphan or dextrorphan, or that blocks at least one major intracellular consequence of NMDA receptor activation, e.g., a ganglioside such as ganglioside GM.sub.1 or GT.sub.1b, a phenothiazine such as trifluoperazine or a naphthalenesulfonamide such as N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide. Morphine is a rapid and effective drug for the treatment of severe pain but its long term administration has been limited due to its negative side effects, principally tolerance and dependence, which develop rapidly after administration. In an effort to make morphine of greater use in the treatment of pain, it has been combined with a variety of substances intended to inhibit one or more of its undesirable side effects. U.S. Pat. No. 2,770,569 describes the combination of morphine with the compound levo-d-hydroxy-N-allylmorphinan which is said to suppress or eliminate such undesirable side reactions of morphine as depression, nausea and vomiting. U.S. Pat. No. 4,126,684 discloses reducing either the addiction liability of an addictive substance such as a narcotic analgesic or a barbiturate or the withdrawal symptoms caused by deprivation of such a substance in an addicted subject by administering the addictive substance, e.g., morphine, with a 4amino-3-p-halophenylbutyric acid. U.S. Pat. No. 4,415,871 describes the prevention of treatment tolerance and physical dependence in chronic morphine treatment by combining the morphine with any of the specific dipeptides indicated therein. U.S. Pat. No. 5,041,446 discloses inhibiting the development of tolerance to morphine by combining the morphine with dapiprazole. U.S. Pat. No. 5,057,519 achieves a reduction in morphine tolerance by combining the morphine with a benzamide antagonist for a subtype of the serotonin receptor, 5-HT.sub.3. Trujillo et al., "Inhibition of morphine tolerance and dependence by the NMDA receptor antagonist MK-801", Science, 251 (4989), pp. 85-87, Jan. 4, 1991; Tanganelli et al., "Glutamate antagonists prevent morphine withdrawal in mice and guinea pigs", Neuroscience Letters, 122(2), pp. 270272, Jan. 28, 1991; Marek et al., "Excitatory amino acid antagonists (kynurenic acid and MK-801) attenuate the development of morphine tolerance in the rat", Brain Research, 547(1), pp. 77-81, Apr. 26, 1991; and, Marek et al., "Delayed application of MK-801 attenuates development of morphine tolerance in rats, Brain Research, 558(1), pp. 163165, Aug. 30, 1991 discuss the role of MK-801 (the compound 5-methyl-10,11-dihydroSH-dibenzo[a,d]cyclohepten-5,10-imine), an NMDA receptor antagonist or blocker, in reducing morphine dependence in laboratory animals. However, MK-801 has been found to be toxic and is therefore unsuitable for pharmaceutical use. In accordance with the present invention, a composition is provided which comprises an addictive substance and at least one nontoxic substance that blocks the N-methyl-D-aspartate receptor or at least one major intracellular consequence of N-methyl-D-aspartate receptor activation. Web site: http://www.delphion.com/details?pn=US05321012__
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Method for treatment of amyotrophic lateral sclerosis comprising administration of DMP Inventor(s): Salazar-Grueso; Edgar F. (Chicago, IL) Assignee(s): Arch Development Corporation (Chicago, IL) Patent Number: 5,229,394 Date filed: July 30, 1990 Abstract: A method for treating ALS (Amyotrophic Lateral Sclerosis) is disclosed. The inventive method comprises the administration of controlled dosages of dextromethorphan in therapeutically effective amounts in a pharmaceutically acceptable vehicle Dextromethorphan (DMP) is a dimethylaminomethyl-substituted phenol, a sigma receptor antagonist known also as d-3-methoxy-N methylmorphinan, a d-isomer of the codeine analog, levorphanol. The inventive method has proven useful in controlling the progression of ALS in afflicted patients. Excerpt(s): This invention relates to a method for treatment of Amyotrophic Lateral Sclerosis and other neurodegenerative disorders. This invention further relates to a method for treatment of Amyotrophic Lateral Sclerosis and other neurodegenerative disorders by administering a medicament in controlled doses of therapeutically effective amounts. Amyotrophic Lateral Sclerosis (ALS) is a progressive degenerative disease of the motor system which is usually relentlessly progressive, leading to death in half the cases within three years of onset. It is related to a group of diverse motor-system diseases which include Huntington's Chorea, Parkinson's disease and Alzheimer's disease. Numerous agents have been tried therapeutically in ALS, but none have been unequivocally demonstrated to benefit the disorder. This suggested to us that the LBMAA might be affecting a neuroreceptor type responsible for the ALS symptoms. It is known that other excitatory amino acids can bind in vitro to neuronal receptors. It has further been demonstrated in recent years that the dextrorotary opioid derivative dextromethorphan (DMP) binds to excitatory amino acid receptors in the brain. DMP has long been known as a highly effective cough suppressant. We, therefore, theorized that since a neuro-excitatory receptor in the brain appears to be adversely affected by LBMAA and may produce the motor degeneration characteristic of ALS, the action of LBMAA with the involved receptors might be antagonized by an agent such as DMP that suppresses central synaptic transmission. Web site: http://www.delphion.com/details?pn=US05229394__
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Method of producing thebaine from codeine and oripavine from morphine Inventor(s): Barber; Randy B. (Berkeley, CA), Rapoport; Henry (Berkeley, CA) Assignee(s): The United States of America as represented by the Department of Health, (Washington, DC) Patent Number: 4,045,440 Date filed: September 16, 1976 Abstract: A method of producing thebaine from codeine and oripavine from morphine which comprises (a) producing the 0-6 methyl ethers from codeine and morphine using potassium hydride and methyl iodide as the O-alkylation agents and (b) subsequently oxidizing the respective 0-6 methyl ethers of codeine and morphine to shift from allylic structure to a dienol ether structure using an oxidizing amount of MnO.sub.2 in
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tetrahydrofuran to produce thebaine from codeine and oripavine from morphine. In the case of morphine, it is preferable to protect the 0-3 position by acetylation prior to the oxidizing step. Both the etherification and oxidizing steps are carried out under a protecting blanket such as nitrogen and the reactions are carried out preferably under atmospheric pressure and ambient temperature with the exception of the etherification affecting the 0-6 position which may be commenced by cooling with ice. Excerpt(s): The present invention is concerned with producing particularly certain phenanthrene opiate derivatives and in particular thebaine and oripavine. It has been found that these members of the opium alkaloid family may be produced by the present process from the most abundant opium alkaloids, namely, morphine and codeine, and the production of thebaine and oripavine, which are quite rare in nature, has greater pharmacological potential for the production of drugs combatting addiction. Essentially, the present process involves starting with codeine and morphine and producing the 0-6 methyl ether from each and further oxidizing the C-ring which contains the 0-6 substituent to oxidize or dehydrogenate and effect a shift from an allyl ether to a dienol ether. This results in the loss of 2 hydrogens from the ring C and the consequent change of.DELTA.sup.7,8 to.DELTA.sup.6,7 and.DELTA.sup.8,14. In the case of morphine which, by this process, produces oripavine, it is preferred to block the 0-3 position of the C ring prior to oxidizing. This may be conveniently done by acetylation to produce the O-acetate, although the reaction will go without this protective step with reduced yield. Web site: http://www.delphion.com/details?pn=US04045440__ •
Non-addictive narcotic antitussive preparation Inventor(s): Portoghese; Philip S. (St. Paul, MN) Assignee(s): Regents of the University of Minnesota (Minneapolis, MN) Patent Number: 4,401,672 Date filed: October 13, 1981 Abstract: Non-addictive narcotic antitussive preparations including a normally addictive narcotic analgesic cough suppressive agent and a highly selective long-acting narcotic antagonist in a pharmaceutically acceptable liquid carrier. The narcotic antagonist is an opioid receptor site-directed alkylating agent. Preparations are disclosed having the effectiveness of codeine and other opiates for cough suppression, but devoid of addictive abuse potential. Excerpt(s): This invention is directed to non-addictive narcotic antitussive preparations and to the method of making and using such preparations. More particularly, the invention is directed to narcotic antitussive preparations containing a highly selective, long-acting narcotic antagonist, such as opioid receptor site-directed alkylating agents, as disclosed in my copending application Ser. No. 245,052, filed Mar. 19, 1981. Among the drugs employed in the control of cough are those which act by depressing the cough center in the medulla. The most effective and widely used of these antitussives are the narcotic analgesic agents. Codeine, hydrocodone, hydromorphone, and related opiates are most commonly employed for this purpose. One of the side effects of these opiates is their abuse potential. For example, the antitussive preparation, Elixir Terpin Hydrate and codeine, was originally sold throughout the United States over-the-counter as an exempt narcotic, but its abuse led to its being placed on a prescription-only status in many states. Clearly there is a need for a cough preparation having the same effectiveness as codeine or other opiates, but devoid of abuse potential. Although there
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are some agents such as dextromethorphan, a synthetic antitussive which lacks abuse potential, codeine continues to be the most effective drug prescribed to inhibit the cough reflex. As described in my aforesaid copending application Ser. No. 245,052, narcotic antagonists have received considerable attention over the past several years, particularly since the discovery of the endorphins. Evidence which supports the concept of multiple opioid receptors and their classification into subtypes, makes it apparent that exogenously administered opioids mediate their manifold effects through several types of receptors. Compounds have been designed that are selective and have prolonged activities due to the attachment of alkylating groups to ligands which are recognized by opioid receptors. The formation of a covalent bond with the receptor enable the drug to remain in the receptor locus and thereby exert its effects for extended periods. The design of such drugs takes into account the location of a nucleophile on the receptor which forms the covalent bond with the reactive group. Compounds produced as the result of such an approach are described, along with the method of making and using them. Web site: http://www.delphion.com/details?pn=US04401672__ •
Non-hydrolyzable analogs of heroin metabolites suitable for use in immunoassay Inventor(s): Rouhani; Riaz (Concord, CA), Sigler; Gerald F. (Carmel, IN) Assignee(s): Microgenics Corporation (Fremont, CA) Patent Number: 6,262,265 Date filed: June 18, 1999 Abstract: Novel chemical analogs are disclosed for the essential heroin metabolite 6-Oacetyl morphine (6MAM). The analogs optionally can be made to contain protein reactive groups, and can be used to form protein conjugates, fluorescently labeled compounds, and solid-phase adsorbants. The proteins conjugates can be used in turn to raise antibodies reactive with 6MAM and having a low cross-reactivity with the closely related opiates, morphine and codeine. The antibodies can be used in combination with labeled analogs in exquisitely sensitive immunoassays suitable for testing for heroin abuse. Excerpt(s): This invention relates generally to the field of determining drug metabolites in biological samples. More specifically, it provides a system of analogs, conjugates and specific antibodies that can be used in assay systems for specific detection or quantitation of heroin abuse. Testing for heroin abuse is complicated by the fact that heroin undergoes rapid metabolism to 6-O-acetyl-morphine (also known as 6monoacetylmorphine, 6MAM). After an intramuscular administration of heroin, 6MAM appears in urine almost immediately. Levels of 6MAM remain positive in urine for about 8 hours, as detected by standard techniques such as GC/MS (Cone et al., Anal. Toxicol. 15:1, 1991). Heroin is then broken down into morphine, which is a metabolite of other opiates such as codeine. A number of tests have been developed for measuring opiates in biological samples. Generally, immunoassays have been unsuccessful at discriminating between 6MAM and related compounds. Other opiate metabolites, such as morphine-3-glucuronide and morphine-6-glucuronide, may be present at levels approximately four to five orders of magnitude greater than 6MAM. Investigators have had to resort to more cumbersome and expensive techniques to determine the identity of an opiate in an unknown sample. Web site: http://www.delphion.com/details?pn=US06262265__
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Papaver somniferum strain with high concentration of thebaine and oripavine Inventor(s): Byrne; Christopher James (Westbury, AU), Fist; Anthony John (Norwood, AU), Gerlach; Wayne Lyle (Killara, AU) Assignee(s): Tasmanian Alkaloids Pty. Ltd. (AU) Patent Number: 6,067,749 Date filed: July 11, 1996 Abstract: There is disclosed an improved poppy straw of a stably reproducing Papaver somniferum for the extraction of thebaine and/or oripavine, the threshed straw having thebaine and oripavine constituting about 50% by weight or greater of the alkaloid combination consisting of morphine, codeine, thebaine and oripavine. Excerpt(s): The present invention relates to the improved production of thebaine and oripavine. More particularly, the present invention relates to the use of a mutagenized Papaver somniferum poppy plant to produce thebaine and oripavine in higher yield. In accordance with one conventional process, thebaine is oxidized to 14-hydroxycodeinone by use of m-chloroperbenzoic acid in an acetic acid/trifluoroacetic acid mixture or by a mixture of hydrogen peroxide and formic acid. 14-hydroxycodeinone is catalytically reduced to oxycodone. Oxycodone is a product sold for use as and analgesic and its production consumes large amounts of thebaine. Oxycodone can be, in turn, Odemethylated with boron tribromide to yield oxymorphone. After blocking of the hydroxyl groups with a suitable blocking agent, such as, acetyl groups, the oxymorphone derivative is reacted with cyanogen bromide in a von Braun demethylation to yield an N-cyanodihydronormorphinone derivative that is thereafter hydrolyzed to 14-hydroxydihydronormorphinone (noroxymorphone). Noroxymorphone can be readily converted to nal-compounds by N-alkylation with appropriate alkyl halide, or acylation with appropriate acyl halide or anhydride, followed by reduction. A more generally applicable process, converts the oxycodone of the above process to noroxycodone by the von Braun N-demethylation followed by conversion to a 3-O-methyl-nal-compound using N-alkylation with an appropriate alkyl halide, or by alkylation with an appropriate alkyl halide, or acylation with appropriate acyl halide or anhydride, followed by reduction. The 3-O-methyl-nal-compound is reacted to a nal-compound by O-demethylation. Web site: http://www.delphion.com/details?pn=US06067749__
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Pharmaceutical composition comprising analgesic and anti-inflammatory agent Inventor(s): Elger; Gordon A. (Huntingdon, GB), Leslie; Stewart T. (Cambridge, GB), Malkowska; Sandra T. A. (Cambridge, GB), Miller; Ronald B. (Basel, CH), Neale; Philip J. (Cambridge, GB) Assignee(s): Euroceltique, S.A. (Luxembourg, LU) Patent Number: 4,844,907 Date filed: August 14, 1986 Abstract: A pharmaceutical composition in the form of a multiphase (especially a bilayered, optionally coated) tablet. The tablet has a narcotic analgesic phase containing a therapeutically effective quantity of a narcotic analgesic or an analgesically effective salt thereof (e.g. codeine phosphate) and a non-steroidal anti-inflammatory phase
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containing a therapeutically effective quantity of a non-steroidal anti-inflammatory carboxylic acid or an anti-inflammatory salt or ester thereof (e.g. ibuprofen). The narcotic analgesic phase is free from a non-steroidal anti-inflammatory carboxylic acid or salt or ester thereof, stearic acid and stearate salt, and the non-steroidal antiinflammatory phase is free from a narcotic analgesic or salt thereof, stearic acid and a stearate salt. Further, both the narcotic analgesic phase and the non-steroidal antiinflammatory phase contain a self-lubricating, compression aid, especially a selflubricating, direct compression aid, such as microcrystalline cellulose. Excerpt(s): This invention relates to a pharmaceutical composition, in particular to a pharmaceutical composition for the relief of mild to severe pain and for the treatment of inflammation in musculo- skeletal disorders. Narcotic analgesics, such as codeine and dihydrocodeine, have been used in the relief of pain, especially mild to severe pain. Severe pain, in particular, requires the use of large and increasing doses of a narcotic analgesic. A major disadvantage of narcotic analgesics is that patients may develop a dependence and tolerance to their action. Further adverse reactions, such as respiratory and circulatory depression, are observed when large doses of narcotic analgesics are used. Web site: http://www.delphion.com/details?pn=US04844907__ •
Pharmaceutical compositions with analgesic properties and the preparation and use thereof Inventor(s): Rothweiler; Herbert (Rheinfelden-Eichsel, DE), Voss; Harald (Bad Homburg, DE) Assignee(s): Ciba-Geigy Corporation (Ardsley, NY) Patent Number: 4,690,927 Date filed: February 3, 1986 Abstract: A pharmaceutical composition with analgesic properties which contains a pharmaceutically acceptable salt of diclofenac and a pharmaceutically acceptable salt of codeine in the weight ratio of about 1:1 to 3:1, and the preparation and use thereof. Excerpt(s): The present invention relates to pharmaceutical compositions with analgesic properties containing two different drugs with the same properties so as to effect an increase in the desired analgesic effect. One of the long-existing primary goals of medicine is the relief of pain. Relief is sought usually by the administration of analgesic drugs which increase the pain threshold. It is difficult to satisfy this requirement with a single chemical entity, as a potent analgesic will normally cause concomitant sideeffects, whereas a drug that gives rise to few or no side-effects will also generally be a less effective analgesic. Almost all analgesic drugs induce reactions other than the relief of pain. Some of these reactions are e.g. gastrointestinal disorders, dizziness, constipation, nausea, and vomiting. Thus when using analgesics in man, considerations other than achieving the primary effect (amalgesia) must be borne in mind, so that novel drugs are sought which have the maximum analgesic effect accompanied by a minimum of side-reactions. There is therefore a continual search for a combination of drugs which will enable the total amount of drug to be reduced and which can be administered in such propertions that maximum analgesic effect can be produced with little or no sideeffects. What is sought is, on the one hand, a potentiation of the therapeutic, i.e. analgesic, effect and, on the other, a reduction of undesirable side-effects. Surprisingly, it has been found that such a potentiating effect is produced by a combination of a
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pharmaceutically acceptable salt of diclofenac and a pharmaceutically acceptable salt of codeine in the weight ratio of about 1:1 to 3:1, but preferably in the ratio of about 1:1. The onset of activity of the combination of this invention is, surprisingly, as rapid as that of the individual components with longer duration of action. For example, the efficacy of the combination lasts 6 hours longer than that of the individual components, namely diclofenac sodium and codeine phosphate. Surprisingly, it has also been found that the analgesic effect is significantly better than that of pentazocine, which is subject to control under the law on dangerous drugs. For example, the analgesic activity of a combination comprising 50 mg of diclofenac sodium and 50 mg of codeine phosphate (ratio of 1:1) is significantly better than that of 50 mg of pentazocine and as good as that of 100 mg of pentazocine but with far better tolerance. The effective dosage thereby attainable brings about a reduction of undesirable side-effects. Web site: http://www.delphion.com/details?pn=US04690927__ •
Pharmaceutical compositions with codeine Inventor(s): Kim; Miwon S. (Princeton Junction, NJ) Assignee(s): Carter-Wallace, Inc. (New York, NY) Patent Number: 4,534,974 Date filed: July 31, 1984 Abstract: Compositions for the relief of pain, muscle spasm and limited mobility associated with acute painful muscoloskeletal conditions are disclosed. Such compositions comprise in combination, a N-monosubstituted-2, 2-dialkyl-1, 3propanediol dicarbamate, aspirin and codeine. Excerpt(s): This invention relates to novel pharmaceutical compositions. More particularly this invention relates to novel therapeutic compositions capable of relieving pain, muscle spasm and limited mobility associated with acute painful muscoloskeletal conditions in warm-blooded animals. c. codeine phosphate. The N-monosubstituted-2, 2-dialkyl-1, 3-propanediol dicarbamates, particularly the N-isopropyl-2-methyyl-2propyl-1, 3-propanediol dicarbamate known as carisoprodol are disclosed in U.S. Pat. No. 2,937,119 and are colorless liquids of high boiling point or low melting solids. They are soluble in most organic solvents but only slightly soluble in water at room temperature. The N-monosubstituted-2, 2-dialkyl-1, 3-propanediol dicarbamates possess strong muscle relaxant activity. The N-monosubstituted-2, 2-dialkyl-1, 3-propanediol dicarbamates, particularly carisoprodol are centrally-acting muscle relaxants that do not directly relax the tense skeletal muscles in warm-blooded animals. In animal studies carisoprodol has been shown to produce muscle relaxation by blocking interneuronal activity and depressing the transmission of polysynaptic neurons in the spinal cord and in the decending reticular formation of the brain. Web site: http://www.delphion.com/details?pn=US04534974__
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Preparation of 14-hydroxy-N-ethoxy-carbonyl-norcodeinone Inventor(s): Kavka; Frank (St. Louis, MO) Assignee(s): Mallinckrodt, Inc. (St. Louis, MO) Patent Number: 4,639,520 Date filed: March 27, 1984 Abstract: N-ethoxycarbonyl-14-hydroxynorcodeinone is prepared by contacting Nethoxycarbonyl-norcodeinone enol acetate with an aromatic or aliphatic mono-basic or poly-basic peroxy-acid under reaction conditions effective for substituting an --OH group in the 14-position of the norcodeinone enol acetate.In a preferred embodiment the reaction conditions include effecting the contacting in the presence of (A) a moderately strong acid having a pK.sub.a of from about 0.3 to about 3.5, (B) an inert organic solvent, and (C) in the substantial absence of water.Codeine is converted to noroxymorphone by an improved process employing the above method for introducing the 14-hydroxy group into the codeine derivative. Excerpt(s): 14-hydroxymorphinans, including such "nal" compounds as naloxone, naltrexone, and nalbuphine are important morphine derivatives due to their behavior as potent analgesics and/or narcotic antagonists. Prior to the present invention, among the most practical synthetic routes to the preparation of these pharmaceuticals have been processes which utilize thebaine as a starting material. In accordance with heretofore known processes, thebaine is oxidized to 14-hydroxycodeinone by use of mchloroperbenzoic acid in an acetic acid/trifluoroacetic acid mixture or by a mixture of hydrogen peroxide and formic acid. 14-hydroxycodeinone is catalytically reduced to oxycodone which in turn is O-demethylated with boron tribromide to yield oxymorphone. After blocking of the hydroxyl groups with suitable blocking agents such as acetyl groups, the oxymorphone derivative is reacted with cyanogen bromide to yield an N-cyanodihydronormorphinone derivative which is thereafter hydrolyzed to 14hydroxydihydronormorphinone (noroxymorphone), an important intermediate for preparation of naloxone, naltrexone and nalbuphine. However, such thebaine-based syntheses are not entirely satisfactory for a number of reasons. For example, thebaine is in limited supply and its cost is high, thereby contributing to high cost of the noroxymorphone and the 14-hydroxymorphinans derived from it. Because of the scarcity and high cost of thebaine, efforts have been made in the art to devise methods for the synthesis of noroxymorphone and noroxycodone from compounds in more plentiful supply than thebaine. However, there is a substantial need in the art for a lower cost, more efficient method of introducing a 14-.beta.-hydroxy group into Nethoxycarbonyl-norcodeinone dienol acetate. There is also a substantial need in the art for an improved process for preparing noroxymorphone from codeine. Web site: http://www.delphion.com/details?pn=US04639520__
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Preparation of codeine from morphine Inventor(s): Hill; Lloyd P. (St. Louis, MO) Assignee(s): Mallinckrodt Inc. (St. Louis, MO) Patent Number: 6,579,985 Date filed: October 21, 2002
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Abstract: An improved process for the preparation of codeine from morphine comprises the steps of a) reacting morphine with a methylating agent in the presence of a hydrocarbon solvent at a temperature of 100 to 215.degree. C. under reflux conditions such that approximately 50% or more of the hydrocarbon solvent is returned to the reaction mixture to substantially avoid the formation of codeine methyl ether; and b) recovering codeine from the reaction mixture. The process may include step a) above followed by b) cooling the reaction mixture to approximately 85.degree. C. and adding water to terminate the reaction; c) raising the pH of the reaction mixture to approximately 11; d) separating the hydrocarbon solvent phase containing codeine and dimethylaniline; and e) adding a dilute mineral or organic acid and approximately 6 to 7 times the volume of water for each volume of hydrocarbon solvent to separate dimethylaniline and codeine. Excerpt(s): This invention relates to the preparation of codeine from morphine and, more particularly, to an improved process for the preparation of codeine which provides for more complete control over the formation of the methylated by-product codeine methyl ether and for a more thorough separation of dimethylaniline and codeine. Codeine is widely used as an analgesic and is the methyl ether of morphine. While it occurs naturally in opium to a small extent, it has been prepared synthetically by methylation of the phenolic hydroxyl group in morphine. Thus, it is known to prepare codeine by the reaction of morphine with a methylating agent such as dimethyl sulfate or trimethylphenyl ammonium ethoxide or trimethylphenyl ammonium hydroxide in the presence of a base such as aqueous sodium hydroxide, or alcoholic sodium ethoxide. See W. R. Heumann, Bulletin on Narcotics, Vol. 10, No. 3, pp. 15-17 (1958); U.S. Pat. No. 4,764,615 and U.S. Pat. No. 6,204,337. Modified conditions of the process described by Heumann have been used commercially for some years. Currently employed processes suffer from significant yield loss, great recycle volume, high operator exposure, and extensive cycle times. The yield loss occurs partly from the current need to remove unreacted morphine and color bodies through precipitation, salt crystalilizations, and carbon treatment. Most of the precipitation and crystallization steps require manual digging of a centrifuge or filter. This creates much operator exposure and greater reliance on personal protection equipment. Allergic symptoms from the narcotics can result through extended exposure. Repetitive motion injuries can also occur from the manual digging. Web site: http://www.delphion.com/details?pn=US06579985__ •
Preparation of naltrexone from codeine and 3-benzylmorphine Inventor(s): Christodoulou; Aris P (New York, NY), Huang; Bao-Shan (Edison, NJ), Ji; Ben-Yi (Edison, NJ), Lu; Yansong (Edison, NJ) Assignee(s): Penick Corporation (Newark, NJ) Patent Number: 6,013,796 Date filed: July 16, 1998 Abstract: For the synthesis of 3-methylnaltrexone from codeine in this invention, codeine is converted to 6-acetylcodeine, which is N-demethylated to 6-acetylcodeine hydrochloride, followed by alkylating the nitrogen to form 17cyclopropylmethylnorcodeine. The latter is oxidized to 17cyclopropylmethylnorcodeinone. For the synthesis of naltrexone from morphine in this invention, morphine is converted to 3-benzylnormorphine as described above in the synthesis of noroxymorphone. 3-Benzylnormorphine is reacted with cyclopropylmethyl
Patents 95
halide to produce 3-benzyl-17cyclopropylmethylnormorphine, a novel compound, which is oxidized to 3-benzyl-17-cyclopropylmethyl-normorphinone, a novel compound, by Swern oxidation. Excerpt(s): This invention relates in general to process for the conversion of normorphinone and its derivatives, which can be synthesized from morphine, to the corresponding 14-hydroxynormorphinone and its derivatives including oxycodone, oxymorphone, noroxymorphone, and naltrexone. Noroxymorphone is a key intermediate for the production of important narcotic analgesics and antagonists. In another aspect, the invention is directed to certain novel intermediates. 14-Hydroxysubstituted morphine derivatives are important narcotic analgesics and/or antagonists. These drugs include oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, and nalmefene. They are readily synthesized from thebaine, which is a minor component of gum opium. As the supply of thebaine is limited and the demand is increasing, therefore, the price of thebaine is high. As a result, many alternative approaches have been made for the preparation of 14-hydroxymorphine derivatives. The reported efforts for preparing these narcotics bearing a 14-hydroxy group from readily abundant starting materials morphine or codeine (a minor component of gum opium, which may also be synthesized by methylation of morphine) are summarized as the following: (1) the conversion of codeine to thebaine through dihydrocodeinone (5.4% yield, H. Rapoport, et al., J. Am. Chem Soc., vol. 89, 1967, p. 1942 and H. Rapoport, et al., J. Org. Chem., vol. 15, 1950, p. 1103), codeinone (20% yield, I. Seki, Chem. Pharm. Bull., vol. 18, 1970, p. 671 and H. Rapoport, et al., J. Am. Chem. Soc., vol. 77, 1955, p. 490) or 6-methyl ether of codeine (using manganese dioxide, 67% yield, R. B. Barber, et al., J. Med. Chem., vol. 18, 1975, p. 1074); (2) the oxidation of codeinone pyrrolidinyl di-enamine to 14-hydroxycodeinone (30-40% yield, I. Seki, Chem. Pharm. Bull., vol. 18, 1970, p. 671); (3) the direct allylic oxidation of codeine to the corresponding 14-hydroxy derivatives with, manganese dioxide (I. Brown, et al., J. Chem. Soc., 1960, p. 4139), and selenium dioxide plus t-butyl hydrogen peroxide (M. A. Schwartz, et al., J. Med. Chem., vol. 24, 1981, p. 1525); and (4) the six-step transformation of codeine to noroxycodone (52% yield) and noroxymorphone (43% yield) using photochemically generated singlet oxygen (M. A. Schwartz, et al., J. Med. Chem. vol. 24, 1981, p. 1525); and (5) the preparation of noroxymorphone from morphine through an intermediate with carbamate protection on the nitrogen atom (17-position) or a carbonate protecton at the 3 position and the carbamate protection at the 17 position of normorphinone dienol acetate with MCPBA in the substantial absence of water (37% yield, Wallace, U.S. Pat. No. 5,112,975). These processes suffer from either low yields, long steps, not amenable to scale-up, or involve the use of environmentally unfriendly heavy metals. Web site: http://www.delphion.com/details?pn=US06013796__ •
Process for the preparation of codeine from morphine Inventor(s): Ayyangar; Nagaraj R. (Maharashtra, IN), Choudhary; Anil R. (Maharashtra, IN), Kalkote; Uttam R. (Maharashtra, IN), Sharma; Vasant K. (Maharashtra, IN) Assignee(s): Council of Scientific & Industrial Research (New Delhi, IN) Patent Number: 4,764,615 Date filed: December 10, 1986 Abstract: Codeine is prepared by reacting morphine with trimethyl phenyl ammonium chloride in the presence of an alkali metal carbonate and a hydrocarbon solvent at a
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Codeine
temperature of from 40.degree. to 120.degree. C. Codeine is recovered from the reaction mixture. Codeine is useful as an analgesic and antitussive drug. Excerpt(s): This invention relates to an improved process for the preparation of codeine from morphine. Codeine is useful as an analgesic and antitussive drug. Codeine is a methylether of morphine. It occurs naturally in opium to the extent of 2 to 4% depending on the source. Codeine is being prepared synthetically from morphine by methylation of phenolic hyroxyl group because the demand for codeine has far exceeded the quantities that are naturally available from opium. It is hitherto been known to prepare codeine by the reaction of morphine with the methylating agent such as dimethyl sulphate or methyl chloride or trimethylphenylammonium ethoxide or trimethylphenylammonium hydroxide in presence of a base such as aqueous sodium hydroxide or alcoholic sodium ethoxide. In this connection following references are made. Rodinov, Bull. Soc. Chim; 39, 305-25 (1926); 45 109-21 (1928); Schwyze Bull. Soc. Chim; 45, 388-92 (1928); Rodinov and Small, Bull. Soc. Chim; 45, 188-89 (1928); M. A. Phillips, Chemists and Druggist, 183, 661 (1965); J. Kesselring and H. Loffer, Ger Pat., 15069 and 15070 (1958); CA 54 485 (1960); S. Stanev and W. Kamedulsk, Farmatsiya (Sofia), 10, 30-5 (1960); CA 55 74605 (1961); W. R. Henmann, Bull. Narcotics, U.N. Dept of social affairs, 10, 15-17 (1958); I. Kostantin, Acta. Pharma, Iugasolav, 23(3), 169- 71 (1973). Web site: http://www.delphion.com/details?pn=US04764615__ •
Process for the stereoselective reduction of 6- and 8-keto morphine and morphinan derivatives with formamidinesulfinic acid and compounds obtained thereby Inventor(s): Chatterjie; Nithiananda (Flushing, NY), Inturrisi; Charles E. (New York, NY) Assignee(s): Cornell Research Foundation, Inc. (Ithaca, NY) Patent Number: 4,089,855 Date filed: April 23, 1976 Abstract: Process for the stereoselective synthesis of 6.beta.-and 8.beta.- hydroxy epimers by the chemical reduction of 6- and 8-keto derivatives in the morphine and morphinan series utilizing alkaline formamidinesulficic acid. The 6.beta.- and 8.beta.hydroxy derivatives obtained according to the invention evidence narcotic antagonist and/or agonist activity and are also useful in the chemical and pharmacological standardization of various morphine and codeine derivatives and metabolites. Excerpt(s): The present invention relates to a process for the stereoselective reduction of 6- and 8-keto phenanthrene derivatives including N-substituted derivatives, employing an alkaline solution of formamidinesulfinic acid to form the corresponding 6.beta.- and 8.beta.-hydroxy epimers thereof. In recent years, there has been considerable interest in the development of narcotic antagonists capable of blocking the euphorigenic and addictive effects of narcotics. Exemplary of such compounds are cyclazocine,Nallylnoroxymorphone (naloxone), N-cyclopropylmethyl-noroxymorphone (naltrexone) and 3,14.beta.-dihydroxy-N-cyclobutulmethylmorphinan (butorphanol). Various derivatives in the morphine and morphinan series have heretofore been prepared which display combined narcotic antagonist-analgetic (agonist) properties. See, for example, U.S. Pat. Nos. 3,393,197; 3,332,950; 3,814,768; 3,819,635; and 3,896,226. Such derivatives having combined antagonist-agonist properties are very desirable as replacements for pure morphine in analgesic applications. As a consequence of the species variation with
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respect to narcotic antagonist-agonist activity and relative potencies of various compounds previously investigated, there has also been considerable interest in delineating the role of biotransformation and metabolites in observed activity for morphine derivatives as well as determination of receptor stereospecificity. Accordingly, synthetic methods for the preparation of 6-keto reduction products of the morphine nucleus compounds have heretofore been described. Web site: http://www.delphion.com/details?pn=US04089855__ •
Sequential benzylic oxidations of the naloxone ring system Inventor(s): Cain; Gary A. (Wilmington, DE), Drummond, Jr.; Spencer (Wilmington, DE) Assignee(s): Endo Pharmaceuticals, Inc. (Chadds Ford, PA) Patent Number: 6,166,211 Date filed: March 7, 2000 Abstract: The present invention pertains to a process for the preparation of the 10-keto analogs of morphinan compounds. In the case of compounds having a 3-hydroxyl group, the 3-methyl ether protected analog is synthesized by selective phenolic methylation in the presence of the basic amino group. When nalbuphine, morphine, or codeine is used as the starting material, the additional 6-hydroxyl group is protected using acetylation. The protected analog is selectively oxidized by treatment with cerium ammonium nitrate to provide the 10-(S)-hydroxy adduct. The 10-(S)-hydroxy adduct is further oxidized to the 10-keto analog. Any protecting groups that were added prior to oxidation are cleaved subsequent to oxidation to form the desired 10-ketomorphinan. Excerpt(s): This invention relates to a process for forming 10-keto derivatives of morphinan compounds. Methods have been reported in the literature for the synthesis of a small number of structurally related 10-ketomorphinans. Methods using CrO.sub.3 as an oxidant (S. Archer et al., J. Med. Chem. 28: 974-976, 1985, and H. Rapoport et al., J. Am. Chem., 77:4330-4335, 1955) suffer from extremely low yields. Methods which use SeO.sub.2 as oxidant (R. T. Uyeda et al., Tetrahedron Lett., 30:5725-5728, 1989) necessitate rendering the ring nitrogen into a non-basic amide form, thereby adding extra synthetic steps. Commonly used methods for effecting 10-oxidations use a phenolic 3-methyl ether protected analog. The classical conditions for morphinan 3methyl ether synthesis require the highly toxic, rather volatile dimethyl sulfate in aqueous NaOH (S. Archer et al., J. Med. Chem. 28: 974-976, 1985, and H. Rapoport et al., J. Am. Chem., 77:4330-4335, 1955). Cerium ammonium nitrate (CAN) has been reported to effect benzylic oxidations on electron rich aromatic compounds in alcoholic (or HOAc) solutions to provide benzyl ether (or acetate) mono adducts (K. Isobe et al., Chem. Pharm. Bull 42: 197-1994). It is therefore an object of the present invention to apply these principals to find a useful oxidation scheme to provide the benzylic 10hydroxyl adduct. Although CAN has been reported under certain conditions to oxidize simple toluenes to aldehydes and ketones (S. B. Lang et al., J. Chem. Soc. (C)2915, 1968 and references therein), no 10-keto adduct was observed by.sup.1 H NMR in the crude oxidation product. The 10-(S)-alcohol was readily oxidized into the 10-ketone analog with the Dess-Martin periodinane (Dess, D. B. and Martin, J. C., J. Org. Chem. 48, 41554158, 1983; Dess, D. B. and Martin, J. C., J. Am. Chem Soc. 113, 7277-7287, 1991; Ireland, R. E. and Liu, L., J. Org. Chem. 58, 2899, 1993; Schrieber, S. L. and Meyer, S. D., J. Org. Chem. 59, 7549-7552, 1994). These pharmaceutical compounds are related to morphinans which have effects such as analgesia, sedation, mood alteration. The 10-keto morphinan
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compounds are the degradation products of morphinans and may therefore be related to the age and condition of the original morphinan compounds. Web site: http://www.delphion.com/details?pn=US06166211__ •
Solid-phase synthesis of codeine from morphine Inventor(s): Corcoran; Robert C. (Laramie, WY), Ma; Junning (North Wales, PA) Assignee(s): The Board of Regents of the University and Community College System of (Reno, NV) Patent Number: 5,981,750 Date filed: November 19, 1996 Abstract: The specification describes a methylation resin comprising methyl(dialkyl)anilinium salts or methyl(diaryl)anilinium salts covalently bonded to the resin. The methylation resin is used in the solid-phase synthesis of codeine from morphine. Accordingly, the specification describes a process for methylating morphine to form codeine by loading morphine onto a methylation resin comprising methyl(dialkyl)anilinium salts or methyl(diaryl)anilinium salts covalently bonded to the resin; contacting the loaded resin with sufficient hydrocarbon or ether solvent to cover the loaded resin; and heating the loaded resin in the hydrocarbon or ether solvent under sufficient conditions to form codeine. The methylating resin may be used to methylate phenolic moieties on other compounds and to esterify compounds containing carboxylic acid moieties. Excerpt(s): This invention relates to a polymeric alkylating reagent and its use in alkylation reactions. In a particular embodiment, this invention relates to a methylation resin and its use in a novel method for synthesizing codeine from morphine. Codeine is widely used as both an analgesic and antitussive drug. Codeine occurs naturally in opium to the extent of 0.3% to 4% depending on the source. Codeine is the methyl ether derivative of morphine, another naturally occurring opiate alkaloid. Morphine is present in opium in the range of 9% to 17% by weight. Although morphine is more abundant and a more potent analgesic drug than codeine, the market demand for codeine far exceeds that for morphine. Codeine is generally prepared by methylating morphine. A trimethylanilinium salt is generally used as the methylating reagent with the counter anion being ethoxide, chloride or hydroxide. The reaction is generally run in toluene or xylene, and when the counter anion is chloride the reaction must be run in the presence of an organic base, such as sodium ethoxide, to remove the proton from the phenoxy group of morphine. Morphine is usually first dissolved in absolute ethanol and then added to the solution of the methylating reagent in a hydrocarbon solvent. Ethanol is distilled out during the reaction. Web site: http://www.delphion.com/details?pn=US05981750__
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Synthesis of 1-substituted isoquinolines Inventor(s): Hendrickson; James B. (9 Acacia St., Cambridge, MA 02138), Rodriguez; Cesar (567 South St., Waltham, MA 02154) Assignee(s): none reported Patent Number: 4,514,569 Date filed: January 28, 1982 Abstract: A method for the synthesis of particular isoquinoline compounds which are useful intermediates in the preparation of members of the family of opium alkaloids, such as morphine and codeine. Steps in the process include the acylation of the isoquinoline nitrogen; reaction of the acylated isoquinoline with a phosphorous compound; and condensation with a benzaldehyde derivative to yield a 1-benzyl isoquinoline. Excerpt(s): The present invention concerns a process for the preparation of certain isoquinoline compounds which can then be taken on to useful compounds such as morphine and codeine. The present invention comprises a process for the preparation of certain isoquinoline compounds which may be taken on to pharmaceutically useful natural and synthetic alkaloids of the morphine and codeine type as well as morphine and codeine themselves. Also part of the present invention are the intermediate products produced in the course of the process of the invention. Z.sup.1 is hydrogen or halogen such as bromo, chloro, iodo or fluoro. Web site: http://www.delphion.com/details?pn=US04514569__
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Synthesis of 4A-aryl-decahydroisoquinolines Inventor(s): Gless; Richard D. (Oakland, CA), Rapoport; Henry (Berkeley, CA), Weller; Dwight D. (Champaigne, IL) Assignee(s): The United States of America as represented by the Department of Health, (Washington, DC) Patent Number: 4,189,583 Date filed: April 26, 1978 Abstract: This invention relates to a process for the production of 4aaryldecahydroisoquinolines where the aryl group is selected as 3-methoxy phenyl. These compounds are morphine analogs and show utility similar to the known morphine, codeine, and thebaine. In this process particular novelty is asserted for the production of a nipecotic ester ethyl 4-(3'-methoxyphenyl)-1-methyl piperidine-3carboxylate. Furthermore, novelty is asserted for the step of conversion of the nipecotates through cyclization to cis- or trans-tert-butyl 1,6-dioxo-4a-(3'methoxyphenyl)-2-methyldecahydroisoquinoline-7-carboxylat e, which may also be easily converted to the keto amide, trans-1,6-dioxo-4a-(3'-methoxyphenyl)-2methyldecahydroisoquinoline. Excerpt(s): Syntheses are presented of 4a-(3'-methoxyphenyl)decahydroisoquinolines with the carbocyclic ring functionalized so as to resemble the substitution pattern in ring C of the morphine alkaloids. A versatile synthesis was developed for the starting 4arylnipecotic acid which was then, via the methylene lactam rearrangement and intramolecular Michael reaction, stereospecifically converted to the 1,6dioxodecahydroisoquinoline, trans-1,6-dioxo-4a-(3'-methoxyphenyl)-2-
100 Codeine
methyldecahydroisoquinoline (keto amide trans-9). Reduction gave ketone trans36 ]trans-4a-(3'-methoxyphenyl)-2-methyl-6-oxodecahydroisoquinoline], and selective functionalization at C-7 led to the key unsaturated ketal, trans-.DELTA.sup.7 -6,6dimethoxy-4a-(3'-methoxyphenyl)-2-methyl-octahydroisoquinoline (39). Hydrolysis yielded codeinone analog,.alpha.,.beta.-unsaturated ketone 40 [trans-.DELTA.sup.7 -4a(3'-methoxyphenyl)-2-methyl-6-oxooctahydroisoquinoline], reduction gave codeine analog.DELTA.sup.7 -allylic alcohol 7, and ether cleavage produced the morphine analog, trans-.DELTA.sup.7 -6.alpha.-hydroxy-4a.alpha.-(3'-hydroxyphenyl)-2methyloctahydroisoquinoli ne (6). Cis-fused analogs were obtained through 9 and ketal amide, 6,6 -ethylenedioxy-4a-(3'-methoxyphenyl)-2-methyl-1-oxodecahydroisoquinoline (34) or trans-.DELTA.sup.7 -4a-(3'-methoxyphenyl)-2-methyl-6oxooctahydroisoquinoline (40) via isomerization at C-8a and were the predominant isomers at equilibrium. Alkali- or acid-catalyzed elimination of methanol from.DELTA.sup.7 -dimethyl ketal 39 produced mainly the thebaine analog,.DELTA.sup.6,.DELTA.sup.8(8a) -6-methoxy-4a-(3'-methoxyphenyl)-2methylhexahydroisoquinoline (8), which could be hydroxylated at C-8a with peracid to 14-hydroxycodeinone analogs,.DELTA.sup.7 -8a-hydroxy-4a-(3'-methoxyphenyl)-2methyl-6-oxooctahydroisoquinolines (57 and 58), but would not participate in DielsAlder cycloaddition with a variety of dienophiles. In an earlier article, Weller and Rapoport, J. of the Am. Chem. Soc., 98:6650 (1976), it was shown that trans- and cis-4aphenyldecahydroisoquinolines (2 and 3) could be prepared but the problem remained of the proper concordance of a different aryl fraction than phenyl as well as the concordance in the C ring, thus decahydroisoquinolines were necessary whose C rings would, with the exception of the C-5 oxygen bridge linkage, mimic the C rings of the hydrophenanthrene opium alkaloids. In order to prepare compounds which were pharmacologically consonant with natural compounds, the 4a-aryl moiety was chosen to be 3-methoxyphenyl. Thus, in the present system, decahydroisoquinolines 6, 7, 8 analogs of morphine, codeine, and thebaine 4 were prepared from a ketoamide, trans1,6-dioxo-4a-(3'-methoxyphenyl)-2-methyldecahydroisoquinoline (trans-9). In addition, although trans-9 possesses the trans ring fusion, the present synthesis allows for both a trans- and cis- material, including the epimeric cis codeine analogs 10 and 11 (cis.DELTA.sup.7 -6.alpha.- and cis-.DELTA.sup. 7 -6.beta.-hydroxy-4a.alpha.-(3'methoxyphenyl)-2-methyloctahydroisoquinolin es). In the plan of the present synthesis of the compounds, the synthesis of the keto amide above required the correct nipecotic ester and previous processes for the production of the nipecotates were unuseable. Web site: http://www.delphion.com/details?pn=US04189583__ •
Synthesis of derivatives of codeine and other 3-O-alkylmorphines Inventor(s): Schwartz; Martin A. (Tallahassee, FL) Assignee(s): The Florida Board of Regents on behalf of The Florida State University (Tallahassee, FL) Patent Number: 4,795,813 Date filed: December 24, 1986 Abstract: A 14-hydroxy group is introduced into a morphinan structure by singlet oxygen reaction with a novel dienol ester of an N-substituted-3-O-alkylnormorphinone. The resultant N-substituted-3-O-alkyl-141-hydroxynormorphinone is also a novel compound which may be catalytically hydrogenated to produce a novel N-substituted3-O-alkylnoroxymorphone. The latter intermediate may be converted to a 3-O-
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alkylnoroxymorphone by hydrolytic removal of the N-substituent and to noroxymorphone by both hydrolysis and O-dealkylation.The dienol ester intermediate is prepared by N-demethylation of codeine or other 3-O-alkylmorphine by reaction with a cyanogen halide or haloformate ester, followed by oxidation of the resultant Nsubstituted-3-O-alkylnormorphine to an N-substituted-3-O-alkylnormorphinone and esterification of the latter with an acid anhydride or acid halide. Excerpt(s): This invention relates to the field of synthesis of 14-hydroxymorphinans and more particularly to a novel and improved process for the preparation of noroxycodone, noroxymorphone and certain novel intermediates useful in such synthesis. 14hydroxymorphinans, such as naloxane, naltrexone, and nalbuphine are important morphine derivatives due to their behavior as potent analgesics and/or narcotic antagonists. Prior to the instant invention, the most practical synthetic routes to the preparation of these pharmaceuticals have utilized thebaine as a starting material. Thus, in accordance with one conventional process, thebaine is oxidized to 14hydroxycodeinone by use of m-chloroperbenzoic acid in an acetic acid/trifluoroacetic acid mixture or by a mixture of hydrogen peroxide and formic acid. 14hydroxycodeinone is catalytically reduced to oxycodone that is in turn O-demethylated with boron tribromide to yield oxymorphone. After blocking of the hydroxyl groups with a suitable blocking agents such as acetyl groups, the oxymorphone derivative is reacted with cyanogen bromide to yield an N-cyanodihydronormorphinone derivative that is thereafter hydrolyzed to 14-hydroxydihydronormorphinone (noroxymorphone). Although the synthesis is effective, the availability of thebaine is limited and its cost high, thereby contributing to high cost of the noroxymorphone and the 14hydroxymorphinans derived from it. Because of the scarcity and high cost of thebaine, efforts have been made in the art to devise new methods for the synthesis of noroxymorphone and noroxycodone. Web site: http://www.delphion.com/details?pn=US04795813__ •
Synthesis of deuterated opiate glucuronides Inventor(s): Nguyen; Duc Tien (Milpitas, CA), Nguyen; Hoa Duc (Orange, CA), Nguyen; Trinh Duc (Santa Ana, CA), Pham; Phuong Thi Ngoc (Orange, CA), Schep; Raymond Albert (Beverly Hills, CA) Assignee(s): High Standard Products Corporation (Inglewood, CA) Patent Number: 5,908,927 Date filed: May 12, 1997 Abstract: A method of synthesizing deuterated morphine-3.beta.-glucuronide, morphine-6.beta.-glucuronide, and codeine-6.beta.-glucuronide is disclosed. The chemicals are used as internal standards for mass spectrometry analyses of morphine, heroin, and codeine uses. They are also useful in the study of metabolism of morphine and codeine. Excerpt(s): This invention relates to methods for chemical synthesis of deuterated codeine-6.beta.-glucuronide, morphine-3.beta.-glucuronide, and morphine-6.beta.glucuronide, to internal standards in diagnostic assays using mass spectrometry to detect codeine, morphine, and heroin uses in biological samples, and to deuterated opiate glucuronides for use in metabolism studies of opiates. Codeine, morphine, and heroin are the three most commonly abused drugs among opiates. Codeine and morphine are natural materials derived from opium while heroin is a synthetic chemical
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made from acetylation of morphine. In human the main metabolic pathway of these opiates is glucuronidation which occurs in liver microsomes. The major metabolite of codeine is codeine-6.beta.-glucuronide while the major metabolite of morphine and heroin is morphine-3.beta.-glucuronide. Unmetabolized codeine, morphine, and heroin constitute only a very small amount in biological samples. Since morphine-3.beta.glucuronide is also the major metabolite of heroin, it is apparent that deacetylation of heroin occurs before glucuronidation. In fact the identification of a minor but very characteristic metabolite called 6-monoacetylmorphine has been established as evidence of heroin use. This 6-monoacetylmorphine is the result of the deacetylation of heroin. Another important aspect of morphine and heroin metabolism is the formation of a second glucuronide metabolite, morphine-6.beta.-glucuronide, which, even though usually found in smaller amount compared to morphine-3.beta.-glucuronide, has been shown to be as potent as morphine itself. Deuterated codeines such as codeine-d3 and codeine-d6 are commercially available and have been used as internal standards for Gas chromatography-Mass spectrometry (GC-MS) analysis of codeine in biological samples. In the process of analysis, deuterated codeine is added in a known amount to samples which are then undergo sample preparation processes before analysis. The use of deuterated codeine as internal standard in GC-MS analysis takes advantage of the fact that any losses of codeine in extraction, derivatization, and transfering processes will also result in similar losses of deuterated codeine. The analysis of codeine using deuterated codeine as internal standard is, therefore, more reliable than the same analysis using codeine analogs as internal standards. Unmetabolized codeine in biological samples are usually in small amount compared to the major metabolite codeine-6.beta.-glucuronide. To increase the sensitivity of GC-MS analysis of codeine, samples usually undergo a hydrolysis step to convert codeine-6.beta.-glucuronide to codeine. This hydrolysis step is very important in GC-MS analysis of opiates and is usually carried out by either acid or base or enzyme. Cares have to be taken in hydrolysis because if the enzyme is not good or if the acid or base is not strong enough, hydrolysis will be incomplete. If the conditions are too harsh, opiates will decompose. Thus if codeine-6.beta.-glucuronide is not completely hydrolysed to codeine, the total codeine concentration in samples will be low and the interpretation of the result can be false negative. It would be desirable to have available deuterated codeine-6.beta.glucuronides to be used as internal standards for GC-MS analysis of codeine, then the incomplete hydrolysis of codeine-6.beta.-glucuronide will likely result in the same incomplete hydrolysis of deuterated codeine-6.beta.-glucuronide. The GC-MS analysis of codeine using deuterated codeine-6.beta.-glucuronides as internal standards, therefore, would be more reliable than the same analysis using deuterated codeines as internal standards. The availability of deuterated codeine-6.beta.-glucuronides also allows direct analysis of codeine-6.beta.-glucuronide in such techniques that do not require sample hydrolysis as Liquid chromatography-Mass spectrometry (LC-MS). So far the analysis of codeine-6.beta.-glucuronide by LCMS using deuterated codeine6.beta.-glucuronides has not been reported. Web site: http://www.delphion.com/details?pn=US05908927__
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Therapeutic agents Inventor(s): Meyer; Michael C. (Gwent, GB7), Pankhania; Mahendra G. (Nottingham, GB2) Assignee(s): Boots Company PLC (Nottingham, GB2) Patent Number: 4,839,176 Date filed: December 8, 1987 Abstract: A solid storage stable composition comprising ibuprofen or a pharmaceutically acceptable salt thereof and codeine or a pharmaceutically acceptable salt thereof together with a sufficient amount of a pharmaceutically acceptable insoluble salt of carboxymethylcellulose to prevent discoloration of the composition. Excerpt(s): This invention relates to pharmaceutical compositions comprising ibuprofen or a pharmaceutically acceptable salt thereof and codeine or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable insoluble salt of carboxymethylcellulose, which are stable on storage. Ibuprofen, the chemical name of which is 2-(4-isobutylphenyl)propionic acid, is a well-known medicament with antiinflammatory, antipyretic and analgesic activities. The uses of ibuprofen include the treatment of pain and inflammation in muscoskeletal disorders such as rheumatic disease and the treatment of pain in a variety of other disorders, for example headache, neuralgia and dysmenorrhoea. Codeine, the chemical name of which is 7,8-didehydro4,5-epoxy-3-methoxy-17-methylmorphinan-6-ol, is also a well-known medicament and has analgesic, narcotic, antispasmodic and antitussive activities. Web site: http://www.delphion.com/details?pn=US04839176__
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Treatment for cocaine addiction Inventor(s): Aigner; Thomas G. (5900 Ryland Dr., Bethesda, MD 20817), Post; Robert M. (3510 Turner La., Chevy Chase, MD 20815), Weiss; Susan R. B. (4522 Chestnut St., Bethesda, MD 20814) Assignee(s): none reported Patent Number: 4,942,182 Date filed: March 1, 1989 Abstract: Chronic oral adminstration of carbamazepine may be used to block reinforcing effects and toxic effects of cocaine. It is preferred that the subject be esstentially "clean" of codeine at the time the treatment with carbamazepine is commenced. Excerpt(s): This invention provides a means of treating cocaine addiction by chronic oral administration of carbamazepine. While it had previously been reported that administration of carbamazepine would prevent epileptic and lidocaine-induced seizures, the use of this medication to overcome toxic and habituating action of cocaine had not previously been known. Cocaine abuse has become a major public health problem in recent years as more reinforcing forms of the drug have become available. Acute intoxication from cocaine is marked by convulsions and cardiac arrhythmias, and chronic cocaine use can be associated with increasing behavioral pathology and toxicity. The mechanisms underlying the reinforcing and toxic effects of cocaine are not fully understood, particularly since cocaine has dual actions as a potentiator of catecholaminergic systems; in particular, the dopamine system, and as a local anesthetic. Although dopaminergic antagonists have shown some success in blocking the
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reinforcing effects of cocaine in experimental animals, there is, at present, no pharmacological treatment that is efficacious and acceptable to patients. Carbamazepine is a major antiepileptic drug that has also been shown to be effective in the treatment of manic-depressive disorder. Recent studies in the Biological Psychiatry Branch have shown that chronic carbamazepine is extremely effective in preventing cocaine-induced seizures and deaths in rats. Carbamazepine is an iminostilbene derivative that is used clinically to treat seizure disorders, trigeminal neuralgia, and, most recently, manicdepressive illness. Carbamazepine is very effective as an anticonvulsant in several experimental seizure paradigms including amygdala kindling, alcohol withdrawal, and maximal electroconvulsive shock, but is less effective on seizures induced by pentylenetetrazole and high-dose picrotoxin. The effectiveness of anticonvulsants has been shown to depend upon the stage of evolution of the seizure process. For example, carbamazepine suppresses completed amygdala-kindled seizures in rats, but is ineffective in preventing their development. While diazepam inhibits the early development and fully-kindled phases of amygdala kindling, it is not effective in the later phase of kindling when seizures occur spontaneously. Conversely, phenytoin shows the opposite profile on amygdala-kindled seizures--it is ineffective in early stages, but blocks spontaneous seizures. Web site: http://www.delphion.com/details?pn=US04942182__
Patent Applications on Codeine As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to codeine: •
Inhalable aerosol medicament for the treatment or prevention of pain Inventor(s): Lecourt, Laurent; (Sevres, FR), Lemaire, Marc; (Paris, FR), Lescure, Franck; (Paris, FR) Correspondence: Young & Thompson; 745 South 23rd Street 2nd Floor; Arlington; VA; 22202 Patent Application Number: 20020033174 Date filed: August 3, 2001 Abstract: The invention concerns the use of at least one gas in combination with at least one active product for manufacturing an inhalable medicament or part of an inhalable medicament intended for the treatment or prevention of pain in humans or animals. The gas is chosen from among helium, oxygen, nitrogen, xenon, hydrogen, carbon monoxide (CO), carbon dioxide (CO.sub.2), argon, krypton, nitrogen monoxide (NO), nitrogen protoxide (N.sub.2O), carbonated hydrocarbons, fluorocarbons and mixtures of several of these gases. The active product is chosen from among paracetamol, acetylsalicylic acid, arylcarboxylic acid, corticosteroids, mineralosteroids, non-steroidal antiinflammatory drugs and their derivatives, codeine and its derivatives, morphine and morphine mimetics.
9
This has been a common practice outside the United States prior to December 2000.
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Excerpt(s): The invention relates to the use of a gas or of a gas mixture, on the one hand, and of a therapeutically active product or substance, on the other hand, for manufacturing all or part of an inhalable medicament, in particular an aerosol, intended for the treatment or prevention of pain. At present, in order to fight pain, the analgesic medicament or medicinal substance is administered either by the enteral route or by the parenteral route so that it can act and either completely or partially alleviate the feeling of pain. The enteral route involves administering a product or an active substance via the patient's digestive tract, that is to say having the patient absorb or swallow by mouth the medicament, for example in the form of a powder, a pill, a tablet or a liquid; or introducing the active substance via the anus, for example in the form of a suppository. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •
Method for preparing oxycodone Inventor(s): Chiu, Fang-Ting; (Chesterfield, VA), Lo, Young S.; (Chester, VA) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P O Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20010005754 Date filed: February 26, 2001 Abstract: A method for the preparation of oxycodone, and salts thereof, from codeine comprising oxidation of codeine to codeinone, formation of an dienolsilyl ether congener of codeinone in strong amine base, oxidation of the dienolsilyl ether congener using peracetic acid, and hydrogenation of the resulting 14-hydroxycodeinone product. Excerpt(s): The present invention relates to an improved method for preparing oxycodone. More particularly, the present invention sets forth a method for preparing oxycodone in high yields that does not require the employment, or synthesis, of thebaine in the reaction scheme. The analgesic activity of Papaver somniferum has been known since antiquity. It has long been understood that the milky juice derived from the unripe seed capsules of this poppy plant possesses potent pharmacological properties. The dried and powdered form of the juice is referred to as opium. Opium comprises about 10% of the juice obtained from the unripe seed capsules of Papaver somniferum. Early in the nineteenth century it was recognized that opium contains numerous alkaloid compounds. The first of these alkaloids to be isolated was morphine, described by Serturner in 1805. The isolation of other alkaloids, including codeine (Robiquet 1832), papaverine (Merck 1848), thebaine, oripavine and noscapine followed in short order. By the middle of the nineteenth century, the use of pure alkaloids rather than crude opium preparations was established medical practice. It is now known that opium contains more than twenty distinct alkaloids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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PRODUCTION OF THEBAINE AND ORIPAVINE Inventor(s): Byrne, Christopher James; (Westbury, AU), Fist, Anthony John; (Norwood, AU), Gerlach, Wayne Lyle; (Killara, AU) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20020106761 Date filed: January 15, 2002 Abstract: There is disclosed an improved poppy straw of a stably reproducing Papaver somniferum for the extraction of thebaine and/or oripavine, the threshed straw having thebaine and oripavine constituting about 50% by weight or greater of the alkaloid combination consisting of morphine, codeine, thebaine and oripavine. Excerpt(s): The present invention relates to the improved production of thebaine and oripavine. More particularly, the present invention relates to the use of a mutagenized Papaver somniferum poppy plant to produce thebaine and oripavine in higher yield. In accordance with one conventional process, thebaine is oxidized to 14-hydroxycodeinone by use of m-chloroperbenzoic acid in an acetic acid/trifluoroacetic acid mixture or by a mixture of hydrogen peroxide and formic acid. 14-hydroxycodeinone is catalytically reduced to oxycodone. Oxycodone is a product sold for use as and analgesic and its production consumes large amounts of thebaine. Oxycodone can be, in turn, Odemethylated with boron tribromide to yield oxymorphone. After blocking of the hydroxyl groups with a suitable blocking agent, such as, acetyl groups, the oxymorphone derivative is reacted with cyanogen bromide in a von Braun demethylation to yield an N-cyanodihydronormorphinone derivative that is thereafter hydrolyzed to 14-hydroxydihydronormorphinone (noroxymorphone). Noroxymorphone can be readily converted to nal-compounds by N-alkylation with appropriate alkyl halide, or acylation with appropriate acyl halide or anhydride, followed by reduction. A more generally applicable process, converts the oxycodone of the above process to noroxycodone by the von Braun N-demethylation followed by conversion to a 3-O-methyl-nal-compound using N-alkylation with an appropriate alkyl halide, or by alkylation with an appropriate alkyl halide, or acylation with appropriate acyl halide or anhydride, followed by reduction. The 3-O-methyl-nal-compound is reacted to a nal-compound by O-demethylation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
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Resin and its use in converting morphine to codeine Inventor(s): Corcoran, Robert C.; (Tie Siding, WY) Correspondence: Finnegan, Henderson, Farabow,; Garrett & Dunner, L.L.P.; 1300 I Street, N.W.; Washington; DC; 20005-3315; US Patent Application Number: 20020082357 Date filed: October 5, 2001 Abstract: A resin and its use as a methylating agent. One embodiment is a resin comprising a solid support and cationic methylated sulfonium, sulfoxonium, selenonium or phosphonium salts immobilized on the solid support. Another embodiment is the use of the resin as a methylating agent, for example in the conversion of morphine to codeine.
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Excerpt(s): This patent application claims the benefit of priority under 35 U.S.C.sctn. 119(e) to U.S. provisional application No. 60/238,697, filed on Oct. 6, 2000. The invention relates to a resin and its use as a methylating agent. One embodiment of the invention is a resin comprising a solid support and at least one cationic methylated sulfonium, sulfoxonium, selenonium or phosphonium salt immobilized on the solid support. Another embodiment of the invention is the use of the resin as a methylating agent, for example in the conversion of morphine to codeine. Methylation of the phenolic hydroxyl group of morphine produces codeine. Use of conventional methylating agents for that conversion, such as iodomethane and dimethylsulfate, suffers from the problem that the methylation may occur competitively at the nitrogen of the morphine molecule to give a quaternary ammonium salt. One method for avoiding this problem involves reacting morphine with a trimethylanilinium salt, for example in the salt's hydroxide form, to give the trimethylanilinium phenolate salt of morphine. Heating this salt leads to methylation of the phenolate with concomitant formation of dimethylaniline. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html
Keeping Current In order to stay informed about patents and patent applications dealing with codeine, you can access the U.S. Patent Office archive via the Internet at the following Web address: http://www.uspto.gov/patft/index.html. You will see two broad options: (1) Issued Patent, and (2) Published Applications. To see a list of issued patents, perform the following steps: Under “Issued Patents,” click “Quick Search.” Then, type “codeine” (or synonyms) into the “Term 1” box. After clicking on the search button, scroll down to see the various patents which have been granted to date on codeine. You can also use this procedure to view pending patent applications concerning codeine. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.
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CHAPTER 5. BOOKS ON CODEINE Overview This chapter provides bibliographic book references relating to codeine. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on codeine include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.
Book Summaries: Online Booksellers Commercial Internet-based booksellers, such as Amazon.com and Barnes&Noble.com, offer summaries which have been supplied by each title’s publisher. Some summaries also include customer reviews. Your local bookseller may have access to in-house and commercial databases that index all published books (e.g. Books in Print®). IMPORTANT NOTE: Online booksellers typically produce search results for medical and non-medical books. When searching for “codeine” at online booksellers’ Web sites, you may discover non-medical books that use the generic term “codeine” (or a synonym) in their titles. The following is indicative of the results you might find when searching for “codeine” (sorted alphabetically by title; follow the hyperlink to view more details at Amazon.com): •
Codeine and Its Alternatives for Pain and Cough Relief (1923081) by N. B. Eddy (1970); ISBN: 924056005X; http://www.amazon.com/exec/obidos/ASIN/924056005X/icongroupinterna
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Codeine Diary: True Confessions of a Reckless Hemophiliac by Tom Andrews; ISBN: 015600657X; http://www.amazon.com/exec/obidos/ASIN/015600657X/icongroupinterna
The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “codeine” (or synonyms) into the search box, and select “books only.”
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From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:10 •
Codeine and certain other analgesic and antitussive agents; a review. Author: Merck Sharp and Dohme. Medical Literature Dept.; Year: 1940; [Rahway, N. J., 1970]
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NTP technical report on the toxicology and carcinogenesis studies of codeine (CAS no. 76-57-3) in F344 Author: National Toxicology Program (U.S.); Year: 1996; [Research Triangle Park, N.C.]: U.S. Dept. of Health and Human Services, Public Health Service, National Institutes of Health; [Springfield, Va.: Available from the National Technical Information Service, 1996]
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Studies on codeine addiction, by C. K. Himmelsbach, Howard L. Andrews, Robert H. Felix, Fred W. Oberst and Lowrey F. Davenport. Author: Himmelsbach, Clifton Keck,; Year: 1994; [Washington, U. S. Govt. print. off., 1940]
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Studies on the pharmacokinetics of morphine and codeine with emphasis on its relation to analgesia Author: Dahlström, Bengt.; Year: 1997; Uppsala: [s.n]; Stockholm: distributor, Almqvist; Wiksell, 1977; ISBN: 9155406971
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The abuse of codeine. A review of codeine addiction and a study of the minimum cough-relieving dose, by Lowrey F. Davenport. Author: Davenport, Lowrey Frederick,; Year: 1990; Washington, U. S. Govt. print. off., 1938
Chapters on Codeine In order to find chapters that specifically relate to codeine, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and codeine using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “codeine” (or synonyms) into the “For these words:” box. The following is a typical result when searching for book chapters on codeine: •
Bowel Dysfunction Following Enterocystoplasty Source: in Webster, G.D. and Goldwasser, B. Urinary Diversion: Scientific Foundations and Clinical Practice. Oxford, England: Isis Medical Media, Ltd. 1995. p. 121-124. Contact: Available from Mosby-Year Book, Inc. 11830 Westline Industrial Drive, St. Louis, MO 63146. (800) 426-4545. Fax (800) 535-9935. E-mail:
[email protected]. PRICE: $125.00. ISBN: 1899066071. Summary: This chapter from a text on urinary diversion considers bowel dysfunction following enterocystoplasty. Continent bladder reconstruction by enterocystoplasty, orthotopic bladder replacement, and continent catheterizable diversions are now
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In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.
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standard procedures in urology. The authors stress that, when a urinary reservoir is constructed utilizing bowel, not only should there be no major alteration in bowel function, but the metabolic sequelae due to the reabsorption of urinary constituents should be minimal. Topics covered include bowel function, the incidence of bowel dysfunction, treatment options, and prevention considerations. Prevention of postoperative diarrhea following reconstructive urologic surgery involves recognition of patients at risk. In the authors' study, troublesome postoperative diarrhea occurred in a small number of patients, mainly those with neuropathic bladders and those with interstitial cystitis following reconstructive urologic surgery. Initial treatment should be cholestyramine, followed by the addition of loperamide and codeine if necessary. Prevention is preferable, and in patients at risk an alternative diversion may be appropriate, along with possible reconstruction of the ileocecal valve when utilized. 4 tables. 14 references. (AA-M).
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CHAPTER 6. MULTIMEDIA ON CODEINE Overview In this chapter, we show you how to keep current on multimedia sources of information on codeine. We start with sources that have been summarized by federal agencies, and then show you how to find bibliographic information catalogued by the National Library of Medicine.
Video Recordings An excellent source of multimedia information on codeine is the Combined Health Information Database. You will need to limit your search to “Videorecording” and “codeine” using the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find video productions, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Videorecording (videotape, videocassette, etc.).” Type “codeine” (or synonyms) into the “For these words:” box. The following is a typical result when searching for video recordings on codeine: •
The AIDS Quarterly, Fall 1990: The Crisis in Poland; to Live With AIDS Contact: WGBH Boston, Health Quarterly, 125 Western Ave, Allston, MA, 02134, (617) 492-2777. Public Broadcasting Service, PBS Video, 1320 Braddock Pl, Alexandria, VA, 22314-1698, (703) 739-5380. Summary: This videorecording, part of a series hosted by Peter Jennings, looks at the crisis in Poland due to the Acquired immunodeficiency syndrome (AIDS) epidemic. It says that Poland is a very traditional country, but that residents are being exposed to a new sight: that of Persons with AIDS (PWA's) living on the street. Most, it says, are Intravneous drug users (IVDU's). The videorecording explains that in Poland, hundreds of thousands of people are addicted to a homemade drug that is 25 percent heroin, 50 percent morphine, and 25 percent codeine; cheap; easy to make; and legal. However, needles are scarce, and usually shared. The Polish government doesn't allow treatment with methadone, and there are six-month waiting lists to get into "cold turkey" detoxification programs. The videorecording presents profiles of addicted and infected persons, portraying their lives as being bleak and devoid of hope. It also examines the
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crisis in health care, where there is a shortage of health-care workers and little money to fund treatment for Human immunodeficiency virus (HIV) infection. It addresses issues of discrimiantion faced by PWA's and looks at the role the Catholic church in Poland plays in ministering to the epidemic. Children's views on the epidemic are studied. It also looks at the closeted lives of the country's homosexuals, who face much discrimiantion. The videorecording says that there are 10,000 registered prostitutes in Warsaw, but that many women who lose their jobs turn to prostitution without a license. Many of these people refuse to tell their clients about their HIV status. The presentation concludes with a brief meditation on living with AIDS by Edmund White, a prominent gay American writer.
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CHAPTER 7. PERIODICALS AND NEWS ON CODEINE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover codeine.
News Services and Press Releases One of the simplest ways of tracking press releases on codeine is to search the news wires. In the following sample of sources, we will briefly describe how to access each service. These services only post recent news intended for public viewing. PR Newswire To access the PR Newswire archive, simply go to http://www.prnewswire.com/. Select your country. Type “codeine” (or synonyms) into the search box. You will automatically receive information on relevant news releases posted within the last 30 days. The search results are shown by order of relevance. Reuters Health The Reuters’ Medical News and Health eLine databases can be very useful in exploring news archives relating to codeine. While some of the listed articles are free to view, others are available for purchase for a nominal fee. To access this archive, go to http://www.reutershealth.com/en/index.html and search by “codeine” (or synonyms). The following was recently listed in this archive for codeine: •
FDA OKs generic versions of Tylenol with codeine Source: Reuters Health eLine Date: August 02, 2002
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Able Labs gets FDA approval for generic versions of Tylenol with Codeine Source: Reuters Industry Breifing Date: August 02, 2002
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FDA says sponsors may market generic acetaminophen/codeine tablets Source: Reuters Industry Breifing Date: May 06, 2002
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Codeine may not be required for post-tonsillectomy pain in children Source: Reuters Medical News Date: May 30, 2000
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Controlled-release codeine effective for patients with osteoarthritis Source: Reuters Medical News Date: April 10, 2000
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Diclofenac/acetaminophen combination superior to codeine/acetaminophen Source: Reuters Medical News Date: December 30, 1999
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Codeine's Efficacy Varies By Ethnicity Source: Reuters Medical News Date: September 09, 1997 The NIH
Within MEDLINEplus, the NIH has made an agreement with the New York Times Syndicate, the AP News Service, and Reuters to deliver news that can be browsed by the public. Search news releases at http://www.nlm.nih.gov/medlineplus/alphanews_a.html. MEDLINEplus allows you to browse across an alphabetical index. Or you can search by date at the following Web page: http://www.nlm.nih.gov/medlineplus/newsbydate.html. Often, news items are indexed by MEDLINEplus within its search engine. Business Wire Business Wire is similar to PR Newswire. To access this archive, simply go to http://www.businesswire.com/. You can scan the news by industry category or company name. Market Wire Market Wire is more focused on technology than the other wires. To browse the latest press releases by topic, such as alternative medicine, biotechnology, fitness, healthcare, legal, nutrition, and pharmaceuticals, access Market Wire’s Medical/Health channel at http://www.marketwire.com/mw/release_index?channel=MedicalHealth. Or simply go to Market Wire’s home page at http://www.marketwire.com/mw/home, type “codeine” (or synonyms) into the search box, and click on “Search News.” As this service is technology oriented, you may wish to use it when searching for press releases covering diagnostic procedures or tests. Search Engines Medical news is also available in the news sections of commercial Internet search engines. See the health news page at Yahoo (http://dir.yahoo.com/Health/News_and_Media/), or
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you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “codeine” (or synonyms). If you know the name of a company that is relevant to codeine, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “codeine” (or synonyms).
Newsletter Articles Use the Combined Health Information Database, and limit your search criteria to “newsletter articles.” Again, you will need to use the “Detailed Search” option. Go directly to the following hyperlink: http://chid.nih.gov/detail/detail.html. Go to the bottom of the search page where “You may refine your search by.” Select the dates and language that you prefer. For the format option, select “Newsletter Article.” Type “codeine” (or synonyms) into the “For these words:” box. You should check back periodically with this database as it is updated every three months. The following is a typical result when searching for newsletter articles on codeine: •
Cause and Treatment of Pain in Chronic Intestinal Pseudo-Obstruction Source: ASAP Forum Journal. 2(1): 7-10. May 1995. Contact: Available from American Society of Adults with Pseudo-Obstruction (ASAP). 19 Carroll Road, Woburn, MA 01801. (617) 935-9776. Fax (617) 933-4151. Summary: This newsletter article addresses the cause and treatment of pain associated with chronic intestinal pseudo-obstruction (CIP). The author defines the current knowledge on the cause of pain, discusses the results obtained with the use of various medications and procedures, including surgical procedures, and provides thoughts on future developments for pain control. The author notes that although CIP produces numerous symptoms and problems, the subjective complaint that most patients have is that of abdominal pain. Specific drug agents covered include antacids; histamine blockers, such as Tagamet, Zantac, and Pepcid; Prilosec, an acid pump inhibitor; Carafate; nonsteroidal anti-inflammatory agents (NSAIDs), including ibuprofen, Motrin, or Orudis; antibiotics including Flagyl and Bactrim; antidepressants, including Librax, Ativan, and Paxil; pain inhibitors, including Darvon, Vicodin, and Lortab; Codeine; Percocet; Demerol; Morphine; Buprenex; Stadol; and Dilaudid.
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Prescribed Medications Source: Fibromyalgia Frontiers. 9(3): 17-22. 2001. Contact: Available from National Fibromyalgia Partnership, Inc. 140 Zinn Way, Linden, VA 22642-5609. (866) 725-4404 toll-free. Fax (540) 622-2998. E-mail:
[email protected]. Website: www.fmpartnership.org.
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Summary: This newsletter article provides health professionals and people who have fibromyalgia (FM) with information on prescription and nonprescription medications that can relieve pain and improve sleep and mood. Categories of drugs used in the treatment of fibromyalgia are analgesics, antiinflammatory drugs, antidepressant medications, muscle relaxants, sleep modifiers, antianxiety medicines, and other medicines used to treat chronic pain. Analgesics are pain killers and can include nonprescription medicines such as aspirin and acetaminophen or prescription strength pain pills such as narcotics, codeine, Vicodin, Darvocet, Oxycontin, and Percocet. Antiinflammatory medicines include aspirin, nonsteroidal antiinflammatory drugs, and corticosteroids. Antidepressant medications include tricyclics and selective serotonin reuptake inhibitors. Muscle relaxants can decrease pain in people who have FM and include Flexeril, Soma, Skelaxin, and Robaxin. Various medications can be used to treat insomnia, including benzodiazepines and hypnotic nonbenzodiazepines. Anxiety is a common problem in FM, but various medicines, including antidepressants and muscle relaxants, can treat it. Other medicines used to treat pain include antiseizure medicines, headache medications, and antibiotics. The article highlights the beneficial and adverse effects of each drug category. In addition, the article presents basic strategies regarding medication use and discusses the use of trigger point injections to manage pain.
Academic Periodicals covering Codeine Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to codeine. In addition to these sources, you can search for articles covering codeine that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”
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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.
U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for codeine. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI® Advice for the Patient® can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with codeine. If you would like more information on a particular medication, the provided hyperlinks will direct you to ample documentation (e.g. typical dosage, side effects, drug-interaction risks, etc.). The
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following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to codeine: Barbiturates, Aspirin, and Codeine •
Systemic - U.S. Brands: Ascomp with Codeine No.3; Butalbital Compound with Codeine; Butinal with Codeine No.3; Fiorinal with Codeine No.3; Idenal with Codeine; Isollyl with Codeine http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202104.html
Narcotic Analgesics and Acetaminophen •
Systemic - U.S. Brands: Allay; Anexsia 5/500; Anexsia 7.5/650; Anolor DH 5; Bancap-HC; Capital with Codeine; Co-Gesic; Darvocet-N 100; Darvocet-N 50; DHCplus; Dolacet; Dolagesic; Duocet; E-Lor; Endocet; EZ III; Hycomed; HycoPap; Hydrocet; Hydrogesic; HY-PHEN; Lorcet 10/650; L http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202392.html
Narcotic Analgesics and Aspirin •
Systemic - U.S. Brands: Damason-P; Darvon Compound-65; Empirin with Codeine No.3; Empirin with Codeine No.4; Endodan; Lortab ASA; Panasal 5/500; PC-Cap; Percodan; Percodan-Demi; Propoxyphene Compound-65; Roxiprin; Synalgos-DC; Talwin Compound http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202393.html
Narcotic Analgesics for Pain Relief •
Systemic - U.S. Brands: Astramorph PF; Buprenex; Cotanal-65; Darvon; DarvonN; Demerol; Dilaudid; Dilaudid-5; Dilaudid-HP; Dolophine; Duramorph; Hydrostat IR; Kadian; Levo-Dromoran; M S Contin; Methadose; MS/L; MS/L Concentrate; MS/S; MSIR; Nubain; Numorphan; OMS Concentrate; http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202390.html
Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.
Mosby’s Drug Consult™ Mosby’s Drug Consult™ database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information
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adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.
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APPENDICES
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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.
NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute11: •
Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm
•
National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/
•
National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html
•
National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25
•
National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm
•
National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm
•
National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375
•
National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/
11
These publications are typically written by one or more of the various NIH Institutes.
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•
National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm
•
National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/
•
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm
•
National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm
•
National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/
•
National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/
•
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm
•
National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html
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National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm
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National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm
•
National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm
•
National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html
•
National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm
•
Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp
•
National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/
•
National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp
•
Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html
•
Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm
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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.12 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:13 •
Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html
•
HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html
•
NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html
•
Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/
•
Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html
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Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html
•
Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/
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Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html
•
Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html
•
Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html
•
MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html
12
Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 13 See http://www.nlm.nih.gov/databases/databases.html.
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•
Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html
•
Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html
The NLM Gateway14 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.15 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “codeine” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total
Items Found 4391 25 919 8 0 5343
HSTAT16 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.17 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.18 Simply search by “codeine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.
14
Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.
15
The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 16 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 17 18
The HSTAT URL is http://hstat.nlm.nih.gov/.
Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.
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Coffee Break: Tutorials for Biologists19 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.20 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.21 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.
Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •
CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.
•
Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.
19 Adapted 20
from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.
The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 21 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.
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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on codeine can appear at any moment and be published by a number of sources, the best approach to finding guidelines is to systematically scan the Internet-based services that post them.
Patient Guideline Sources The remainder of this chapter directs you to sources which either publish or can help you find additional guidelines on topics related to codeine. Due to space limitations, these sources are listed in a concise manner. Do not hesitate to consult the following sources by either using the Internet hyperlink provided, or, in cases where the contact information is provided, contacting the publisher or author directly. The National Institutes of Health The NIH gateway to patients is located at http://health.nih.gov/. From this site, you can search across various sources and institutes, a number of which are summarized below. Topic Pages: MEDLINEplus The National Library of Medicine has created a vast and patient-oriented healthcare information portal called MEDLINEplus. Within this Internet-based system are “health topic pages” which list links to available materials relevant to codeine. To access this system, log on to http://www.nlm.nih.gov/medlineplus/healthtopics.html. From there you can either search using the alphabetical index or browse by broad topic areas. Recently, MEDLINEplus listed the following when searched for “codeine”:
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•
Other guides Alcoholism http://www.nlm.nih.gov/medlineplus/alcoholism.html Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.html
You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on codeine. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •
Interaction of Prescription Drugs With Commonly-Abused Drugs Among Dialysis Patients Source: American Kidney Fund Newsletter for Health Professionals. 7(1): [p. 9-14]. 1990. Summary: This article consists of a comprehensive chart detailing the effects of commonly abused drugs on dialysis patients. This chart is intended as a reference guide, and pulls together information heretofore unavailable in a single place. For each of fifteen drugs, the common name, generic name, class of drug, actions, indictions, methods of abuse, side effects, signs and symptoms of overdose, interactions, capability of dialyzing (if known), addictive potential, and signs and symptoms of withdrawal are provided. The fifteen drugs covered are: heroin; morphine; Demerol; codeine; Talwin; Quaalude; Nembutal; Seconal; phenobarbital; Restoril (temaepam); alium (diazepam); Dalmane (flurazepam); crank and ice (amphetamine, methamphetamine); cocaine; and crack (cocaine).
•
Medications for Inflammatory Bowel Disease Source: New York, NY: Crohn's and Colitis Foundation of America, Inc. (CCFA). 199x. 20 p. Contact: Available from Crohn's and Colitis Foundation of America, Inc. (CCFA). 386 Park Avenue South, 17th Floor, New York, NY 10016-8804. (800) 343-3637 or (800) 9322423 or (212) 685-3440. Fax (212) 779-4098. Website: www.ccfa.org. E-mail:
[email protected] PRICE: Single copy free. Summary: This brochure reviews for health professionals the available information on both the standard drug therapy for inflammatory bowel disease (IBD) and the agents under investigation. Topics include 5-ASA agents, including sulfasalazine, topical and
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oral forms of aminosalicylates, slow-release agents (mesalamine), chemically linked agents (olsalazine), and the side effects of these drugs; corticosteroids in topical, oral, parenteral, and rapidly-metabolized forms; immunomodulators, including 6mercaptopurine and azathioprine, cyclosporin, and methotrexate; antibiotics, including metronidazole, ciproflaxin, and antituberculous agents; lipoxygenase inhibitors; nicotine; antidiarrheal agents, including loperamide, diphenoxylate with atropine, codeine, and deodorized tincture of opium; anticholinergic agents; psychotropic agents; miscellaneous agents that show potential benefit; and drugs that may exacerbate colitis. The brochure includes a section on the management of the pediatric patient, including the use of sulfasalazine, aminosalicylates, corticosteroids, immunomodulators, antibiotics, and antidiarrheal agents. It also addresses specific issues of adolescents. •
Antidiarrheal Therapy Source: Canadian Journal of Gastroenterology. 13(3): 207-208. April 1999. Contact: Available from Pulsus Group, Inc. 2902 South Sheridan Way, Oakville, Ontario, Canada L6J 7L6. Summary: This fact sheet, from a professional journal of gastroenterology, guides patients who have been advised to use an antidiarrheal medication. The fact sheet describes various medications used to control diarrhea and the potential risks involved in taking these drugs. Diarrhea is defined as more water in the stool than normal. Antidiarrheal medications are helpful for occasional or short term treatment of diarrhea that the physician does not feel is specifically caused by an inflammatory or serious infectious disease of the intestines. Patients with irritable bowel syndrome (IBS) occasionally take these medications to control diarrhea. The most commonly used antidiarrheal medications are loperamide hydrochloride (Apo Loperamide or Imodium), diphenoxylate with atropine (Lomotil), codeine, bismuth subsalicylate (Pepto Bismol), and cholestyramine (Questran). Most of these medications (all except cholestyramine) work by slowing the movement of food through the intestines. This gives the intestine more time to absorb the water and makes the stool less watery. Cholestyramine binds to the bile in the intestines, helping certain patients (particularly those who have had surgery to remove a section of their small intestine) have fewer problems with diarrhea. These medications are generally very safe for patients with mild diarrhea but can be potentially dangerous for patients with severe diarrhea. Patients are encouraged to work closely with their physicians to manage any problems. The NIH Search Utility
The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to codeine. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html.
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Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •
AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats
•
Family Village: http://www.familyvillage.wisc.edu/specific.htm
•
Google: http://directory.google.com/Top/Health/Conditions_and_Diseases/
•
Med Help International: http://www.medhelp.org/HealthTopics/A.html
•
Open Directory Project: http://dmoz.org/Health/Conditions_and_Diseases/
•
Yahoo.com: http://dir.yahoo.com/Health/Diseases_and_Conditions/
•
WebMD®Health: http://my.webmd.com/health_topics
Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to codeine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with codeine. The National Health Information Center (NHIC) The National Health Information Center (NHIC) offers a free referral service to help people find organizations that provide information about codeine. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “codeine” (or a synonym), and you will receive information on all relevant organizations listed in the database. Health Hotlines directs you to toll-free numbers to over 300 organizations. You can access this database directly at http://www.sis.nlm.nih.gov/hotlines/. On this page, you are given the option to search by keyword or by browsing the subject list. When you have received
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your search results, click on the name of the organization for its description and contact information. The Combined Health Information Database Another comprehensive source of information on healthcare associations is the Combined Health Information Database. Using the “Detailed Search” option, you will need to limit your search to “Organizations” and “codeine”. Type the following hyperlink into your Web browser: http://chid.nih.gov/detail/detail.html. To find associations, use the drop boxes at the bottom of the search page where “You may refine your search by.” For publication date, select “All Years.” Then, select your preferred language and the format option “Organization Resource Sheet.” Type “codeine” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “codeine” (or a synonym) into the search box, and click “Submit Query.”
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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.
Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.22
Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.
Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of
22
Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.
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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)23: •
Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/
•
Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)
•
Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm
•
California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html
•
California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html
•
California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html
•
California: Gateway Health Library (Sutter Gould Medical Foundation)
•
California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/
•
California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp
•
California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html
•
California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/
•
California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/
•
California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/
•
California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html
•
California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/
•
Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/
•
Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/
•
Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/
23
Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.
Finding Medical Libraries
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Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml
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Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm
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Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html
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Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm
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Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp
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Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/
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Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm
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Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html
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Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/
•
Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm
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Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/
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Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/
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Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/
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Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm
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Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html
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Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm
•
Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/
•
Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/
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Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10
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Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/
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Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html
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Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp
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Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp
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Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/
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Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html
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Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm
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Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp
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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/
•
Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html
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Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/
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Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm
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Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/
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Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html
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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm
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Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330
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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)
•
National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html
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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/
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National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/
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Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm
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New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/
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New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm
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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm
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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/
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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html
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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/
•
New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html
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New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/
•
Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm
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Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp
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Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/
•
Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/
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Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml
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Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html
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Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html
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Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml
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Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp
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Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm
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Quebec, Canada: Medical Library (Montreal General Hospital), http://www.mghlib.mcgill.ca/
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South Dakota: Rapid City Regional Hospital Medical Library (Rapid City Regional Hospital), http://www.rcrh.org/Services/Library/Default.asp
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Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/
•
Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/
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Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72
143
ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •
ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html
•
MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp
•
Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/
•
Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html
•
On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/
•
Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp
•
Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm
Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a). The NIH suggests the following Web sites in the ADAM Medical Encyclopedia when searching for information on codeine: •
Basic Guidelines for Codeine Codeine overdose Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002613.htm
•
Signs & Symptoms for Codeine Bluish colored - fingernails and lips Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003215.htm Breathing - shallow Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003071.htm Coma Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003202.htm Drowsiness Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003208.htm
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Low blood pressure Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003083.htm Muscle spasticity Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm No breathing Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003069.htm Spasms Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003193.htm Vomiting Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003117.htm Weak pulse Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003078.htm •
Diagnostics and Tests for Codeine Gastric lavage Web site: http://www.nlm.nih.gov/medlineplus/ency/article/003882.htm
•
Background Topics for Codeine Acute Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002215.htm Breathing - slow and labored Web site: http://www.nlm.nih.gov/medlineplus/ency/article/000007.htm Intravenous Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002383.htm Respiratory Web site: http://www.nlm.nih.gov/medlineplus/ency/article/002290.htm
Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •
Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical
•
MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html
•
Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/
Online Glossaries 145
•
Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine
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CODEINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 6-Mercaptopurine: An antimetabolite antineoplastic agent with immunosuppressant properties. It interferes with nucleic acid synthesis by inhibiting purine metabolism and is used, usually in combination with other drugs, in the treatment of or in remission maintenance programs for leukemia. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acquired Immunodeficiency Syndrome: An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive Tlymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. [NIH] Acyl: Chemical signal used by bacteria to communicate. [NIH] Acylation: The addition of an organic acid radical into a molecule. [NIH] Adduct: Complex formed when a carcinogen combines with DNA or a protein. [NIH] Adenine: A purine base and a fundamental unit of adenine nucleotides. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic Agonists: Drugs that bind to and activate adrenergic receptors. [NIH]
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Adverse Effect: An unwanted side effect of treatment. [NIH] Aerosol: A solution of a drug which can be atomized into a fine mist for inhalation therapy. [EU]
Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Ageing: A physiological or morphological change in the life of an organism or its parts, generally irreversible and typically associated with a decline in growth and reproductive vigor. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Airway: A device for securing unobstructed passage of air into and out of the lungs during general anesthesia. [NIH] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Alkylating Agents: Highly reactive chemicals that introduce alkyl radicals into biologically active molecules and thereby prevent their proper functioning. Many are used as antineoplastic agents, but most are very toxic, with carcinogenic, mutagenic, teratogenic, and immunosuppressant actions. They have also been used as components in poison gases. [NIH]
Alkylation: The covalent bonding of an alkyl group to an organic compound. It can occur by a simple addition reaction or by substitution of another functional group. [NIH] Alleles: Mutually exclusive forms of the same gene, occupying the same locus on homologous chromosomes, and governing the same biochemical and developmental process. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH]
Dictionary 149
Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amebiasis: Infection with any of various amebae. It is an asymptomatic carrier state in most individuals, but diseases ranging from chronic, mild diarrhea to fulminant dysentery may occur. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Ammonium Chloride: An acidifying agent that is used as an expectorant and a diuretic. [NIH]
Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Amygdala: Almond-shaped group of basal nuclei anterior to the inferior horn of the lateral ventricle of the brain, within the temporal lobe. The amygdala is part of the limbic system. [NIH]
Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]
Anaphylaxis: An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory
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distress, vascular collapse, systemic shock, and death. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Anorexia: Lack or loss of appetite for food. Appetite is psychologic, dependent on memory and associations. Anorexia can be brought about by unattractive food, surroundings, or company. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antiasthmatic: An agent that relieves the spasm of asthma. [EU] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]
Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood
Dictionary 151
thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antidote: A remedy for counteracting a poison. [EU] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]
Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimetabolite: A chemical that is very similar to one required in a normal biochemical reaction in cells. Antimetabolites can stop or slow down the reaction. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]
Antipruritic: Relieving or preventing itching. [EU] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antipsychotic Agents: Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in schizophrenia, senile dementia, transient psychosis following surgery or myocardial infarction, etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. [NIH] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and
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febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Antitussive Agents: Agents that suppress cough. They act centrally on the medullary cough center. Expectorants, also used in the treatment of cough, act locally. [NIH] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Apoptosis: One of the two mechanisms by which cell death occurs (the other being the pathological process of necrosis). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA (DNA fragmentation) at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth. [NIH] Aqueous: Having to do with water. [NIH] Arachidonate 12-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 12-hydroperoxyarachidonate (12-HPETE) which is itself rapidly converted by a peroxidase to 12-hydroxy-5,8,10,14-eicosatetraenoate (12-HETE). The 12-hydroperoxides are preferentially formed in platelets. EC 1.13.11.31. [NIH] Arachidonate 15-Lipoxygenase: An enzyme that catalyzes the oxidation of arachidonic acid to yield 15-hydroperoxyarachidonate (15-HPETE) which is rapidly converted to 15-hydroxy5,8,11,13-eicosatetraenoate (15-HETE). The 15-hydroperoxides are preferentially formed in neutrophils and lymphocytes. EC 1.13.11.33. [NIH] Arachidonate Lipoxygenases: Enzymes catalyzing the oxidation of arachidonic acid to hydroperoxyarachidonates (HPETES). These products are then rapidly converted by a peroxidase to hydroxyeicosatetraenoic acids (HETES). The positional specificity of the enzyme reaction varies from tissue to tissue. The final lipoxygenase pathway leads to the leukotrienes. EC 1.13.11.- . [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Argon: A noble gas with the atomic symbol Ar, atomic number 18, and atomic weight 39.948. It is used in fluorescent tubes and wherever an inert atmosphere is desired and nitrogen cannot be used. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH]
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Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atmospheric Pressure: The pressure at any point in an atmosphere due solely to the weight of the atmospheric gases above the point concerned. [NIH] Atropine: A toxic alkaloid, originally from Atropa belladonna, but found in other plants, mainly Solanaceae. [NIH] Attenuated: Strain with weakened or reduced virulence. [NIH] Attenuation: Reduction of transmitted sound energy or its electrical equivalent. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autoradiography: A process in which radioactive material within an object produces an image when it is in close proximity to a radiation sensitive emulsion. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriostatic: 1. Inhibiting the growth or multiplication of bacteria. 2. An agent that inhibits the growth or multiplication of bacteria. [EU] Bacterium: Microscopic organism which may have a spherical, rod-like, or spiral unicellular or non-cellular body. Bacteria usually reproduce through asexual processes. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of
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donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Behavior Therapy: The application of modern theories of learning and conditioning in the treatment of behavior disorders. [NIH] Belladonna: A species of very poisonous Solanaceous plants yielding atropine (hyoscyamine), scopolamine, and other belladonna alkaloids, used to block the muscarinic autonomic nervous system. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]
Benzaldehyde: A colorless oily liquid used as a flavoring agent and to make dyes, perfumes, and pharmaceuticals. Benzaldehyde is chemically related to benzene. [NIH] Benzamides: Benzoic acid amides. [NIH] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Bethanechol: A slowly hydrolyzed muscarinic agonist with no nicotinic effects. Bethanechol is generally used to increase smooth muscle tone, as in the GI tract following abdominal surgery or in urinary retention in the absence of obstruction. It may cause hypotension, cardiac rate changes, and bronchial spasms. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH]
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Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bismuth: A metallic element that has the atomic symbol Bi, atomic number 83 and atomic weight 208.98. [NIH] Bismuth Subsalicylate: A nonprescription medicine such as Pepto-Bismol. Used to treat diarrhea, heartburn, indigestion, and nausea. It is also part of the treatment for ulcers caused by the bacterium Helicobacter pylori (HELL-uh-koh-BAK-tur py-LOH-ree). [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Blood-Brain Barrier: Specialized non-fenestrated tightly-joined endothelial cells (tight junctions) that form a transport barrier for certain substances between the cerebral capillaries and the brain tissue. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Boron: A trace element with the atomic symbol B, atomic number 5, and atomic weight 10.81. Boron-10, an isotope of boron, is used as a neutron absorber in boron neutron capture therapy. [NIH] Boron Neutron Capture Therapy: A technique for the treatment of neoplasms, especially gliomas and melanomas in which boron-10, an isotope, is introduced into the target cells followed by irradiation with thermal neutrons. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachytherapy: A collective term for interstitial, intracavity, and surface radiotherapy. It uses small sealed or partly-sealed sources that may be placed on or near the body surface or within a natural body cavity or implanted directly into the tissues. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut
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walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]
Breakdown: A physical, metal, or nervous collapse. [NIH] Broad-spectrum: Effective against a wide range of microorganisms; said of an antibiotic. [EU] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Bronchial Spasm: Spasmodic contraction of the smooth muscle of the bronchi. [NIH] Bronchoscopy: Endoscopic examination, therapy or surgery of the bronchi. [NIH] Bulimia: Episodic binge eating. The episodes may be associated with the fear of not being able to stop eating, depressed mood, or self-deprecating thoughts (binge-eating disorder) and may frequently be terminated by self-induced vomiting (bulimia nervosa). [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen
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move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carboxymethylcellulose: It is used as an emulsifier, thickener, suspending agent, etc., in cosmetics and pharmaceuticals; in research as a culture medium; in chromatography as a stabilizer for reagents; and therapeutically as a bulk laxative with antacid properties. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Carcinogenesis: The process by which normal cells are transformed into cancer cells. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case-Control Studies: Studies which start with the identification of persons with a disease of interest and a control (comparison, referent) group without the disease. The relationship of an attribute to the disease is examined by comparing diseased and non-diseased persons with regard to the frequency or levels of the attribute in each group. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] Cecum: The beginning of the large intestine. The cecum is connected to the lower part of the small intestine, called the ileum. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell Death: The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability. [NIH] Cell Differentiation: Progressive restriction of the developmental potential and increasing specialization of function which takes place during the development of the embryo and
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leads to the formation of specialized cells, tissues, and organs. [NIH] Cell Division: The fission of a cell. [NIH] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH] Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrospinal: Pertaining to the brain and spinal cord. [EU] Cerebrospinal fluid: CSF. The fluid flowing around the brain and spinal cord. Cerebrospinal fluid is produced in the ventricles in the brain. [NIH] Cerium: An element of the rare earth family of metals. It has the atomic symbol Ce, atomic number 58, and atomic weight 140.12. Cerium is a malleable metal used in industrial applications. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chlorpheniramine: A histamine H1 antagonist used in allergic reactions, hay fever, rhinitis, urticaria, and asthma. It has also been used in veterinary applications. One of the most widely used of the classical antihistaminics, it generally causes less drowsiness and sedation than promethazine. [NIH] Chlorpromazine: The prototypical phenothiazine antipsychotic drug. Like the other drugs in this class chlorpromazine's antipsychotic actions are thought to be due to long-term adaptation by the brain to blocking dopamine receptors. Chlorpromazine has several other actions and therapeutic uses, including as an antiemetic and in the treatment of intractable hiccup. [NIH] Cholecystokinin: A 33-amino acid peptide secreted by the upper intestinal mucosa and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH]
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Cholestyramine: Strongly basic anion exchange resin whose main constituent is polystyrene trimethylbenzylammonium as Cl(-) anion. It exchanges chloride ions with bile salts, thus decreasing their concentration and that of cholesterol. It is used as a hypocholesteremic in diarrhea and biliary obstruction and as an antipruritic. [NIH] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Cholinergic Agonists: Drugs that bind to and activate cholinergic receptors. [NIH] Chromatin: The material of chromosomes. It is a complex of DNA, histones, and nonhistone proteins (chromosomal proteins, non-histone) found within the nucleus of a cell. [NIH] Chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH] C-kit receptor: A protein on the surface of some cells that binds to stem cell factor (a substance that causes certain types of cells to grow). Altered forms of this receptor may be associated with some types of cancer. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Cofactor: A substance, microorganism or environmental factor that activates or enhances the
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action of another entity such as a disease-causing agent. [NIH] Cognitive behavior therapy: A system of psychotherapy based on the premise that distorted or dysfunctional thinking, which influences a person's mood or behavior, is common to all psychosocial problems. The focus of therapy is to identify the distorted thinking and to replace it with more rational, adaptive thoughts and beliefs. [NIH] Colitis: Inflammation of the colon. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix 'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques
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for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories applicable to molecular biology and areas of computer-based techniques for solving biological problems including manipulation of models and datasets. [NIH] Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes. [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Consumption: Pulmonary tuberculosis. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]
Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Corneum: The superficial layer of the epidermis containing keratinized cells. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU]
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Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Cortisone: A natural steroid hormone produced in the adrenal gland. It can also be made in the laboratory. Cortisone reduces swelling and can suppress immune responses. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Craniotomy: An operation in which an opening is made in the skull. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cutaneous: Having to do with the skin. [NIH] Cyanoacrylates: A group of compounds having the general formula CH2=C(CN)-COOR; it polymerizes on contact with moisture; used as tissue adhesive; higher homologs have hemostatic and antibacterial properties. [NIH] Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes. [NIH] Cyclazocine: An analgesic with mixed narcotic agonist-antagonist properties. [NIH] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH]
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Cystitis: Inflammation of the urinary bladder. [EU] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deletion: A genetic rearrangement through loss of segments of DNA (chromosomes), bringing sequences, which are normally separated, into close proximity. [NIH] Dementia: An acquired organic mental disorder with loss of intellectual abilities of sufficient severity to interfere with social or occupational functioning. The dysfunction is multifaceted and involves memory, behavior, personality, judgment, attention, spatial relations, language, abstract thought, and other executive functions. The intellectual decline is usually progressive, and initially spares the level of consciousness. [NIH] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]
Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Dendritic: 1. Branched like a tree. 2. Pertaining to or possessing dendrites. [EU] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Depolarization: The process or act of neutralizing polarity. In neurophysiology, the reversal of the resting potential in excitable cell membranes when stimulated, i.e., the tendency of the cell membrane potential to become positive with respect to the potential outside the cell. [EU] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Deprivation: Loss or absence of parts, organs, powers, or things that are needed. [EU]
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Dermatitis: Any inflammation of the skin. [NIH] Desensitization: The prevention or reduction of immediate hypersensitivity reactions by administration of graded doses of allergen; called also hyposensitization and immunotherapy. [EU] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Dextrorphan: Dextro form of levorphanol. It acts as a noncompetitive NMDA receptor antagonist, among other effects, and has been proposed as a neuroprotective agent. It is also a metabolite of dextromethorphan. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diarrhoea: Abnormal frequency and liquidity of faecal discharges. [EU] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diflunisal: A salicylate derivative and anti-inflammatory analgesic with actions and side effects similar to those of aspirin. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Dihydromorphine: A semisynthetic analgesic used in the study of narcotic receptors. It has abuse potential. [NIH] Dihydroxy: AMPA/Kainate antagonist. [NIH]
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Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH] Dipeptides: Peptides composed of two amino acid units. [NIH] Diphenoxylate: A meperidine congener used as an antidiarrheal, usually in combination with atropine. At high doses, it acts like morphine. Its unesterified metabolite difenoxin has similar properties and is used similarly. It has little or no analgesic activity. [NIH] Diploid: Having two sets of chromosomes. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Domesticated: Species in which the evolutionary process has been influenced by humans to meet their needs. [NIH] Domperidone: A specific blocker of dopamine receptors. It speeds gastrointestinal peristalsis, causes prolactin release, and is used as antiemetic and tool in the study of dopaminergic mechanisms. [NIH] Dopa: The racemic or DL form of DOPA, an amino acid found in various legumes. The dextro form has little physiologic activity but the levo form (levodopa) is a very important physiologic mediator and precursor and pharmacological agent. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH]
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Dopamine Antagonists: Drugs that bind to but do not activate dopamine receptors, thereby blocking the actions of dopamine or exogenous agonists. Many drugs used in the treatment of psychotic disorders (antipsychotic agents) are dopamine antagonists, although their therapeutic effects may be due to long-term adjustments of the brain rather than to the acute effects of blocking dopamine receptors. Dopamine antagonists have been used for several other clinical purposes including as antiemetics, in the treatment of Tourette syndrome, and for hiccup. [NIH] Doping: The action of administering a drug to someone before a sports event (originally to a horse before a race); the substance thus administered. [EU] Dorsal: 1. Pertaining to the back or to any dorsum. 2. Denoting a position more toward the back surface than some other object of reference; same as posterior in human anatomy; superior in the anatomy of quadrupeds. [EU] Dorsum: A plate of bone which forms the posterior boundary of the sella turcica. [NIH] Dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent. [NIH] Drive: A state of internal activity of an organism that is a necessary condition before a given stimulus will elicit a class of responses; e.g., a certain level of hunger (drive) must be present before food will elicit an eating response. [NIH] Drug Evaluation: Any process by which toxicity, metabolism, absorption, elimination, preferred route of administration, safe dosage range, etc., for a drug or group of drugs is determined through clinical assessment in humans or veterinary animals. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duodenum: The first part of the small intestine. [NIH] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dysmenorrhoea: Painful menstruation. [EU] Dysphoric: A feeling of unpleasantness and discomfort. [NIH] Eczema: A pruritic papulovesicular dermatitis occurring as a reaction to many endogenous and exogenous agents (Dorland, 27th ed). [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Electrode: Component of the pacing system which is at the distal end of the lead. It is the interface with living cardiac tissue across which the stimulus is transmitted. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the
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chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]
Emaciation: Clinical manifestation of excessive leanness usually caused by disease or a lack of nutrition. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Embryogenesis: The process of embryo or embryoid formation, whether by sexual (zygotic) or asexual means. In asexual embryogenesis embryoids arise directly from the explant or on intermediary callus tissue. In some cases they arise from individual cells (somatic cell embryoge). [NIH] Emulsion: A preparation of one liquid distributed in small globules throughout the body of a second liquid. The dispersed liquid is the discontinuous phase, and the dispersion medium is the continuous phase. When oil is the dispersed liquid and an aqueous solution is the continuous phase, it is known as an oil-in-water emulsion, whereas when water or aqueous solution is the dispersed phase and oil or oleaginous substance is the continuous phase, it is known as a water-in-oil emulsion. Pharmaceutical emulsions for which official standards have been promulgated include cod liver oil emulsion, cod liver oil emulsion with malt, liquid petrolatum emulsion, and phenolphthalein in liquid petrolatum emulsion. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]
Endorphin: Opioid peptides derived from beta-lipotropin. Endorphin is the most potent naturally occurring analgesic agent. It is present in pituitary, brain, and peripheral tissues. [NIH]
Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] Endotoxins: Toxins closely associated with the living cytoplasm or cell wall of certain microorganisms, which do not readily diffuse into the culture medium, but are released upon lysis of the cells. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enteric Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]
Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Ephedrine: An alpha- and beta-adrenergic agonist that may also enhance release of norepinephrine. It has been used in the treatment of several disorders including asthma,
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heart failure, rhinitis, and urinary incontinence, and for its central nervous system stimulatory effects in the treatment of narcolepsy and depression. It has become less extensively used with the advent of more selective agonists. [NIH] Epidemic: Occurring suddenly in numbers clearly in excess of normal expectancy; said especially of infectious diseases but applied also to any disease, injury, or other healthrelated event occurring in such outbreaks. [EU] Epidermis: Nonvascular layer of the skin. It is made up, from within outward, of five layers: 1) basal layer (stratum basale epidermidis); 2) spinous layer (stratum spinosum epidermidis); 3) granular layer (stratum granulosum epidermidis); 4) clear layer (stratum lucidum epidermidis); and 5) horny layer (stratum corneum epidermidis). [NIH] Epinephrine: The active sympathomimetic hormone from the adrenal medulla in most species. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. It is used in asthma and cardiac failure and to delay absorption of local anesthetics. [NIH] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythromycin: A bacteriostatic antibiotic substance produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]
Esterification: The process of converting an acid into an alkyl or aryl derivative. Most frequently the process consists of the reaction of an acid with an alcohol in the presence of a trace of mineral acid as catalyst or the reaction of an acyl chloride with an alcohol. Esterification can also be accomplished by enzymatic processes. [NIH] Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Ethylmorphine: A narcotic analgesic and antitussive. It is metabolized in the liver by ethylmorphine-N-demethylase and used as an indicator of liver function. [NIH] Etodolac: A nonsteroidal anti-inflammatory agent with potent analgesic and antiarthritic properties. It has been shown to be effective in the treatment of osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, and in the alleviation of postoperative pain. [NIH] Evacuation: An emptying, as of the bowels. [EU] Evoke: The electric response recorded from the cerebral cortex after stimulation of a peripheral sense organ. [NIH] Evoked Potentials: The electric response evoked in the central nervous system by stimulation of sensory receptors or some point on the sensory pathway leading from the receptor to the cortex. The evoked stimulus can be auditory, somatosensory, or visual, although other modalities have been reported. Event-related potentials is sometimes used synonymously with evoked potentials but is often associated with the execution of a motor,
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cognitive, or psychophysiological task, as well as with the response to a stimulus. [NIH] Excitability: Property of a cardiac cell whereby, when the cell is depolarized to a critical level (called threshold), the membrane becomes permeable and a regenerative inward current causes an action potential. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Excitatory Amino Acids: Endogenous amino acids released by neurons as excitatory neurotransmitters. Glutamic acid is the most common excitatory neurotransmitter in the brain. Aspartic acid has been regarded as an excitatory transmitter for many years, but the extent of its role as a transmitter is unclear. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]
Exocrine: Secreting outwardly, via a duct. [EU] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expectorant: 1. Promoting the ejection, by spitting, of mucus or other fluids from the lungs and trachea. 2. An agent that promotes the ejection of mucus or exudate from the lungs, bronchi, and trachea; sometimes extended to all remedies that quiet cough (antitussives). [EU]
Expiration: The act of breathing out, or expelling air from the lungs. [EU] Expiratory: The volume of air which leaves the breathing organs in each expiration. [NIH] External-beam radiation: Radiation therapy that uses a machine to aim high-energy rays at the cancer. Also called external radiation. [NIH] Extracellular: Outside a cell or cells. [EU] Extracellular Space: Interstitial space between cells, occupied by fluid as well as amorphous and fibrous substances. [NIH] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] Faecal: Pertaining to or of the nature of feces. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli.
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[NIH]
Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Feces: The excrement discharged from the intestines, consisting of bacteria, cells exfoliated from the intestines, secretions, chiefly of the liver, and a small amount of food residue. [EU] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. [NIH] Fistula: Abnormal communication most commonly seen between two internal organs, or between an internal organ and the surface of the body. [NIH] Flame Ionization: Pyrolysis of organic compounds at the temperature of a hydrogen-air flame to produce ionic intermediates which can be collected and the resulting ion current measured by gas chromatography. [NIH] Flatus: Gas passed through the rectum. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flurazepam: A benzodiazepine derivative used mainly as a hypnotic. [NIH] Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting carbonic anhydrase. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gamma Rays: Very powerful and penetrating, high-energy electromagnetic radiation of shorter wavelength than that of x-rays. They are emitted by a decaying nucleus, usually between 0.01 and 10 MeV. They are also called nuclear x-rays. [NIH] Gamma-Endorphin: An endogenous opioid peptide derived from the pro-opiomelanocortin precursor peptide. It differs from alpha-endorphin by one amino acid. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Ganglioside: Protein kinase C's inhibitor which reduces ischemia-related brain damage. [NIH]
Gap Junctions: Connections between cells which allow passage of small molecules and electric current. Gap junctions were first described anatomically as regions of close apposition between cells with a narrow (1-2 nm) gap between cell membranes. The variety in the properties of gap junctions is reflected in the number of connexins, the family of proteins which form the junctions. [NIH]
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Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gas exchange: Primary function of the lungs; transfer of oxygen from inhaled air into the blood and of carbon dioxide from the blood into the lungs. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]
Gastroenterology: A subspecialty of internal medicine concerned with the study of the physiology and diseases of the digestive system and related structures (esophagus, liver, gallbladder, and pancreas). [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrointestinal Transit: Passage of food (sometimes in the form of a test meal) through the gastrointestinal tract as measured in minutes or hours. The rate of passage through the intestine is an indicator of small bowel function. [NIH] Gelatin: A product formed from skin, white connective tissue, or bone collagen. It is used as a protein food adjuvant, plasma substitute, hemostatic, suspending agent in pharmaceutical preparations, and in the manufacturing of capsules and suppositories. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]
Generator: Any system incorporating a fixed parent radionuclide from which is produced a daughter radionuclide which is to be removed by elution or by any other method and used in a radiopharmaceutical. [NIH] Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Giardiasis: An infection of the small intestine caused by the flagellated protozoan Giardia lamblia. It is spread via contaminated food and water and by direct person-to-person contact. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]
Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH]
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Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glucuronosyltransferase: A family of enzymes accepting a wide range of substrates, including phenols, alcohols, amines, and fatty acids. They function as drug-metabolizing enzymes that catalyze the conjugation of UDPglucuronic acid to a variety of endogenous and exogenous compounds. EC 2.4.1.17. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]
Glutethimide: A hypnotic and sedative. Its use has been largely superseded by other drugs. [NIH]
Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Grade: The grade of a tumor depends on how abnormal the cancer cells look under a microscope and how quickly the tumor is likely to grow and spread. Grading systems are different for each type of cancer. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Graft Rejection: An immune response with both cellular and humoral components, directed against an allogeneic transplant, whose tissue antigens are not compatible with those of the recipient. [NIH] Gram-negative: Losing the stain or decolorized by alcohol in Gram's method of staining, a primary characteristic of bacteria having a cell wall composed of a thin layer of peptidoglycan covered by an outer membrane of lipoprotein and lipopolysaccharide. [EU] Gram-positive: Retaining the stain or resisting decolorization by alcohol in Gram's method of staining, a primary characteristic of bacteria whose cell wall is composed of a thick layer of peptidologlycan with attached teichoic acids. [EU] Granulocytes: Leukocytes with abundant granules in the cytoplasm. They are divided into three groups: neutrophils, eosinophils, and basophils. [NIH] Gravis: Eruption of watery blisters on the skin among those handling animals and animal products. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]
Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH]
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Guinea Pigs: A common name used for the family Caviidae. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. [NIH]
Gynaecological: Pertaining to gynaecology. [EU] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Hair Color: Color of hair or fur. [NIH] Haploid: An organism with one basic chromosome set, symbolized by n; the normal condition of gametes in diploids. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heartburn: Substernal pain or burning sensation, usually associated with regurgitation of gastric juice into the esophagus. [NIH] Hematopoiesis: The development and formation of various types of blood cells. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]
Hepatic: Refers to the liver. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU]
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Heterotrophic: Pertaining to organisms that are consumers and dependent on other organisms for their source of energy (food). [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homicide: The killing of one person by another. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hybrid: Cross fertilization between two varieties or, more usually, two species of vines, see also crossing. [NIH] Hydrocodone: Narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydromorphone: An opioid analgesic made from morphine and used mainly as an analgesic. It has a shorter duration of action than morphine. [NIH] Hydroxylation: Hydroxylate, to introduce hydroxyl into (a compound or radical) usually by replacement of hydrogen. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypotension: Abnormally low blood pressure. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the
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therapy of rheumatism and arthritis. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Ileocecal Valve: A valve that connects the lower part of the small intestine and the upper part of the large intestine (ileum and cecum). Controls the flow of fluid in the intestines and prevents backflow. [NIH] Ileum: The lower end of the small intestine. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group. [NIH]
Immune response: The activity of the immune system against foreign substances (antigens). [NIH]
Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]
effects
of
foreign
Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunodeficiency: The decreased ability of the body to fight infection and disease. [NIH] Immunodeficiency syndrome: The inability of the body to produce an immune response. [NIH]
Immunoglobulin: A protein that acts as an antibody. [NIH] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] Immunosuppressant: An agent capable of suppressing immune responses. [EU] Immunosuppressive: Describes the ability to lower immune system responses. [NIH] Immunosuppressive therapy: Therapy used to decrease the body's immune response, such as drugs given to prevent transplant rejection. [NIH] Immunotherapy: Manipulation of the host's immune system in treatment of disease. It includes both active and passive immunization as well as immunosuppressive therapy to prevent graft rejection. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Implant radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called [NIH] Impotence: The inability to perform sexual intercourse. [NIH]
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In vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Indigestion: Poor digestion. Symptoms include heartburn, nausea, bloating, and gas. Also called dyspepsia. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]
Infertility: The diminished or absent ability to conceive or produce an offspring while sterility is the complete inability to conceive or produce an offspring. [NIH] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Inflammatory bowel disease: A general term that refers to the inflammation of the colon and rectum. Inflammatory bowel disease includes ulcerative colitis and Crohn's disease. [NIH]
Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inhalation: The drawing of air or other substances into the lungs. [EU] Inlay: In dentistry, a filling first made to correspond with the form of a dental cavity and then cemented into the cavity. [NIH] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Insomnia: Difficulty in going to sleep or getting enough sleep. [NIH] Interindividual: Occurring between two or more individuals. [EU] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Internal Medicine: A medical specialty concerned with the diagnosis and treatment of
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diseases of the internal organ systems of adults. [NIH] Internal radiation: A procedure in which radioactive material sealed in needles, seeds, wires, or catheters is placed directly into or near the tumor. Also called brachytherapy, implant radiation, or interstitial radiation therapy. [NIH] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestinal Pseudo-Obstruction: Obstruction of the intestines that is functional, not mechanical. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Involuntary: Reaction occurring without intention or volition. [NIH] Ion Channels: Gated, ion-selective glycoproteins that traverse membranes. The stimulus for channel gating can be a membrane potential, drug, transmitter, cytoplasmic messenger, or a mechanical deformation. Ion channels which are integral parts of ionotropic neurotransmitter receptors are not included. [NIH] Ionization: 1. Any process by which a neutral atom gains or loses electrons, thus acquiring a net charge, as the dissociation of a substance in solution into ions or ion production by the passage of radioactive particles. 2. Iontophoresis. [EU] Ionizing: Radiation comprising charged particles, e. g. electrons, protons, alpha-particles, etc., having sufficient kinetic energy to produce ionization by collision. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Irradiation: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Irradiation is also called radiation therapy, radiotherapy, and x-ray therapy. [NIH] Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress.
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Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isopropyl: A gene mutation inducer. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Keratin: A class of fibrous proteins or scleroproteins important both as structural proteins and as keys to the study of protein conformation. The family represents the principal constituent of epidermis, hair, nails, horny tissues, and the organic matrix of tooth enamel. Two major conformational groups have been characterized, alpha-keratin, whose peptide backbone forms an alpha-helix, and beta-keratin, whose backbone forms a zigzag or pleated sheet structure. [NIH] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to indomethacin. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Krypton: A noble gas that is found in the atmosphere. It has the atomic symbol Kr, atomic number 36, atomic weight 83.80, and has been used in electric bulbs. [NIH] Kynurenic Acid: A broad-spectrum excitatory amino acid antagonist used as a research tool. [NIH]
Lactulose: A mild laxative. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Latent: Phoria which occurs at one distance or another and which usually has no troublesome effect. [NIH] Lavage: A cleaning of the stomach and colon. Uses a special drink and enemas. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative.
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[EU]
Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Lesion: An area of abnormal tissue change. [NIH] Leukemia: Cancer of blood-forming tissue. [NIH] Leukotrienes: A family of biologically active compounds derived from arachidonic acid by oxidative metabolism through the 5-lipoxygenase pathway. They participate in host defense reactions and pathophysiological conditions such as immediate hypersensitivity and inflammation. They have potent actions on many essential organs and systems, including the cardiovascular, pulmonary, and central nervous system as well as the gastrointestinal tract and the immune system. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]
Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Life cycle: The successive stages through which an organism passes from fertilized ovum or spore to the fertilized ovum or spore of the next generation. [NIH] Ligands: A RNA simulation method developed by the MIT. [NIH] Limbic: Pertaining to a limbus, or margin; forming a border around. [EU] Limbic System: A set of forebrain structures common to all mammals that is defined functionally and anatomically. It is implicated in the higher integration of visceral, olfactory, and somatic information as well as homeostatic responses including fundamental survival behaviors (feeding, mating, emotion). For most authors, it includes the amygdala, epithalamus, gyrus cinguli, hippocampal formation (see hippocampus), hypothalamus, parahippocampal gyrus, septal nuclei, anterior nuclear group of thalamus, and portions of the basal ganglia. (Parent, Carpenter's Human Neuroanatomy, 9th ed, p744; NeuroNames, http://rprcsgi.rprc.washington.edu/neuronames/index.html (September 2, 1998)). [NIH] Linkage: The tendency of two or more genes in the same chromosome to remain together from one generation to the next more frequently than expected according to the law of independent assortment. [NIH] Lipid: Fat. [NIH] Lipoxygenase: An enzyme of the oxidoreductase class that catalyzes reactions between linoleate and other fatty acids and oxygen to form hydroperoxy-fatty acid derivatives. Related enzymes in this class include the arachidonate lipoxygenases, arachidonate 5lipoxygenase, arachidonate 12-lipoxygenase, and arachidonate 15-lipoxygenase. EC 1.13.11.12. [NIH] Lipoxygenase Inhibitors: Compounds or agents that combine with lipoxygenase and thereby prevent its substrate-enzyme combination with arachidonic acid and the formation of the eicosanoid products hydroxyeicosatetraenoic acid and various leukotrienes. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH]
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Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Locomotion: Movement or the ability to move from one place or another. It can refer to humans, vertebrate or invertebrate animals, and microorganisms. [NIH] Locomotor: Of or pertaining to locomotion; pertaining to or affecting the locomotive apparatus of the body. [EU] Loperamide: 4-(p-Chlorophenyl)-4-hydroxy-N.N-dimethyl-alpha,alpha-diphenyl-1piperidine butyramide hydrochloride. Synthetic anti-diarrheal agent with a long duration of action; it is not significantly absorbed from the gut, has no effect on the adrenergic system or central nervous system, but may antagonize histamine and interfere with acetylcholine release locally. [NIH] Loperamide hydrochloride: An antidiarrheal drug. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphocyte Count: A count of the number of lymphocytes in the blood. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Macrophage Inflammatory Protein-1: A chemokine that is chemotactic for neutrophils and monocytes, stimulates macrophages, and may play a role in regulating hematopoiesis. Its two variants, MIP-1alpha and MIP-1beta, are 60% homologous to each other. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Manic: Affected with mania. [EU] Mastication: The act and process of chewing and grinding food in the mouth. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical
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Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meiosis: A special method of cell division, occurring in maturation of the germ cells, by means of which each daughter nucleus receives half the number of chromosomes characteristic of the somatic cells of the species. [NIH] Melanin: The substance that gives the skin its color. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methamphetamine: A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] Methyl Ethers: A group of compounds that contain the general formula R-OCH3. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Metronidazole: Antiprotozoal used in amebiasis, trichomoniasis, giardiasis, and as treponemacide in livestock. It has also been proposed as a radiation sensitizer for hypoxic cells. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985, p133), this substance may reasonably be anticipated to be a carcinogen (Merck, 11th ed). [NIH]
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MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microdialysis: A technique for measuring extracellular concentrations of substances in tissues, usually in vivo, by means of a small probe equipped with a semipermeable membrane. Substances may also be introduced into the extracellular space through the membrane. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]
Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Miosis: Pupillary constriction. This may result from congenital absence of the dilatator pupillary muscle, defective sympathetic innervation, or irritation of the conjunctiva or cornea. [NIH] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Mitosis: A method of indirect cell division by means of which the two daughter nuclei normally receive identical complements of the number of chromosomes of the somatic cells of the species. [NIH] Mobility: Capability of movement, of being moved, or of flowing freely. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH]
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Monoclonal: An antibody produced by culturing a single type of cell. It therefore consists of a single species of immunoglobulin molecules. [NIH] Monocyte: A type of white blood cell. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphine Dependence: Strong dependence, both physiological and emotional, upon morphine. [NIH] Morphine Derivatives: Analogs or derivatives of morphine. [NIH] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor Activity: The physical activity of an organism as a behavioral phenomenon. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]
Mucins: A secretion containing mucopolysaccharides and protein that is the chief constituent of mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multidose: Occurring in, or using multiple doses. [EU] Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural junction (curare and related compounds). [EU] Muscle Relaxation: That phase of a muscle twitch during which a muscle returns to a resting position. [NIH] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Mutagenic: Inducing genetic mutation. [EU] Myasthenia: Muscular debility; any constitutional anomaly of muscle. [EU] Mydriatic: 1. Dilating the pupil. 2. Any drug that dilates the pupil. [EU] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Naive: Used to describe an individual who has never taken a certain drug or class of drugs (e. g., AZT-naive, antiretroviral-naive), or to refer to an undifferentiated immune system cell. [NIH] Nalbuphine: A narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu opioid receptors. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH]
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Narcolepsy: A condition of unknown cause characterized by a periodic uncontrollable tendency to fall asleep. [NIH] Narcosis: A general and nonspecific reversible depression of neuronal excitability, produced by a number of physical and chemical aspects, usually resulting in stupor. [NIH] Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Neoplasms: New abnormal growth of tissue. Malignant neoplasms show a greater degree of anaplasia and have the properties of invasion and metastasis, compared to benign neoplasms. [NIH] Neostigmine: A cholinesterase inhibitor used in the treatment of myasthenia gravis and to reverse the effects of muscle relaxants such as gallamine and tubocurarine. Neostigmine, unlike physostigmine, does not cross the blood-brain barrier. [NIH] Nephritis: Inflammation of the kidney; a focal or diffuse proliferative or destructive process which may involve the glomerulus, tubule, or interstitial renal tissue. [EU] Nephropathy: Disease of the kidneys. [EU] Nephrotoxic: Toxic or destructive to kidney cells. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU]
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Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]
Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Neutrons: Electrically neutral elementary particles found in all atomic nuclei except light hydrogen; the mass is equal to that of the proton and electron combined and they are unstable when isolated from the nucleus, undergoing beta decay. Slow, thermal, epithermal, and fast neutrons refer to the energy levels with which the neutrons are ejected from heavier nuclei during their decay. [NIH] Neutrophils: Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes. [NIH] Nicotine: Nicotine is highly toxic alkaloid. It is the prototypical agonist at nicotinic cholinergic receptors where it dramatically stimulates neurons and ultimately blocks synaptic transmission. Nicotine is also important medically because of its presence in tobacco smoke. [NIH] Nitrazepam: A benzodiazepine derivative used as an anticonvulsant and hypnotic. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]
Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Noscapine: A naturally occurring opium alkaloid that is a centrally acting antitussive agent. [NIH]
Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH]
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Nuclei: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Octreotide: A potent, long-acting somatostatin octapeptide analog which has a wide range of physiological actions. It inhibits growth hormone secretion, is effective in the treatment of hormone-secreting tumors from various organs, and has beneficial effects in the management of many pathological states including diabetes mellitus, orthostatic hypertension, hyperinsulinism, hypergastrinemia, and small bowel fistula. [NIH] Odour: A volatile emanation that is perceived by the sense of smell. [EU] Ofloxacin: An orally administered broad-spectrum quinolone antibacterial drug active against most gram-negative and gram-positive bacteria. [NIH] Oncogene: A gene that normally directs cell growth. If altered, an oncogene can promote or allow the uncontrolled growth of cancer. Alterations can be inherited or caused by an environmental exposure to carcinogens. [NIH] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Opioid Peptides: The endogenous peptides with opiate-like activity. The three major classes currently recognized are the enkephalins, the dynorphins, and the endorphins. Each of these families derives from different precursors, proenkephalin, prodynorphin, and proopiomelanocortin, respectively. There are also at least three classes of opioid receptors, but the peptide families do not map to the receptors in a simple way. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Opportunistic Infections: An infection caused by an organism which becomes pathogenic under certain conditions, e.g., during immunosuppression. [NIH] Orderly: A male hospital attendant. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Oxazepam: A benzodiazepine used in the treatment of anxiety, alcohol withdrawal, and insomnia. [NIH]
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Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]
Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxytocic: 1. Pertaining to, characterized by, or promoting oxytocia (= rapid labor). 2. An agent that hastens evacuation of the uterus by stimulating contractions of the myometrium. [EU]
Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]
Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH] Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used
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in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Papilla: A small nipple-shaped elevation. [NIH] Papillary: Pertaining to or resembling papilla, or nipple. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pathologic Processes: The abnormal mechanisms and forms involved in the dysfunctions of tissues and organs. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]
Pelvic: Pertaining to the pelvis. [EU] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Pentylenetetrazole: A pharmaceutical agent that displays activity as a central nervous system and respiratory stimulant. It is considered a non-competitive GABA antagonist. Pentylenetetrazole has been used experimentally to study seizure phenomenon and to identify pharmaceuticals that may control seizure susceptibility. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peracetic Acid: A liquid that functions as a strong oxidizing agent. It has an acrid odor and is used as a disinfectant. [NIH] Perennial: Lasting through the year of for several years. [EU] Perineal: Pertaining to the perineum. [EU] Perineum: The area between the anus and the sex organs. [NIH] Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]
Peristalsis: The rippling motion of muscles in the intestine or other tubular organs characterized by the alternate contraction and relaxation of the muscles that propel the contents onward. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH]
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Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] Phenobarbital: A barbituric acid derivative that acts as a nonselective central nervous system depressant. It promotes binding to inhibitory GABA subtype receptors, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. [NIH] Phenotype: The outward appearance of the individual. It is the product of interactions between genes and between the genotype and the environment. This includes the killer phenotype, characteristic of yeasts. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phenylpropanolamine: A sympathomimetic that acts mainly by causing release of norepinephrine but also has direct agonist activity at some adrenergic receptors. It is most commonly used as a nasal vasoconstrictor and an appetite depressant. [NIH] Phospholipases: A class of enzymes that catalyze the hydrolysis of phosphoglycerides or glycerophosphatidates. EC 3.1.-. [NIH] Phosphorous: Having to do with or containing the element phosphorus. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]
Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]
Physiology: The science that deals with the life processes and functions of organismus, their cells, tissues, and organs. [NIH] Physostigmine: A cholinesterase inhibitor that is rapidly absorbed through membranes. It can be applied topically to the conjunctiva. It also can cross the blood-brain barrier and is used when central nervous system effects are desired, as in the treatment of severe anticholinergic toxicity. [NIH] Picrotoxin: A noncompetitive antagonist at GABA-A receptors and thus a convulsant. Picrotoxin blocks the GABA-activated chloride ionophore. Although it is most often used as a research tool, it has been used as a CNS stimulant and an antidote in poisoning by CNS depressants, especially the barbiturates. [NIH] Pilot study: The initial study examining a new method or treatment. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins
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that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]
Polymorphic: Occurring in several or many forms; appearing in different forms at different stages of development. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Pons: The part of the central nervous system lying between the medulla oblongata and the mesencephalon, ventral to the cerebellum, and consisting of a pars dorsalis and a pars ventralis. [NIH] Pontine: A brain region involved in the detection and processing of taste. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postoperative: After surgery. [NIH] Postsynaptic: Nerve potential generated by an inhibitory hyperpolarizing stimulation. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the
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convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Preclinical: Before a disease becomes clinically recognizable. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Predisposition: A latent susceptibility to disease which may be activated under certain conditions, as by stress. [EU] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prednisone: A synthetic anti-inflammatory glucocorticoid derived from cortisone. It is biologically inert and converted to prednisolone in the liver. [NIH] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Presynaptic: Situated proximal to a synapse, or occurring before the synapse is crossed. [EU] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Proglumide: 4-Benzamido-N,N-dipropylglutaramic acid. A drug that exerts an inhibitory effect on gastric secretion and reduces gastrointestinal motility. It is used clinically in the drug therapy of gastrointestinal ulcers. [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Progressive disease: Cancer that is increasing in scope or severity. [NIH] Prolactin: Pituitary lactogenic hormone. A polypeptide hormone with a molecular weight of about 23,000. It is essential in the induction of lactation in mammals at parturition and is synergistic with estrogen. The hormone also brings about the release of progesterone from lutein cells, which renders the uterine mucosa suited for the embedding of the ovum should fertilization occur. [NIH] Promethazine: A phenothiazine derivative with histamine H1-blocking, antimuscarinic, and sedative properties. It is used as an antiallergic, in pruritus, for motion sickness and sedation, and also in animals. [NIH] Prone: Having the front portion of the body downwards. [NIH] Pro-Opiomelanocortin: A precursor protein, MW 30,000, synthesized mainly in the anterior pituitary gland but also found in the hypothalamus, brain, and several peripheral tissues. It incorporates the amino acid sequences of ACTH and beta-lipotropin. These two hormones,
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in turn, contain the biologically active peptides MSH, corticotropin-like intermediate lobe peptide, alpha-lipotropin, endorphins, and methionine enkephalin. [NIH] Prophase: The first phase of cell division, in which the chromosomes become visible, the nucleus starts to lose its identity, the spindle appears, and the centrioles migrate toward opposite poles. [NIH] Propofol: A widely used anesthetic. [NIH] Propoxyphene: A narcotic analgesic structurally related to methadone. Only the dextroisomer has an analgesic effect; the levo-isomer appears to exert an antitussive effect. [NIH] Prospective study: An epidemiologic study in which a group of individuals (a cohort), all free of a particular disease and varying in their exposure to a possible risk factor, is followed over a specific amount of time to determine the incidence rates of the disease in the exposed and unexposed groups. [NIH] Prostitution: The practice of indulging in promiscuous sexual relations for money. [NIH] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Protein Subunits: Single chains of amino acids that are the units of a multimeric protein. They can be identical or non-identical subunits. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritic: Pertaining to or characterized by pruritus. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychiatric: Pertaining to or within the purview of psychiatry. [EU] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] Psychotropic: Exerting an effect upon the mind; capable of modifying mental activity; usually applied to drugs that effect the mental state. [EU] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among
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alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]
Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Ventilation: The total volume of gas per minute inspired or expired measured in liters per minute. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]
Pupil: The aperture in the iris through which light passes. [NIH] Purines: A series of heterocyclic compounds that are variously substituted in nature and are known also as purine bases. They include adenine and guanine, constituents of nucleic acids, as well as many alkaloids such as caffeine and theophylline. Uric acid is the metabolic end product of purine metabolism. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] Quaternary: 1. Fourth in order. 2. Containing four elements or groups. [EU] Quinidine: An optical isomer of quinine, extracted from the bark of the Cinchona tree and similar plant species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking sodium and potassium currents across cellular membranes. It prolongs cellular action potential, and decreases automaticity. Quinidine also blocks muscarinic and alphaadrenergic neurotransmission. [NIH] Quinine: An alkaloid derived from the bark of the cinchona tree. It is used as an antimalarial drug, and is the active ingredient in extracts of the cinchona that have been used for that purpose since before 1633. Quinine is also a mild antipyretic and analgesic and has been used in common cold preparations for that purpose. It was used commonly and as a bitter and flavoring agent, and is still useful for the treatment of babesiosis. Quinine is also useful in some muscular disorders, especially nocturnal leg cramps and myotonia congenita, because of its direct effects on muscle membrane and sodium channels. The mechanisms of its antimalarial effects are not well understood. [NIH] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radiation therapy: The use of high-energy radiation from x-rays, gamma rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body in the area near cancer cells (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy. [NIH]
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Radioactive: Giving off radiation. [NIH] Radioimmunotherapy: Radiotherapy where cytotoxic radionuclides are linked to antibodies in order to deliver toxins directly to tumor targets. Therapy with targeted radiation rather than antibody-targeted toxins (immunotoxins) has the advantage that adjacent tumor cells, which lack the appropriate antigenic determinants, can be destroyed by radiation cross-fire. Radioimmunotherapy is sometimes called targeted radiotherapy, but this latter term can also refer to radionuclides linked to non-immune molecules (radiotherapy). [NIH] Radiolabeled: Any compound that has been joined with a radioactive substance. [NIH] Radiopharmaceutical: Any medicinal product which, when ready for use, contains one or more radionuclides (radioactive isotopes) included for a medicinal purpose. [NIH] Radiotherapy: The use of ionizing radiation to treat malignant neoplasms and other benign conditions. The most common forms of ionizing radiation used as therapy are x-rays, gamma rays, and electrons. A special form of radiotherapy, targeted radiotherapy, links a cytotoxic radionuclide to a molecule that targets the tumor. When this molecule is an antibody or other immunologic molecule, the technique is called radioimmunotherapy. [NIH] Randomized: Describes an experiment or clinical trial in which animal or human subjects are assigned by chance to separate groups that compare different treatments. [NIH] Randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which treatment is best. It is the patient's choice to be in a randomized trial. [NIH] Raphe Nuclei: Collections of small neurons centrally scattered among many fibers from the level of the trochlear nucleus in the midbrain to the hypoglossal area in the medulla oblongata. [NIH] Rationalize: To attribute one's actions to rational and creditable motives without adequate analysis of the true and unconscious motives. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refractory: Not readily yielding to treatment. [EU]
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Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Reliability: Used technically, in a statistical sense, of consistency of a test with itself, i. e. the extent to which we can assume that it will yield the same result if repeated a second time. [NIH]
Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Respiratory System: The tubular and cavernous organs and structures, by means of which pulmonary ventilation and gas exchange between ambient air and the blood are brought about. [NIH] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Reticular: Coarse-fibered, netlike dermis layer. [NIH] Reticular Formation: A region extending from the pons & medulla oblongata through the mesencephalon, characterized by a diversity of neurons of various sizes and shapes, arranged in different aggregations and enmeshed in a complicated fiber network. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Rheumatism: A group of disorders marked by inflammation or pain in the connective tissue structures of the body. These structures include bone, cartilage, and fat. [NIH] Rheumatoid: Resembling rheumatism. [EU] Rheumatoid arthritis: A form of arthritis, the cause of which is unknown, although infection, hypersensitivity, hormone imbalance and psychologic stress have been suggested as possible causes. [NIH] Rhinitis: Inflammation of the mucous membrane of the nose. [NIH] Ribose: A pentose active in biological systems usually in its D-form. [NIH] Rigidity: Stiffness or inflexibility, chiefly that which is abnormal or morbid; rigor. [EU] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Saliva: The clear, viscous fluid secreted by the salivary glands and mucous glands of the
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mouth. It contains mucins, water, organic salts, and ptylin. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Sclerosis: A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sebaceous: Gland that secretes sebum. [NIH] Sebaceous gland: Gland that secretes sebum. [NIH] Sebum: The oily substance secreted by sebaceous glands. It is composed of keratin, fat, and cellular debris. [NIH] Secobarbital: A barbiturate that is used as a sedative. Secobarbital is reported to have no anti-anxiety activity. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from glycine or threonine. It is involved in the biosynthesis of purines, pyrimidines, and other amino acids. [NIH] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important
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physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shock: The general bodily disturbance following a severe injury; an emotional or moral upset occasioned by some disturbing or unexpected experience; disruption of the circulation, which can upset all body functions: sometimes referred to as circulatory shock. [NIH]
Side effect: A consequence other than the one(s) for which an agent or measure is used, as the adverse effects produced by a drug, especially on a tissue or organ system other than the one sought to be benefited by its administration. [EU] Signal Transduction: The intercellular or intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GABA-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptormediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. [NIH] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]
Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of
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dissolving; the component of a solution that is present in greater amount. [EU] Somatostatin: A polypeptide hormone produced in the hypothalamus, and other tissues and organs. It inhibits the release of human growth hormone, and also modulates important physiological functions of the kidney, pancreas, and gastrointestinal tract. Somatostatin receptors are widely expressed throughout the body. Somatostatin also acts as a neurotransmitter in the central and peripheral nervous systems. [NIH] Sparteine: An alkaloid isolated from lupin beans, Lupinus luteus and Lupinus niger. It has been used as an oxytocic and an anti-arrhythmia agent. It has also been of interest because of genetic variation in its metabolism. [NIH] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spasticity: A state of hypertonicity, or increase over the normal tone of a muscle, with heightened deep tendon reflexes. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Sperm: The fecundating fluid of the male. [NIH] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [EU] Spike: The activation of synapses causes changes in the permeability of the dendritic membrane leading to changes in the membrane potential. This difference of the potential travels along the axon of the neuron and is called spike. [NIH] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spondylitis: Inflammation of the vertebrae. [EU] Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Stabilizer: A device for maintaining constant X-ray tube voltage or current. [NIH] Stem Cell Factor: Hematopoietic growth factor and the ligand of the c-kit receptor CD117 (proto-oncogene protein C-kit). It is expressed during embryogenesis and provides a key signal in multiple aspects of mast-cell differentiation and function. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this
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group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]
Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Striatum: A higher brain's domain thus called because of its stripes. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] Subacute: Somewhat acute; between acute and chronic. [EU] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Subspecies: A category intermediate in rank between species and variety, based on a smaller number of correlated characters than are used to differentiate species and generally conditioned by geographical and/or ecological occurrence. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]
Substrate: A substance upon which an enzyme acts. [EU] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Suppressive: Tending to suppress : effecting suppression; specifically : serving to suppress activity, function, symptoms. [EU] Supraspinal: Above the spinal column or any spine. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]
Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sweat Glands: Sweat-producing structures that are embedded in the dermis. Each gland
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consists of a single tube, a coiled body, and a superficial duct. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Synapses: Specialized junctions at which a neuron communicates with a target cell. At classical synapses, a neuron's presynaptic terminal releases a chemical transmitter stored in synaptic vesicles which diffuses across a narrow synaptic cleft and activates receptors on the postsynaptic membrane of the target cell. The target may be a dendrite, cell body, or axon of another neuron, or a specialized region of a muscle or secretory cell. Neurons may also communicate through direct electrical connections which are sometimes called electrical synapses; these are not included here but rather in gap junctions. [NIH] Synapsis: The pairing between homologous chromosomes of maternal and paternal origin during the prophase of meiosis, leading to the formation of gametes. [NIH] Synaptic: Pertaining to or affecting a synapse (= site of functional apposition between neurons, at which an impulse is transmitted from one neuron to another by electrical or chemical means); pertaining to synapsis (= pairing off in point-for-point association of homologous chromosomes from the male and female pronuclei during the early prophase of meiosis). [EU] Synaptic Transmission: The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors. These activated receptors modulate ion channels and/or secondmessenger systems to influence the postsynaptic cell. Electrical transmission is less common in the nervous system, and, as in other tissues, is mediated by gap junctions. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Temporal Lobe: Lower lateral part of the cerebral hemisphere. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testicles: The two egg-shaped glands found inside the scrotum. They produce sperm and male hormones. Also called testes. [NIH] Tetrahydrocannabinol: A psychoactive compound extracted from the resin of Cannabis sativa (marihuana, hashish). The isomer delta-9-tetrahydrocannabinol (THC) is considered the most active form, producing characteristic mood and perceptual changes associated with this compound. Dronabinol is a synthetic form of delta-9-THC. [NIH] Tetrahydropapaveroline: A leukomaine (animal alkaloid) formed in brain and liver from dopamine and L-dopa; it may be implicated in psychiatric problems. [NIH]
Dictionary 201
Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] Thoracic: Having to do with the chest. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombomodulin: A cell surface glycoprotein of endothelial cells that binds thrombin and serves as a cofactor in the activation of protein C and its regulation of blood coagulation. [NIH]
Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Trachea: The cartilaginous and membranous tube descending from the larynx and branching into the right and left main bronchi. [NIH] Tractus: A part of some structure, usually that part along which something passes. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of
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ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Triazolam: A short-acting benzodiazepine used in the treatment of insomnia. Some countries temporarily withdrew triazolam from the market because of concerns about adverse reactions, mostly psychological, associated with higher dose ranges. Its use at lower doses with appropriate care and labeling has been reaffirmed by the FDA and most other countries. [NIH] Trichomoniasis: An infection with the protozoan parasite Trichomonas vaginalis. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trifluoperazine: A phenothiazine with actions similar to chlorpromazine. It is used as an antipsychotic and an antiemetic. [NIH] Trifluoroacetic Acid: A very strong halogenated derivative of acetic acid. It is used in acid catalyzed reactions, especially those where an ester is cleaved in peptide synthesis. [NIH] Trigeminal: Cranial nerve V. It is sensory for the eyeball, the conjunctiva, the eyebrow, the skin of face and scalp, the teeth, the mucous membranes in the mouth and nose, and is motor to the muscles of mastication. [NIH] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tubocurarine: A neuromuscular blocker and active ingredient in curare; plant based alkaloid of Menispermaceae. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]
Urban Population: The inhabitants of a city or town, including metropolitan areas and suburban areas. [NIH] Urea: A compound (CO(NH2)2), formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids. [NIH]
Dictionary 203
Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]
Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Uridine Diphosphate Glucuronic Acid: A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinary tract: The organs of the body that produce and discharge urine. These include the kidneys, ureters, bladder, and urethra. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urology: A surgical specialty concerned with the study, diagnosis, and treatment of diseases of the urinary tract in both sexes and the genital tract in the male. It includes the specialty of andrology which addresses both male genital diseases and male infertility. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasectomy: An operation to cut or tie off the two tubes that carry sperm out of the testicles. [NIH]
Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venom: That produced by the poison glands of the mouth and injected by the fangs of poisonous snakes. [NIH] Venous: Of or pertaining to the veins. [EU] Ventral: 1. Pertaining to the belly or to any venter. 2. Denoting a position more toward the belly surface than some other object of reference; same as anterior in human anatomy. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH]
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Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitreous Humor: The transparent, colorless mass of gel that lies behind the lens and in front of the retina and fills the center of the eyeball. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Waiting Lists: Prospective patient listings for appointments. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]
Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU] Xenon: A noble gas with the atomic symbol Xe, atomic number 54, and atomic weight 131.30. It is found in the earth's atmosphere and has been used as an anesthetic. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH] X-ray therapy: The use of high-energy radiation from x-rays to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials called radioisotopes. Radioisotopes produce radiation and can be placed in or near the tumor or in the area near cancer cells. This type of radiation treatment is called internal radiation therapy, implant radiation, interstitial radiation, or brachytherapy. Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. X-ray therapy is also called radiation therapy, radiotherapy, and irradiation. [NIH] Yeasts: A general term for single-celled rounded fungi that reproduce by budding. Brewers' and bakers' yeasts are Saccharomyces cerevisiae; therapeutic dried yeast is dried yeast. [NIH] Yohimbine: A plant alkaloid with alpha-2-adrenergic blocking activity. Yohimbine has been used as a mydriatic and in the treatment of impotence. It is also alleged to be an aphrodisiac. [NIH]
Zymogen: Inactive form of an enzyme which can then be converted to the active form, usually by excision of a polypeptide, e. g. trypsinogen is the zymogen of trypsin. [NIH]
Dictionary 205
207
INDEX 6 6-Mercaptopurine, 133, 147 A Abdominal, 52, 117, 147, 154, 178, 187 Abdominal Pain, 52, 117, 147, 178 Acceptor, 147, 187 Acetylcholine, 147, 159, 180, 185 Acquired Immunodeficiency Syndrome, 28, 147 Acyl, 90, 106, 147, 168 Acylation, 90, 99, 106, 147 Adduct, 97, 147 Adenine, 147, 193 Adenosine, 15, 147, 156, 189 Adjuvant, 14, 147, 171 Adrenal Cortex, 147, 162 Adrenergic, 15, 147, 150, 151, 165, 167, 168, 180, 189, 193, 200, 204 Adrenergic Agonists, 15, 147 Adverse Effect, 9, 15, 118, 148, 197 Aerosol, 104, 105, 148 Affinity, 148, 153, 164, 197 Ageing, 68, 148 Agonist, 13, 14, 15, 83, 84, 96, 148, 154, 156, 162, 165, 167, 183, 185, 189 Agoraphobia, 148, 175, 187 Airway, 7, 148 Aldehydes, 97, 148 Alertness, 148, 156 Algorithms, 148, 154 Alimentary, 32, 75, 148, 188 Alkaline, 96, 148, 149, 156, 187 Alkylating Agents, 88, 148 Alkylation, 87, 90, 98, 106, 148 Alleles, 12, 148 Allergen, 148, 164 Allylamine, 148, 149 Alternative medicine, 116, 149 Amebiasis, 149, 181 Amine, 83, 105, 149, 174 Amino Acid Sequence, 149, 150, 191 Amino Acids, 13, 149, 168, 169, 188, 192, 196, 202 Ammonia, 149, 199, 202 Ammonium Chloride, 95, 149 Amnestic, 149, 182 Amphetamine, 6, 44, 66, 132, 149, 164 Amygdala, 104, 149, 179
Anaesthesia, 19, 22, 25, 27, 36, 41, 43, 46, 48, 49, 50, 51, 54, 58, 59, 64, 66, 68, 149, 176 Analog, 80, 87, 97, 100, 149, 164, 186 Analytes, 59, 149 Anaphylaxis, 57, 75, 149 Anatomical, 150, 175, 196 Androgens, 147, 150, 162 Anesthesia, 6, 19, 31, 34, 47, 59, 72, 148, 150, 162, 182, 191 Anesthetics, 4, 150, 153, 168 Anions, 150, 177 Ankle, 26, 150 Anorexia, 34, 150, 202 Antagonism, 150, 156 Antiallergic, 150, 162, 191 Anti-Anxiety Agents, 150, 191 Antiasthmatic, 73, 150 Antibacterial, 150, 162, 186 Antibiotic, 4, 150, 156, 168, 191 Antibiotic Prophylaxis, 4, 150, 191 Antibodies, 89, 150, 180, 190, 194 Antibody, 4, 148, 150, 151, 160, 174, 175, 176, 177, 180, 183, 193, 194, 198, 204 Anticholinergic, 133, 150, 189 Anticoagulant, 150, 192 Anticonvulsant, 14, 104, 151, 157, 185 Antidepressant, 5, 118, 151, 170, 175 Antidote, 151, 189 Antiemetic, 151, 158, 165, 181, 202 Antiepileptic, 104, 151 Antigen, 37, 148, 149, 150, 151, 160, 174, 175, 176, 180 Anti-infective, 151, 174 Anti-Inflammatory Agents, 117, 151, 153, 162, 178 Antimetabolite, 147, 151 Antineoplastic, 147, 148, 151, 162 Antineoplastic Agents, 148, 151 Antipruritic, 151, 159 Antipsychotic, 151, 158, 166, 184, 202 Antipsychotic Agents, 151, 166 Antipyretic, 3, 9, 103, 147, 151, 164, 170, 193 Antispasmodic, 103, 152, 186 Antitussive, 17, 23, 65, 85, 88, 96, 98, 103, 110, 152, 164, 168, 185, 186, 192 Antitussive Agents, 110, 152
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Anus, 105, 152, 155, 188, 194 Anxiety, 118, 150, 152, 186, 187, 196 Anxiolytic, 4, 152, 182, 186 Apoptosis, 22, 26, 152 Aqueous, 84, 94, 96, 97, 152, 153, 163, 167, 174, 179 Arachidonate 12-Lipoxygenase, 152, 179 Arachidonate 15-Lipoxygenase, 152, 179 Arachidonate Lipoxygenases, 152, 179 Arachidonic Acid, 152, 179 Arginine, 152, 185 Argon, 104, 152 Aromatic, 93, 97, 152 Arrhythmia, 152, 198 Arterial, 148, 152, 174, 192 Arteries, 152, 155, 161, 182 Arteriolar, 152, 155 Arterioles, 152, 155, 156 Arthroplasty, 52, 153 Arthroscopy, 22, 34, 153 Articular, 153, 186 Aspartate, 10, 14, 86, 153, 164 Aspirin, 4, 20, 22, 31, 34, 35, 37, 45, 47, 76, 92, 118, 120, 153, 164 Assay, 11, 89, 153, 175 Astrocytes, 153, 182 Asymptomatic, 149, 153, 187 Atmospheric Pressure, 29, 88, 153 Atropine, 133, 153, 154, 165 Attenuated, 6, 153 Attenuation, 10, 153 Auditory, 153, 168 Autodigestion, 153, 187 Autoradiography, 15, 153 B Back Pain, 27, 153 Bacteria, 83, 147, 150, 151, 153, 154, 161, 170, 172, 182, 186, 201, 203 Bactericidal, 153, 168 Bacteriostatic, 153, 168 Bacterium, 153, 155, 161 Barbiturate, 86, 153, 196 Base, 8, 82, 94, 96, 98, 102, 105, 147, 153, 163, 178, 200, 202 Behavior Therapy, 154 Belladonna, 153, 154 Benign, 154, 173, 184, 194 Benzaldehyde, 99, 154 Benzamides, 4, 154 Benzene, 154 Benzodiazepines, 118, 154 Bethanechol, 4, 154
Bile, 55, 133, 154, 159, 170, 172, 179, 199 Bile Acids, 154, 199 Bile Acids and Salts, 154 Biliary, 154, 159, 187 Biliary Tract, 154, 187 Bilirubin, 154, 172 Bioavailability, 23, 26, 81, 154 Biochemical, 23, 148, 151, 154, 186, 196 Biosynthesis, 152, 154, 196, 203 Biotechnology, 18, 19, 110, 116, 127, 154 Biotransformation, 97, 155 Bismuth, 133, 155 Bismuth Subsalicylate, 133, 155 Bladder, 110, 155, 163, 176, 184, 203 Bloating, 155, 176, 178 Blood Platelets, 155, 196 Blood pressure, 144, 155, 174, 197 Blood vessel, 155, 157, 167, 169, 171, 178, 197, 201, 203 Blood-Brain Barrier, 155, 184, 189 Body Fluids, 29, 38, 155, 197 Bone Marrow, 154, 155, 162, 175, 180 Boron, 90, 93, 101, 106, 155 Boron Neutron Capture Therapy, 155 Bowel, 74, 110, 132, 155, 164, 171, 176, 177, 178, 186, 199 Bowel Movement, 155, 164, 199 Brachytherapy, 155, 177, 193, 204 Bradykinin, 57, 155, 178, 185 Branch, 104, 141, 156, 188, 192, 198, 201 Breakdown, 12, 156, 164, 171 Broad-spectrum, 156, 178, 186 Bronchi, 156, 168, 169, 201 Bronchial, 154, 156, 174 Bronchial Spasm, 154, 156 Bronchoscopy, 59, 68, 156 Bulimia, 34, 156 Bupivacaine, 156, 179 Buprenorphine, 6, 11, 156 Butorphanol, 6, 96, 156 C Caffeine, 3, 11, 22, 31, 34, 50, 57, 64, 76, 156, 193 Calcium, 156, 160, 188, 197 Calcium Channels, 156, 188 Capillary, 23, 36, 55, 155, 156, 204 Capillary Permeability, 155, 156 Capsules, 60, 75, 81, 105, 157, 171 Carbamazepine, 103, 157 Carbohydrate, 157, 162, 190 Carbon Dioxide, 22, 104, 156, 157, 163, 171, 195
Index 209
Carboxymethylcellulose, 103, 157 Carcinogen, 147, 157, 181 Carcinogenesis, 110, 157 Carcinogenic, 148, 154, 157, 199 Cardiac, 103, 148, 154, 156, 157, 166, 168, 169, 179, 182, 183, 193, 199 Cardiorespiratory, 157, 182 Cardiovascular, 149, 156, 157, 169, 179, 197 Case report, 48, 51, 157, 159 Case-Control Studies, 4, 157 Catecholamine, 157, 165, 189 Cations, 157, 177 Caudal, 8, 18, 157, 190 Cecum, 157, 175, 178 Cell Death, 152, 157, 184 Cell Differentiation, 157, 197, 198 Cell Division, 153, 158, 181, 182, 189, 192 Cell proliferation, 158, 197 Cell Respiration, 158, 195 Cellobiose, 158 Cellulose, 91, 158, 189 Central Nervous System Infections, 158, 173 Centrifugation, 158, 182 Cerebral, 155, 158, 161, 168, 188, 192, 198, 200 Cerebrospinal, 42, 45, 158 Cerebrospinal fluid, 42, 45, 158 Cerium, 97, 158 Character, 158, 163 Chlorpheniramine, 55, 65, 158 Chlorpromazine, 158, 202 Cholecystokinin, 58, 158 Cholesterol, 154, 158, 159, 199 Cholestyramine, 111, 133, 159 Cholinergic, 4, 151, 159, 185 Cholinergic Agonists, 4, 159 Chromatin, 152, 159, 185 Chromosome, 159, 161, 173, 179 Chronic renal, 3, 53, 159, 202 CIS, 12, 80, 99, 100, 159 Cisplatin, 159, 186 C-kit receptor, 159, 198 Clinical study, 159, 161 Clinical trial, 5, 11, 16, 38, 127, 159, 161, 162, 194 Cloning, 154, 159 Coca, 159 Cocaine, 11, 22, 32, 36, 58, 59, 65, 103, 132, 159 Cofactor, 159, 192, 201
Cognitive behavior therapy, 5, 160 Colitis, 132, 133, 160, 176, 178 Collagen, 160, 171, 190 Collapse, 150, 156, 160 Colloidal, 160, 167 Complement, 160 Complementary and alternative medicine, 71, 78, 160 Complementary medicine, 71, 160 Computational Biology, 127, 160 Computer Simulation, 7, 161 Concomitant, 91, 107, 161 Cone, 32, 37, 41, 51, 58, 59, 65, 67, 89, 161, 199 Congestion, 85, 151, 161, 168 Conjugated, 154, 161, 163 Conjugation, 155, 161, 172 Conjunctiva, 161, 182, 189, 202 Connective Tissue, 155, 160, 161, 170, 171, 195 Consciousness, 149, 150, 161, 163, 165 Constipation, 84, 91, 151, 161, 178 Constriction, 9, 161, 178, 182 Consumption, 13, 21, 49, 61, 72, 161, 187 Contraindications, ii, 161 Controlled clinical trial, 33, 53, 161 Controlled study, 58, 161 Convulsions, 64, 103, 151, 153, 161 Corneum, 32, 65, 161, 168 Coronary, 161, 162, 182 Coronary Thrombosis, 162, 182 Cortex, 162, 168 Cortical, 162, 169, 196 Corticosteroid, 56, 162, 191 Cortisol, 32, 162 Cortisone, 162, 191 Cranial, 162, 173, 184, 202 Craniocerebral Trauma, 162, 173 Craniotomy, 48, 162 Crystallization, 94, 162 Curare, 162, 183, 202 Curative, 162, 201 Cutaneous, 37, 57, 61, 162 Cyanoacrylates, 67, 162 Cyanogen Bromide, 90, 93, 101, 106, 162 Cyclazocine, 96, 162 Cyclic, 13, 156, 162, 172, 185 Cyclosporine, 4, 162 Cystitis, 111, 132, 163 Cytochrome, 12, 23, 28, 43, 45, 60, 163 Cytoplasm, 152, 163, 167, 172, 185 Cytotoxic, 163, 186, 194, 197
210 Codeine
Cytotoxic chemotherapy, 163, 186 D Databases, Bibliographic, 127, 163 Decarboxylation, 163, 174 Degenerative, 87, 163, 186 Deletion, 152, 163 Dementia, 147, 151, 163 Demethylation, 29, 43, 45, 90, 101, 106, 163 Dendrites, 163, 185 Dendritic, 163, 198 Density, 158, 163, 190 Depolarization, 163, 197 Depressive Disorder, 104, 163 Deprivation, 86, 163 Dermatitis, 21, 30, 39, 46, 53, 164, 166 Desensitization, 15, 164 Detoxification, 12, 30, 51, 54, 113, 164, 172 Deuterium, 11, 164, 174 Dextroamphetamine, 149, 164, 181 Dextromethorphan, 12, 14, 49, 85, 86, 87, 89, 164 Dextrorphan, 86, 164 Diabetes Mellitus, 164, 173, 186 Diagnostic procedure, 79, 116, 164 Dialyzer, 164, 173 Diarrhea, 17, 52, 76, 111, 133, 149, 155, 159, 164, 178 Diarrhoea, 71, 164 Diclofenac, 18, 26, 32, 36, 42, 50, 73, 91, 92, 116, 164 Diclofenac Sodium, 36, 73, 92, 164 Diflunisal, 22, 26, 27, 34, 61, 164 Digestion, 148, 154, 155, 164, 176, 177, 179, 199 Digestive system, 164, 171 Digestive tract, 105, 164, 197 Dihydromorphine, 27, 29, 55, 164 Dihydroxy, 96, 164 Dilatation, 165, 191, 203 Dilation, 155, 165, 203 Dimethyl, 80, 94, 96, 97, 100, 165, 180 Dipeptides, 86, 165 Diphenoxylate, 133, 165 Diploid, 165, 189 Direct, iii, 91, 95, 102, 119, 165, 171, 187, 189, 193, 194, 200 Discrimination, 9, 30, 165 Disinfectant, 165, 168, 188 Disposition, 26, 31, 32, 41, 42, 45, 59, 65, 73, 165 Dissociation, 148, 165, 177 Distal, 165, 166, 192
Diuresis, 156, 165 Diuretic, 149, 165 Dizziness, 91, 165, 187 Domesticated, 165, 173 Domperidone, 4, 165 Dopa, 165, 200 Dopamine, 4, 103, 149, 151, 158, 159, 164, 165, 166, 181, 182, 200 Dopamine Antagonists, 4, 166 Doping, 43, 61, 166 Dorsal, 8, 166, 190 Dorsum, 166 Dose-dependent, 9, 166 Drive, ii, vi, 4, 18, 63, 110, 166 Drug Evaluation, 44, 66, 166 Drug Interactions, 4, 10, 50, 120, 121, 166 Drug Tolerance, 166, 201 Duodenum, 154, 166, 167, 171, 199 Dyes, 154, 166, 185 Dysmenorrhoea, 103, 166 Dysphoric, 163, 166 E Eczema, 39, 166 Efficacy, 5, 7, 9, 10, 14, 15, 22, 23, 27, 32, 33, 34, 38, 54, 64, 71, 92, 116, 166 Electrode, 29, 166 Electrolyte, 74, 162, 166, 182, 190, 197, 202 Electrons, 154, 166, 177, 187, 193, 194 Electrophoresis, 23, 167 Emaciation, 147, 167 Embryo, 157, 167, 176 Embryogenesis, 167, 198 Emulsion, 153, 167 Encapsulated, 67, 167 Endorphin, 167, 170 Endoscopic, 153, 156, 167, 182 Endothelium, 167, 185 Endothelium-derived, 167, 185 Endotoxins, 160, 167, 178 End-stage renal, 159, 167 Enteric Nervous System, 4, 167 Environmental Health, 126, 128, 167 Enzymatic, 12, 156, 160, 167, 168, 174 Enzyme, 5, 57, 102, 152, 167, 172, 176, 179, 182, 197, 199, 201, 204 Ephedrine, 35, 65, 167 Epidemic, 113, 168 Epidermis, 161, 168, 178 Epinephrine, 147, 165, 168, 185, 202 Erythema, 168, 203 Erythromycin, 4, 168 Esophagus, 164, 168, 171, 173, 194, 199
Index 211
Esterification, 101, 168 Ethanol, 47, 98, 168 Ether, 11, 71, 80, 87, 88, 94, 95, 97, 98, 100, 105, 168 Ethylmorphine, 34, 61, 168 Etodolac, 19, 168 Evacuation, 161, 168, 171, 178, 187 Evoke, 168, 199 Evoked Potentials, 49, 168 Excitability, 17, 169, 184, 193 Excitatory, 86, 87, 169, 172, 178 Excitatory Amino Acids, 87, 169 Exercise Test, 169 Exercise Tolerance, 33, 169 Exocrine, 158, 169, 187 Exogenous, 155, 166, 169, 172, 192 Expectorant, 85, 149, 169 Expiration, 7, 169, 195 Expiratory, 17, 169 External-beam radiation, 169, 177, 193, 204 Extracellular, 153, 161, 169, 182, 197 Extracellular Space, 169, 182 Extraction, 22, 29, 35, 36, 38, 84, 90, 102, 106, 169 Extrapyramidal, 151, 165, 169 Exudate, 169, 186 F Faecal, 164, 169 Family Planning, 127, 169 Fat, 152, 154, 155, 162, 169, 179, 195, 196, 197, 199 Fatigue, 169, 173, 188 Fatty acids, 170, 172, 179 Feces, 161, 169, 170, 199 Fentanyl, 6, 10, 38, 60, 170 Fibrosis, 148, 170, 196 Fistula, 170, 186 Flame Ionization, 54, 170 Flatus, 170, 171 Fluorescence, 29, 55, 170 Fluoxetine, 12, 82, 170 Flurazepam, 132, 170 Flurbiprofen, 26, 37, 170 Forearm, 155, 170 Fungi, 83, 161, 170, 182, 204 G Gallbladder, 147, 154, 158, 164, 170, 171 Gamma Rays, 170, 193, 194 Gamma-Endorphin, 170 Ganglia, 147, 151, 167, 170, 179, 184, 200 Ganglioside, 86, 170
Gap Junctions, 170, 200 Gas exchange, 171, 195 Gastric, 19, 144, 153, 171, 173, 174, 191 Gastric Emptying, 19, 171 Gastrin, 171, 174 Gastroenterology, 20, 57, 133, 171 Gastrointestinal, 4, 32, 61, 65, 91, 156, 158, 165, 168, 171, 179, 191, 196, 198, 199 Gastrointestinal tract, 168, 171, 179, 196, 198 Gastrointestinal Transit, 65, 171 Gelatin, 81, 171, 172, 199, 201 Gene, 110, 148, 154, 171, 178, 186 Generator, 17, 171 Genetics, 7, 161, 171 Genital, 171, 203 Genotype, 171, 189 Giardiasis, 171, 181 Gland, 147, 162, 171, 187, 189, 196, 199 Glomerular, 171, 195 Glomerulus, 171, 184 Glucocorticoid, 171, 191 Glucose, 158, 164, 171, 173, 194 Glucuronic Acid, 172, 203 Glucuronides, 23, 29, 45, 47, 101, 172 Glucuronosyltransferase, 72, 172 Glutamate, 86, 164, 172, 189 Glutathione Peroxidase, 172, 196 Glutethimide, 36, 43, 66, 172 Glycine, 154, 172, 196 Governing Board, 172, 190 Grade, 26, 172 Graft, 172, 174, 175 Graft Rejection, 172, 175 Gram-negative, 172, 186 Gram-positive, 172, 186 Granulocytes, 172, 197, 204 Gravis, 172, 184 Groin, 172, 176 Growth, 39, 51, 148, 150, 152, 153, 157, 158, 172, 180, 184, 186, 189, 198, 202 Guanylate Cyclase, 172, 185 Guinea Pigs, 86, 173 Gynaecological, 71, 173 H Habitual, 3, 158, 173 Hair Color, 10, 173 Haploid, 173, 189 Headache, 23, 37, 58, 103, 118, 156, 173 Headache Disorders, 173 Heart failure, 33, 168, 173 Heartburn, 155, 173, 176
212 Codeine
Hematopoiesis, 173, 180 Heme, 12, 154, 163, 173 Hemodialysis, 33, 164, 173 Hemoglobin, 173 Hemorrhage, 162, 173 Hemostasis, 173, 197 Hepatic, 9, 29, 173 Hepatotoxicity, 9, 15, 173 Heredity, 171, 173 Heterotrophic, 170, 174 Hiccup, 158, 166, 174 Histamine, 40, 56, 57, 117, 151, 158, 174, 180, 191 Histidine, 174 Homicide, 8, 174 Homologous, 148, 174, 180, 200 Hormonal, 4, 162, 174 Hormone, 39, 162, 168, 171, 174, 186, 191, 195, 197, 198 Hormone Replacement Therapy, 39, 174 Host, 174, 175, 179, 204 Hybrid, 17, 174 Hydrocodone, 6, 9, 11, 25, 39, 40, 41, 56, 59, 60, 83, 84, 85, 88, 174 Hydrogen Peroxide, 90, 93, 95, 101, 106, 172, 174 Hydrolysis, 43, 47, 80, 100, 101, 102, 155, 158, 159, 174, 189 Hydromorphone, 11, 39, 41, 56, 60, 88, 174 Hydroxylation, 23, 83, 174 Hyperalgesia, 14, 174 Hypersensitivity, 15, 148, 149, 164, 174, 179, 195 Hypertension, 173, 174, 186, 202 Hypnotic, 118, 153, 170, 172, 174, 182, 185 Hypotension, 41, 51, 151, 154, 161, 174 I Ibuprofen, 5, 18, 20, 22, 25, 26, 35, 41, 45, 47, 50, 52, 64, 81, 85, 91, 103, 117, 174 Id, 69, 75, 82, 134, 140, 142, 175 Ileocecal Valve, 111, 175 Ileum, 157, 175 Imipramine, 32, 58, 175 Immune response, 147, 151, 162, 172, 175, 199, 204 Immune system, 175, 179, 180, 183, 203, 204 Immunity, 147, 175 Immunization, 175 Immunoassay, 10, 89, 175 Immunodeficiency, 113, 147, 175 Immunodeficiency syndrome, 113, 175
Immunoglobulin, 150, 175, 183 Immunologic, 175, 194 Immunology, 28, 30, 37, 40, 56, 57, 61, 147, 148, 175 Immunosuppressant, 4, 147, 148, 175 Immunosuppressive, 171, 175 Immunosuppressive therapy, 175 Immunotherapy, 61, 164, 175 Impairment, 6, 24, 175 Implant radiation, 175, 177, 193, 204 Impotence, 175, 188, 204 In vitro, 42, 87, 176 In vivo, 18, 176, 182 Incontinence, 168, 176 Indicative, 109, 176, 188, 203 Indigestion, 155, 176 Indomethacin, 176, 178 Induction, 49, 150, 151, 176, 191 Infarction, 46, 151, 162, 176, 182 Infection, 4, 44, 114, 147, 149, 171, 175, 176, 180, 186, 195, 199, 202, 203, 204 Infertility, 176, 203 Inflammatory bowel disease, 132, 176 Ingestion, 9, 15, 25, 64, 66, 72, 73, 176, 181, 190 Inguinal, 33, 176 Inhalation, 148, 174, 176, 190 Inlay, 176, 195 Inotropic, 165, 176 Insight, 14, 17, 176 Insomnia, 118, 176, 186, 202 Interindividual, 43, 176 Intermittent, 4, 176 Internal Medicine, 171, 176 Internal radiation, 177, 193, 204 Interstitial, 3, 111, 132, 155, 169, 177, 184, 195, 204 Intervertebral, 177, 180 Intervertebral Disk Displacement, 177, 180 Intestinal, 32, 117, 158, 177 Intestinal Pseudo-Obstruction, 117, 177 Intestine, 133, 154, 155, 171, 177, 178, 188 Intoxication, 25, 51, 103, 177, 204 Intracellular, 86, 156, 176, 177, 185, 190, 194, 196, 197 Intramuscular, 19, 48, 64, 89, 177, 188 Intrathecal, 15, 177 Intravenous, 19, 41, 51, 54, 144, 177, 188 Intrinsic, 7, 12, 148, 177 Involuntary, 177, 183, 194, 198 Ion Channels, 153, 177, 185, 200
Index 213
Ionization, 29, 38, 52, 177 Ionizing, 177, 194 Ions, 11, 153, 156, 159, 165, 166, 174, 177, 182 Irradiation, 84, 155, 177, 204 Irritable Bowel Syndrome, 133, 177 Ischemia, 170, 178 Isopropyl, 92, 178 J Joint, 153, 178, 186, 198 K Kallidin, 155, 178 Kb, 126, 178 Keratin, 178, 196 Keto, 80, 96, 97, 99, 100, 178 Ketorolac, 19, 35, 44, 66, 178 Ketorolac Tromethamine, 19, 178 Kidney Disease, 3, 126, 178 Krypton, 104, 178 Kynurenic Acid, 86, 178 L Lactulose, 57, 74, 178 Large Intestine, 157, 164, 175, 177, 178, 194, 197 Laryngeal, 7, 17, 178 Larynx, 8, 178, 201 Latent, 178, 191 Lavage, 144, 178 Laxative, 157, 178 Lens, 179, 204 Lesion, 179, 202 Leukemia, 147, 179 Leukotrienes, 152, 179 Levo, 86, 120, 165, 179, 192 Levorphanol, 87, 164, 179 Library Services, 140, 179 Lidocaine, 5, 103, 179 Life cycle, 170, 179 Ligands, 89, 179 Limbic, 16, 149, 179 Limbic System, 149, 179 Linkage, 80, 100, 158, 179 Lipid, 156, 178, 179, 182 Lipoxygenase, 133, 152, 179 Lipoxygenase Inhibitors, 133, 179 Liver Transplantation, 4, 180 Localized, 167, 176, 180, 189, 202, 203 Locomotion, 180, 189 Locomotor, 64, 180 Loperamide, 4, 74, 111, 133, 180 Loperamide hydrochloride, 133, 180 Low Back Pain, 44, 66, 180
Lumbar, 153, 177, 180 Lymphatic, 167, 176, 180 Lymphocyte, 147, 151, 180 Lymphocyte Count, 147, 180 Lymphoid, 150, 180 Lysine, 33, 44, 66, 77, 180 M Macrophage, 40, 180 Macrophage Inflammatory Protein-1, 40, 180 Malignant, 6, 33, 147, 151, 180, 184, 194 Mania, 45, 180 Manic, 104, 151, 180 Mastication, 180, 202 Mediate, 89, 165, 180 Mediator, 158, 165, 180, 197 Medicament, 87, 103, 104, 105, 180, 199 MEDLINE, 127, 180 Medullary, 18, 152, 164, 181 Meiosis, 181, 200 Melanin, 24, 181, 202 Memory, 150, 163, 181 Menstruation, 166, 181 Mental Health, iv, 5, 126, 128, 181, 192 Meperidine, 6, 14, 165, 181 Meta-Analysis, 22, 56, 64, 181 Metabolite, 28, 36, 50, 51, 82, 89, 102, 155, 164, 165, 181 Metastasis, 181, 184 Metastatic, 33, 181 Methamphetamine, 132, 181 Methanol, 22, 80, 100, 181 Methionine, 165, 181, 192 Methyl Ethers, 87, 181 Methylphenidate, 6, 11, 181 Metoclopramide, 4, 181 Metronidazole, 133, 181 MI, 44, 144, 182 Microbe, 182, 201 Microdialysis, 40, 182 Microorganism, 159, 182, 204 Microsomal, 29, 45, 182 Midazolam, 59, 68, 182 Mineralocorticoids, 147, 162, 182 Miosis, 182 Miotic, 49, 182 Mitochondrial Swelling, 182, 184 Mitosis, 152, 182 Mobility, 52, 92, 182 Modification, 83, 182, 193 Molecular, 11, 43, 127, 129, 154, 161, 162, 178, 182, 191, 194, 202
214 Codeine
Molecular Structure, 182, 202 Molecule, 107, 147, 151, 153, 157, 160, 165, 167, 174, 182, 187, 194, 197 Monoamine, 82, 149, 164, 182 Monoclonal, 4, 177, 183, 193, 204 Monocyte, 40, 183 Morphine Dependence, 86, 183 Morphine Derivatives, 93, 95, 97, 101, 183 Morphological, 148, 167, 183 Motility, 4, 32, 176, 183, 191, 197 Motion Sickness, 183, 184, 191 Motor Activity, 161, 183 Motor nerve, 183 Mucins, 183, 196 Mucosa, 158, 183, 191 Mucus, 169, 183 Multidose, 41, 183 Muscle relaxant, 92, 118, 150, 183, 184 Muscle Relaxation, 92, 183 Muscle tension, 183 Mutagenic, 148, 183 Myasthenia, 183, 184 Mydriatic, 165, 183, 204 Myocardium, 182, 183 N Naive, 60, 183 Nalbuphine, 6, 93, 95, 97, 101, 183 Naloxone, 32, 93, 95, 96, 97, 183 Naltrexone, 10, 93, 94, 95, 96, 101, 183 Narcolepsy, 33, 164, 168, 181, 184 Narcosis, 184 Narcotic Antagonists, 83, 89, 93, 96, 101, 184 Nausea, 86, 91, 151, 155, 176, 184, 186, 187, 202, 203 NCI, 1, 125, 159, 184 Necrosis, 3, 152, 176, 182, 184 Need, 3, 4, 9, 15, 88, 93, 94, 110, 113, 117, 135, 159, 184, 201 Neoplasms, 147, 151, 155, 184, 194 Neostigmine, 4, 184 Nephritis, 3, 184 Nephropathy, 3, 178, 184 Nephrotoxic, 4, 184 Nerve, 15, 147, 150, 163, 167, 180, 183, 184, 190, 191, 195, 196, 199, 202 Nervous System, 147, 149, 154, 156, 158, 159, 164, 168, 170, 179, 180, 181, 183, 184, 185, 188, 189, 190, 196, 198, 199, 200 Neural, 4, 66, 184 Neuralgia, 103, 104, 184 Neurogenic, 17, 184, 203
Neuroleptic, 151, 184, 186 Neuronal, 7, 87, 156, 184, 185 Neurons, 7, 18, 92, 159, 163, 169, 170, 183, 185, 194, 195, 200 Neurosurgery, 19, 64, 185 Neurotoxicity, 164, 185 Neurotransmitters, 169, 185 Neutrons, 155, 177, 185, 193 Neutrophils, 152, 172, 180, 185 Nicotine, 11, 133, 185 Nitrazepam, 64, 185 Nitric Oxide, 10, 185 Nitrogen, 54, 88, 94, 95, 97, 99, 104, 107, 148, 149, 150, 152, 185, 202 Norepinephrine, 147, 165, 167, 185, 189 Noscapine, 105, 185 Nuclear, 161, 167, 170, 179, 184, 185 Nuclei, 149, 161, 166, 179, 182, 185, 186, 192 Nucleic acid, 147, 185, 186, 193 Nucleus, 8, 97, 152, 159, 162, 163, 164, 170, 177, 181, 185, 186, 192, 194 O Octreotide, 4, 74, 186 Odour, 152, 186, 202 Ofloxacin, 10, 186 Oncogene, 186, 198 Ondansetron, 4, 186 On-line, 38, 143, 186 Opioid Peptides, 186 Opium, 7, 73, 80, 83, 84, 88, 94, 95, 96, 98, 99, 100, 101, 105, 133, 183, 185, 186, 187 Opportunistic Infections, 147, 186 Orderly, 11, 186 Orthostatic, 151, 186 Osteoarthritis, 31, 61, 116, 168, 186 Outpatient, 6, 13, 186 Overdose, 8, 36, 58, 67, 132, 143, 186 Oxazepam, 32, 186 Oxidation, 95, 97, 101, 105, 147, 152, 155, 163, 172, 187 Oxidation-Reduction, 155, 187 Oxides, 74, 187 Oxycodone, 5, 6, 8, 10, 11, 14, 16, 24, 39, 59, 60, 82, 83, 84, 90, 93, 95, 101, 105, 106, 187 Oxygen Consumption, 169, 187, 195 Oxytocic, 187, 198 P Paediatric, 19, 25, 27, 187 Pain Threshold, 14, 82, 91, 187 Palliative, 67, 187, 201
Index 215
Pancreas, 21, 147, 164, 171, 187, 198 Pancreatic, 158, 187 Pancreatitis, 20, 21, 48, 187 Panic, 175, 187 Panic Disorder, 175, 187 Papaverine, 105, 186, 187 Papilla, 188 Papillary, 3, 188 Parenteral, 49, 67, 105, 133, 188 Patch, 24, 28, 30, 188, 201 Pathologic, 152, 161, 174, 188, 195, 203 Pathologic Processes, 152, 188 Patient Education, 5, 132, 138, 140, 144, 188 Pelvic, 71, 188 Pemoline, 6, 188 Pentylenetetrazole, 104, 188 Peptide, 158, 170, 178, 186, 188, 192, 202 Peracetic Acid, 105, 188 Perennial, 85, 188 Perineal, 18, 41, 188 Perineum, 188 Periodontal disease, 170, 188 Periodontitis, 19, 188 Peristalsis, 165, 188 Pharmaceutical Preparations, 158, 168, 171, 188 Pharmacodynamic, 6, 41, 49, 188 Pharmacokinetic, 40, 47, 50, 188 Pharmacologic, 4, 5, 14, 150, 189, 201, 203 Pharmacotherapy, 4, 22, 23, 33, 35, 54, 64, 81, 189 Phenobarbital, 28, 132, 189 Phenotype, 25, 32, 64, 189 Phenyl, 80, 95, 99, 100, 181, 189 Phenylpropanolamine, 65, 189 Phospholipases, 189, 197 Phosphorous, 99, 189 Phosphorus, 156, 189 Physical Therapy, 5, 189 Physiologic, 148, 154, 165, 181, 189, 194, 195 Physiology, 7, 33, 39, 171, 189 Physostigmine, 184, 189 Picrotoxin, 104, 189 Pilot study, 21, 28, 64, 189 Pituitary Gland, 162, 189, 191 Plants, 73, 148, 153, 154, 157, 159, 171, 185, 189, 201 Plasma, 9, 10, 27, 28, 29, 32, 35, 38, 42, 51, 55, 62, 65, 67, 150, 171, 173, 182, 189, 190 Plasma cells, 150, 190
Platelet Activation, 190, 197 Platelet Aggregation, 185, 190 Platelets, 152, 185, 190 Poisoning, 47, 177, 184, 189, 190 Polyethylene, 81, 190 Polymorphic, 23, 30, 39, 190 Polymorphism, 34, 72, 190 Polysaccharide, 74, 151, 158, 190, 203 Pons, 190, 195 Pontine, 8, 190 Posterior, 153, 166, 187, 190 Postoperative, 4, 6, 13, 20, 22, 23, 35, 49, 52, 53, 56, 64, 67, 72, 81, 111, 168, 178, 181, 190 Postsynaptic, 190, 197, 200 Potassium, 87, 182, 190, 193 Potentiate, 82, 190 Potentiating, 82, 91, 190 Potentiation, 74, 91, 190, 197 Practice Guidelines, 128, 190 Precipitation, 94, 191 Preclinical, 9, 191 Precursor, 152, 165, 167, 170, 185, 191, 202 Predisposition, 12, 191 Prednisolone, 191 Prednisone, 4, 191 Premedication, 59, 68, 191 Presynaptic, 18, 191, 200 Prevalence, 59, 191 Probe, 72, 182, 191 Procaine, 179, 191 Proglumide, 58, 191 Progression, 3, 87, 191 Progressive, 3, 87, 157, 159, 163, 166, 172, 184, 186, 190, 191, 195 Progressive disease, 3, 191 Prolactin, 165, 191 Promethazine, 77, 158, 191 Prone, 30, 191 Pro-Opiomelanocortin, 170, 186, 191 Prophase, 192, 200 Propofol, 4, 192 Propoxyphene, 6, 47, 62, 68, 120, 192 Prospective study, 54, 192 Prostitution, 114, 192 Protein Binding, 42, 192 Protein C, 10, 15, 89, 149, 178, 192, 202 Protein S, 15, 17, 110, 154, 168, 192 Protein Subunits, 15, 192 Protons, 174, 177, 192, 193 Proximal, 165, 191, 192 Pruritic, 24, 166, 192
216 Codeine
Pruritus, 25, 151, 191, 192, 202 Psychiatric, 16, 66, 192, 200 Psychic, 192, 196 Psychomotor, 6, 11, 49, 57, 157, 184, 192 Psychotherapy, 160, 192 Psychotomimetic, 149, 164, 192 Psychotropic, 133, 192 Public Health, 9, 16, 47, 103, 110, 128, 192 Public Policy, 127, 192 Publishing, 18, 193 Pulmonary, 155, 161, 169, 179, 193, 195, 199, 203 Pulmonary Artery, 155, 193, 203 Pulmonary Ventilation, 193, 195 Pulse, 144, 193 Pupil, 165, 182, 183, 193 Purines, 193, 196 Q Quality of Life, 9, 193 Quaternary, 107, 193 Quinidine, 41, 42, 193 Quinine, 193 R Race, 85, 165, 166, 193 Radiation, 153, 169, 170, 177, 181, 193, 194, 204 Radiation therapy, 169, 177, 193, 204 Radioactive, 153, 174, 175, 177, 185, 193, 194, 204 Radioimmunotherapy, 194 Radiolabeled, 177, 193, 194, 204 Radiopharmaceutical, 171, 194 Radiotherapy, 71, 155, 177, 193, 194, 204 Randomized, 13, 18, 26, 31, 33, 41, 48, 53, 58, 67, 71, 166, 194 Randomized clinical trial, 13, 194 Raphe Nuclei, 8, 194 Rationalize, 12, 194 Reabsorption, 111, 194 Reagent, 98, 162, 194 Receptor, 7, 10, 13, 15, 86, 87, 88, 97, 151, 159, 161, 164, 165, 168, 186, 189, 194, 197 Receptors, Serotonin, 194, 197 Rectal, 19, 43, 50, 57, 60, 64, 194 Rectum, 152, 155, 164, 170, 171, 176, 178, 194, 199 Refer, 1, 160, 165, 170, 180, 183, 184, 185, 194 Reflex, 7, 31, 89, 194 Reflux, 94, 194 Refractory, 27, 194 Regimen, 166, 189, 195
Relaxant, 187, 195 Reliability, 50, 195 Remission, 147, 195 Renal failure, 3, 24, 195 Resorption, 170, 194, 195 Respiration, 33, 157, 162, 195 Respiratory System, 16, 195 Restoration, 4, 189, 195 Reticular, 92, 195 Reticular Formation, 92, 195 Retina, 179, 195, 204 Rheumatism, 24, 175, 195 Rheumatoid, 168, 195 Rheumatoid arthritis, 168, 195 Rhinitis, 158, 168, 195 Ribose, 147, 195 Rigidity, 189, 195 Risk factor, 192, 195 S Salicylate, 164, 195 Saliva, 10, 28, 54, 67, 195, 196 Salivary, 164, 195, 196 Salivary glands, 164, 195, 196 Schizoid, 196, 204 Schizophrenia, 151, 196, 204 Schizotypal Personality Disorder, 196, 204 Sclerosis, 87, 196 Screening, 159, 196 Sebaceous, 196 Sebaceous gland, 196 Sebum, 32, 65, 196 Secobarbital, 64, 196 Secretion, 32, 162, 174, 182, 183, 186, 191, 196 Secretory, 196, 200 Sedative, 11, 153, 159, 172, 175, 182, 191, 196 Seizures, 54, 103, 157, 196 Selenium, 95, 196 Semisynthetic, 164, 187, 196 Sensibility, 149, 174, 196 Serine, 12, 196 Serologic, 175, 196 Serotonin, 5, 82, 86, 118, 151, 170, 186, 189, 194, 196, 202 Serum, 25, 34, 40, 55, 64, 72, 160, 182, 196, 197 Shock, 104, 150, 197, 202 Side effect, 4, 6, 9, 13, 15, 82, 84, 86, 88, 119, 132, 133, 148, 151, 164, 197, 201 Signal Transduction, 15, 17, 197 Signs and Symptoms, 132, 195, 197, 202
Index 217
Skeletal, 58, 91, 92, 150, 162, 193, 197, 198 Skeleton, 178, 197 Skull, 162, 197, 200 Small intestine, 133, 157, 166, 171, 174, 175, 177, 197 Smooth muscle, 4, 148, 154, 156, 174, 183, 187, 197, 198, 199 Social Environment, 193, 197 Sodium, 22, 26, 65, 92, 94, 96, 98, 164, 182, 193, 194, 197, 199 Soft tissue, 61, 155, 197 Solvent, 93, 94, 95, 98, 154, 168, 181, 197 Somatostatin, 186, 198 Sparteine, 25, 34, 64, 198 Spasm, 92, 150, 152, 174, 198 Spastic, 178, 198 Spasticity, 144, 198 Spatial disorientation, 165, 198 Specialist, 134, 165, 198 Species, 96, 154, 162, 165, 168, 173, 174, 181, 182, 183, 193, 198, 199, 202, 204 Specificity, 72, 148, 152, 156, 198 Sperm, 150, 159, 198, 200, 203 Sphincter, 178, 198 Spike, 7, 198 Spinal cord, 15, 92, 153, 158, 167, 177, 184, 185, 194, 198, 200 Spondylitis, 168, 198 Sprains and Strains, 69, 180, 198 Stabilizer, 157, 198 Stem Cell Factor, 40, 159, 198 Steroid, 154, 162, 172, 198 Stimulant, 149, 156, 164, 174, 178, 181, 188, 189, 199 Stimulus, 6, 10, 166, 168, 177, 194, 199, 201 Stomach, 147, 153, 164, 168, 171, 174, 178, 184, 194, 197, 199 Stool, 57, 74, 133, 176, 177, 178, 199 Stress, 111, 157, 162, 177, 184, 191, 195, 199, 203 Striatum, 17, 199 Stupor, 184, 199 Subacute, 176, 199 Subarachnoid, 173, 199 Subclinical, 176, 196, 199 Subcutaneous, 188, 199 Subspecies, 198, 199 Substance P, 168, 181, 196, 199 Substrate, 12, 30, 179, 199 Suppositories, 46, 57, 60, 66, 171, 199 Suppression, 18, 88, 162, 199 Suppressive, 88, 199
Supraspinal, 7, 199 Surfactant, 81, 199 Sweat, 28, 58, 199 Sweat Glands, 199 Sympathetic Nervous System, 185, 200 Sympathomimetic, 149, 164, 165, 168, 181, 185, 189, 200 Symptomatic, 5, 58, 150, 187, 200 Synapses, 185, 198, 200 Synapsis, 200 Synaptic, 87, 185, 197, 200 Synaptic Transmission, 87, 185, 200 Synergistic, 9, 15, 82, 83, 191, 200 Systemic, 120, 150, 155, 168, 176, 177, 191, 193, 200, 204 T Temporal, 8, 149, 173, 200 Temporal Lobe, 149, 200 Teratogenic, 148, 200 Testicles, 200, 203 Tetrahydrocannabinol, 74, 200 Tetrahydropapaveroline, 42, 200 Thermal, 12, 36, 73, 155, 165, 185, 201 Thoracic, 68, 153, 201 Threonine, 12, 196, 201 Threshold, 169, 174, 201 Thrombin, 190, 192, 201 Thrombomodulin, 192, 201 Thrombosis, 192, 201 Tolerance, 7, 9, 10, 14, 15, 33, 84, 85, 86, 91, 92, 156, 201 Topical, 132, 168, 174, 201 Toxic, iv, 16, 86, 97, 103, 148, 153, 154, 161, 162, 175, 181, 184, 185, 196, 201 Toxicity, 47, 103, 166, 189, 201 Toxins, 151, 156, 167, 172, 176, 194, 201 Trace element, 155, 201 Trachea, 8, 156, 169, 178, 201 Tractus, 8, 201 Tramadol, 6, 19, 22, 27, 48, 56, 60, 61, 71, 83, 84, 201 Transdermal, 38, 60, 201 Transduction, 197, 201 Transfection, 154, 201 Translation, 168, 201 Translocation, 168, 202 Transmitter, 147, 153, 165, 169, 177, 180, 185, 200, 202 Transplantation, 50, 159, 175, 202 Trauma, 184, 187, 202 Triazolam, 11, 202 Trichomoniasis, 181, 202
218 Codeine
Tricyclic, 5, 175, 202 Trifluoperazine, 86, 202 Trifluoroacetic Acid, 90, 93, 101, 106, 202 Trigeminal, 104, 202 Tryptophan, 160, 196, 202 Tuberculosis, 161, 202 Tubocurarine, 184, 202 Tyrosine, 165, 202 U Ulcer, 57, 202 Unconscious, 150, 175, 194, 202 Uraemia, 187, 202 Urban Population, 50, 202 Urea, 199, 202, 203 Uremia, 195, 203 Urethra, 203 Uridine Diphosphate, 172, 203 Uridine Diphosphate Glucuronic Acid, 172, 203 Urinary, 21, 35, 36, 37, 42, 43, 61, 68, 110, 154, 163, 168, 176, 202, 203 Urinary Retention, 154, 203 Urinary tract, 203 Urology, 111, 203 Urticaria, 30, 36, 149, 158, 203 V Vaccine, 147, 203 Vascular, 148, 150, 167, 173, 176, 185, 203 Vasculitis, 187, 203 Vasectomy, 19, 203
Vasodilation, 188, 203 Vasodilator, 156, 165, 174, 188, 203 Vein, 177, 185, 203 Venom, 61, 203 Venous, 192, 203 Ventral, 8, 190, 203 Ventricle, 149, 193, 203 Venules, 155, 156, 204 Vertebrae, 177, 198, 204 Vesicular, 182, 204 Veterinary Medicine, 127, 204 Virulence, 153, 201, 204 Virus, 114, 147, 158, 201, 204 Vitreous Humor, 31, 204 Vitro, 204 Vivo, 40, 204 W Waiting Lists, 113, 204 White blood cell, 150, 180, 183, 190, 204 Withdrawal, 3, 9, 86, 104, 132, 181, 186, 204 X Xenon, 104, 204 X-ray, 170, 177, 185, 193, 194, 198, 204 X-ray therapy, 177, 204 Y Yeasts, 170, 189, 204 Yohimbine, 13, 204 Z Zymogen, 192, 204
Index 219
220 Codeine
