Hydrocodone: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

HYDROCODONE A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES

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., 1960Hydrocodone: 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: 0-597-83936-0 1. Hydrocodone-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.

Copyright Notice If a physician wishes to copy limited passages from this book for patient use, this right is automatically granted without written permission from ICON Group International, Inc. (ICON Group). However, all of ICON Group publications have copyrights. With exception to the above, copying our publications in whole or in part, for whatever reason, is a violation of copyright laws and can lead to penalties and fines. Should you want to copy tables, graphs, or other materials, please contact us to request permission (E-mail: [email protected]). ICON Group often grants permission for very limited reproduction of our publications for internal use, press releases, and academic research. Such reproduction requires confirmed permission from ICON Group International Inc. The disclaimer above must accompany all reproductions, in whole or in part, of this book.

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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 hydrocodone. 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 HYDROCODONE ........................................................................................ 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Hydrocodone ................................................................................. 4 The National Library of Medicine: PubMed .................................................................................. 8 CHAPTER 2. NUTRITION AND HYDROCODONE .............................................................................. 17 Overview...................................................................................................................................... 17 Finding Nutrition Studies on Hydrocodone ................................................................................ 17 Federal Resources on Nutrition ................................................................................................... 20 Additional Web Resources ........................................................................................................... 20 CHAPTER 3. DISSERTATIONS ON HYDROCODONE.......................................................................... 23 Overview...................................................................................................................................... 23 Dissertations on Hydrocodone ..................................................................................................... 23 Keeping Current .......................................................................................................................... 23 CHAPTER 4. PATENTS ON HYDROCODONE .................................................................................... 25 Overview...................................................................................................................................... 25 Patents on Hydrocodone .............................................................................................................. 25 Patent Applications on Hydrocodone .......................................................................................... 30 Keeping Current .......................................................................................................................... 33 CHAPTER 5. PERIODICALS AND NEWS ON HYDROCODONE .......................................................... 35 Overview...................................................................................................................................... 35 News Services and Press Releases................................................................................................ 35 Academic Periodicals covering Hydrocodone .............................................................................. 36 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 39 Overview...................................................................................................................................... 39 U.S. Pharmacopeia....................................................................................................................... 39 Commercial Databases ................................................................................................................. 40 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 45 Overview...................................................................................................................................... 45 NIH Guidelines............................................................................................................................ 45 NIH Databases............................................................................................................................. 47 Other Commercial Databases....................................................................................................... 50 APPENDIX B. PATIENT RESOURCES ................................................................................................. 51 Overview...................................................................................................................................... 51 Patient Guideline Sources............................................................................................................ 51 Finding Associations.................................................................................................................... 53 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 55 Overview...................................................................................................................................... 55 Preparation................................................................................................................................... 55 Finding a Local Medical Library.................................................................................................. 55 Medical Libraries in the U.S. and Canada ................................................................................... 55 ONLINE GLOSSARIES.................................................................................................................. 61 Online Dictionary Directories ..................................................................................................... 61 HYDROCODONE DICTIONARY ............................................................................................... 63 INDEX ................................................................................................................................................ 85

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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 hydrocodone 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 hydrocodone, 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 hydrocodone, 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 hydrocodone. 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 Hydrocodone, 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 hydrocodone. 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 HYDROCODONE Overview In this chapter, we will show you how to locate peer-reviewed references and studies on hydrocodone.

The Combined Health Information Database The Combined Health Information Database summarizes studies across numerous federal agencies. To limit your investigation to research studies and hydrocodone, 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 “hydrocodone” (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: •

Drug/Nutrient Interactions Involving Twenty of the Most Commonly Prescribed Medications in the United States Source: Journal of Practical Hygiene. 9(1): 39-48. January-February 2000. Contact: Available from Montage Media Corporation. 1000 Wyckoff Avenue, Mahwah, NJ 07430-3164. (201) 891-3200. Summary: The increased use of prescribed medication in the United States has established the need for dental professionals to understand the possible interactions between medications and nutrients. This article discusses interactions between nutrients and the 20 most commonly prescribed medications in 1998: conjugated estrogen, levothyroxine, amoxicillin, hydrocodone, fluoxetine, omeprazole, azithromycin, atorvastin, amlodipine, loratine, digoxin, sertaline, aerosol, paroxetine, amoxicillin,

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lisinopril, enalapril, amoxicillin clavulanate potassium, and cephalexin. In addition, a discussion of practical considerations for the dental hygiene practice is provided. The authors stress that thoroughly completing and reviewing the dental patient's medical and drug history, as well as conducting a diet assessment, are methods by which the dental hygienist can determine if a patient's health is at risk due to drug and nutrient interactions. 3 figures. 2 tables. 38 references.

Federally Funded Research on Hydrocodone The U.S. Government supports a variety of research studies relating to hydrocodone. 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 hydrocodone. 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 hydrocodone. The following is typical of the type of information found when searching the CRISP database for hydrocodone: •

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

2 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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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 •

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

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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 •

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 2003; Project Start 01-MAY-1995; Project End 30-JUN-2008 Summary: (provided by applicant): Opioid abuse remains a significant public health problem despite continued research and the availability of new drugs for treatment. In addition to the ongoing problem of heroin abuse is a growing concern about the recreational use of potent, efficacious opioid analgesics such as oxycodone. This is a competing continuation of a grant that has developed novel drug discrimination procedures for studying opioid dependence and withdrawal; those procedures have been used in concert with other measures of opioid activity to examine a range of pharmacologic and behavioral parameters that contribute to the abuse and dependence liability of morphine and related opioids. Studies proposed in this renewal exploit these discrimination procedures to focus on the neuropharmacology of opioid dependence and withdrawal as well as the role of opioid withdrawal in drug taking. AIM I characterizes the neuropharmacology of opioid withdrawal in rhesus monkeys by examining monoaminergic drugs for their ability to modulate discriminative stimulus and other effects (directly observable and HPA activation) of opioid withdrawal in monkeys. These studies build upon published data from this laboratory showing that dopamine uptake blockers attenuate discriminative stimulus and not other indices of withdrawal. AIM II combines a well-established drug discrimination procedure with i.v. self administration in monkeys to examine the effects of withdrawal on self administration of cocaine and mu agonists that vary in efficacy. AIM III provides a comprehensive set of descriptive data from rhesus monkeys on the behavioral pharmacology of several prescription opioids that are believed to be increasingly abused, including oxycodone, oxymorphone, hydrocodone and hydromorphone. While it is assumed that these opioids have exclusively morphine-like actions, there are limited data available to support that view. The four opioids will be compared to morphine using measures of drug discrimination, antinociception, and respiration. Finally, studies under AIM IV investigate the relationship between opioid tolerance and dependence, on the one hand, and constitutive activity and inverse agonism at opioid receptors, on the other hand, using drug discrimination procedures in pigeons with varying degrees of morphine tolerance and dependence. These studies should provide insight to the lasting neurobiological changes that can occur as a consequence of chronic drug treatment. Collectively these studies will apply drug discrimination and other procedures to important question regarding opioid dependence, withdrawal and abuse and will provide information that will facilitate the development of new therapeutics for opioid abuse. 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

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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 (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: MECHANISM DYSFUNCTION

OF

OPIATE

INDUCED

AUDIOVESTIBULAR

Principal Investigator & Institution: Ishiyama, Gail P.; Surgery; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-JUL-2002; Project End 30-JUN-2007 Summary: (provided by applicant): The focus of this project will be the cellular and molecular mechanism mediating opiate-induced deafness and vestibular dysfunction. Profound bilateral deafness requiring cochlear implantation secondary to chronic high dose use of acetaminophen/hydrocodone has been reported by our Neurotology Clinic. Heroin and propoxyphene have also been associated with profound deafness and vestibular dysfunction. These experiments will test the hypotheses that: 1) There is a differential expression of opioid receptor mRNA in the rat and human auditory and vestibular periphery. 2) There is conservation of mRNA opioid receptor expression between rodent and human. 3) There is a higher degree of opioid receptor expression in the auditory than vestibular periphery. 4) NMDA and opioid receptors colocalize within the inner cochlear and type I vestibular hair cell. 5) Activation of opioid receptors in the inner ear will induce similar changes in cellular signaling pathways as activation in the central nervous system. 6) Chronic opiates induce opioid receptor mediated supersensitivity state, characterized by increased activation of adenylate cyclase, cAMPresponse element binding protein (CREB), mitogen- activated kinase (MAP kinase), and Akt (a serine/threonine protein kinase). In order to accomplish these objectives, inner ear tissues will be used for reverse-transcription-polymerase chain reaction (RT-PCR), in situ hybridization, immunohistochernistry, morphological studies, and biochemical assays in both in vitro and in vivo models of acute and chronic opiate use. Information gained during the five year period will also provide basic science data relevant to the

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normal function of opioid signaling in the audiovestibular periphery. The mentored clinical scientist development award (MCSDA) is critical for the principal investigator to master the molecular and cellular biological techniques needed to establish herself as an academic neurotologist as it allows protected and mentored time. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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.3 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 hydrocodone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “hydrocodone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for hydrocodone (hyperlinks lead to article summaries): •

A comparison of oral ketorolac and hydrocodone-acetaminophen for analgesia after ambulatory surgery: arthroscopy versus laparoscopic tubal ligation. Author(s): White PF, Joshi GP, Carpenter RL, Fragen RJ. Source: Anesthesia and Analgesia. 1997 July; 85(1): 37-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9212119&dopt=Abstract

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A double-blind, single-dose comparison of the analgesic efficacy of tramadol/acetaminophen combination tablets, hydrocodone/acetaminophen combination tablets, and placebo after oral surgery. Author(s): Fricke JR Jr, Karim R, Jordan D, Rosenthal N. Source: Clinical Therapeutics. 2002 June; 24(6): 953-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117085&dopt=Abstract

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A phase II study of hydrocodone for cough in advanced cancer. Author(s): Homsi J, Walsh D, Nelson KA, Sarhill N, Rybicki L, Legrand SB, Davis MP. Source: Am J Hosp Palliat Care. 2002 January-February; 19(1): 49-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12171425&dopt=Abstract

3 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 pilot study comparing ketoprofen and acetaminophen with hydrocodone for the relief of postoperative periodontal discomfort. Author(s): Reed KL, Smith JR, Lie T, Adams DF. Source: Anesthesia Progress. 1997 Spring; 44(2): 49-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9481960&dopt=Abstract

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Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain. Author(s): Wideman GL, Keffer M, Morris E, Doyle RT Jr, Jiang JG, Beaver WT. Source: Clinical Pharmacology and Therapeutics. 1999 January; 65(1): 66-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9951432&dopt=Abstract

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Analgesic efficacy of a hydrocodone with ibuprofen combination compared with ibuprofen alone for the treatment of acute postoperative pain. Author(s): Sunshine A, Olson NZ, O'Neill E, Ramos I, Doyle R. Source: Journal of Clinical Pharmacology. 1997 October; 37(10): 908-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9505982&dopt=Abstract

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Capillary GLC assay for carbinoxamine and hydrocodone in human serum using nitrogen-sensitive detection. Author(s): Hoffman DJ, Leveque MJ, Thomson T. Source: Journal of Pharmaceutical Sciences. 1983 November; 72(11): 1342-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6644600&dopt=Abstract

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Characterizing the subjective, psychomotor, and physiological effects of a hydrocodone combination product (Hycodan) in non-drug-abusing volunteers. Author(s): Zacny JP. Source: Psychopharmacology. 2003 January; 165(2): 146-56. Epub 2002 October 29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12404072&dopt=Abstract

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Cognitive and motor function after administration of hydrocodone bitartrate plus ibuprofen, ibuprofen alone, or placebo in healthy subjects with exercise-induced muscle damage: a randomized, repeated-dose, placebo-controlled study. Author(s): Allen GJ, Hartl TL, Duffany S, Smith SF, VanHeest JL, Anderson JM, Hoffman JR, Kraemer WJ, Maresh CM. Source: Psychopharmacology. 2003 March; 166(3): 228-33. Epub 2003 January 28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12552363&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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Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of moderate or severe acute low back pain. Author(s): Palangio M, Morris E, Doyle RT Jr, Dornseif BE, Valente TJ. Source: Clinical Therapeutics. 2002 January; 24(1): 87-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833838&dopt=Abstract

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Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain. Author(s): Palangio M, Wideman GL, Keffer M, Landau CJ, Morris E, Doyle RT Jr, Jiang JG, Damask M, de Padova A. Source: Clinical Therapeutics. 2000 May; 22(5): 600-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10868557&dopt=Abstract

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Comparative metabolism of hydrocodone in man, rat, guinea pig, rabbit, and dog. Author(s): Cone EJ, Darwin WD, Gorodetzky CW, Tan T. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1978 JulyAugust; 6(4): 488-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=28931&dopt=Abstract

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Comparison of oral ketorolac and hydrocodone for pain relief after anterior cruciate ligament reconstruction. Author(s): Barber FA, Gladu DE. Source: Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 1998 September; 14(6): 605-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9754479&dopt=Abstract

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CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Author(s): Otton SV, Schadel M, Cheung SW, Kaplan HL, Busto UE, Sellers EM. Source: Clinical Pharmacology and Therapeutics. 1993 November; 54(5): 463-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7693389&dopt=Abstract

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Deafness associated with abuse of hydrocodone/acetaminophen. Author(s): Oh AK, Ishiyama A, Baloh RW. Source: Neurology. 2000 June 27; 54(12): 2345. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10881270&dopt=Abstract

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Death associated with inadvertent hydrocodone overdose in a child with a respiratory tract infection. Author(s): Morrow PL, Faris EC. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 1987 March; 8(1): 60-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3554987&dopt=Abstract

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Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain. Author(s): Palangio M, Wideman GL, Keffer M, Landau CJ, Morris E, Doyle RT Jr, Jiang JG, Damask M, de Padova A. Source: Clinical Therapeutics. 2000 August; 22(8): 990-1002. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10972635&dopt=Abstract

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Effects of hydrocodone bitartrate on breathing pattern of patients with chronic obstructive pulmonary disease and restrictive lung disease. Author(s): Sackner MA. Source: The Mount Sinai Journal of Medicine, New York. 1984 April; 51(2): 222-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6610123&dopt=Abstract

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Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults. Author(s): Gimbel JS, Brugger A, Zhao W, Verburg KM, Geis GS. Source: Clinical Therapeutics. 2001 February; 23(2): 228-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11293556&dopt=Abstract

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Forensic drug testing for opiates. VI. Urine testing for hydromorphone, hydrocodone, oxymorphone, and oxycodone with commercial opiate immunoassays and gas chromatography-mass spectrometry. Author(s): Smith ML, Hughes RO, Levine B, Dickerson S, Darwin WD, Cone EJ. Source: Journal of Analytical Toxicology. 1995 January-February; 19(1): 18-26. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7536861&dopt=Abstract

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Gas chromatographic determination of hydrocodone in serum. Author(s): Barnhart JW, Caldwell WJ. Source: Journal of Chromatography. 1977 January 11; 130: 243-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=856847&dopt=Abstract

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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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Hiccup and apparent myoclonus after hydrocodone: review of the opiate-related hiccup and myoclonus literature. Author(s): Lauterbach EC. Source: Clinical Neuropharmacology. 1999 March-April; 22(2): 87-92. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10202603&dopt=Abstract

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Hydrocodone for cough in advanced cancer. Author(s): Homsi J, Walsh D, Nelson KA, LeGrand SB, Davis M. Source: Am J Hosp Palliat Care. 2000 September-October; 17(5): 342-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11886059&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

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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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Hydromorphone detected in bile following hydrocodone ingestion. Author(s): Park JI, Nakamura GR, Griesemer EC, Noguchi TT. Source: J Forensic Sci. 1982 January; 27(1): 223-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6178789&dopt=Abstract

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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

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Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability. Author(s): Kaplan HL, Busto UE, Baylon GJ, Cheung SW, Otton SV, Somer G, Sellers EM. Source: The Journal of Pharmacology and Experimental Therapeutics. 1997 April; 281(1): 103-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9103485&dopt=Abstract

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Methodological considerations in the evaluation of analgesic combinations: acetaminophen (paracetamol) and hydrocodone in postpartum pain. Author(s): Beaver WT, McMillan D. Source: British Journal of Clinical Pharmacology. 1980 October; 10 Suppl 2: 215S-223S. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7192153&dopt=Abstract

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Pain relief after dental impaction surgery using ketorolac, hydrocodone plus acetaminophen, or placebo. Author(s): Fricke J, Halladay SC, Bynum L, Francisco CA. Source: Clinical Therapeutics. 1993 May-June; 15(3): 500-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8364942&dopt=Abstract

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Postmortem oxycodone and hydrocodone blood concentrations. Author(s): Spiller HA. Source: J Forensic Sci. 2003 March; 48(2): 429-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12665006&dopt=Abstract

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Profound hearing loss associated with hydrocodone/acetaminophen abuse. Author(s): Friedman RA, House JW, Luxford WM, Gherini S, Mills D. Source: The American Journal of Otology. 2000 March; 21(2): 188-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10733182&dopt=Abstract

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Quantification of the O- and N-demethylated metabolites of hydrocodone and oxycodone in human liver microsomes using liquid chromatography with ultraviolet absorbance detection. Author(s): Menelaou A, Hutchinson MR, Quinn I, Christensen A, Somogyi AA. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 February 25; 785(1): 81-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12535841&dopt=Abstract

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Radioimmunoassay of hydromorphone and hydrocodone in human plasma. Author(s): Honigberg IL, Stewart JT. Source: Journal of Pharmaceutical Sciences. 1980 October; 69(10): 1171-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6158568&dopt=Abstract

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Simultaneous determination of hydrocodone and hydromorphone in human plasma by liquid chromatography with tandem mass spectrometric detection. Author(s): Chen YL, Hanson GD, Jiang X, Naidong W. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 March 25; 769(1): 55-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11936695&dopt=Abstract

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Simultaneous determination of hydromorphone, hydrocodone and their 6alpha- and 6beta-hydroxy metabolites in urine using selected ion recording with methane chemical ionization. Author(s): Cone EJ, Darwin WD. Source: Biomed Mass Spectrom. 1978 April; 5(4): 291. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=76483&dopt=Abstract

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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

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The detection of hydrocodone in meconium: two case studies. Author(s): Moore CM, Deitermann D, Lewis D, Leikin J. Source: Journal of Analytical Toxicology. 1995 October; 19(6): 514-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8926748&dopt=Abstract

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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

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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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Toxicity and abuse of hydrocodone bitartrate. Author(s): Morrison AB. Source: Can Med Assoc J. 1979 June 9; 120(11): 1338. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=455181&dopt=Abstract

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Tramadol or hydrocodone-acetaminophen for acute musculoskeletal pain? Author(s): Marshall RC. Source: The Journal of Family Practice. 1998 November; 47(5): 330-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9834758&dopt=Abstract

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Tramadol versus hydrocodone-acetaminophen in acute musculoskeletal pain: a randomized, double-blind clinical trial. Author(s): Turturro MA, Paris PM, Larkin GL. Source: Annals of Emergency Medicine. 1998 August; 32(2): 139-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9701294&dopt=Abstract

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CHAPTER 2. NUTRITION AND HYDROCODONE Overview In this chapter, we will show you how to find studies dedicated specifically to nutrition and hydrocodone.

Finding Nutrition Studies on Hydrocodone 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.4 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 “hydrocodone” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

4 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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Hydrocodone

The following information is typical of that found when using the “Full IBIDS Database” to search for “hydrocodone” (or a synonym): •

A comparison of oral ketorolac and hydrocodone-acetaminophen for analgesia after ambulatory surgery: arthroscopy versus laparoscopic tubal ligation. Author(s): Department of Anesthesiology and Pain Management, University of Texas Southwestern Medical Center at Dallas, 75235-9068, USA. Source: White, P F Joshi, G P Carpenter, R L Fragen, R J Anesth-Analg. 1997 July; 85(1): 37-43 0003-2999

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A double-blind, single-dose comparison of the analgesic efficacy of tramadol/acetaminophen combination tablets, hydrocodone/acetaminophen combination tablets, and placebo after oral surgery. Author(s): Austin Oral Surgery Associates, Texas 78703, USA. Source: Fricke, J R Jr Karim, R Jordan, D Rosenthal, N Clin-Ther. 2002 June; 24(6): 953-68 0149-2918

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A phase II study of hydrocodone for cough in advanced cancer. Author(s): Harry R. Horvitz Center for Palliative Medicine (a World Health Organization Demonstration Project in Palliative Medicine), Cleveland Clinic Taussig Cancer Center, Ohio, USA. Source: Homsi, J Walsh, D Nelson, K A Sarhill, N Rybicki, L Legrand, S B Davis, M P Am-J-Hosp-Palliat-Care. 2002 Jan-February; 19(1): 49-56 1049-9091

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A pilot study comparing ketoprofen and acetaminophen with hydrocodone for the relief of postoperative periodontal discomfort. Author(s): Department of Biological Structure and Function, School of Dentistry, Oregon Health Sciences University, Portland, USA. Source: Reed, K L Smith, J R Lie, T Adams, D F Anesth-Prog. 1997 Spring; 44(2): 49-54 0003-3006

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Analgesic efficacy of a combination of hydrocodone with ibuprofen in postoperative pain. Author(s): Brookwood Medical Center, Birmingham, AL, USA. Source: Wideman, G L Keffer, M Morris, E Doyle, R T Jiang, J G Beaver, W T ClinPharmacol-Ther. 1999 January; 65(1): 66-76 0009-9236

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Combination hydrocodone and ibuprofen versus combination codeine and acetaminophen for the treatment of chronic pain. Author(s): Medical Affairs Department, Knoll Pharmaceutical Company, Mount Olive, New Jersey 07828-1234, USA. [email protected] Source: Palangio, M Damask, M J Morris, E Doyle, R T Jiang, J G Landau, C J de Padova, A Clin-Ther. 2000 July; 22(7): 879-92 0149-2918

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CYP2D6 phenotype determines the metabolic conversion of hydrocodone to hydromorphone. Author(s): Clinical Research and Treatment Institute, Addiction Research Foundation of Ontario, Toronto, Canada. Source: Otton, S V Schadel, M Cheung, S W Kaplan, H L Busto, U E Sellers, E M ClinPharmacol-Ther. 1993 November; 54(5): 463-72 0009-9236

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Death associated with inadvertent hydrocodone overdose in a child with a respiratory tract infection. Source: Morrow, P L Faris, E C Am-J-Forensic-Med-Pathol. 1987 March; 8(1): 60-3 01957910

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Dose-response effect of combination hydrocodone with ibuprofen in patients with moderate to severe postoperative pain. Author(s): Medical Affairs Department, Knoll Pharmaceutical Company, Mount Olive, New Jersey 07828-1234, USA. [email protected] Source: Palangio, M Wideman, G L Keffer, M Landau, C J Morris, E Doyle, R T Jiang, J G Damask, M de Padova, A Clin-Ther. 2000 August; 22(8): 990-1002 0149-2918

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Effect of cytochrome P450 2D1 inhibition on hydrocodone metabolism and its behavioral consequences in rats. Author(s): Addiction Research Foundation, Toronto, Ontario, Canada. Source: Tomkins, D M Otton, S V Joharchi, N Li, N Y Balster, R F Tyndale, R F Sellers, E M J-Pharmacol-Exp-Ther. 1997 March; 280(3): 1374-82 0022-3565

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Efficacy and tolerability of celecoxib versus hydrocodone/acetaminophen in the treatment of pain after ambulatory orthopedic surgery in adults. Author(s): Arizona Research Center LLC, Phoenix 85023, USA. [email protected] Source: Gimbel, J S Brugger, A Zhao, W Verburg, K M Geis, G S Clin-Ther. 2001 February; 23(2): 228-41 0149-2918

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Hydrocodone for cough in advanced cancer. Author(s): Horvitz Center for Palliative Medicine, The Cleveland Clinic Taussig Cancer Center, Ohio, USA. Source: Homsi, J Walsh, D Nelson K, A LeGrand S, B Davis, M Am-J-Hosp-Palliat-Care. 2000 Sep-October; 17(5): 342-6 1049-9091

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Hydrocodone versus codeine in acute musculoskeletal pain. Author(s): University of Pittsburgh Affiliated Residency in Emergency Medicine, Pennsylvania. Source: Turturro, M A Paris, P M Yealy, D M Menegazzi, J J Ann-Emerg-Med. 1991 October; 20(10): 1100-3 0196-0644

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Inhibition of cytochrome P450 2D6 metabolism of hydrocodone to hydromorphone does not importantly affect abuse liability. Author(s): Biobehavioural Research Department, Women's College Hospital, Toronto, Ontario, Canada. Source: Kaplan, H L Busto, U E Baylon, G J Cheung, S W Otton, S V Somer, G Sellers, E M J-Pharmacol-Exp-Ther. 1997 April; 281(1): 103-8 0022-3565

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Inhibitors of cytochrome P450 differentially modify discriminative-stimulus and antinociceptive effects of hydrocodone and hydromorphone in rhesus monkeys. Author(s): Department of Pharmacology and Neuroscience Center of Excellence, Louisiana State University Medical Center, New Orleans 70112, USA. Source: Lelas, S Wegert, S Otton, S V Sellers, E M France, C P Drug-Alcohol-Depend. 1999 May 3; 54(3): 239-49 0376-8716

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Tramadol or hydrocodone-acetaminophen for acute musculoskeletal pain? Author(s): Naval Hospital, Bremerton, Washington, USA. [email protected] Source: Marshall, R C J-Fam-Pract. 1998 November; 47(5): 330-1 0094-3509

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Tramadol versus hydrocodone-acetaminophen in acute musculoskeletal pain: a randomized, double-blind clinical trial. Author(s): Department of Emergency Medicine, The Mercy Hospital of Pittsburgh, PA, USA. [email protected] Source: Turturro, M A Paris, P M Larkin, G L Ann-Emerg-Med. 1998 August; 32(2): 13943 0196-0644

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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

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The following is a specific Web list relating to hydrocodone; 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 Sprains and Strains Source: Healthnotes, Inc.; www.healthnotes.com

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CHAPTER 3. DISSERTATIONS ON HYDROCODONE Overview In this chapter, we will give you a bibliography on recent dissertations relating to hydrocodone. We will also provide you with information on how to use the Internet to stay current on dissertations. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical dissertations that use the generic term “hydrocodone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hydrocodone, we have not necessarily excluded nonmedical dissertations in this bibliography.

Dissertations on Hydrocodone ProQuest Digital Dissertations, the largest archive of academic dissertations available, is located at the following Web address: http://wwwlib.umi.com/dissertations. From this archive, we have compiled the following list covering dissertations devoted to hydrocodone. You will see that the information provided includes the dissertation’s title, its author, and the institution with which the author is associated. The following covers recent dissertations found when using this search procedure: •

Inflammatory Cytokine, Adrenal and Autonomic Hormonal Responses to Eccentric Exercise-induced Muscle Damage: Influence of Ibuprofen and Hydrocodone Bitartrate with Ibuprofen by Scheett, Timothy Paul; PhD from The University of Connecticut, 2002, 226 pages http://wwwlib.umi.com/dissertations/fullcit/3062097

Keeping Current Ask the medical librarian at your library if it has full and unlimited access to the ProQuest Digital Dissertations database. From the library, you should be able to do more complete searches via http://wwwlib.umi.com/dissertations.

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CHAPTER 4. PATENTS ON HYDROCODONE 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.5 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 “hydrocodone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on hydrocodone, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Hydrocodone By performing a patent search focusing on hydrocodone, 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 will tell you how to obtain this information later in the chapter. The following is an 5Adapted

from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Hydrocodone

example of the type of information that you can expect to obtain from a patent search on hydrocodone: •

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 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__

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•

Fluorination of precursors for fluorine analogs of hydrocodone and oxycodone Inventor(s): Henderson; Rosetta M. (Wilmington, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 4,236,008 Date filed: September 19, 1978 Abstract: Process of reacting hydrocodone or oxycodone salt or amide with a fluorinating agent to obtain fluorinated derivatives. Excerpt(s): This invention relates to a fluorination process for production of precursors for fluorine analogs of hydrocodone and oxycodone. The latter exhibit analgesic and/or narcotic antagonist properties in mammals. Morphine and codeine analgesics exhibit toxic properties or have addictive action. Considerable effort has been made to find derivatives that are free from these qualities and still have analgesic effects. Compounds which are narcotic antagonists are also useful in medicine, such as treatment of addicts. According to published reports, "diethylaminosulfur trifluoride (DAST) is a convenient reagent for replacing the carbonyl oxygen of aldehydes and ketones with two fluorine atoms." W. J. Middleton, J. Org. Chem., 40, 574 (1975), "New Fluorinating Reagents, Dialkylaminosulfur Fluorides." L. N. Markovskij, V. E. Pashinnik, and A. V. Kirsanov, Synthesis, 787 (1973). Middleton used CCl.sub.3 F, diglyme, methylene chloride, and benzene as reaction solvents and temperatures from 25.degree. to 85.degree. C. The Russian Workers used no added solvents; the carbonyl compound and dialkylaminosulfur trifluoride were simply mixed in equal molar amounts and heated. In accordance with the process of the invention, many cyclic and acyclic ketones are transformed by DAST into vinyl fluorides as well as gem-difluorides. Web site: http://www.delphion.com/details?pn=US04236008__

•

Fluoro analogs of hydrocodone and oxycodone useful as analgesics, narcotic antagonists or both Inventor(s): Boswell, Jr.; George A. (Wilmington, DE), Henderson; Rosetta M. (Wilmington, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 4,241,065 Date filed: July 2, 1979 Abstract: 6-Fluoro analogs of hydrocodone and oxycodone are analgesics and/or narcotic antagonists. Exemplary are 17-cyclopropylmethyl-4,5-epoxy-6,6-difluoro-3methoxymorphinan and 17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-6-fluoro-3methoxy- and -3-acetoxymorphinan. Excerpt(s): This invention relates to fluorine analogs of hydrocodone and oxycodone and their analgesic and/or narcotic antagonist properties in mammals. Morphine and codeine analgesics exhibit toxic properties or have addictive action. Considerable effort has been made to find derivatives that are free from these qualities and still have analgesic effects. Compounds which are narcotic antagonists are also useful in medicine, such as treatment of addicts. and pharmaceutically acceptable salts of the compound. Web site: http://www.delphion.com/details?pn=US04241065__

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•

Hydrocodone/ibuprofen pharmaceutical compositions and method Inventor(s): Arnold; John D. (Kansas City, MO) Assignee(s): Brighton Pharmaceutical, Inc. (Kansas City, MO) Patent Number: 4,587,252 Date filed: December 18, 1984 Abstract: Pharmaceutical compositions containing hydrocodone or a pharmaceutically acceptable acid addition salt thereof and ibuprofen or a pharmaceutically acceptable salt thereof are useful in treating pain in mammals. Excerpt(s): This invention relates to pharmaceutical compositions possessing analgesic activity. Hydrocodone (7,8-dihydrocodienone) is a centrally acting narcotic analgesic agent with actions qualitatively similar to those of codeine. The compound is 4,5-alphaepoxy-3-methoxy-17-methylmorphinan-6-one. The preparation of hydrocodone and its pharmaceutically acceptable acid addition salts are described in, for example, Pfister and Tischler, U.S. Pat. No. 2,715,626, Merck Index, (Ninth Edition) Entry No. 4672 (1976). Ibuprofen is an antiinflammatory agent and has also been recommended for the relief of pain in man and animals. The compound is 2-(4-isobutylphenyl)propionic acid and it is described, together with its pharmaceutically acceptable salts, in, for example, U.K. Patent Specification No. 971,700. This invention provides a combination of these two agents. The combination provides an analgesic effect greater than that obtained by increasing the dose of either constituent administered alone. The adverse effects produced by such combination are considered to be less than those produced by an equi-analgesic dose of one of the constituents. Web site: http://www.delphion.com/details?pn=US04587252__

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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

Patents 29

(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__ •

Morphinone reductase for the preparation of hydromorphone and hydrocodone Inventor(s): Bruce; Neil C. (Cambridge, GB), French; Christopher E. (Palmerston North, NZ), Hailes; Anne M. (Erith, GB) Assignee(s): MacFarlan Smith Limited (Edinburgh, GB) Patent Number: 5,571,685 Date filed: November 30, 1994 Abstract: A morphinone reductase enzyme and related process provide for the preparation of hydromorphone from morphinone and hydrocodone from neopinone or codeinone. The enzyme has no significant activity with compounds of similar ring structure, has a molecular weight of approximately 81 kilodaltons and is composed of two identical subunits. The enzyme uses NADH as a cofactor and displays no significant enzymatic activity in the reverse direction. Excerpt(s): This invention relates to a new enzyme and to its use. Current synthesises of the analgesic hydromorphone (dihydromorphinone) and the antitussive hydrocodone (dihydrocodeinone) use uneconomic reagents, chemical catalysts and activating groups, and have undesirable effects on the environment. For example, hydromorphone is made by catalytic reduction of morphine with finely-divided platinum or palladium in acidic media. The product is purified by the addition of sulphur dioxide gas to saturation point. This mixture is left to crystallise over a period of 4-5 days, the complex is filtered, dried, and then decomposed by heating at 90.degree. C. in concentrated hydrochloric acid until sulphur dioxide evolution ceases. Biocatalysts can provide a cleaner technology. However, the range of enzyme activities presently available is rather limited, and these enzymes do not catalyse the reaction required. Web site: http://www.delphion.com/details?pn=US05571685__

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Preparation of narcotic analgesics Inventor(s): Kant; Joydeep (Cherry Hill, NJ), Mudryk; Bogdan (Downingtown, PA), Sapino; Chester (Sewell, NJ) Assignee(s): Johnson Matthey Public Limited Company (London, GB2) Patent Number: 5,847,142 Date filed: April 3, 1997 Abstract: A novel process for preparing narcotic analgesics such as hydrocodone and hydromorphone using catalytic amounts of homogeneous organometallic complexes is disclosed. Excerpt(s): The present invention relates to a novel process for preparing narcotic analgesics such as hydrocodone and hydromorphone using catalytic amounts of homogeneous organometallic complexes. Hydrocodone and hydromorphone are both

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Hydrocodone

semi-synthetic opioid analgesics with multiple actions qualitatively similar to those of codeine and morphine, involving the central nervous system and smooth muscle. The precise mechanism of action of these opiates is not known, although it is believed to relate to the existence of opiate receptors in the central nervous system. Both hydrocodone and hydromorphone have been prepared in the past by a variety of processes including hydrogenation of codeinone (Arch. Pharm. (1920), 258, 295), oxidation of dihydrocodeine (DE 415097; U.S. Pat. No. 2,715,626), oxidation of dihydromorphine (J. Org. Chem. (1950) 15, 1103, U.S. Pat. No. 2,628,962; U.S. Pat. No. 2,654,756; U.S. Pat. No. 2,649,454), by electrolytic reduction of morphine (J. Pharm. Soc. Japan (1936), 56, 44 and (1942), 62, 347) or by catalytic rearrangement of either codeine or morphine (DE 623821, Appl. Radiat. Isot. (1987) 38, 651). However, all these processes involve a two-step process which is not cost-effective. Web site: http://www.delphion.com/details?pn=US05847142__

Patent Applications on Hydrocodone As of December 2000, U.S. patent applications are open to public viewing.6 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 hydrocodone: •

Combination sustained release-immediate release oral dosage forms with an opioid analgesic and a non-opioid analgesic Inventor(s): Jim, Fai; (Franklin Square, NY), Kao, Huaihung; (Syosset, NY), Zeng, Yadi; (Fort Lee, NJ) Correspondence: Kramer Levin Naftalis & Frankel Llp; 919 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030092724 Date filed: September 17, 2002 Abstract: The present invention relates to new and useful oral tablet compositions which include an immediate release portion having an opioid analgesic and a non-opioid analgesic, providing for a rapid onset of therapeutic effect, and a sustained release portion of an opioid analgesic and a non-opioid analgesic, providing for a relatively longer duration of therapeutic effect. A multilayer oral dosage form containing a sustained release layer, which includes oxycodone and APAP, hydrocodone and APAP, or oxymorphone and APAP, and an immediate release layer containing the same active ingredients as the sustained release layer, is also disclosed. Also disclosed are oral tablet compositions, containing a sustained release core, which includes oxycodone and APAP, hydrocodone and APAP, or oxymorphone and APAP, and an immediate release coating containing the same active ingredients as the sustained release core, are also disclosed. In addition, methods of making and using such oral tablet compositions are disclosed. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/322,667, filed Sep. 17, 2001 and U.S. Provisional Application Serial No. 60/323,546, filed Sep. 19, 2001, the specifications of which are incorporated by reference into this

6

This has been a common practice outside the United States prior to December 2000.

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application in their entirety. The present invention relates to new and useful oral tablet compositions that include an immediate release portion having a combination of an opioid analgesic and a non-opioid analgesic, which will provide a rapid onset of therapeutic effect, and a sustained release portion with a combination of an opioid analgesic and a non-opioid analgesic, which will provide for a longer duration of therapeutic effect. Sustained release oral dosage forms of therapeutically active substances are well known in the pharmaceutical arts. These dosage forms provide a relatively long duration of action as the active agent is gradually released in the gastrointestinal tract. However, they may not provide a sufficiently early onset of therapeutic effect as is commonly seen with some immediate release dosage forms. On the other hand, though immediate release dosage forms may provide early onset of activities, the duration of therapeutic effect may be relatively short, which might require repeated dosing every few hours or so. Unless the dosing of the immediate release dosage form is carefully monitored, maintaining a constant plasma level of active agents without wide fluctuations is often difficult. Hence, an orally administered tablet formulation which provides a favorable dissolution profile which may lead to a relatively constant plasma level of active agents and which provides both an early onset and a long duration of therapeutic effect would be highly desirable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Controlled release hydrocodone formulations Inventor(s): Huang, Hua-Pin; (Englewood Cliffs, NJ), Masselink, John K.; (Old Tappan, NJ), Oshlack, Benjamin; (New York, NY), Tonelli, Alfred P.; (Congers, NY) Correspondence: Davidson, Davidson & Kappel, Llc; 14th Floor; 485 Seventh Avenue; New York; NY; 10018; US Patent Application Number: 20020192277 Date filed: October 30, 2001 Abstract: A solid oral controlled-release dosage form of hydrocodone is disclosed, the dosage form comprising an analgesically effective amount of hydrocodone or a pharmaceutically acceptable salt thereof, and controlled release material. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/244,424, filed Oct. 30, 2000, which is hereby incorporated by reference. The present invention is directed to hydrocodone formulations exhibiting a therapeutic effect for at least about 24 hours or more when administered to a human patient. Once-a-day sustained release opioid formulations are disclosed in U.S. Pat. Nos. 5,478,577; 5,672,360; 5,958,459; 6,103,261; 6,143,332; 5,965,161; 5,958,452 and 5,968,551. All documents cited herein, including the foregoing, are incorporated by reference in their entireties for all purposes. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hydrocodone therapy Inventor(s): Barclay, Glen E.; (Sunnyvale, CA), Childers, Jerry D.; (Menlo Park, CA), Guittard, George V.; (Cupertino, CA), Kuczynski, Anthony L.; (Mountain View, CA), Wong, Patrick S.-L.; (Palo Alto, CA) Correspondence: Alza Corporation; P O Box 7210; Intellectual Property Department; Mountain View; CA; 940397210 Patent Application Number: 20030077320 Date filed: December 18, 2002 Abstract: A hydrocodone composition, a hydrocodone dosage form, and a method of administering hydrocodone are disclosed and indicated for hydrocodone therapy. Excerpt(s): This invention pertains to a novel therapeutic composition comprising hydrocodone. The invention concerns also a novel dosage form comprising hydrocodone. Additionally, the invention relates to a novel method of administering a dose of hydrocodone from a therapeutic composition, and to a novel method of administering a dose of hydrocodone from a dosage form that in both administrations are for producing antitussive and analgesic therapy. Hydrocodone is chemically 4,5epoxy-3-methoxy-17-methyl-morphinan-6- -one. The synthesis of hydrocodone and its pharmaceutically acceptable acid addition salts are described in U.S. Pat. No. 2,71 5,629 issued to Pfister et al, and in the Merck Index, 11th Edition, page 757, entry 4708 (1989). Hydrocodone is a narcotic antitussive and analgesic. The mechanism of physiological and pharmacological actions of hydrocodone is believed that it acts directly by depressing the cough centers for its antitussive therapy. At antitussive doses, hydrocodone exerts also analgesic effects. Hydrocodone exhibits a complex pattern of metabolism including O-demethylation, N-dimethylation and 6-keto reduction to the corresponding 6-.beta.-hydroxy metabolites. The prior art administers hydrocodone in conventional tablet and syrup forms, which forms dose-dump hydrocodone thereby providing a concentration of hydrocodone followed by an absence of hydrocodone. This pharmaceodynamic variability with its fluctuation in hydrocodone availability to hydrocodone receptor sites produces uncertainty as it is unknown if a dose of hydrocodone is present for needed therapy. The prior art is deficient in providing controlled hydrocodone therapy to a patient seeking such therapy. The pharmacological properties of hydrocodone are known in The Pharmacological Basis of Therapy, by Gilman and Rall, 8th Edition, pg. 497, (1990); and in Pharmaceutical Sciences, Remington, 17th Ed., pg. 1104, (1985). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Hydromorphone and hydrocodone compositions and methods for their synthesis Inventor(s): Gault, Robert; (Grosse Pointe Woods, MI), Harclerode, William H.; (Asbury, NJ), Sandison, Mark D.; (Dearborn, MI) Correspondence: Lahive & Cockfield; 28 State Street; Boston; MA; 02109; US Patent Application Number: 20030045720 Date filed: September 27, 2002 Abstract: A method for the preparation of a ketone from a narcotic alkaloid having an allyl alcohol moiety is disclosed. The method includes mixing the narcotic alkaloid with an acid in the presence of a catalyst wherein the method is carried out in the substantial

Patents 33

absence of hydrogen gas. The method is useful for preparing hydromorphone and hydrocodone compositions having novel impurity profiles. Compositions comprising hydromorphone and hydrocodone are also disclosed. Excerpt(s): This application claims priority to U.S. Provisional Patent Applications, Ser. Nos. 60/164,364, 60/164,505, and 60/164,536, each entitled "Method of Synthesizing Hydromorphone and Hydrocodone," and filed on Nov. 9, 1999. The entire contents of each of these three provisional applications are hereby incorporated herein by reference. Hydromorphone hydrochloride (sold as Dilaudid, Laudicon, Hydromorphan) is a narcotic analgesic and one of its principle uses is the relief of pain (Physicians Desk Reference, p. 1383; Merck Index, 4700). The precise mechanism of hydromorphone hydrochloride is not known, although it is believed to relate to the existence of opiate receptors in the central nervous system. There is no intrinsic limit to the analgesic effect of hydromorphone hydrochloride; like morphine, adequate doses will relieve even the most severe pain. Hydromorphone hydrochloride is also a centrally acting narcotic antitussive which acts directly on the cough reflex center. In addition, it produces drowsiness, changes in mood and mental clouding, depresses the respiratory center, stimulates the vomiting center, produces pinpoint constriction of the pupil, enhances parasympathetic activity, elevates cerabrospinal fluid pressure, increases biliary pressure and also produces transient hyperglycemia. 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 hydrocodone, 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 “hydrocodone” (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 hydrocodone. You can also use this procedure to view pending patent applications concerning hydrocodone. 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. PERIODICALS AND NEWS ON HYDROCODONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover hydrocodone.

News Services and Press Releases One of the simplest ways of tracking press releases on hydrocodone 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 “hydrocodone” (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 hydrocodone. 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 “hydrocodone” (or synonyms). The following was recently listed in this archive for hydrocodone: •

FDA approves Vintage's generic version of hydrocodone-acetaminophen Source: Reuters Industry Breifing Date: June 05, 2000

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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 “hydrocodone” (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 you can use this Web site’s general news search page at http://news.yahoo.com/. Type in “hydrocodone” (or synonyms). If you know the name of a company that is relevant to hydrocodone, 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 “hydrocodone” (or synonyms).

Academic Periodicals covering Hydrocodone Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to hydrocodone. In addition to

Periodicals and News

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these sources, you can search for articles covering hydrocodone 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 6. 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 hydrocodone. 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 non-profit 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 hydrocodone. 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 hydrocodone: Hydrocodone and Ibuprofen •

Systemic - U.S. Brands: Vicoprofen http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203600.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 adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by

Researching Medications

41

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.

43

APPENDICES

45

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 Institute7: •

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/

7

These publications are typically written by one or more of the various NIH Institutes.

46

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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

•

National Institute of Environmental Health Sciences (NIEHS); environmental health information available at http://www.niehs.nih.gov/external/facts.htm

•

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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47

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.8 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:9 •

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

•

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/

•

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

8

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). 9 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 Combined Health Information Database

A comprehensive source of information on clinical guidelines written for professionals is the Combined Health Information Database. You will need to limit your search to one of the following: Brochure/Pamphlet, Fact Sheet, or Information Package, and “hydrocodone” using the “Detailed Search” option. Go directly to the following hyperlink: 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 the publication date, select “All Years.” Select your preferred language and the format option “Fact Sheet.” Type “hydrocodone” (or synonyms) into the “For these words:” box. The following is a sample result: •

Drug/Nutrient Interactions Involving Twenty of the Most Commonly Prescribed Medications in the United States Source: Journal of Practical Hygiene. 9(1): 39-48. January-February 2000. Contact: Available from Montage Media Corporation. 1000 Wyckoff Avenue, Mahwah, NJ 07430-3164. (201) 891-3200. Summary: The increased use of prescribed medication in the United States has established the need for dental professionals to understand the possible interactions between medications and nutrients. This article discusses interactions between nutrients and the 20 most commonly prescribed medications in 1998: conjugated estrogen, levothyroxine, amoxicillin, hydrocodone, fluoxetine, omeprazole, azithromycin, atorvastin, amlodipine, loratine, digoxin, sertaline, aerosol, paroxetine, amoxicillin, lisinopril, enalapril, amoxicillin clavulanate potassium, and cephalexin. In addition, a discussion of practical considerations for the dental hygiene practice is provided. The authors stress that thoroughly completing and reviewing the dental patient's medical and drug history, as well as conducting a diet assessment, are methods by which the dental hygienist can determine if a patient's health is at risk due to drug and nutrient interactions. 3 figures. 2 tables. 38 references.

The NLM Gateway10 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.11 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “hydrocodone” (or synonyms) into the search box and click “Search.” The results will 10 11

Adapted from NLM: http://gateway.nlm.nih.gov/gw/Cmd?Overview.x.

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).

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49

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 202 0 429 0 0 631

HSTAT12 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.13 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.14 Simply search by “hydrocodone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

Coffee Break: Tutorials for Biologists15 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.16 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.17 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/. 12

Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html.

13

The HSTAT URL is http://hstat.nlm.nih.gov/.

14

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. 15 Adapted from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html. 16 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. 17 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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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/.

51

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 hydrocodone 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 hydrocodone. 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 hydrocodone. 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 “hydrocodone”:

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•

Other guides About Your Medicines http://www.nlm.nih.gov/medlineplus/aboutyourmedicines.html Alcohol Consumption http://www.nlm.nih.gov/medlineplus/alcoholconsumption.html Prescription Drug Abuse http://www.nlm.nih.gov/medlineplus/prescriptiondrugabuse.html Restless Legs http://www.nlm.nih.gov/medlineplus/restlesslegs.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 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 hydrocodone. 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. 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

Patient Resources

53

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to hydrocodone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with hydrocodone. 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 hydrocodone. 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 “hydrocodone” (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 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 “hydrocodone”. 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 “hydrocodone” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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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 “hydrocodone” (or a synonym) into the search box, and click “Submit Query.”

55

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.18

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

18

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)19: •

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/

19

Abstracted from http://www.nlm.nih.gov/medlineplus/libraries.html.

Finding Medical Libraries

57

•

Connecticut: Waterbury Hospital Health Center Library (Waterbury Hospital, Waterbury), http://www.waterburyhospital.com/library/consumer.shtml

•

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

•

Delaware: Lewis B. Flinn Library (Delaware Academy of Medicine, Wilmington), http://www.delamed.org/chls.html

•

Georgia: Family Resource Library (Medical College of Georgia, Augusta), http://cmc.mcg.edu/kids_families/fam_resources/fam_res_lib/frl.htm

•

Georgia: Health Resource Center (Medical Center of Central Georgia, Macon), http://www.mccg.org/hrc/hrchome.asp

•

Hawaii: Hawaii Medical Library: Consumer Health Information Service (Hawaii Medical Library, Honolulu), http://hml.org/CHIS/

•

Idaho: DeArmond Consumer Health Library (Kootenai Medical Center, Coeur d’Alene), http://www.nicon.org/DeArmond/index.htm

•

Illinois: Health Learning Center of Northwestern Memorial Hospital (Chicago), http://www.nmh.org/health_info/hlc.html

•

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

•

Kentucky: University of Kentucky - Health Information Library (Chandler Medical Center, Lexington), http://www.mc.uky.edu/PatientEd/

•

Louisiana: Alton Ochsner Medical Foundation Library (Alton Ochsner Medical Foundation, New Orleans), http://www.ochsner.org/library/

•

Louisiana: Louisiana State University Health Sciences Center Medical LibraryShreveport, http://lib-sh.lsuhsc.edu/

•

Maine: Franklin Memorial Hospital Medical Library (Franklin Memorial Hospital, Farmington), http://www.fchn.org/fmh/lib.htm

•

Maine: Gerrish-True Health Sciences Library (Central Maine Medical Center, Lewiston), http://www.cmmc.org/library/library.html

•

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/

•

Maine: Southern Maine Medical Center Health Sciences Library (Southern Maine Medical Center, Biddeford), http://www.smmc.org/services/service.php3?choice=10

•

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

•

Manitoba, Canada: J.W. Crane Memorial Library (Deer Lodge Centre, Winnipeg), http://www.deerlodge.mb.ca/crane_library/about.asp

•

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

•

Massachusetts: Baystate Medical Center Library (Baystate Health System), http://www.baystatehealth.com/1024/

•

Massachusetts: Boston University Medical Center Alumni Medical Library (Boston University Medical Center), http://med-libwww.bu.edu/library/lib.html

•

Massachusetts: Lowell General Hospital Health Sciences Library (Lowell General Hospital, Lowell), http://www.lowellgeneral.org/library/HomePageLinks/WWW.htm

•

Massachusetts: Paul E. Woodard Health Sciences Library (New England Baptist Hospital, Boston), http://www.nebh.org/health_lib.asp

•

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

•

Massachusetts: UMass HealthNet (University of Massachusetts Medical School, Worchester), http://healthnet.umassmed.edu/

•

Michigan: Botsford General Hospital Library - Consumer Health (Botsford General Hospital, Library & Internet Services), http://www.botsfordlibrary.org/consumer.htm

•

Michigan: Helen DeRoy Medical Library (Providence Hospital and Medical Centers), http://www.providence-hospital.org/library/

•

Michigan: Marquette General Hospital - Consumer Health Library (Marquette General Hospital, Health Information Center), http://www.mgh.org/center.html

•

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

•

Michigan: Sladen Library & Center for Health Information Resources - Consumer Health Information (Detroit), http://www.henryford.com/body.cfm?id=39330

•

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

•

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/

•

National: NN/LM List of Libraries Serving the Public (National Network of Libraries of Medicine), http://nnlm.gov/members/

Finding Medical Libraries

59

•

Nevada: Health Science Library, West Charleston Library (Las Vegas-Clark County Library District, Las Vegas), http://www.lvccld.org/special_collections/medical/index.htm

•

New Hampshire: Dartmouth Biomedical Libraries (Dartmouth College Library, Hanover), http://www.dartmouth.edu/~biomed/resources.htmld/conshealth.htmld/

•

New Jersey: Consumer Health Library (Rahway Hospital, Rahway), http://www.rahwayhospital.com/library.htm

•

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/

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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/

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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/

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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/

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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

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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

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MedicineNet.com Medical Dictionary (MedicineNet, Inc.): http://www.medterms.com/Script/Main/hp.asp

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Merriam-Webster Medical Dictionary (Inteli-Health, Inc.): http://www.intelihealth.com/IH/

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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/

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Rare Diseases Terms (Office of Rare Diseases): http://ord.aspensys.com/asp/diseases/diseases.asp

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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).

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

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Patient Education: Glossaries (DMOZ Open Directory Project): http://dmoz.org/Health/Education/Patient_Education/Glossaries/

•

Web of Online Dictionaries (Bucknell University): http://www.yourdictionary.com/diction5.html#medicine

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HYDROCODONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-alpha: Enzyme converting testosterone to dihydrotestosterone. [NIH] Abdomen: That portion of the body that lies between the thorax and the pelvis. [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] Adenylate Cyclase: An enzyme of the lyase class that catalyzes the formation of cyclic AMP and pyrophosphate from ATP. EC 4.6.1.1. [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] 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] 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] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] 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] 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] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments.

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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] 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 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] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [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] Amniotic Fluid: Amniotic cavity fluid which is produced by the amnion and fetal lungs and kidneys. [NIH] Amoxicillin: A broad-spectrum semisynthetic antibiotic similar to ampicillin except that its resistance to gastric acid permits higher serum levels with oral administration. [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] Ampicillin: Semi-synthetic derivative of penicillin that functions as an orally active broadspectrum antibiotic. [NIH] 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] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Annealing: The spontaneous alignment of two single DNA strands to form a double helix. [NIH]

Anterior Cruciate Ligament: A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly

Dictionary 65

between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [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] Antidepressant: A drug used to treat depression. [NIH] 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-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antimicrobial: Killing microorganisms, or suppressing their multiplication or growth. [EU] Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Aperture: A natural hole of perforation, especially one in a bone. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Auditory: Pertaining to the sense of hearing. [EU] Azithromycin: A semi-synthetic macrolide antibiotic structurally related to erythromycin. It has been used in the treatment of Mycobacterium avium intracellulare infections, toxoplasmosis, and cryptosporidiosis. [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 donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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] Bilateral: Affecting both the right and left side of body. [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

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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] Bile Ducts: Tubes that carry bile from the liver to the gallbladder for storage and to the small intestine for use in digestion. [NIH] Bile Pigments: Pigments that give a characteristic color to bile including: bilirubin, biliverdine, and bilicyanin. [NIH] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] 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] Bladder: The organ that stores urine. [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] 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] 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] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [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] Calcium: A basic element found in nearly all organized tissues. It is a member of the

Dictionary 67

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 channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] 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] Carcinogenic: Producing carcinoma. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Catalyse: To speed up a chemical reaction. [EU] 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] Celecoxib: A drug that reduces pain. Celecoxib belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is being studied for cancer prevention. [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 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] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cephalexin: A semisynthetic cephalosporin antibiotic with antimicrobial activity similar to that of cephaloridine or cephalothin, but somewhat less potent. It is effective against both gram-positive and gram-negative organisms. [NIH] Cephaloridine: A cephalosporin antibiotic. [NIH] Cephalothin: A cephalosporin antibiotic. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] 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] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [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] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH]

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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] Cochlea: The part of the internal ear that is concerned with hearing. It forms the anterior part of the labyrinth, is conical, and is placed almost horizontally anterior to the vestibule. [NIH]

Cochlear: Of or pertaining to the cochlea. [EU] Cochlear Implantation: Surgical insertion of an electronic device implanted beneath the skin with electrodes to the cochlear nerve to create sound sensation in persons with sensorineural deafness. [NIH] Cochlear Nerve: The cochlear part of the 8th cranial nerve (vestibulocochlear nerve). The cochlear nerve fibers originate from neurons of the spiral ganglion and project peripherally to cochlear hair cells and centrally to the cochlear nuclei (cochlear nucleus) of the brain stem. They mediate the sense of hearing. [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 action of another entity such as a disease-causing agent. [NIH] Computational Biology: A field of biology concerned with the development of techniques 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] Concentric: Having a common center of curvature or symmetry. [NIH] Congestion: Excessive or abnormal accumulation of blood in a part. [EU] Conjugated: Acting or operating as if joined; simultaneous. [EU] 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] 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 study: An experiment or clinical trial that includes a comparison (control) group. [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] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cryptosporidiosis: Parasitic intestinal infection with severe diarrhea caused by a protozoan, Cryptosporidium. It occurs in both animals and humans. [NIH] Curative: Tending to overcome disease and promote recovery. [EU]

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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] 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] 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] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Denaturation: Rupture of the hydrogen bonds by heating a DNA solution and then cooling it rapidly causes the two complementary strands to separate. [NIH] Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

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] Diagnostic procedure: A method used to identify a disease. [NIH] Diaphragm: The musculofibrous partition that separates the thoracic cavity from the abdominal cavity. Contraction of the diaphragm increases the volume of the thoracic cavity aiding inspiration. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Dihydromorphine: A semisynthetic analgesic used in the study of narcotic receptors. It has

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abuse potential. [NIH] Dihydrotestosterone: Anabolic agent. [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] 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] 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] Dosage Forms: Completed forms of the pharmaceutical preparation in which prescribed doses of medication are included. They are designed to resist action by gastric fluids, prevent vomiting and nausea, reduce or alleviate the undesirable taste and smells associated with oral administration, achieve a high concentration of drug at target site, or produce a delayed or long-acting drug effect. They include capsules, liniments, ointments, pharmaceutical solutions, powders, tablets, etc. [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] 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] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [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] 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] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [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] 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] 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] 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] Estrogen: One of the two female sex hormones. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Eukaryotic Cells: Cells of the higher organisms, containing a true nucleus bounded by a nuclear membrane. [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] 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] 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] Fallopian Tubes: Two long muscular tubes that transport ova from the ovaries to the uterus. They extend from the horn of the uterus to the ovaries and consist of an ampulla, an infundibulum, an isthmus, two ostia, and a pars uterina. The walls of the tubes are composed of three layers: mucosal, muscular, and serosal. [NIH] Family Planning: Programs or services designed to assist the family in controlling

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reproduction by either improving or diminishing fertility. [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. [NIH]

Fats: One of the three main classes of food and a source of energy in the body. Bile dissolves fats, and enzymes break them down. This process moves fats into cells. [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] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Flatus: Gas passed through the rectum. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [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] Food Technology: The application of knowledge to the food industry. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] 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] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [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]

Genetic testing: Analyzing DNA to look for a genetic alteration that may indicate an increased risk for developing a specific disease or disorder. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [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

Dictionary 73

participate in blood production. [NIH] Glottis: The vocal apparatus of the larynx, consisting of the true vocal cords (plica vocalis) and the opening between them (rima glottidis). [NIH] Glutamate: Excitatory neurotransmitter of the brain. [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] 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] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hepatic: Refers to the liver. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Hiccup: A spasm of the diaphragm that causes a sudden inhalation followed by rapid closure of the glottis which produces a sound. [NIH] Homogeneous: Consisting of or composed of similar elements or ingredients; of a uniform quality throughout. [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] Hydrochloric Acid: A strong corrosive acid that is commonly used as a laboratory reagent. It is formed by dissolving hydrogen chloride in water. Gastric acid is the hydrochloric acid component of gastric juice. [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] Hydromorphone: An opioid analgesic made from morphine and used mainly as an analgesic. It has a shorter duration of action than morphine. [NIH] Hyperglycemia: Abnormally high blood sugar. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic 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] 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] 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] Impaction: The trapping of an object in a body passage. Examples are stones in the bile duct or hardened stool in the colon. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] In Situ Hybridization: A technique that localizes specific nucleic acid sequences within intact chromosomes, eukaryotic cells, or bacterial cells through the use of specific nucleic acid-labeled probes. [NIH] 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] 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]

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] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Inner ear: The labyrinth, comprising the vestibule, cochlea, and semicircular canals. [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] 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]

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Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Involuntary: Reaction occurring without intention or volition. [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] 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] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Joint: The point of contact between elements of an animal skeleton with the parts that surround and support it. [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] Keto: It consists of 8 carbon atoms and within the endotoxins, it connects poysaccharide and lipid A. [NIH] Ketoprofen: An ibuprofen-type anti-inflammatory analgesic and antipyretic. It is used in the treatment of rheumatoid arthritis and osteoarthritis. [NIH] Ketorolac: A drug that belongs to a family of drugs called nonsteroidal anti-inflammatory agents. It is being studied in cancer prevention. [NIH] Labyrinth: The internal ear; the essential part of the organ of hearing. It consists of an osseous and a membranous portion. [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] Levothyroxine: Levo isomer of the thyroid hormone thyroxine. It is used for replacement therapy in reduced or absent thyroid function. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Lipid: Fat. [NIH] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [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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Localized: Cancer which has not metastasized yet. [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] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Meconium: The thick green-to-black mucilaginous material found in the intestines of a fullterm fetus. It consists of secretions of the intestinal glands, bile pigments, fatty acids, amniotic fluid, and intrauterine debris. It constitutes the first stools passed by a newborn. [NIH]

Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Meninges: The three membranes that cover and protect the brain and spinal cord. [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] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [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] 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] 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] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] 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] 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] Morphological: Relating to the configuration or the structure of live organs. [NIH]

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Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myoclonus: Involuntary shock-like contractions, irregular in rhythm and amplitude, followed by relaxation, of a muscle or a group of muscles. This condition may be a feature of some central nervous systems diseases (e.g., epilepsy, myoclonic). Nocturnal myoclonus may represent a normal physiologic event or occur as the principal feature of the nocturnal myoclonus syndrome. (From Adams et al., Principles of Neurology, 6th ed, pp102-3). [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] 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] 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] 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] 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] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [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

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the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [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] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [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] Osteoarthritis: Degeneration of articular cartilage. Primary osteoarthritis is very common in older persons, especially affecting weight-bearing joints. Articular cartilage becomes soft, frayed and thinned. [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] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] 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]

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] Palladium: A chemical element having an atomic weight of 106.4, atomic number of 46, and the symbol Pd. It is a white, ductile metal resembling platinum, and following it in abundance and importance of applications. It is used in dentistry in the form of gold, silver, and copper alloys. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Pharmaceutical Solutions: Homogeneous liquid preparations that contain one or more chemical substances dissolved, i.e., molecularly dispersed, in a suitable solvent or mixture of mutually miscible solvents. For reasons of their ingredients, method of preparation, or use, they do not fall into another group of products. [NIH]

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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] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] 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] 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]

Pilot study: The initial study examining a new method or treatment. [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 that form blood clots are in plasma. [NIH] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

Polymerase: An enzyme which catalyses the synthesis of DNA using a single DNA strand as a template. The polymerase copies the template in the 5'-3'direction provided that sufficient quantities of free nucleotides, dATP and dTTP are present. [NIH] Polymerase Chain Reaction: In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships. [NIH] Postoperative: After surgery. [NIH] Postoperative Period: The period following a surgical operation. [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] 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 convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Preclinical: Before a disease becomes clinically recognizable. [EU]

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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] 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] 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] 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] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychotomimetic: Psychosis miming. [NIH] 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 alternatives to guide and determine present and future decisions. [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] 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] Radioactive: Giving off radiation. [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] 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] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] 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

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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] 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] 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] Screening: Checking for disease when there are no symptoms. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. [NIH] Semicircular canal: Three long canals of the bony labyrinth of the ear, forming loops and opening into the vestibule by five openings. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU] Sequencing: The determination of the order of nucleotides in a DNA or RNA chain. [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 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]

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Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [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] 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] 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] 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] Strand: DNA normally exists in the bacterial nucleus in a helix, in which two strands are coiled together. [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] 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] 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] 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] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH]

Dictionary 83

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] 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] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tin: A trace element that is required in bone formation. It has the atomic symbol Sn, atomic number 50, and atomic weight 118.71. [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] 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] Toxoplasmosis: The acquired form of infection by Toxoplasma gondii in animals and man. [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] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Tubal ligation: An operation to tie the fallopian tubes closed. This procedure prevents pregnancy by blocking the passage of eggs from the ovaries to the uterus. [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] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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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] Uterus: The small, hollow, pear-shaped organ in a woman's pelvis. This is the organ in which a fetus develops. Also called the womb. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasodilator: An agent that widens blood vessels. [NIH] Vestibular: Pertaining to or toward a vestibule. In dental anatomy, used to refer to the tooth surface directed toward the vestibule of the mouth. [EU] Vestibule: A small, oval, bony chamber of the labyrinth. The vestibule contains the utricle and saccule, organs which are part of the balancing apparatus of the ear. [NIH] 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] 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] 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] 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]

85

INDEX 5 5-alpha, 28, 63 A Abdomen, 63, 75, 82 Acceptor, 63, 78 Acetaminophen, 5, 7, 8, 9, 10, 11, 13, 15, 18, 19, 35, 40, 63 Adenylate Cyclase, 7, 63 Adrenergic, 63, 70, 71, 82 Adverse Effect, 5, 28, 63, 81 Aerosol, 3, 48, 63 Affinity, 63, 69 Agonist, 26, 63, 66, 70, 77 Aldehydes, 27, 63 Algorithms, 63, 66 Alkaloid, 32, 63, 66, 68, 76 Allylamine, 63, 64 Alternative medicine, 36, 63 Amine, 26, 64 Amino Acids, 64, 71, 80, 81 Amlodipine, 3, 48, 64 Ammonia, 64 Amniotic Fluid, 64, 76 Amoxicillin, 3, 48, 64 Amphetamine, 5, 64, 69 Ampicillin, 64 Analgesic, 5, 8, 9, 13, 18, 26, 27, 28, 29, 30, 31, 32, 33, 63, 64, 66, 68, 69, 73, 75, 76, 78, 80, 83 Analog, 64, 69 Anatomical, 64, 74 Angina, 64 Angina Pectoris, 64 Anions, 64, 75 Annealing, 64, 79 Anterior Cruciate Ligament, 10, 64 Antibiotic, 64, 65, 66, 67, 71 Antibody, 63, 65, 74 Antidepressant, 65, 72 Antigen, 63, 65, 74 Anti-inflammatory, 28, 63, 65, 67, 73, 75 Anti-Inflammatory Agents, 65, 67, 75 Antimicrobial, 65, 67 Antipyretic, 5, 63, 65, 75 Antitussive, 28, 29, 32, 33, 65, 69, 78, 80 Aperture, 65, 80 Arteries, 65, 66, 68, 76 Arthroscopy, 8, 10, 18, 65

Aspartate, 65, 69 Assay, 7, 9, 65, 74 Attenuated, 5, 65 Auditory, 7, 65 Azithromycin, 3, 48, 65 B Base, 65, 75 Benzene, 27, 65 Bilateral, 7, 65 Bile, 12, 65, 66, 72, 74, 75, 76 Bile Acids, 65, 66 Bile Acids and Salts, 65, 66 Bile Ducts, 66 Bile Pigments, 66, 76 Biliary, 33, 66 Biochemical, 7, 66, 81 Biosynthesis, 66, 81 Biotechnology, 8, 36, 47, 66 Bladder, 66, 83, 84 Blood vessel, 66, 67, 71, 82, 84 Bone Marrow, 65, 66, 76 Branch, 59, 66, 77, 80, 82, 83 Breakdown, 66, 69, 72 Broad-spectrum, 64, 66 Bronchi, 66, 71, 83 Bronchitis, 66, 67 Buprenorphine, 5, 66 Butorphanol, 5, 66 C Calcium, 64, 66, 67 Calcium channel blocker, 64, 67 Capsules, 67, 70, 72 Carbon Dioxide, 67, 69, 81 Carcinogenic, 65, 67 Cardiovascular, 64, 67, 81 Catalyse, 29, 67 Catecholamine, 67, 70 Cations, 67, 75 Celecoxib, 11, 19, 67 Cell, 7, 63, 66, 67, 71, 73, 75, 77, 79, 80, 81, 83 Cell Respiration, 67, 81 Central Nervous System, 7, 30, 33, 64, 65, 67, 68, 69, 72, 76, 77, 78, 81 Cephalexin, 4, 48, 67 Cephaloridine, 67 Cephalothin, 67 Cerebral, 67, 71, 80

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Cholesterol, 65, 66, 67 Chronic, 5, 6, 7, 10, 11, 18, 66, 67, 74, 76, 82 Chronic Obstructive Pulmonary Disease, 11, 67 Clinical trial, 4, 15, 19, 47, 67, 68, 80 Cloning, 66, 67 Coal, 65, 67 Coca, 68 Cocaine, 6, 68 Cochlea, 68, 74 Cochlear, 7, 68 Cochlear Implantation, 7, 68 Cochlear Nerve, 68 Codeine, 5, 7, 10, 12, 14, 18, 19, 26, 27, 28, 30, 40, 68, 69, 73, 78 Cofactor, 29, 68, 80 Computational Biology, 47, 68 Concentric, 19, 68 Congestion, 29, 68 Conjugated, 3, 48, 66, 68, 69 Consciousness, 64, 68, 70 Constipation, 26, 68 Constriction, 6, 33, 68 Contraindications, ii, 68 Controlled study, 9, 68 Coronary, 64, 68, 76 Coronary Thrombosis, 68, 76 Cryptosporidiosis, 65, 68 Curative, 68, 83 Cyclic, 27, 63, 69 Cytochrome, 13, 19, 69 D Databases, Bibliographic, 47, 69 Demethylation, 32, 69 Denaturation, 69, 79 Dental Caries, 69, 72 Deuterium, 7, 69, 73 Dextroamphetamine, 64, 69, 76 Dextromethorphan, 28, 69 Diagnostic procedure, 25, 36, 69 Diaphragm, 69, 73 Digestion, 65, 66, 69, 75, 82 Dihydromorphine, 30, 69 Dihydrotestosterone, 63, 70, 80 Direct, iii, 39, 70, 80 Discrimination, 6, 70 Dissociation, 63, 70, 75 Dopamine, 6, 64, 68, 69, 70, 76 Dosage Forms, 30, 31, 70 Dose-dependent, 5, 70 Drug Interactions, 40, 41, 70 Drug Tolerance, 70, 83

Duct, 70, 74, 78 Duodenum, 65, 70, 82 E Efficacy, 5, 6, 8, 9, 11, 18, 19, 70 Electrolyte, 70, 79 Electrons, 65, 70, 75, 78 Emphysema, 67, 71 Enalapril, 4, 48, 71 Endotoxins, 71, 75 Environmental Health, 46, 48, 71 Enzymatic, 29, 67, 69, 71, 79 Enzyme, 29, 63, 71, 75, 76, 79, 80, 84 Epinephrine, 63, 70, 71, 77, 83 Erythromycin, 65, 71 Estrogen, 3, 48, 71 Ether, 7, 71 Eukaryotic Cells, 71, 74 Evacuation, 68, 71 Evoke, 71, 82 Expectorant, 28, 71 Expiration, 71, 80 Extrapyramidal, 70, 71 Exudate, 71, 78 F Fallopian Tubes, 71, 83 Family Planning, 47, 71 Fatigue, 72, 73, 78 Fats, 66, 67, 72, 78 Fatty acids, 72, 76 Feces, 68, 72, 82 Femur, 64, 72 Fentanyl, 5, 72 Fetus, 72, 76, 84 Flatus, 72 Fluorine, 27, 72 Fluoxetine, 3, 48, 72 Food Technology, 72, 76 G Gallbladder, 66, 72 Ganglia, 72, 77 Gas, 7, 11, 14, 29, 33, 64, 67, 72, 73, 77 Gasoline, 65, 72 Gastric, 64, 70, 72, 73 Gastric Acid, 64, 72 Gastrointestinal, 31, 71, 72, 81 Gastrointestinal tract, 31, 72, 81 Gelatin, 72, 73, 83 Gene, 66, 72 Genetic testing, 72, 79 Genotype, 72, 79 Gland, 72, 82, 83 Glottis, 73

Index 87

Glutamate, 69, 73 Glycine, 66, 73, 81 Governing Board, 73, 79 Gram-negative, 67, 73 Gram-positive, 67, 73 Growth, 65, 73, 76, 79, 83 H Heart failure, 73, 75 Heme, 69, 73 Hepatic, 5, 73 Hepatotoxicity, 5, 73 Hiccup, 12, 73 Homogeneous, 29, 73, 78 Hormone, 71, 73, 75, 81, 82, 83 Hydrochloric Acid, 29, 73 Hydrogen, 33, 63, 64, 65, 69, 73, 76, 78, 80 Hydromorphone, 6, 7, 10, 11, 12, 13, 14, 18, 19, 29, 32, 33, 73 Hyperglycemia, 33, 73 Hypertension, 64, 71, 73, 75 I Ibuprofen, 9, 10, 11, 18, 19, 23, 28, 40, 73, 75 Id, 20, 52, 58, 60, 74 Immunoassay, 7, 74 Immunologic, 74 Impaction, 13, 74 Impairment, 5, 74 In situ, 7, 74 In Situ Hybridization, 7, 74 In vitro, 7, 74, 79 In vivo, 7, 74 Infarction, 68, 74, 76 Infection, 11, 18, 68, 74, 76, 81, 82, 83 Inflammation, 28, 65, 66, 71, 74, 81 Ingestion, 5, 12, 74 Inhalation, 63, 73, 74, 76 Inner ear, 7, 74 Inotropic, 70, 74 Insight, 6, 74 Intervertebral, 74, 76 Intervertebral Disk Displacement, 74, 76 Intestinal, 68, 74, 76 Intestines, 72, 74, 75, 76 Intoxication, 75, 84 Intracellular, 74, 75, 79 Intrinsic, 33, 63, 75 Involuntary, 75, 77, 80, 82 Ionization, 14, 75 Ions, 7, 65, 70, 73, 75 Iris, 75, 80

J Joint, 65, 75, 82 K Kb, 46, 75 Keto, 32, 75 Ketoprofen, 9, 18, 75 Ketorolac, 8, 10, 13, 18, 75 L Labyrinth, 68, 74, 75, 81, 84 Levo, 40, 75, 80 Levorphanol, 69, 75 Levothyroxine, 3, 48, 75 Library Services, 58, 75 Ligament, 64, 75, 82 Ligation, 75 Lipid, 75 Lisinopril, 4, 48, 75 Liver, 5, 13, 63, 65, 66, 69, 72, 73, 75 Localized, 69, 74, 76, 79 Low Back Pain, 10, 76 Lumbar, 74, 76 Lymphatic, 74, 76 M Malignant, 5, 76 Meconium, 14, 76 Mediate, 68, 70, 76 MEDLINE, 47, 76 Medullary, 69, 76 Meninges, 67, 76 Mental Health, iv, 4, 46, 49, 76, 80 Meperidine, 5, 76 Methylene Chloride, 27, 76 Methylphenidate, 5, 76 MI, 32, 61, 76 Microorganism, 68, 76, 84 Molecular, 7, 29, 47, 49, 66, 68, 76 Molecule, 65, 70, 76, 78, 80 Monoamine, 64, 69, 76 Morphine, 5, 6, 7, 12, 14, 26, 27, 29, 30, 33, 66, 68, 73, 76, 77, 78 Morphological, 7, 76 Mucilaginous, 76, 77 Mucus, 71, 77 Myocardium, 64, 76, 77 Myoclonus, 12, 77 N Nalbuphine, 5, 77 Narcolepsy, 69, 76, 77 Narcosis, 77 Narcotic, 27, 28, 29, 32, 33, 40, 66, 69, 72, 73, 75, 76, 77, 78, 80, 83 Narcotic Antagonists, 27, 77

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Hydrocodone

Nausea, 70, 77 Necrosis, 74, 76, 77 Need, 3, 48, 53, 77, 83 Nerve, 63, 68, 77, 82, 83 Nervous System, 30, 64, 67, 77, 82 Neurons, 68, 72, 77 Neuropharmacology, 6, 12, 77 Neurotoxicity, 69, 77 Nitrogen, 9, 63, 64, 77 Norepinephrine, 63, 70, 77 Nucleic acid, 74, 77, 78, 80 Nucleus, 68, 69, 71, 74, 78, 80, 82 O Ointments, 70, 78 Opium, 76, 78 Osteoarthritis, 75, 78 Outpatient, 4, 78 Ovaries, 71, 78, 83 Overdose, 11, 18, 78 Oxidation, 30, 63, 69, 78 Oxycodone, 4, 6, 7, 10, 11, 12, 13, 14, 26, 27, 30, 78 Oxygen Consumption, 78, 81 P Palladium, 29, 78 Palliative, 18, 19, 78, 83 Paroxetine, 3, 48, 78 Pemoline, 5, 78 Pharmaceutical Solutions, 70, 78 Pharmacodynamic, 5, 79 Pharmacologic, 6, 79, 83 Phenotype, 10, 18, 79 Phenyl, 76, 79 Physiologic, 63, 66, 77, 79, 80 Pilot study, 9, 18, 79 Plants, 63, 67, 68, 78, 79, 83 Plasma, 5, 13, 14, 31, 72, 79 Platinum, 29, 78, 79 Polymerase, 7, 79 Polymerase Chain Reaction, 7, 79 Postoperative, 4, 9, 10, 11, 18, 19, 76, 79 Postoperative Period, 9, 18, 79 Potassium, 4, 48, 79 Practice Guidelines, 49, 79 Preclinical, 6, 79 Precursor, 70, 71, 77, 80, 83 Propoxyphene, 4, 7, 40, 80 Protein S, 66, 71, 80 Proteins, 64, 65, 71, 76, 77, 79, 80, 81, 83 Protons, 73, 80 Psychic, 80 Psychomotor, 5, 9, 80

Psychotomimetic, 64, 69, 80 Public Health, 6, 49, 80 Public Policy, 47, 80 Pupil, 33, 80 Purines, 80, 81 R Race, 29, 80 Radioactive, 73, 75, 80 Randomized, 9, 15, 19, 70, 80 Reagent, 27, 73, 80 Receptor, 7, 32, 65, 69, 70, 80, 81 Rectum, 72, 80 Reductase, 29, 80 Refer, 1, 80, 84 Reflex, 33, 80 Regimen, 70, 80 Respiration, 6, 67, 80 Rheumatism, 74, 81 Rheumatoid, 75, 81 Rheumatoid arthritis, 75, 81 S Schizoid, 81, 84 Schizophrenia, 81, 84 Schizotypal Personality Disorder, 81, 84 Screening, 67, 81 Sedative, 68, 81 Self Administration, 6, 81 Semicircular canal, 74, 81 Semisynthetic, 64, 67, 69, 78, 81 Sequencing, 79, 81 Serine, 7, 81 Serologic, 74, 81 Serotonin, 72, 78, 81 Serum, 9, 11, 64, 81 Shock, 77, 81 Side effect, 5, 26, 39, 63, 81, 83 Smooth muscle, 30, 63, 76, 82 Solvent, 65, 76, 78, 82 Spasm, 73, 82 Specialist, 53, 82 Species, 71, 80, 82, 84 Spinal cord, 67, 76, 77, 80, 82 Sprains and Strains, 21, 76, 82 Stimulant, 64, 69, 76, 78, 82 Stimulus, 5, 6, 19, 80, 82 Stomach, 72, 73, 75, 77, 82 Stool, 74, 82 Strand, 79, 82 Stress, 4, 48, 67, 77, 81, 82 Stupor, 77, 82 Subacute, 74, 82 Subclinical, 74, 82

Index 89

Sympathomimetic, 64, 69, 70, 71, 78, 82 Synergistic, 5, 26, 82 Systemic, 40, 71, 74, 82 T Testosterone, 63, 80, 82 Therapeutics, 6, 8, 9, 10, 11, 13, 26, 41, 83 Thermal, 70, 79, 83 Threonine, 7, 81, 83 Thyroid, 75, 83 Thyroxine, 75, 83 Tin, 79, 83 Tissue, 65, 66, 70, 71, 72, 75, 76, 77, 81, 82, 83 Tolerance, 5, 6, 26, 66, 83 Toxic, iv, 27, 65, 83 Toxicity, 14, 70, 83 Toxicology, 4, 11, 12, 14, 26, 48, 83 Toxins, 65, 71, 74, 83 Toxoplasmosis, 65, 83 Trace element, 72, 83 Trachea, 66, 71, 83 Tramadol, 4, 8, 15, 18, 19, 26, 83

Transfection, 66, 83 Transmitter, 70, 77, 83 Tubal ligation, 8, 18, 83 Tyrosine, 70, 83 U Unconscious, 74, 83 Urethra, 83, 84 Urine, 7, 11, 12, 14, 66, 83, 84 Uterus, 71, 78, 83, 84 V Vascular, 63, 74, 84 Vasodilator, 70, 84 Vestibular, 7, 84 Vestibule, 68, 74, 81, 84 Veterinary Medicine, 47, 84 Virulence, 65, 83, 84 Vitro, 84 Vivo, 84 W Withdrawal, 6, 76, 84 Y Yeasts, 79, 84

90

Hydrocodone

Index 91

92

Hydrocodone