Tramadol - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

TRAMADOL A M EDICAL D ICTIONARY , B IBLIOGRAPHY , AND A NNOTATED R ESEARCH G UIDE TO I NTERNET R E FERENCES J AMES N. P...

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TRAMADOL 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 2004 by ICON Group International, Inc. Copyright 2004 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., 1960Tramadol: 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: 0-597-84102-0 1. Tramadol-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 tramadol. 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 TRAMADOL ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Tramadol ....................................................................................... 5 The National Library of Medicine: PubMed .................................................................................. 7 CHAPTER 2. NUTRITION AND TRAMADOL ..................................................................................... 51 Overview...................................................................................................................................... 51 Finding Nutrition Studies on Tramadol...................................................................................... 51 Federal Resources on Nutrition ................................................................................................... 59 Additional Web Resources ........................................................................................................... 59 CHAPTER 3. ALTERNATIVE MEDICINE AND TRAMADOL ............................................................... 61 Overview...................................................................................................................................... 61 National Center for Complementary and Alternative Medicine.................................................. 61 Additional Web Resources ........................................................................................................... 63 General References ....................................................................................................................... 64 CHAPTER 4. DISSERTATIONS ON TRAMADOL ................................................................................. 65 Overview...................................................................................................................................... 65 Dissertations on Tramadol........................................................................................................... 65 Keeping Current .......................................................................................................................... 65 CHAPTER 5. PATENTS ON TRAMADOL ............................................................................................ 67 Overview...................................................................................................................................... 67 Patents on Tramadol .................................................................................................................... 67 Patent Applications on Tramadol ................................................................................................ 84 Keeping Current ........................................................................................................................ 102 CHAPTER 6. PERIODICALS AND NEWS ON TRAMADOL ................................................................ 103 Overview.................................................................................................................................... 103 News Services and Press Releases.............................................................................................. 103 Academic Periodicals covering Tramadol .................................................................................. 106 CHAPTER 7. RESEARCHING MEDICATIONS .................................................................................. 107 Overview.................................................................................................................................... 107 U.S. Pharmacopeia..................................................................................................................... 107 Commercial Databases ............................................................................................................... 108 APPENDIX A. PHYSICIAN RESOURCES .......................................................................................... 111 Overview.................................................................................................................................... 111 NIH Guidelines.......................................................................................................................... 111 NIH Databases........................................................................................................................... 113 Other Commercial Databases..................................................................................................... 115 APPENDIX B. PATIENT RESOURCES ............................................................................................... 117 Overview.................................................................................................................................... 117 Patient Guideline Sources.......................................................................................................... 117 Finding Associations.................................................................................................................. 119 APPENDIX C. FINDING MEDICAL LIBRARIES ................................................................................ 121 Overview.................................................................................................................................... 121 Preparation................................................................................................................................. 121 Finding a Local Medical Library................................................................................................ 121 Medical Libraries in the U.S. and Canada ................................................................................. 121 ONLINE GLOSSARIES................................................................................................................ 127 Online Dictionary Directories ................................................................................................... 127

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TRAMADOL DICTIONARY....................................................................................................... 129 INDEX .............................................................................................................................................. 177

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

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

Pharmacological Treatment of Painful Diabetic Neuropathy Source: Clinical Diabetes. 18(3): 116-118. 2000. Contact: Available from American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Website: www.diabetes.org. Summary: This article reviews studies on the effectiveness of various drugs in managing diabetic neuropathy. Control of pain is a major goal for most patients and their physicians in managing diabetic neuropathy. Studies have demonstrated the effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen and sulindac; tricyclic antidepressants such as amitriptyline, imipramine, nortriptyline, and desipramine; serotonin reuptake inhibitors such as paroxetine and fluoxetine; and anticonvulsants such as gabapentin and carbamazepine. Although NSAIDs can offer

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pain relief, especially in patients with musculoskeletal or joint abnormalities secondary to long term neuropathy, the tricyclic antidepressants remain the most commonly used drugs in the treatment of painful neuropathy. In addition, several other oral agents including the anti-arrythmic agent mexiletine, tramadol, and topical capsaicin cream have been found to be effective in relieving pain associated with diabetic neuropathy. Other nonsystemic pain control treatments that have been studied include transcutaneous electrical nerve stimulation units and acupuncture. 28 references. •

Effective Management of Chronic Pain. The Analgesic Dilemma Source: Postgraduate Medicine. 100(3):281-284,287- 290,293,296; September 1996. Summary: This journal article for health professionals discusses the effective management of chronic pain by using prescription analgesics. The goals of chronic pain management are identified, and barriers to achieving them are highlighted. Prescription medications that can be used as analgesics for chronic pain are described, focusing on nonsteroidal anti-inflammatory drugs, opioids, and tramadol hydrochloride. Opioid use is discussed in terms of limiting factors, patient selection, and goals. Adjuvant medications that may be used in the management of selected chronic pain states are also highlighted, including antidepressants, antiarrhythmics, anticonvulsants, calcium channel blockers, antiadrenergics, and topical agents. 27 references, 1 figure, and 5 tables. (AA-M).

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Strategies To Control Chronic Musculoskeletal Pain: A Guide to Drug Therapy Source: Consultant. 39(10): 2773-2776,2781. October 1999. Summary: This journal article provides health professionals with information on controlling musculoskeletal pain with drug therapy. Factors to consider in selecting pharmacologic therapy include the type, pathology, and severity of pain; comorbid conditions and concomitant medications; individual response; and patient preference. Drug therapy options include acetaminophen, nonsteroidal anti-inflammatory drugs (NSAIDs), tramadol, opioid analgesics, antidepressants, and other nonnarcotic medications. Acetaminophen and over the counter NSAIDs are recommended for mild to moderate pain. If moderate pain is not controlled by these agents, tramadol or the lowest anti-inflammatory dose of a prescription NSAID should be prescribed for the shortest possible time. Moderate to severe pain that is not adequately controlled should be treated with tramadol or with opioids if necessary. Topical capsaicin cream is an effective secondary treatment for localized osteoarthritis pain. Systemic corticosteroids are useful for patients who have inflammatory rheumatic diseases. Antidepressants have not been approved by the Food and Drug Administration for pain management; however, they may decrease the pain signal by modulating serotonin, norepinephrine, or dopamine at the neurosynaptic junctions. Acute mild to moderate side effects of therapy can often be avoided by dose titration, or they can be managed symptomatically. For example, constipation, a troublesome side effect of opioids, can be treated or prevented with proper diet and a stool softener. A stepwise approach to drug treatment should be used. 1 figure, 2 tables, and 29 references. (AA-M).

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Chronic Low Back Pain: New Perspectives and Treatment Guidelines for Primary Care: Part II Source: Managed Care Interface. 11(3): 71-75. 1998. Summary: This journal article, the second of two parts, provides health professionals with treatment guidelines for chronic low back pain. Low back pain is a major factor in

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work-related disability and has important socioeconomic repercussions. Although little evidence exists regarding the best treatment for chronic low back pain, it is possible to set treatment goals. These goals are: achieving rapid pain control, restoring function quickly, and minimizing adverse drug reactions. The goals can be met through nonpharmacologic and pharmacologic measures. The article discusses the efficacy and side effects of various pharmacologic interventions for managing low back pain; these are acetaminophen, aspirin and nonsteroidal anti-inflammatory drugs, tramadol, opioid analgesics, muscle relaxants, tricyclic antidepressants, anticonvulsants, and corticosteroid injections. Guidelines are offered for selecting drug therapy in the elderly, in people who have upper gastrointestinal disease or cardiovascular disease, and in people who are taking other medications. Indications for referral to another health care provider are also discussed. 1 figure, 1 table, and 18 references. (AA-M). •

Current and Emerging Treatments for the Diabetic Neuropathies Source: Diabetes Reviews. 7(4): 379-386. 1999. Contact: Available from American Diabetes Association, Inc. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 232-3472. Summary: This review article focuses on the therapeutic approach to patients who have symptomatic diabetic neuropathies. Diabetic neuropathy is a diagnosis that requires exclusion of other causes because there are no diagnostic tests that confirm that the symptoms and signs are definitely a result of diabetes. For those patients who have painful or paresthetic symptoms, optimal stable glycemic control should be the first goal, keeping in mind that insulin is not always required in type 2 diabetes. The tricyclic drugs, usually amitriptyline or imipramine, remain the first line drug therapy for painful symptoms. Their efficacy has been confirmed in several controlled trials. Of the newer agents, the anticonvulsant gabapentin seems to offer many of the benefits of the tricyclic agents without the troublesome side effects, and the centrally acting drug tramadol has proven efficacy for short term treatment. Topical or nonpharmacologic treatments may help in some cases. Some data support the use of topical capsaicin, and long term open trials suggest a possible benefit of acupuncture. Of new agents that may modify pathogenetic mechanisms leading to neuropathy, the antioxidant alpha-lipoic acid shows promise from a number of controlled studies. Recent developments in autonomic neuropathy include the arrival of sildenafil, which appears to help up to 60 percent of patients who have erectile dysfunction. Topical glycopyrrolate is another new therapy for autonomic dysfunction. In a randomized trial, it was confirmed to markedly reduce gustatory sweating. Finally, whereas less than 20 percent of neuropathic patients experience symptoms, all neuropathic patients are at potential risk of insensitive foot ulceration and require education in preventive foot care, regular podiatry, and frequent follow up. 2 tables. 84 references. (AA-M).

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

Project Title: BEHAVIORAL EFFECTS OF OPIOIDS IN VOLUNTEERS Principal Investigator & Institution: Zacny, James P.; Associate Professor; Anesthesia and Critical Care; University of Chicago 5801 S Ellis Ave Chicago, Il 60637 Timing: Fiscal Year 2001; Project Start 15-MAR-1995; Project End 29-FEB-2004 Summary: Until recently, little attention had been paid to characterizing behavioral effects of opioids in normal volunteers (i.e., volunteers with no history of drug or alcohol dependence) using the rigorous testing methodologies that had been employed in the studies with abusers. For the past three years, we have employed an abuse liability/behavioral toxicology testing methodology to examine the effects of a number of different opioids that are typically given to patients for postoperative pain. This application will have four series of studies that are logical continuations of studies from the previous grant period. In the first series of studies, we will focus on opioids that are typically given to patients who are recovering from outpatient surgery. These patients might be at home or at work, engaging in different activities that may or may not be adversely affected by the opioids. It is vitally important to understand the behavioral toxicology of these opioids, yet rigorous toxicology studies (employing multiple measures of behavior and examining a range of doses that might be used by patients) have not been conducted to date. Therefore, we plan to continue our opioid characterization studies in normal volunteers, focusing on four oral drugs commonly used in outpatient settings: hydrocodone, oxycodone, propoxyphene, and tramadol. In the second series of studies, we will follow up on a study from the previous granting period in which some of morphine's subjective effects were attenuated by a painful stimulus. In four studies, we will use a cumulative dosing procedure recently developed in our laboratory to examine the degree to which a painful stimulus modulates the subjective and psychomotor effects of morphine, meperidine, butorphanol and nalbuphine. We will study different opioids at different doses and at different levels of painful stimulation in order to better understand how pain, which frequently accompanies opioid administration in patients, modulates behavioral effects of opioids. In the third series of studies, we will again follow up on a previous study from our laboratory in which we demonstrated that a painful stimulus modulated the reinforcing effects of an opioid, fentanyl. We propose to utilize a patient controlled analgesia (PCA) methodology to examine the degree to which four different opioids- morphine, meperidine, nalbuphine and butorphanol- maintain self-administration, and the degree to which self-administration is modulated by a painful stimulus. In the fourth series of studies, the effects of psychomotor stimulants alone and in combination with an opioid will be examined. Psychomotor stimulants are often given as adjuncts to opioids in patients suffering from chronic malignant pain to offset the sedating and impairing effects of high-dose opioid therapy. We will study buprenorphine in combination with three psychomotor stimulants- d-amphetamine, methylphenidate, and pemoline- to

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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

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

A comparative study of tramadol and pethidine in laparoscopic interval sterilization. Author(s): Chaturachinda K, Tangtrakul S, Pausawasdi S, Padmasuta K, O-Prasertsawat P. Source: J Med Assoc Thai. 1988 March; 71 Suppl 1: 55-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3047303&dopt=Abstract

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A comparative study on the analgesic effect of tramadol, tramadol plus magnesium, and tramadol plus ketamine for postoperative pain management after major abdominal surgery. Author(s): Unlugenc H, Gunduz M, Ozalevli M, Akman H. Source: Acta Anaesthesiologica Scandinavica. 2002 September; 46(8): 1025-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12190807&dopt=Abstract

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A comparison of epidural tramadol and epidural morphine for postoperative analgesia. Author(s): Baraka A, Jabbour S, Ghabash M, Nader A, Khoury G, Sibai A. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1993 April; 40(4): 308-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8485789&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 comparison of once-daily tramadol with normal release tramadol in the treatment of pain in osteoarthritis. Author(s): Adler L, McDonald C, O'Brien C, Wilson M. Source: The Journal of Rheumatology. 2002 October; 29(10): 2196-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12375333&dopt=Abstract

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A comparison of single dose caudal tramadol, tramadol plus bupivacaine and bupivacaine administration for postoperative analgesia in children. Author(s): Gunduz M, Ozcengiz D, Ozbek H, Isik G. Source: Paediatric Anaesthesia. 2001 May; 11(3): 323-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11359591&dopt=Abstract

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A comparison of the antinociceptive effects of imipramine, tramadol and anpirtoline. Author(s): Hummel T, Hummel C, Friedel I, Pauli E, Kobal G. Source: British Journal of Clinical Pharmacology. 1994 April; 37(4): 325-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8018453&dopt=Abstract

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A comparison of the effects of codeine and tramadol on laryngeal reactivity. Author(s): Szekely SM, Vickers MD. Source: European Journal of Anaesthesiology. 1992 March; 9(2): 111-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1555550&dopt=Abstract

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A comparison of the effects of intravenous tramadol, codeine, and morphine on gastric emptying in human volunteers. Author(s): Crighton IM, Martin PH, Hobbs GJ, Cobby TF, Fletcher AJ, Stewart PD. Source: Anesthesia and Analgesia. 1998 August; 87(2): 445-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9706948&dopt=Abstract

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A comparison of the effects of tramadol and morphine on gastric emptying in man. Author(s): Murphy DB, Sutton A, Prescott LF, Murphy MB. Source: Anaesthesia. 1997 December; 52(12): 1224-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9485982&dopt=Abstract

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A comparison of the pharmacokinetics, clinical efficacy, and tolerability of once-daily tramadol tablets with normal release tramadol capsules. Author(s): Bodalia B, McDonald CJ, Smith KJ, O'Brien C, Cousens L. Source: Journal of Pain and Symptom Management. 2003 February; 25(2): 142-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12590030&dopt=Abstract

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A comparison of tramadol, amitriptyline, and meperidine for postepidural anesthetic shivering in parturients. Author(s): Tsai YC, Chu KS. Source: Anesthesia and Analgesia. 2001 November; 93(5): 1288-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11682416&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 postmarketing surveillance program to monitor Ultram (tramadol hydrochloride) abuse in the United States. Author(s): Cicero TJ, Adams EH, Geller A, Inciardi JA, Munoz A, Schnoll SH, Senay EC, Woody GE. Source: Drug and Alcohol Dependence. 1999 November 1; 57(1): 7-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10617309&dopt=Abstract

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A recovering physician being monitored by the Mississippi Recovering Physicians Program and prescribed Ultram. Author(s): Carr GD. Source: J Miss State Med Assoc. 2002 December; 43(12): 376. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12647497&dopt=Abstract

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A risk-benefit assessment of tramadol in the management of pain. Author(s): Radbruch L, Grond S, Lehmann KA. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1996 July; 15(1): 8-29. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8862961&dopt=Abstract

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Abuse of combinations of carisoprodol and tramadol. Author(s): Reeves RR, Liberto V. Source: Southern Medical Journal. 2001 May; 94(5): 512-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11372804&dopt=Abstract

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Abuse potential and pharmacological comparison of tramadol and morphine. Author(s): Preston KL, Jasinski DR, Testa M. Source: Drug and Alcohol Dependence. 1991 January; 27(1): 7-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2029860&dopt=Abstract

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Abuse, dependence, or withdrawal associated with tramadol. Author(s): Brinker A, Bonnel RA, Beitz J. Source: The American Journal of Psychiatry. 2002 May; 159(5): 881; Author Reply 881-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11986164&dopt=Abstract

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Achiral and chiral determination of tramadol and its metabolites in urine by capillary electrophoresis. Author(s): Kurth B, Blaschke G. Source: Electrophoresis. 1999 March; 20(3): 555-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10217171&dopt=Abstract

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Achiral and chiral high-performance liquid chromatographic determination of tramadol and its major metabolites in urine after oral administration of racemic tramadol. Author(s): Elsing B, Blaschke G. Source: Journal of Chromatography. 1993 February 26; 612(2): 223-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8468380&dopt=Abstract

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Acute abstinence syndrome following abrupt cessation of long-term use of tramadol (Ultram): a case study. Author(s): Freye E, Levy J. Source: European Journal of Pain (London, England). 2000; 4(3): 307-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10985875&dopt=Abstract

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Acute effects of tramadol in methadone-maintained volunteers. Author(s): Cami J, Lamas X, Farre M. Source: Drugs. 1994; 47 Suppl 1: 39-43. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7517825&dopt=Abstract

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Adding ketoprofen to intravenous patient-controlled analgesia with tramadol after major gynecological cancer surgery: a double-blinded, randomized, placebocontrolled clinical trial. Author(s): Tuncer S, Pirbudak L, Balat O, Capar M. Source: Eur J Gynaecol Oncol. 2003; 24(2): 181-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12701975&dopt=Abstract

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Affinity, potency and efficacy of tramadol and its metabolites at the cloned human mu-opioid receptor. Author(s): Gillen C, Haurand M, Kobelt DJ, Wnendt S. Source: Naunyn-Schmiedeberg's Archives of Pharmacology. 2000 August; 362(2): 116-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10961373&dopt=Abstract

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An evaluation of the efficacy and tolerability of oral tramadol hydrochloride tablets for the treatment of postsurgical pain in children. Author(s): Finkel JC, Rose JB, Schmitz ML, Birmingham PK, Ulma GA, Gunter JB, Cnaan A, Cote CJ, Medve RA, Schreiner MS. Source: Anesthesia and Analgesia. 2002 June; 94(6): 1469-73, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032009&dopt=Abstract

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Analgesia after day case laparoscopic sterilisation. A comparison of tramadol with paracetamol/dextropropoxyphene and paracetamol/codeine combinations. Author(s): Crighton IM, Hobbs GJ, Wrench IJ. Source: Anaesthesia. 1997 July; 52(7): 649-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9244023&dopt=Abstract

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Analgesia after intracranial surgery: a double-blind, prospective comparison of codeine and tramadol. Author(s): Jeffrey HM, Charlton P, Mellor DJ, Moss E, Vucevic M. Source: British Journal of Anaesthesia. 1999 August; 83(2): 245-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10618937&dopt=Abstract

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Analgesia for adenotonsillectomy in children and young adults: a comparison of tramadol, pethidine and nalbuphine. Author(s): van den Berg AA, Montoya-Pelaez LF, Halliday EM, Hassan I, Baloch MS. Source: European Journal of Anaesthesiology. 1999 March; 16(3): 186-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10225169&dopt=Abstract

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Analgesic activity of tramadol and pentazocine in postoperative pain. Author(s): Magrini M, Rivolta G, Bolis C, Furiosi D. Source: Int J Clin Pharmacol Res. 1998; 18(2): 87-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9675626&dopt=Abstract

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Analgesic effects of dihydrocodeine and tramadol when administered either in the morning or evening. Author(s): Hummel T, Kraetsch HG, Lotsch J, Hepper M, Liefhold J, Kobal G. Source: Chronobiology International. 1995 February; 12(1): 62-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7750159&dopt=Abstract

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Analgesic efficacy and safety of tramadol enantiomers in comparison with the racemate: a randomised, double-blind study with gynaecological patients using intravenous patient-controlled analgesia. Author(s): Grond S, Meuser T, Zech D, Hennig U, Lehmann KA. Source: Pain. 1995 September; 62(3): 313-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8657431&dopt=Abstract

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Tramadol

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Analgesic efficacy of tramadol 2 mg kg(-1) for paediatric day-case adenoidectomy. Author(s): Viitanen H, Annila P. Source: British Journal of Anaesthesia. 2001 April; 86(4): 572-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11573636&dopt=Abstract

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Analgesic efficacy of tramadol if coadministered with ondansetron. Author(s): Stamer UM, Stuber F. Source: Anesthesia and Analgesia. 2001 December; 93(6): 1626. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11726465&dopt=Abstract

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Analgesic oral efficacy of tramadol hydrochloride in postoperative pain. Author(s): Sunshine A, Olson NZ, Zighelboim I, DeCastro A, Minn FL. Source: Clinical Pharmacology and Therapeutics. 1992 June; 51(6): 740-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1351804&dopt=Abstract

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Analgesics in ophthalmic practice: a review of the oral non-narcotic agent tramadol. Author(s): Gaynes BI, Barkin RL. Source: Optometry and Vision Science : Official Publication of the American Academy of Optometry. 1999 July; 76(7): 455-61. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10445636&dopt=Abstract

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Anaphylactoid reactions and histamine release do not occur after application of the opioid tramadol. Author(s): Barth H, Giertz H, Schmal A, Lorenz W. Source: Agents Actions. 1987 April; 20(3-4): 310-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2440284&dopt=Abstract

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Assay of tramadol in urine by capillary electrophoresis using laser-induced native fluorescence detection. Author(s): Soetebeer UB, Schierenberg MO, Schulz H, Grunefeld G, Andresen P, Blaschke G. Source: J Chromatogr B Biomed Sci Appl. 2000 August 18; 745(2): 271-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11043746&dopt=Abstract

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Assessment of analgesia in man: tramadol controlled release formula vs. tramadol standard formulation. Author(s): Hummel T, Roscher S, Pauli E, Frank M, Liefhold J, Fleischer W, Kobal G. Source: European Journal of Clinical Pharmacology. 1996; 51(1): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8880048&dopt=Abstract

Studies

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Automated determination of tramadol enantiomers in human plasma using solidphase extraction in combination with chiral liquid chromatography. Author(s): Ceccato A, Chiap P, Hubert P, Crommen J. Source: J Chromatogr B Biomed Sci Appl. 1997 September 26; 698(1-2): 161-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9367204&dopt=Abstract

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Bioavailability of enteral tramadol formulations. 1st communication: capsules. Author(s): Lintz W, Barth H, Osterloh G, Schmidt-Bothelt E. Source: Arzneimittel-Forschung. 1986 August; 36(8): 1278-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3778568&dopt=Abstract

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Bioavailability of tramadol after i.m. injection in comparison to i.v. infusion. Author(s): Lintz W, Beier H, Gerloff J. Source: Int J Clin Pharmacol Ther. 1999 April; 37(4): 175-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10235420&dopt=Abstract

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Bioavailability of tramadol hydrochloride from tramadol--capsules 50 mg. Author(s): Dyderski S, Szkutnik D, Zgrabczynska M, Drobnik L. Source: Acta Pol Pharm. 2001 September-October; 58(5): 345-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11876441&dopt=Abstract

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Bioequivalence study of tramadol by intramuscular administration in healthy volunteers. Author(s): Chao CK, Yu LL, Su LL, Liu CM, Yang TH, Chen CM. Source: Arzneimittel-Forschung. 2000 July; 50(7): 636-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10965421&dopt=Abstract

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Caudal bupivacaine-tramadol combination for postoperative analgesia in pediatric herniorrhaphy. Author(s): Senel AC, Akyol A, Dohman D, Solak M. Source: Acta Anaesthesiologica Scandinavica. 2001 July; 45(6): 786-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11421842&dopt=Abstract

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Caudal tramadol for postoperative analgesia in hypospadias surgery. Author(s): Russell W. Source: British Journal of Anaesthesia. 1998 March; 80(3): 408-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9623450&dopt=Abstract

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Caudal tramadol for postoperative analgesia in pediatric hypospadias surgery. Author(s): Prosser DP, Davis A, Booker PD, Murray A. Source: British Journal of Anaesthesia. 1997 September; 79(3): 293-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9389843&dopt=Abstract

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Tramadol

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Chronic urticaria with multiple NSAID intolerance: is tramadol always a safe alternative analgesic? Author(s): Asero R. Source: J Investig Allergol Clin Immunol. 2003; 13(1): 56-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12861852&dopt=Abstract

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Clinical investigation on the development of dependence during oral therapy with tramadol. Author(s): Richter W, Barth H, Flohe L, Giertz H. Source: Arzneimittel-Forschung. 1985; 35(11): 1742-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4091874&dopt=Abstract

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Combination analgesic efficacy: individual patient data meta-analysis of single-dose oral tramadol plus acetaminophen in acute postoperative pain. Author(s): Edwards JE, McQuay HJ, Moore RA. Source: Journal of Pain and Symptom Management. 2002 February; 23(2): 121-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11844632&dopt=Abstract

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Comparison of caudal morphine and tramadol for postoperative pain control in children undergoing inguinal herniorrhaphy. Author(s): Ozcengiz D, Gunduz M, Ozbek H, Isik G. Source: Paediatric Anaesthesia. 2001 July; 11(4): 459-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11442865&dopt=Abstract

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Comparison of caudal tramadol vs bupivacaine for post-operative analgesia in children undergoing hypospadias surgery. Author(s): Batra YK, Prasad MK, Arya VK, Chari P, Yaddanapudi LN. Source: Int J Clin Pharmacol Ther. 1999 May; 37(5): 238-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10363622&dopt=Abstract

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Comparison of efficacy and side effects of epidural tramadol and morphine in patients undergoing laminectomy: a repeated dose study. Author(s): Yaddanapudi LN, Wig J, Singh B, Tewari MK. Source: Neurology India. 2000 December; 48(4): 398-400. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11146613&dopt=Abstract

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Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction. Author(s): Silvasti M, Svartling N, Pitkanen M, Rosenberg PH. Source: European Journal of Anaesthesiology. 2000 July; 17(7): 448-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10964147&dopt=Abstract

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Comparison of local anaesthetic effects of tramadol with prilocaine for minor surgical procedures. Author(s): Altunkaya H, Ozer Y, Kargi E, Babuccu O. Source: British Journal of Anaesthesia. 2003 March; 90(3): 320-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12594144&dopt=Abstract

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Comparison of patient-controlled analgesia (PCA) with tramadol or morphine. Author(s): Pang WW, Mok MS, Lin CH, Yang TF, Huang MH. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1999 November; 46(11): 1030-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10566922&dopt=Abstract

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Comparison of respiratory effects of tramadol and oxycodone. Author(s): Tarkkila P, Tuominen M, Lindgren L. Source: Journal of Clinical Anesthesia. 1997 November; 9(7): 582-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9347436&dopt=Abstract

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Comparison of respiratory effects of tramadol and pethidine. Author(s): Tarkkila P, Tuominen M, Lindgren L. Source: European Journal of Anaesthesiology. 1998 January; 15(1): 64-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9522144&dopt=Abstract

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Comparison of the analgesic efficacy of metamizole and tramadol in experimental pain. Author(s): Rohdewald P, Granitzki HW, Neddermann E. Source: Pharmacology. 1988; 37(4): 209-17. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3057512&dopt=Abstract

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Comparison of the efficacy and tolerability of a paracetamol/codeine fixed-dose combination with tramadol in patients with refractory chronic back pain. Author(s): Muller FO, Odendaal CL, Muller FR, Raubenheimer J, Middle MV, Kummer M. Source: Arzneimittel-Forschung. 1998 June; 48(6): 675-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9689426&dopt=Abstract

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Comparison of tilidine/naloxone, tramadol and bromfenac in experimental pain: a double-blind randomized crossover study in healthy human volunteers. Author(s): Hogger P, Rohdewald P. Source: Int J Clin Pharmacol Ther. 1999 August; 37(8): 377-85. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10475140&dopt=Abstract

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Comparison of tramadol and morphine via subcutaneous PCA following major orthopaedic surgery. Author(s): Hopkins D, Shipton EA, Potgieter D, Van derMerwe CA, Boon J, De Wet C, Murphy J. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1998 May; 45(5 Pt 1): 435-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9598258&dopt=Abstract

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Comparison of tramadol and tramadol/droperidol mixture for patient-controlled analgesia. Author(s): Ng KF, Tsui SL, Yang JC, Ho ET. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1997 August; 44(8): 810-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9260007&dopt=Abstract

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Comparison of tramadol with morphine for post-operative pain following abdominal surgery. Author(s): Stubhaug A. Source: European Journal of Anaesthesiology. 1996 July; 13(4): 416-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8842669&dopt=Abstract

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Comparison of tramadol with morphine for post-operative pain following abdominal surgery. Author(s): Vickers MD, Paravicini D. Source: European Journal of Anaesthesiology. 1995 May; 12(3): 265-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7641716&dopt=Abstract

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Concordance between tramadol and dextromethorphan parent/metabolite ratios: the influence of CYP2D6 and non-CYP2D6 pathways on biotransformation. Author(s): Abdel-Rahman SM, Leeder JS, Wilson JT, Gaedigk A, Gotschall RR, Medve R, Liao S, Spielberg SP, Kearns GL. Source: Journal of Clinical Pharmacology. 2002 January; 42(1): 24-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11808821&dopt=Abstract

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Contribution of monoaminergic modulation to the analgesic effect of tramadol. Author(s): Desmeules JA, Piguet V, Collart L, Dayer P. Source: British Journal of Clinical Pharmacology. 1996 January; 41(1): 7-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8824687&dopt=Abstract

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Control of acute pain after major abdominal surgery in 585 patients given tramadol and ketorolac by intravenous infusion. Author(s): Pieri M, Meacci L, Santini L, Santini G, Dollorenzo R, Sansevero A. Source: Drugs Exp Clin Res. 2002; 28(2-3): 113-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12224377&dopt=Abstract

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Control of non-malignant chronic pain conditions in Japan and the possible future role of tramadol. Author(s): Itoh T. Source: European Journal of Pain (London, England). 2001; 5 Suppl A: 87-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798225&dopt=Abstract

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Control of shivering under regional anesthesia in obstetric patients with tramadol. Author(s): Chan AM, Ng KF, Tong EW, Jan GS. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1999 March; 46(3): 253-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10210050&dopt=Abstract

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Correlation of tramadol pharmacokinetics and CYP2D6*10 genotype in Malaysian subjects. Author(s): Gan SH, Ismail R, Wan Adnan WA, Wan Z. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 September 5; 30(2): 189-195. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12191703&dopt=Abstract

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Criteria for use of tramadol hydrochloride in adult inpatients and outpatients. Author(s): Taniguchi G, Icaza I. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 1997 March 15; 54(6): 696-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9075503&dopt=Abstract

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Debilitating reaction following the initial dose of tramadol. Author(s): Gleason PP, Frye RF, O'Toole T. Source: The Annals of Pharmacotherapy. 1997 October; 31(10): 1150-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9337439&dopt=Abstract

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Dependence on tramadol. Author(s): Ehrenreich H, Poser W. Source: Clin Investig. 1993 December; 72(1): 76. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8136623&dopt=Abstract

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Determination of tramadol by capillary gas chromatography with flame ionization detection. Application to human and rabbit pharmacokinetic studies. Author(s): Ho ST, Wan JJ, Liaw WJ, Ho CM, Li JH. Source: J Chromatogr B Biomed Sci Appl. 1999 December 24; 736(1-2): 89-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10676987&dopt=Abstract

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Determination of tramadol in human plasma by capillary gas chromatography-mass spectrometry using solid-phase extraction. Author(s): Merslavic M, Zupancic-Kralj L. Source: J Chromatogr B Biomed Sci Appl. 1997 May 23; 693(1): 222-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9200539&dopt=Abstract

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Determination of tramadol in human serum by capillary gas chromatography with nitrogen-selective detection. Author(s): Becker R, Lintz W. Source: Journal of Chromatography. 1986 April 25; 377: 213-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3711210&dopt=Abstract

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Direct chiral assay of tramadol and detection of the phase II metabolite O-demethyl tramadol glucuronide in human urine using capillary electrophoresis with laserinduced native fluorescence detection. Author(s): Soetebeer UB, Schierenberg MO, Schulz H, Andresen P, Blaschke G. Source: J Chromatogr B Biomed Sci Appl. 2001 December 5; 765(1): 3-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11817307&dopt=Abstract

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Direct determination of tramadol glucuronides in human urine by high-performance liquid chromatography with fluorescence detection. Author(s): Overbeck P, Blaschke G. Source: J Chromatogr B Biomed Sci Appl. 1999 September 10; 732(1): 185-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517235&dopt=Abstract

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Dose dependent time course of the analgesic effect of a sustained-release preparation of tramadol on experimental phasic and tonic pain. Author(s): Thurauf N, Fleischer WK, Liefhold J, Schmid O, Kobal G. Source: British Journal of Clinical Pharmacology. 1996 February; 41(2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8838437&dopt=Abstract

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Double-blind randomized study of tramadol vs. paracetamol in analgesia after daycase tonsillectomy in children. Author(s): Pendeville PE, Von Montigny S, Dort JP, Veyckemans F. Source: European Journal of Anaesthesiology. 2000 September; 17(9): 576-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11029125&dopt=Abstract

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Double-blind randomized trial of tramadol for the treatment of the pain of diabetic neuropathy. Author(s): Harati Y, Gooch C, Swenson M, Edelman S, Greene D, Raskin P, Donofrio P, Cornblath D, Sachdeo R, Siu CO, Kamin M. Source: Neurology. 1998 June; 50(6): 1842-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9633738&dopt=Abstract

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Double-blind study with dipyrone versus tramadol and butylscopolamine in acute renal colic pain. Author(s): Stankov G, Schmieder G, Zerle G, Schinzel S, Brune K. Source: World Journal of Urology. 1994; 12(3): 155-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7951343&dopt=Abstract

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Double-blind, single-dose comparison of bromfenac sodium, tramadol, and placebo after oral surgery. Author(s): Mehlisch DR. Source: Journal of Clinical Pharmacology. 1998 May; 38(5): 455-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9602960&dopt=Abstract

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Drug dependence and abuse potential of tramadol. Author(s): Liu ZM, Zhou WH, Lian Z, Mu Y, Ren ZH, Cao JQ, Cai ZJ. Source: Zhongguo Yao Li Xue Bao. 1999 January; 20(1): 52-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10437125&dopt=Abstract

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Drug dependence potential of 1-(m-methoxyphenyl)-2-dimethylaminomethyl)cyclohexan-1-ol hydrochloride (tramadol) tested in monkeys. Author(s): Yanagita T. Source: Arzneimittel-Forschung. 1978; 28(1A): 158-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=415747&dopt=Abstract

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Effect of intrathecal tramadol administration on postoperative pain after transurethral resection of prostate. Author(s): Alhashemi JA, Kaki AM. Source: British Journal of Anaesthesia. 2003 October; 91(4): 536-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14504156&dopt=Abstract

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Effect of modern analgesic drugs (tramadol, pentazocine, and buprenorphine) on the bile duct sphincter in man. Author(s): Staritz M, Poralla T, Manns M, Meyer Zum Buschenfelde KH. Source: Gut. 1986 May; 27(5): 567-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3699566&dopt=Abstract

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Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis. Author(s): Wilder-Smith CH, Hill L, Osler W, O'Keefe S. Source: Digestive Diseases and Sciences. 1999 June; 44(6): 1107-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10389680&dopt=Abstract

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Effect of tramadol on depth of anaesthesia. Author(s): Coetzee JF, Maritz JS, du Toit JC. Source: British Journal of Anaesthesia. 1996 March; 76(3): 415-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8785144&dopt=Abstract

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Effect of tramadol on electroencephalographic and auditory-evoked response variables during light anaesthesia. Author(s): Vaughan DJ, Shinner G, Thornton C, Brunner MD. Source: British Journal of Anaesthesia. 2000 November; 85(5): 705-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11094584&dopt=Abstract

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Effectiveness of tramadol as an analgesic in oral surgery. Author(s): Kumara R, Zacharias M. Source: N Z Dent J. 2002 March; 98(431): 9-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12017904&dopt=Abstract

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Effects of morphine and tramadol on somatic and visceral sensory function and gastrointestinal motility after abdominal surgery. Author(s): Wilder-Smith CH, Hill L, Wilkins J, Denny L. Source: Anesthesiology. 1999 September; 91(3): 639-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10485772&dopt=Abstract

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Effects of tramadol and meperidine on respiration, plasma catecholamine concentrations, and hemodynamics. Author(s): Mildh LH, Leino KA, Kirvela OA. Source: Journal of Clinical Anesthesia. 1999 June; 11(4): 310-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10470633&dopt=Abstract

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Effects of tramadol and tilidine/naloxone on oral-caecal transit and pupillary light reflex. Author(s): Freye E, Latasch L. Source: Arzneimittel-Forschung. 2000 January; 50(1): 24-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10683712&dopt=Abstract

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Effects of tramadol in humans: assessment of its abuse potential. Author(s): Preston KL, Jasinski DR. Source: Nida Res Monogr. 1989; 95: 392. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2701307&dopt=Abstract

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Efficacy and safety of dipyrone versus tramadol in the management of pain after hysterectomy: a randomized, double-blind, multicenter study. Author(s): Torres LM, Rodriguez MJ, Montero A, Herrera J, Calderon E, Cabrera J, Porres R, de la Torre MR, Martinez T, Gomez JL, Ruiz J, Garcia-Magaz I, Camara J, Ortiz P. Source: Regional Anesthesia and Pain Medicine. 2001 March-April; 26(2): 118-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11251134&dopt=Abstract

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Efficacy and safety of oral tramadol and pentazocine for postoperative pain following prolapsed intervertebral disc repair. Author(s): Kupers R, Callebaut V, Debois V, Camu F, Verborgh C, Coppejans H, Adriaensen H. Source: Acta Anaesthesiol Belg. 1995; 46(1): 31-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7618427&dopt=Abstract

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Efficacy and safety of tramadol HCl in breakthrough musculoskeletal pain attributed to osteoarthritis. Author(s): Roth SH. Source: The Journal of Rheumatology. 1998 July; 25(7): 1358-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9676769&dopt=Abstract

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Efficacy and safety of tramadol versus morphine for moderate and severe postoperative pain with special regard to respiratory depression. Author(s): Houmes RJ, Voets MA, Verkaaik A, Erdmann W, Lachmann B. Source: Anesthesia and Analgesia. 1992 April; 74(4): 510-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1554117&dopt=Abstract

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Efficacy and side effects of tramadol versus oxycodone for patient-controlled analgesia after maxillofacial surgery. Author(s): Silvasti M, Tarkkila P, Tuominen M, Svartling N, Rosenberg PH. Source: European Journal of Anaesthesiology. 1999 December; 16(12): 834-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10747212&dopt=Abstract

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Efficacy and tolerability of lornoxicam versus tramadol in postoperative pain. Author(s): Staunstrup H, Ovesen J, Larsen UT, Elbaek K, Larsen U, Kroner K. Source: Journal of Clinical Pharmacology. 1999 August; 39(8): 834-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10434236&dopt=Abstract

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Efficacy of tramadol in treatment of chronic low back pain. Author(s): Schnitzer TJ, Gray WL, Paster RZ, Kamin M. Source: The Journal of Rheumatology. 2000 March; 27(3): 772-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10743823&dopt=Abstract

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Efficacy of tramadol in treatment of chronic low back pain. Author(s): Whitney E. Source: The Journal of Rheumatology. 2000 December; 27(12): 2938. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11128691&dopt=Abstract

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Enantiomeric determination of tramadol and its main metabolite Odesmethyltramadol in human plasma by liquid chromatography-tandem mass spectrometry. Author(s): Ceccato A, Vanderbist F, Pabst JY, Streel B. Source: J Chromatogr B Biomed Sci Appl. 2000 October 1; 748(1): 65-76. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11092587&dopt=Abstract

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Enantiomeric separation of tramadol and its active metabolite in human plasma by chiral high-performance liquid chromatography: application to pharmacokinetic studies. Author(s): Campanero MA, Calahorra B, Valle M, Troconiz IF, Honorato J. Source: Chirality. 1999; 11(4): 272-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10224654&dopt=Abstract

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Enantiomeric separation of tramadol hydrochloride and its metabolites by cyclodextrin-mediated capillary zone electrophoresis. Author(s): Chan EC, Ho PC. Source: J Chromatogr B Biomed Sci Appl. 1998 April 10; 707(1-2): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9613961&dopt=Abstract

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Epidural tramadol for postoperative pain after Cesarean section. Author(s): Siddik-Sayyid S, Aouad-Maroun M, Sleiman D, Sfeir M, Baraka A. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1999 August; 46(8): 731-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10451131&dopt=Abstract

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Epidural tramadol for postoperative pain relief. Author(s): Delilkan AE, Vijayan R. Source: Anaesthesia. 1993 April; 48(4): 328-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8494137&dopt=Abstract

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Epidural tramadol for postoperative pain relief. Author(s): Fu YP, Chan KH, Lee TK, Chang JC, Daiy YP, Lee TY. Source: Ma Zui Xue Za Zhi. 1991 September; 29(3): 648-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1758261&dopt=Abstract

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Evaluation of intravenous tramadol for use in the prehospital situation by ambulance paramedics. Author(s): Ward ME, Radburn J, Morant S. Source: Prehospital Disaster Med. 1997 April-June; 12(2): 158-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10187002&dopt=Abstract

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Evaluation of the combination of flurbiprofen and tramadol for management of endodontic pain. Author(s): Doroschak AM, Bowles WR, Hargreaves KM. Source: Journal of Endodontics. 1999 October; 25(10): 660-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10687523&dopt=Abstract

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Fatal hepatic failure following accidental tramadol overdose. Author(s): Loughrey MB, Loughrey CM, Johnston S, O'Rourke D. Source: Forensic Science International. 2003 July 8; 134(2-3): 232-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12850423&dopt=Abstract

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Fatal overdose of tramadol and alprazolam. Author(s): Michaud K, Augsburger M, Romain N, Giroud C, Mangin P. Source: Forensic Science International. 1999 November 8; 105(3): 185-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10643652&dopt=Abstract

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Fatal overdoses of tramadol: is benzodiazepine a risk factor of lethality? Author(s): Clarot F, Goulle JP, Vaz E, Proust B. Source: Forensic Science International. 2003 June 24; 134(1): 57-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12842359&dopt=Abstract

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Fatality due to ingestion of tramadol alone. Author(s): Musshoff F, Madea B. Source: Forensic Science International. 2001 February 15; 116(2-3): 197-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11182272&dopt=Abstract

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Galactorrhoea induced by a pharmacodynamic interaction between citalopram, alprazolam and tramadol: a case report. Author(s): Bondolfi G, Rubin C, Bryois C, Eap CB. Source: Therapie. 1997 January-February; 52(1): 76-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9183928&dopt=Abstract

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Hear my song: auditory hallucinations with tramadol hydrochloride. Author(s): Keeley PW, Foster G, Whitelaw L. Source: Bmj (Clinical Research Ed.). 2000 December 23-30; 321(7276): 1608. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11124199&dopt=Abstract

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High-dose tramadol in comparison to low-dose morphine for cancer pain relief. Author(s): Grond S, Radbruch L, Meuser T, Loick G, Sabatowski R, Lehmann KA. Source: Journal of Pain and Symptom Management. 1999 September; 18(3): 174-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10517038&dopt=Abstract

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High-performance liquid chromatographic assay for the simultaneous determination of tramadol and its metabolites in microsomal fractions of human liver. Author(s): Paar WD, Frankus P, Dengler HJ. Source: Journal of Chromatography. B, Biomedical Applications. 1996 November 15; 686(2): 221-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8971603&dopt=Abstract

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High-performance liquid chromatographic determination of tramadol and its Odesmethylated metabolite in blood plasma. Application to a bioequivalence study in humans. Author(s): Nobilis M, Kopecky J, Kvetina J, Chladek J, Svoboda Z, Vorisek V, Perlik F, Pour M, Kunes J. Source: J Chromatogr A. 2002 March 8; 949(1-2): 11-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11999728&dopt=Abstract

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High-performance liquid chromatographic determination of tramadol in human plasma. Author(s): Nobilis M, Pastera J, Anzenbacher P, Svoboda D, Kopecky J, Perlik F. Source: Journal of Chromatography. B, Biomedical Applications. 1996 May 31; 681(1): 177-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8798927&dopt=Abstract

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High-performance liquid chromatographic method for determination of tramadol in human plasma. Author(s): Yeh GC, Sheu MT, Yen CL, Wang YW, Liu CH, Ho HO. Source: J Chromatogr B Biomed Sci Appl. 1999 February 19; 723(1-2): 247-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080652&dopt=Abstract

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How to taper tramadol dose. Author(s): Belgrade MJ. Source: Postgraduate Medicine. 2002 February; 111(2): 111. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868307&dopt=Abstract

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Identification of cytochrome P-450 isoforms responsible for cis-tramadol metabolism in human liver microsomes. Author(s): Subrahmanyam V, Renwick AB, Walters DG, Young PJ, Price RJ, Tonelli AP, Lake BG. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 2001 August; 29(8): 1146-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11454734&dopt=Abstract

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Identification of tramadol and its metabolites in blood from drug-related deaths and drug-impaired drivers. Author(s): Goeringer KE, Logan BK, Christian GD. Source: Journal of Analytical Toxicology. 1997 November-December; 21(7): 529-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9399121&dopt=Abstract

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Impact of CYP2D6 genotype on postoperative tramadol analgesia. Author(s): Stamer UM, Lehnen K, Hothker F, Bayerer B, Wolf S, Hoeft A, Stuber F. Source: Pain. 2003 September; 105(1-2): 231-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499440&dopt=Abstract

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Impact of experimentally-induced expectancy on the analgesic efficacy of tramadol in chronic pain patients: a 2 x 2 factorial, randomized, placebo-controlled, double-blind trial. Author(s): de Craen AJ, Lampe-Schoenmaeckers AJ, Kraal JW, Tijssen JG, Kleijnen J. Source: Journal of Pain and Symptom Management. 2001 March; 21(3): 210-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11239740&dopt=Abstract

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In vitro metabolism of the analgesic agent, tramadol-N-oxide, in mouse, rat, and human. Author(s): Wu WN, McKown LA, Codd EE, Raffa RB. Source: Eur J Drug Metab Pharmacokinet. 2002 July-September; 27(3): 193-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12365201&dopt=Abstract

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Incidence of first-time idiopathic seizures in users of tramadol. Author(s): Gasse C, Derby L, Vasilakis-Scaramozza C, Jick H. Source: Pharmacotherapy. 2000 June; 20(6): 629-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10853617&dopt=Abstract

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Increased nausea and dizziness when using tramadol for post-operative patientcontrolled analgesia (PCA) compared with morphine after intraoperative loading with morphine. Author(s): Ng KF, Tsui SL, Yang JC, Ho ET. Source: European Journal of Anaesthesiology. 1998 September; 15(5): 565-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9785072&dopt=Abstract

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Ineffective analgesia after extradural tramadol hydrochloride in patients undergoing total knee replacement. Author(s): Grace D, Fee JP. Source: Anaesthesia. 1995 June; 50(6): 555-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7618676&dopt=Abstract

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Influence of oral tramadol on the dynamic ventilatory response to carbon dioxide in healthy volunteers. Author(s): Nieuwenhuijs D, Bruce J, Drummond GB, Warren PM, Dahan A. Source: British Journal of Anaesthesia. 2001 December; 87(6): 860-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11878687&dopt=Abstract

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Influence of pre- or intraoperational use of tramadol (preemptive or preventive analgesia) on tramadol requirement in the early postoperative period. Author(s): Wordliczek J, Banach M, Garlicki J, Jakowicka-Wordliczek J, Dobrogowski J. Source: Polish Journal of Pharmacology. 2002 November-December; 54(6): 693-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12866726&dopt=Abstract

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Influence of tramadol on the ventilatory response to hypoxia in humans. Author(s): Warren PM, Taylor JH, Nicholson KE, Wraith PK, Drummond GB. Source: British Journal of Anaesthesia. 2000 August; 85(2): 211-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992826&dopt=Abstract

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Influences of tramadol on emergence characteristics from sevoflurane anesthesia in pediatric ambulatory surgery. Author(s): Fan KT, Lee TH, Yu KL, Tang CS, Lu DV, Chen PY, Soo LY. Source: Kaohsiung J Med Sci. 2000 May; 16(5): 255-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969521&dopt=Abstract

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Interaction between tramadol and phenprocoumon. Author(s): Madsen H, Rasmussen JM, Brosen K. Source: Lancet. 1997 August 30; 350(9078): 637. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9288050&dopt=Abstract

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Intradermal injection of tramadol has local anesthetic effect: a comparison with lidocaine. Author(s): Pang WW, Mok MS, Chang DP, Yang TF, Lin CH, Huang MH. Source: Acta Anaesthesiol Sin. 1998 September; 36(3): 133-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9874860&dopt=Abstract

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Intraoperative loading attenuates nausea and vomiting of tramadol patient-controlled analgesia. Author(s): Pang WW, Mok MS, Huang S, Hung CP, Huang MH. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2000 October; 47(10): 968-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11032271&dopt=Abstract

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Intravenous regional anaesthesia using lignocaine and tramadol. Author(s): Tan SM, Pay LL, Chan ST. Source: Ann Acad Med Singapore. 2001 September; 30(5): 516-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11603137&dopt=Abstract

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Intravenous single-dose tramadol versus meperidine for pain relief in renal colic. Author(s): Eray O, Cete Y, Oktay C, Karsli B, Akca S, Cete N, Ersoy F. Source: European Journal of Anaesthesiology. 2002 May; 19(5): 368-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12095018&dopt=Abstract

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Intravenous tramadol compared to propacetamol for postoperative analgesia following thyroidectomy. Author(s): Dejonckheere M, Desjeux L, Deneu S, Ewalenko P. Source: Acta Anaesthesiol Belg. 2001; 52(1): 29-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11307656&dopt=Abstract

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Intravenous tramadol for post-operative pain--comparison of intermittent dose regimens with and without maintenance infusion. Author(s): Chrubasik J, Buzina M, Schulte-Monting J, Atanassoff P, Alon E. Source: European Journal of Anaesthesiology. 1992 January; 9(1): 23-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1735395&dopt=Abstract

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Intravenous tramadol versus epidural morphine for postthoracotomy pain relief: a placebo-controlled double-blind trial. Author(s): James MF, Heijke SA, Gordon PC. Source: Anesthesia and Analgesia. 1996 July; 83(1): 87-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8659771&dopt=Abstract

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Investigation of racial variations in the metabolism of tramadol. Author(s): Ogunleye DS. Source: Eur J Drug Metab Pharmacokinet. 2001 January-June; 26(1-2): 95-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11554441&dopt=Abstract

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Is there interaction between tramadol and phenprocoumon? Author(s): Boeijinga JK, van Meegen E, van den Ende R, Schook CE, Cohen AF. Source: Lancet. 1997 November 22; 350(9090): 1552-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9388428&dopt=Abstract

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Is tramadol an antidepressant? Author(s): Halfpenny DM, Callado LF, Stamford JA. Source: British Journal of Anaesthesia. 1999 March; 82(3): 480-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10434840&dopt=Abstract

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Ketorolac vs tramadol in the treatment of postoperative pain during maxillofacial surgery. Author(s): Zackova M, Taddei S, Calo P, Bellocchio A, Zanello M. Source: Minerva Anestesiol. 2001 September; 67(9): 641-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11731754&dopt=Abstract

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Labelling studies for structure elucidation of a new hydroxymetabolite of tramadol. Author(s): Potyka U, Paar WD, Sauerbruch T, von Unruh GE. Source: Isotopes in Environmental and Health Studies. 1998; 34(1-2): 119-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9854846&dopt=Abstract

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Lack of analgesic effect of 50 and 100 mg oral tramadol after orthopaedic surgery: a randomized, double-blind, placebo and standard active drug comparison. Author(s): Stubhaug A, Grimstad J, Breivik H. Source: Pain. 1995 July; 62(1): 111-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7478700&dopt=Abstract

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Lack of interaction between tramadol and coumarins. Author(s): Boeijinga JK, van Meegen E, van den Ende R, Schook CE, Cohen AF. Source: Journal of Clinical Pharmacology. 1998 October; 38(10): 966-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9807979&dopt=Abstract

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Lethal combination of tramadol and multiple drugs affecting serotonin. Author(s): Ripple MG, Pestaner JP, Levine BS, Smialek JE. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 2000 December; 21(4): 370-4. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11111800&dopt=Abstract

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Local anesthetic effect of tramadol, metoclopramide, and lidocaine following intradermal injection. Author(s): Pang WW, Mok MS, Chang DP, Huang MH. Source: Regional Anesthesia and Pain Medicine. 1998 November-December; 23(6): 580-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9840854&dopt=Abstract

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Maintenance of the long-term effectiveness of tramadol in treatment of the pain of diabetic neuropathy. Author(s): Harati Y, Gooch C, Swenson M, Edelman SV, Greene D, Raskin P, Donofrio P, Cornblath D, Olson WH, Kamin M. Source: Journal of Diabetes and Its Complications. 2000 March-April; 14(2): 65-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10959067&dopt=Abstract

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Mania and tramadol-fluoxetine combination. Author(s): Gonzalez-Pinto A, Imaz H, De Heredia JL, Gutierrez M, Mico JA. Source: The American Journal of Psychiatry. 2001 June; 158(6): 964-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11384912&dopt=Abstract

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Metabolism of the analgesic drug ULTRAM (tramadol hydrochloride) in humans: API-MS and MS/MS characterization of metabolites. Author(s): Wu WN, McKown LA, Liao S. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 2002 May; 32(5): 411-25. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12065063&dopt=Abstract

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Methadone detoxification of tramadol dependence. Author(s): Leo RJ, Narendran R, DeGuiseppe B. Source: Journal of Substance Abuse Treatment. 2000 October; 19(3): 297-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11027901&dopt=Abstract

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Method development and validation of a high-performance liquid chromatographic method for tramadol in human plasma using liquid-liquid extraction. Author(s): Gan SH, Ismail R, Wan Adnan WA, Wan Z. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 May 25; 772(1): 123-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12016023&dopt=Abstract

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Metoclopramide decreases emesis but increases sedation in tramadol patientcontrolled analgesia. Author(s): Pang WW, Wu HS, Lin CH, Chang DP, Huang MH. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 December; 49(10): 1029-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12477672&dopt=Abstract

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Mood alterations and tramadol. Author(s): Pinkofsky HB, Woodward RA, Reeves RR. Source: The American Journal of Psychiatry. 1996 June; 153(6): 843-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8633712&dopt=Abstract

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Multicenter trial comparing tramadol and morphine for pain after abdominal surgery. Author(s): Gritti G, Verri M, Launo C, Palermo S, Novelli GP, Casali R, Paoletti F, Boanelli A, Tufano R, Leone D. Source: Drugs Exp Clin Res. 1998; 24(1): 9-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9604144&dopt=Abstract

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Nefopam and tramadol for the prevention of shivering during neuraxial anesthesia. Author(s): Bilotta F, Pietropaoli P, Sanita' R, Liberatori G, Rosa G. Source: Regional Anesthesia and Pain Medicine. 2002 July-August; 27(4): 380-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12132062&dopt=Abstract

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New clinical experience with tramadol. Author(s): Sunshine A. Source: Drugs. 1994; 47 Suppl 1: 8-18. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7517826&dopt=Abstract

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New reports on dental analgesics. NSAIDs and cardiovascular effects, celecoxib for dental pain, and a new analgesic--tramadol with acetaminophen. Author(s): Wynn RL. Source: Gen Dent. 2002 May-June; 50(3): 218-20, 22. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12116507&dopt=Abstract

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Nightmares and hallucinations after long-term intake of tramadol combined with antidepressants. Author(s): Devulder J, De Laat M, Dumoulin K, Renson A, Rolly G. Source: Acta Clin Belg. 1996; 51(3): 184-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8766220&dopt=Abstract

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Nonsteroidal anti-inflammatory drugs, traditional opioids, and tramadol: contrasting therapies for the treatment of chronic pain. Author(s): Aronson MD. Source: Clinical Therapeutics. 1997 May-June; 19(3): 420-32; Discussion 367-8. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9220207&dopt=Abstract

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Novel use of tramadol hydrochloride in the treatment of Tourette's syndrome. Author(s): Shapira NA, McConville BJ, Pagnucco ML, Norman AB, Keck PE Jr. Source: The Journal of Clinical Psychiatry. 1997 April; 58(4): 174-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9164430&dopt=Abstract

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NSAIDS, COX-2 inhibitors and tramadol: acute postoperative pain management in day-case surgery patients. Author(s): Chan YW. Source: Singapore Med J. 2001 May; 42(5): 189-92. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11513053&dopt=Abstract

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Observer-blind study with metamizole versus tramadol and butylscopolamine in acute biliary colic pain. Author(s): Schmieder G, Stankov G, Zerle G, Schinzel S, Brune K. Source: Arzneimittel-Forschung. 1993 November; 43(11): 1216-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8292068&dopt=Abstract

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Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT(3) spinal receptor involvement in acute pain in humans. Author(s): Arcioni R, della Rocca M, Romano S, Romano R, Pietropaoli P, Gasparetto A. Source: Anesthesia and Analgesia. 2002 June; 94(6): 1553-7, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032025&dopt=Abstract

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Open-label pilot study of tramadol hydrochloride in treatment-refractory obsessivecompulsive disorder. Author(s): Shapira NA, Keck PE Jr, Goldsmith TD, McConville BJ, Eis M, McElroy SL. Source: Depression and Anxiety. 1997; 6(4): 170-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9559288&dopt=Abstract

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Opiate withdrawal after tramadol and patient-controlled analgesia. Author(s): Thomas AN, Suresh M. Source: Anaesthesia. 2000 August; 55(8): 826-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10947728&dopt=Abstract

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Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial. Author(s): Brema F, Pastorino G, Martini MC, Gottlieb A, Luzzani M, Libretti A, Sacca L, Cigolari S. Source: Int J Clin Pharmacol Res. 1996; 16(4-5): 109-16. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9172009&dopt=Abstract

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Oral tramadol for the treatment of pain of 7-30 days' duration in children. Author(s): Rose JB, Finkel JC, Arquedas-Mohs A, Himelstein BP, Schreiner M, Medve RA. Source: Anesthesia and Analgesia. 2003 January; 96(1): 78-81, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12505927&dopt=Abstract

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Oral tramadol, a mu-opioid agonist and monoamine reuptake-blocker, and morphine for strong cancer-related pain. Author(s): Wilder-Smith CH, Schimke J, Osterwalder B, Senn HJ. Source: Annals of Oncology : Official Journal of the European Society for Medical Oncology / Esmo. 1994 February; 5(2): 141-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8186157&dopt=Abstract

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Oral tramadol: analgesic efficacy in children following multiple dental extractions. Author(s): Roelofse JA, Payne KA. Source: European Journal of Anaesthesiology. 1999 July; 16(7): 441-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457875&dopt=Abstract

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Pain control after hysterectomy: an observer-blind, randomised trial of lornoxicam versus tramadol. Author(s): Ilias W, Jansen M. Source: Br J Clin Pract. 1996 June; 50(4): 197-202. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8759565&dopt=Abstract

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Pain management in dental practice: tramadol vs. codeine combinations. Author(s): Moore PA. Source: The Journal of the American Dental Association. 1999 July; 130(7): 1075-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10422401&dopt=Abstract

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Pain relief during and following outpatient curettage and hysterosalpingography: a double blind study to compare the efficacy and safety of tramadol versus naproxen. Cobra Research Group. Author(s): Peters AA, Witte EH, Damen AC, Holm JP, Drogendijk AC, vd Velde EA, Trimbos JB. Source: European Journal of Obstetrics, Gynecology, and Reproductive Biology. 1996 May; 66(1): 51-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8735759&dopt=Abstract

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Parenteral tramadol in postoperative pain relief. Author(s): Wang JH, Chan KH, Lee TY. Source: Ma Zui Xue Za Zhi. 1989 September; 27(3): 283-6. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2607917&dopt=Abstract

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Patient-controlled analgesia with tramadol versus tramadol plus lysine acetyl salicylate. Author(s): Pang W, Huang S, Tung CC, Huang MH. Source: Anesthesia and Analgesia. 2000 November; 91(5): 1226-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11049913&dopt=Abstract

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Patient-controlled epidural analgesia after major urologic surgeries. A comparison of tramadol with or without bupivacaine. Author(s): Aribogan A, Doruk N, Aridogan A, Akin S, Balcioglu O. Source: Urologia Internationalis. 2003; 71(2): 168-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12890955&dopt=Abstract

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Perioperative antinociceptive effects of tramadol. A prospective, randomized, doubleblind comparison with morphine. Author(s): Naguib M, Seraj M, Attia M, Samarkandi AH, Seet M, Jaroudi R. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1998 December; 45(12): 1168-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10051934&dopt=Abstract

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Peroral tramadol premedication increases postoperative nausea and delays homereadiness in day-case knee arthroscopy patients. Author(s): Liukkonen K, Santanen U, Pere P, Erkola O, Rautoma P. Source: Scand J Surg. 2002; 91(4): 365-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12558088&dopt=Abstract

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Pethidine versus tramadol for pain relief during labor. Author(s): Keskin HL, Keskin EA, Avsar AF, Tabuk M, Caglar GS. Source: International Journal of Gynaecology and Obstetrics: the Official Organ of the International Federation of Gynaecology and Obstetrics. 2003 July; 82(1): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12834936&dopt=Abstract

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Pharmacokinetic properties of tramadol sustained release capsules. 1st communication: investigation of dose linearity. Author(s): Schulz HU, Raber M, Schurer M, Amschler S, Momberger H. Source: Arzneimittel-Forschung. 1999 July; 49(7): 582-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10442205&dopt=Abstract

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Pharmacokinetic properties of tramadol sustained release capsules. 2nd communication: investigation of relative bioavailability and food interaction. Author(s): Raber M, Schulz HU, Schurer M, Bias-Imhoff U, Momberger H. Source: Arzneimittel-Forschung. 1999 July; 49(7): 588-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10442206&dopt=Abstract

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Pharmacokinetic properties of tramadol sustained release capsules. 3rd communication: investigation of relative bioavailability under steady state conditions. Author(s): Raber M, Schulz HU, Schurer M, Krupp S, Momberger H. Source: Arzneimittel-Forschung. 1999 July; 49(7): 594-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10442207&dopt=Abstract

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Pharmacokinetics of enantiomers of trans-tramadol and its active metabolite, trans-Odemethyltramadol, in human subjects. Author(s): Liu HC, Liu TJ, Yang YY, Hou YN. Source: Acta Pharmacologica Sinica. 2001 January; 22(1): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11730570&dopt=Abstract

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Pharmacokinetics of oral tramadol drops for postoperative pain relief in children aged 4 to 7 years--a pilot study. Author(s): Payne KA, Roelofse JA, Shipton EA. Source: Anesthesia Progress. 2002 Winter; 49(4): 109-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12779111&dopt=Abstract

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Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 2nd communication: drops with ethanol. Author(s): Lintz W, Barth H, Becker R, Frankus E, Schmidt-Bothelt E. Source: Arzneimittel-Forschung. 1998 May; 48(5): 436-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9638309&dopt=Abstract

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Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 3rd Communication: suppositories. Author(s): Lintz W, Barth H, Osterloh G, Schmidt-Bothelt E. Source: Arzneimittel-Forschung. 1998 September; 48(9): 889-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9793614&dopt=Abstract

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Pharmacokinetics of tramadol and bioavailability of enteral tramadol formulations. 4th communication: drops (without ethanol). Author(s): Lintz W, Becker R, Gerloff J, Terlinden R. Source: Arzneimittel-Forschung. 2000 February; 50(2): 99-108. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10719611&dopt=Abstract

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Pharmacokinetics of tramadol in a hemodialysis patient. Author(s): Izzedine H, Launay-Vacher V, Abbara C, Aymard G, Bassilios N, Deray G. Source: Nephron. 2002; 92(3): 755-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12372979&dopt=Abstract

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Pharmacokinetics of tramadol in children after i.v. or caudal epidural administration. Author(s): Murthy BV, Pandya KS, Booker PD, Murray A, Lintz W, Terlinden R. Source: British Journal of Anaesthesia. 2000 March; 84(3): 346-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10793594&dopt=Abstract

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Pharmacokinetics, efficacy, and safety of analgesia with a focus on tramadol HCl. Author(s): Gibson TP. Source: The American Journal of Medicine. 1996 July 31; 101(1A): 47S-53S. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8764760&dopt=Abstract

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Pharmacology and clinical experience with tramadol in osteoarthritis. Author(s): Katz WA. Source: Drugs. 1996; 52 Suppl 3: 39-47. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8911798&dopt=Abstract

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Physical dependence on Ultram (tramadol hydrochloride): both opioid-like and atypical withdrawal symptoms occur. Author(s): Senay EC, Adams EH, Geller A, Inciardi JA, Munoz A, Schnoll SH, Woody GE, Cicero TJ. Source: Drug and Alcohol Dependence. 2003 April 1; 69(3): 233-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12633909&dopt=Abstract

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Polymorphic CYP2D6 mediates O-demethylation of the opioid analgesic tramadol. Author(s): Paar WD, Poche S, Gerloff J, Dengler HJ. Source: European Journal of Clinical Pharmacology. 1997; 53(3-4): 235-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9476037&dopt=Abstract

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Possible interaction of tramadol and antidepressants. Author(s): Reus VI, Rawitscher L. Source: The American Journal of Psychiatry. 2000 May; 157(5): 839. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10784494&dopt=Abstract

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Possible serotonin syndrome associated with tramadol and sertraline coadministration. Author(s): Mason BJ, Blackburn KH. Source: The Annals of Pharmacotherapy. 1997 February; 31(2): 175-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9034418&dopt=Abstract

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Postanaesthetic shivering--a new look at tramadol. Author(s): Mathews S, Al Mulla A, Varghese PK, Radim K, Mumtaz S. Source: Anaesthesia. 2002 April; 57(4): 394-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11949644&dopt=Abstract

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Post-mortem SNP analysis of CYP2D6 gene reveals correlation between genotype and opioid drug (tramadol) metabolite ratios in blood. Author(s): Levo A, Koski A, Ojanpera I, Vuori E, Sajantila A. Source: Forensic Science International. 2003 July 29; 135(1): 9-15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12893130&dopt=Abstract

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Postoperative analgesia at home after ambulatory hand surgery: a controlled comparison of tramadol, metamizol, and paracetamol. Author(s): Rawal N, Allvin R, Amilon A, Ohlsson T, Hallen J. Source: Anesthesia and Analgesia. 2001 February; 92(2): 347-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11159230&dopt=Abstract

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Post-operative analgesia with tramadol: a controlled study compared with an analgesic combination. Author(s): Canepa G, Di Somma C, Ghia M, Vadala A, Reali M, Cerruti S, Stasi M, Trezzi P. Source: Int J Clin Pharmacol Res. 1993; 13(1): 43-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8509235&dopt=Abstract

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Post-operative effects of tramadol administered at wound closure. Author(s): De Witte J, Rietman GW, Vandenbroucke G, Deloof T. Source: European Journal of Anaesthesiology. 1998 March; 15(2): 190-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9587725&dopt=Abstract

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Postoperative patient-controlled analgesia with tramadol: analgesic efficacy and minimum effective concentrations. Author(s): Lehmann KA, Kratzenberg U, Schroeder-Bark B, Horrichs-Haermeyer G. Source: The Clinical Journal of Pain. 1990 September; 6(3): 212-20. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2135015&dopt=Abstract

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Postoperative sensitization and pain after cesarean delivery and the effects of single im doses of tramadol and diclofenac alone and in combination. Author(s): Wilder-Smith CH, Hill L, Dyer RA, Torr G, Coetzee E. Source: Anesthesia and Analgesia. 2003 August; 97(2): 526-33, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873948&dopt=Abstract

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Potential interaction between tramadol and warfarin. Author(s): Scher ML, Huntington NH, Vitillo JA. Source: The Annals of Pharmacotherapy. 1997 May; 31(5): 646-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9161668&dopt=Abstract

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Preemptive analgesia with tramadol and fentanyl in pediatric neurosurgery. Author(s): Chiaretti A, Viola L, Pietrini D, Piastra M, Savioli A, Tortorolo L, Caldarelli M, Stoppa F, Di Rocco C. Source: Child's Nervous System : Chns : Official Journal of the International Society for Pediatric Neurosurgery. 2000 February; 16(2): 93-9; Discussion 100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10663814&dopt=Abstract

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Pre-emptive analgesic efficacy of tramadol compared with morphine after major abdominal surgery. Author(s): Unlugenc H, Ozalevli M, Gunes Y, Guler T, Isik G. Source: British Journal of Anaesthesia. 2003 August; 91(2): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12878619&dopt=Abstract

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Preoperative adjuvant epidural tramadol: the effect of different doses on postoperative analgesia and pain processing. Author(s): Wilder-Smith CH, Wilder-Smith OH, Farschtschian M, Naji P. Source: Acta Anaesthesiologica Scandinavica. 1998 March; 42(3): 299-305. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9542556&dopt=Abstract

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Prospective and randomized trial of intravenous tenoxicam versus fentanyl and tramadol for analgesia in outpatient extracorporeal lithotripsy. Author(s): Chia YY, Liu K. Source: Acta Anaesthesiol Sin. 1998 March; 36(1): 17-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9807845&dopt=Abstract

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Prospective multicenter evaluation of tramadol exposure. Author(s): Spiller HA, Gorman SE, Villalobos D, Benson BE, Ruskosky DR, Stancavage MM, Anderson DL. Source: Journal of Toxicology. Clinical Toxicology. 1997; 35(4): 361-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9204095&dopt=Abstract

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Quantitative determination of tramadol in human serum by gas chromatographymass spectrometry. Author(s): Lintz W, Uragg H. Source: Journal of Chromatography. 1985 May 31; 341(1): 65-79. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4019697&dopt=Abstract

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Rapid remission of OCD with tramadol hydrochloride. Author(s): Goldsmith TB, Shapira NA, Keck PE Jr. Source: The American Journal of Psychiatry. 1999 April; 156(4): 660-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10200754&dopt=Abstract

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Recovery following tonsillectomy a comparison between tramadol and morphine for analgesia. Author(s): Chew ST, Ip-Yam PC, Kong CF. Source: Singapore Med J. 2003 June; 44(6): 296-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14560861&dopt=Abstract

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Relief of posttonsillectomy pain with low-dose tramadol given at induction of anesthesia in children. Author(s): Ozkose Z, Akcabay M, Kemaloglu YK, Sezenler S. Source: International Journal of Pediatric Otorhinolaryngology. 2000 July 14; 53(3): 20714. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10930636&dopt=Abstract

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Remifentanil and tramadol. Author(s): Duthie DJ. Source: British Journal of Anaesthesia. 1998 July; 81(1): 51-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9771272&dopt=Abstract

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Respiratory and analgesic effects of meperidine and tramadol in patients undergoing orthopedic surgery. Author(s): Tarradell R, Pol O, Farre M, Barrera E, Puig MM. Source: Methods Find Exp Clin Pharmacol. 1996 April; 18(3): 211-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8738073&dopt=Abstract

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Respiratory depression following oral tramadol in a patient with impaired renal function. Author(s): Barnung SK, Treschow M, Borgbjerg FM. Source: Pain. 1997 May; 71(1): 111-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9200181&dopt=Abstract

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Role of epidural tramadol hydrochloride on postoperative pain relief in caesarean section delivery. Author(s): Pan AK, Mukherjee P, Rudra A. Source: J Indian Med Assoc. 1997 April; 95(4): 105-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9357271&dopt=Abstract

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Role of tramadol in reducing pain on propofol injection. Author(s): Wong WH, Cheong KF. Source: Singapore Med J. 2001 May; 42(5): 193-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11513054&dopt=Abstract

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Seizure after overdose of tramadol. Author(s): Tobias JD. Source: Southern Medical Journal. 1997 August; 90(8): 826-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9258310&dopt=Abstract

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Seizures reported with tramadol. Author(s): Kahn LH, Alderfer RJ, Graham DJ. Source: Jama : the Journal of the American Medical Association. 1997 November 26; 278(20): 1661. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9388083&dopt=Abstract

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Serotonin syndrome as a result of fluoxetine in a patient with tramadol abuse: plasma level-correlated symptomatology. Author(s): Lange-Asschenfeldt C, Weigmann H, Hiemke C, Mann K. Source: Journal of Clinical Psychopharmacology. 2002 August; 22(4): 440-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12172351&dopt=Abstract

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Serotonin syndrome attributed to tramadol addition to paroxetine therapy. Author(s): Egberts AC, ter Borgh J, Brodie-Meijer CC. Source: International Clinical Psychopharmacology. 1997 May; 12(3): 181-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9248876&dopt=Abstract

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Serotonin syndrome following the administration of tramadol with paroxetine. Author(s): Lantz MS, Buchalter EN, Giambanco V. Source: International Journal of Geriatric Psychiatry. 1998 May; 13(5): 343-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9658268&dopt=Abstract

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Serotonin syndrome with fluoxetine plus tramadol. Author(s): Kesavan S, Sobala GM. Source: Journal of the Royal Society of Medicine. 1999 September; 92(9): 474-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10645303&dopt=Abstract

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Serum concentrations of tramadol enantiomers during patient-controlled analgesia. Author(s): Grond S, Meuser T, Uragg H, Stahlberg HJ, Lehmann KA. Source: British Journal of Clinical Pharmacology. 1999 August; 48(2): 254-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10417506&dopt=Abstract

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Severe cerebral depression after intoxication with tramadol in a 6-month-old infant. Author(s): Riedel F, von Stockhausen HB. Source: European Journal of Clinical Pharmacology. 1984; 26(5): 631-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6468480&dopt=Abstract

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Simultaneous stereoselective analysis by capillary electrophoresis of tramadol enantiomers and their main phase I metabolites in urine. Author(s): Rudaz S, Veuthey JL, Desiderio C, Fanali S. Source: J Chromatogr A. 1999 June 18; 846(1-2): 227-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10420614&dopt=Abstract

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Simultaneous stereoselective analysis of tramadol and its main phase I metabolites by on-line capillary zone electrophoresis-electrospray ionization mass spectrometry. Author(s): Ruda S, Cherkaoui S, Dayer P, Fanali S, Veuthey JL. Source: J Chromatogr A. 2000 February 4; 868(2): 295-303. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10701679&dopt=Abstract

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Single-patient data meta-analysis of 3453 postoperative patients: oral tramadol versus placebo, codeine and combination analgesics. Author(s): Moore RA, McQuay HJ. Source: Pain. 1997 February; 69(3): 287-94. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9085303&dopt=Abstract

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Slowing the initial titration rate of tramadol improves tolerability. Author(s): Ruoff GE. Source: Pharmacotherapy. 1999 January; 19(1): 88-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9917081&dopt=Abstract

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Slowing the titration rate of tramadol HCl reduces the incidence of discontinuation due to nausea and/or vomiting: a double-blind randomized trial. Author(s): Petrone D, Kamin M, Olson W. Source: Journal of Clinical Pharmacy and Therapeutics. 1999 April; 24(2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10380063&dopt=Abstract

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Slow-release tramadol for treatment of chronic malignant pain--an open multicenter trial. Author(s): Petzke F, Radbruch L, Sabatowski R, Karthaus M, Mertens A. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2001 January; 9(1): 48-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11147143&dopt=Abstract

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Studies on dependence on tramadol in rats. Author(s): Murano T, Yamamoto H, Endo N, Kudo Y, Okada N, Masuda Y, Yano I. Source: Arzneimittel-Forschung. 1978; 28(1A): 152-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=580209&dopt=Abstract

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Suicide by tramadol overdose. Author(s): Lusthof KJ, Zweipfenning PG. Source: Journal of Analytical Toxicology. 1998 May-June; 22(3): 260. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9669891&dopt=Abstract

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Supplementation of general anaesthesia with tramadol or fentanyl in parturients undergoing elective caesarean section. Author(s): Baraka A, Siddik S, Assaf B. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 1998 July; 45(7): 631-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9717593&dopt=Abstract

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The addition of a tramadol infusion to morphine patient-controlled analgesia after abdominal surgery: a double-blinded, placebo-controlled randomized trial. Author(s): Webb AR, Leong S, Myles PS, Burn SJ. Source: Anesthesia and Analgesia. 2002 December; 95(6): 1713-8, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12456445&dopt=Abstract

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The addition of droperidol or clonidine to epidural tramadol shortens onset time and increases duration of postoperative analgesia. Author(s): Gurses E, Sungurtekin H, Tomatir E, Balci C, Gonullu M. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2003 February; 50(2): 147-52. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560305&dopt=Abstract

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The addition of tramadol to lidocaine does not reduce tourniquet and postoperative pain during iv regional anesthesia. Author(s): Langlois G, Estebe JP, Gentili ME, Kerdiles L, Mouilleron P, Ecoffey C. Source: Canadian Journal of Anaesthesia = Journal Canadien D'anesthesie. 2002 February; 49(2): 165-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11823394&dopt=Abstract

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The analgesic efficacy of tramadol versus ketorolac in day-case laparoscopic sterilisation. Author(s): Putland AJ, McCluskey A. Source: Anaesthesia. 1999 April; 54(4): 382-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10455841&dopt=Abstract

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The effect of tramadol in painful polyneuropathy in relation to serum drug and metabolite levels. Author(s): Sindrup SH, Madsen C, Brosen K, Jensen TS. Source: Clinical Pharmacology and Therapeutics. 1999 December; 66(6): 636-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10613620&dopt=Abstract

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The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients. Author(s): Sacerdote P, Bianchi M, Gaspani L, Manfredi B, Maucione A, Terno G, Ammatuna M, Panerai AE. Source: Anesthesia and Analgesia. 2000 June; 90(6): 1411-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10825330&dopt=Abstract

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The effects of tramadol on postoperative nausea, vomiting and headache after ENT surgery. A placebo-controlled comparison with equipotent doses of nalbuphine and pethidine. Author(s): van den Berg AA, Halliday E, Lule EK, Baloch MS. Source: Acta Anaesthesiologica Scandinavica. 1999 January; 43(1): 28-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9926184&dopt=Abstract

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The effects of tramadol versus fentanyl in attenuating hemodynamic response following tracheal intubation. Author(s): Pang WW, Lei CH, Chang DP, Tung CC, Huang MH. Source: Acta Anaesthesiol Sin. 1999 December; 37(4): 191-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10670117&dopt=Abstract

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The effects of two single doses of tramadol on sleep: a randomized, cross-over trial in healthy volunteers. Author(s): Walder B, Tramer MR, Blois R. Source: European Journal of Anaesthesiology. 2001 January; 18(1): 36-42. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11270008&dopt=Abstract

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The experimental toxicology of tramadol: an overview. Author(s): Matthiesen T, Wohrmann T, Coogan TP, Uragg H. Source: Toxicology Letters. 1998 March 16; 95(1): 63-71. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9650647&dopt=Abstract

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The peripheral analgesic effect of tramadol in reducing propofol injection pain: a comparison with lidocaine. Author(s): Pang WW, Huang PY, Chang DP, Huang MH. Source: Regional Anesthesia and Pain Medicine. 1999 May-June; 24(3): 246-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10338176&dopt=Abstract

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The prevention of pain from injection of rocuronium by ondansetron, lidocaine, tramadol, and fentanyl. Author(s): Memis D, Turan A, Karamanlioglu B, Sut N, Pamukcu Z. Source: Anesthesia and Analgesia. 2002 June; 94(6): 1517-20, Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12032018&dopt=Abstract

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The prevention of propofol injection pain by tramadol or ondansetron. Author(s): Memis D, Turan A, Karamanlioglu B, Kaya G, Pamukcu Z. Source: European Journal of Anaesthesiology. 2002 January; 19(1): 47-51. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11913803&dopt=Abstract

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The respiratory effects of tramadol in children under halothane an anaesthesia. Author(s): Bosenberg AT, Ratcliffe S. Source: Anaesthesia. 1998 October; 53(10): 960-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9893539&dopt=Abstract

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The risk of seizures associated with tramadol. Author(s): Jick H, Derby LE, Vasilakis C, Fife D. Source: Pharmacotherapy. 1998 May-June; 18(3): 607-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9620111&dopt=Abstract

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The role of tricyclic antidepressants and tramadol in palliative care. Author(s): Thulasimani M, Ramaswamy S. Source: Postgraduate Medical Journal. 2002 February; 78(916): 124. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11807215&dopt=Abstract

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The tramadol option. Author(s): Desmeules JA. Source: European Journal of Pain (London, England). 2000; 4 Suppl A: 15-21. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11310478&dopt=Abstract

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The use of tramadol following day--case oral surgery. Author(s): Broome IJ, Robb HM, Raj N, Girgis Y, Wardall GJ. Source: Anaesthesia. 1999 March; 54(3): 289-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10364869&dopt=Abstract

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Tissue distribution of tramadol and metabolites in an overdose fatality. Author(s): Moore KA, Cina SJ, Jones R, Selby DM, Levine B, Smith ML. Source: The American Journal of Forensic Medicine and Pathology : Official Publication of the National Association of Medical Examiners. 1999 March; 20(1): 98-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10208348&dopt=Abstract

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Tramadol added to lidocaine for intravenous regional anesthesia. Author(s): Acalovschi I, Cristea T, Margarit S, Gavrus R. Source: Anesthesia and Analgesia. 2001 January; 92(1): 209-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11133629&dopt=Abstract

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Tramadol added to mepivacaine prolongs the duration of an axillary brachial plexus blockade. Author(s): Kapral S, Gollmann G, Waltl B, Likar R, Sladen RN, Weinstabl C, Lehofer F. Source: Anesthesia and Analgesia. 1999 April; 88(4): 853-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10195537&dopt=Abstract

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Tramadol allows reduction of naproxen dose among patients with naproxenresponsive osteoarthritis pain: a randomized, double-blind, placebo-controlled study. Author(s): Schnitzer TJ, Kamin M, Olson WH. Source: Arthritis and Rheumatism. 1999 July; 42(7): 1370-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10403264&dopt=Abstract

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Tramadol and acetaminophen tablets for dental pain. Author(s): Medve RA, Wang J, Karim R. Source: Anesthesia Progress. 2001 Summer; 48(3): 79-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11724223&dopt=Abstract

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Tramadol and beta-cyclodextrin piroxicam: effective multimodal balanced analgesia for the intra- and postoperative period. Author(s): Lauretti GR, Mattos AL, Lima IC. Source: Reg Anesth. 1997 May-June; 22(3): 243-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9168216&dopt=Abstract

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Tramadol distribution in four postmortem cases. Author(s): Levine B, Ramcharitar V, Smialek JE. Source: Forensic Science International. 1997 April 18; 86(1-2): 43-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9153781&dopt=Abstract

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Tramadol drops in children: analgesic efficacy, lack of respiratory effects, and normal recovery times. Author(s): Payne KA, Roelofse JA. Source: Anesthesia Progress. 1999 Summer; 46(3): 91-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11692348&dopt=Abstract

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Tramadol for the treatment of the pain of diabetic neuropathy. Author(s): Moulin D. Source: Neurology. 1999 April 12; 52(6): 1301. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10214772&dopt=Abstract

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Tramadol hydrochloride: an overview of current use. Author(s): Bamigbade TA, Langford RM. Source: Hosp Med. 1998 May; 59(5): 373-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9722388&dopt=Abstract

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Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction. Author(s): Moore PA, Crout RJ, Jackson DL, Schneider LG, Graves RW, Bakos L. Source: Journal of Clinical Pharmacology. 1998 June; 38(6): 554-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9650546&dopt=Abstract

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Tramadol in musculoskeletal pain--a survey. Author(s): Reig E. Source: Clinical Rheumatology. 2002 February; 21 Suppl 1: S9-11; Discussion S11-2. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11954901&dopt=Abstract

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Tramadol in the fibromyalgia syndrome: a controlled clinical trial versus placebo. Author(s): Biasi G, Manca S, Manganelli S, Marcolongo R. Source: Int J Clin Pharmacol Res. 1998; 18(1): 13-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9604730&dopt=Abstract

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Tramadol in the management of post-operative pain: a double-blind, placebo- and active drug-controlled study. Author(s): Stamer UM, Maier C, Grond S, Veh-Schmidt B, Klaschik E, Lehmann KA. Source: European Journal of Anaesthesiology. 1997 November; 14(6): 646-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9466103&dopt=Abstract

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Tramadol infusion for postthoracotomy pain relief: a placebo-controlled comparison with epidural morphine. Author(s): Bloch MB, Dyer RA, Heijke SA, James MF. Source: Anesthesia and Analgesia. 2002 March; 94(3): 523-8; Table of Contents. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11867369&dopt=Abstract

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Tramadol or fentanyl analgesia for ambulatory knee arthroscopy. Author(s): Cagney B, Williams O, Jennings L, Buggy D. Source: European Journal of Anaesthesiology. 1999 March; 16(3): 182-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10225168&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 or morphine administered during operation: a study of immediate postoperative effects after abdominal hysterectomy. Author(s): Coetzee JF, van Loggerenberg H. Source: British Journal of Anaesthesia. 1998 November; 81(5): 737-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10193286&dopt=Abstract

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Tramadol post-marketing surveillance in health care professionals. Author(s): Knisely JS, Campbell ED, Dawson KS, Schnoll SH. Source: Drug and Alcohol Dependence. 2002 September 1; 68(1): 15-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12167549&dopt=Abstract

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Tramadol reduces the sweating, vasoconstriction, and shivering thresholds. Author(s): De Witte JL, Kim JS, Sessler DI, Bastanmehr H, Bjorksten AR. Source: Anesthesia and Analgesia. 1998 July; 87(1): 173-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9661569&dopt=Abstract

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Tramadol relieves pain and allodynia in polyneuropathy: a randomised, doubleblind, controlled trial. Author(s): Sindrup SH, Andersen G, Madsen C, Smith T, Brosen K, Jensen TS. Source: Pain. 1999 October; 83(1): 85-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10506675&dopt=Abstract

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Tramadol revisited. Author(s): Budd K, Langford R. Source: British Journal of Anaesthesia. 1999 April; 82(4): 493-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10472210&dopt=Abstract

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Tramadol suppositories are less suitable for post-operative pain relief than rectal acetaminophen/codeine. Author(s): Pluim MA, Wegener JT, Rupreht J, Vulto AG. Source: European Journal of Anaesthesiology. 1999 July; 16(7): 473-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10457880&dopt=Abstract

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Tramadol 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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Tramadol versus meperidine in the treatment of shivering during spinal anaesthesia. Author(s): Kaya M, Sariyildiz O, Karakus D, Ozalp G, Kadiogullari DN. Source: European Journal of Anaesthesiology. 2003 April; 20(4): 332-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12703840&dopt=Abstract

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Tramadol withdrawal in a neonate. Author(s): Meyer FP, Rimasch H, Blaha B, Banditt P. Source: European Journal of Clinical Pharmacology. 1997; 53(2): 159-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9403290&dopt=Abstract

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Tramadol. Author(s): Pasero C, McCaffery M. Source: The American Journal of Nursing. 2003 February; 103(2): 71, 73. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12582344&dopt=Abstract

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Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial. Author(s): Mullican WS, Lacy JR; TRAMAP-ANAG-006 Study Group. Source: Clinical Therapeutics. 2001 September; 23(9): 1429-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11589258&dopt=Abstract

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Tramadol/acetaminophen combination tablets for the treatment of osteoarthritis flare pain: a multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group, add-on study. Author(s): Silverfield JC, Kamin M, Wu SC, Rosenthal N; CAPSS-105 Study Group. Source: Clinical Therapeutics. 2002 February; 24(2): 282-97. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11911558&dopt=Abstract

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Tramadol/paracetamol. Author(s): McClellan K, Scott LJ. Source: Drugs. 2003; 63(11): 1079-86; Discussion 1087-8. Review. Erratum In: Drugs. 2003; 63(16): 1636. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12749738&dopt=Abstract

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Tramadol: a review of its use in perioperative pain. Author(s): Scott LJ, Perry CM. Source: Drugs. 2000 July; 60(1): 139-76. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10929933&dopt=Abstract

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Tramadol-induced mania. Author(s): Watts BV, Grady TA. Source: The American Journal of Psychiatry. 1997 November; 154(11): 1624. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9356578&dopt=Abstract

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Tramadol--present and future. Author(s): Shipton EA. Source: Anaesthesia and Intensive Care. 2000 August; 28(4): 363-74. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10969362&dopt=Abstract

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Tramadol-warfarin interaction. Author(s): Sabbe JR, Sims PJ, Sims MH. Source: Pharmacotherapy. 1998 July-August; 18(4): 871-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9692666&dopt=Abstract

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Treatment of pain with sustained-release tramadol 100, 150, 200 mg: results of a postmarketing surveillance study. Author(s): Nossol S, Schwarzbold M, Stadler T. Source: Int J Clin Pract. 1998 March; 52(2): 115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9624795&dopt=Abstract

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Treatment of refractory major depression with tramadol monotherapy. Author(s): Shapira NA, Verduin ML, DeGraw JD. Source: The Journal of Clinical Psychiatry. 2001 March; 62(3): 205-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11305709&dopt=Abstract

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Treatment of restless legs syndrome with tramadol: an open study. Author(s): Lauerma H, Markkula J. Source: The Journal of Clinical Psychiatry. 1999 April; 60(4): 241-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10221285&dopt=Abstract

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Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects. Author(s): Wilder-Smith CH, Hill L, Spargo K, Kalla A. Source: Pain. 2001 March; 91(1-2): 23-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11240075&dopt=Abstract

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Use of intravenous patient-controlled analgesia for the documentation of synergy between tramadol and metamizol. Author(s): Montes A, Warner W, Puig MM. Source: British Journal of Anaesthesia. 2000 August; 85(2): 217-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10992827&dopt=Abstract

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Validation of a high-performance liquid chromatography method for tramadol and odesmethyltramadol in human plasma using solid-phase extraction. Author(s): Gan SH, Ismail R. Source: J Chromatogr B Biomed Sci Appl. 2001 August 15; 759(2): 325-35. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11499486&dopt=Abstract

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Venlafaxine-tramadol similarities. Author(s): Markowitz JS, Patrick KS. Source: Medical Hypotheses. 1998 August; 51(2): 167-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9881825&dopt=Abstract

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Withdrawal syndrome after long-term treatment with tramadol. Author(s): Rodriguez Villamanan JC, Albaladejo Blanco C, Sanchez Sanchez A, Carvajal A, Martin Arias L, Garcia del Pozo J. Source: The British Journal of General Practice : the Journal of the Royal College of General Practitioners. 2000 May; 50(454): 406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10897546&dopt=Abstract

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Withdrawal syndrome from tramadol hydrochloride. Author(s): Barsotti CE, Mycyk MB, Reyes J. Source: The American Journal of Emergency Medicine. 2003 January; 21(1): 87-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12563592&dopt=Abstract

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

Finding Nutrition Studies on Tramadol 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 “tramadol” (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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The following information is typical of that found when using the “Full IBIDS Database” to search for “tramadol” (or a synonym): •

A comparison of epidural tramadol and epidural morphine for postoperative analgesia. Author(s): Department of Anesthesiology, American University of Beirut, Lebanon. Source: Baraka, A Jabbour, S Ghabash, M Nader, A Khoury, G Sibai, A Can-J-Anaesth. 1993 April; 40(4): 308-13 0832-610X

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A comparison of the effects of codeine and tramadol on laryngeal reactivity. Author(s): Department of Anaesthetics, University of Wales, College of Medicine, Heath Park, Cardiff. Source: Szekely, S M Vickers, M D Eur-J-Anaesthesiol. 1992 March; 9(2): 111-20 02650215

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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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An evaluation of the efficacy and tolerability of oral tramadol hydrochloride tablets for the treatment of postsurgical pain in children. Author(s): Department of Anesthesiology, Children's National Medical Center, George Washington University, 111 Michigan Avenue NW, Washington, DC 20010, USA. [email protected] Source: Finkel, Julia C Rose, John B Schmitz, Michael L Birmingham, Patrick K Ulma, George A Gunter, Joel B Cnaan, Avital Cote, Charles J Medve, Robert A Schreiner, Mark S Anesth-Analg. 2002 June; 94(6): 1469-73, table of contents 0003-2999

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Analgesia after intracranial surgery: a double-blind, prospective comparison of codeine and tramadol. Author(s): Department of Anaesthesia, Leeds General Infirmary, UK. Source: Jeffrey, H M Charlton, P Mellor, D J Moss, E Vucevic, M Br-J-Anaesth. 1999 August; 83(2): 245-9 0007-0912

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Analgesia for adenotonsillectomy in children and young adults: a comparison of tramadol, pethidine and nalbuphine. Author(s): Department of Anesthesia, King Khaled Eye Specialist Hospital, Riyadh, Kingdom of Saudi Arabia. Source: van den Berg, A A Montoya Pelaez, L F Halliday, E M Hassan, I Baloch, M S Eur-J-Anaesthesiol. 1999 March; 16(3): 186-94 0265-0215

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Analgesic activity of tramadol and pentazocine in postoperative pain. Author(s): Anesthesiology and Intensive Care Division, Ospedale Maggiore, Lodi, Italy. Source: Magrini, M Rivolta, G Bolis, C Furiosi, D Int-J-Clin-Pharmacol-Res. 1998; 18(2): 87-92 0251-1649

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Analgesic effects of dihydrocodeine and tramadol when administered either in the morning or evening. Author(s): Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nurnberg, Germany. Source: Hummel, T Kraetsch, H G Lotsch, J Hepper, M Liefhold, J Kobal, G ChronobiolInt. 1995 February; 12(1): 62-72 0742-0528

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Antidepressant-like effects of tramadol and other central analgesics with activity on monoamines reuptake, in helpless rats. Author(s): Unit of Neuropsychopharmacology, Department of Neuroscience, Faculty of Medicine, University of Cadiz. Plz Fragela 9, 11003, Cadiz, Spain. Source: Rojas Corrales, M O Berrocoso, E Gibert Rahola, J Mico, J A Life-Sci. 2002 November 29; 72(2): 143-52 0024-3205

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Antinociception, tolerance, and physical dependence comparison between morphine and tramadol. Author(s): Department of Pharmacology, Faculty of Medicine, Universidad de Chile, Santiago. Source: Miranda, H F Pinardi, G Pharmacol-Biochem-Behavolume 1998 December; 61(4): 357-60 0091-3057

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Attenuation of c-Fos expression in the rat lumbosacral spinal cord by morphine or tramadol following noxious colorectal distention. Author(s): Department of Pharmacology, University of Iowa College of Medicine, Iowa City 52242, USA. Source: Traub, R J Stitt, S Gebhart, G F Brain-Res. 1995 December 1; 701(1-2): 175-82 0006-8993

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Comparison of caudal morphine and tramadol for postoperative pain control in children undergoing inguinal herniorrhaphy. Author(s): Department of Anaesthesiology, Faculty of Medicine, Cukurova University, 01330 Balcal 1, Adana, Turkey. [email protected] Source: Ozcengiz, D Gunduz, M Ozbek, H Isik, G Paediatr-Anaesth. 2001 July; 11(4): 459-64 1155-5645

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Comparison of intravenous patient-controlled analgesia with tramadol versus morphine after microvascular breast reconstruction. Author(s): Department of Anaesthesia, Toolo Hospital, Helsinki University Central Hospital, PO Box 266, Fin-00029 HYKS, Helsinki, Finland. Source: Silvasti, M Svartling, N Pitkanen, M Rosenberg, P H Eur-J-Anaesthesiol. 2000 July; 17(7): 448-55 0265-0215

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Comparison of patient-controlled analgesia (PCA) with tramadol or morphine. Author(s): Department of Anesthesia, Show-Chwan Memorial Hospital, Changhua, Taiwan, ROC. Source: Pang, W W Mok, M S Lin, C H Yang, T F Huang, M H Can-J-Anaesth. 1999 November; 46(11): 1030-5 0832-610X

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Comparison of the efficacy and tolerability of a paracetamol/codeine fixed-dose combination with tramadol in patients with refractory chronic back pain. Author(s): South Africa Clinical Trials (Pty.) Ltd., George, South Africa. Source: Muller, F O Odendaal, C L Muller, F R Raubenheimer, J Middle, M V Kummer, M Arzneimittelforschung. 1998 June; 48(6): 675-9 0004-4172

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Comparison of tilidine/naloxone, tramadol and bromfenac in experimental pain: a double-blind randomized crossover study in healthy human volunteers. Author(s): Institut fur Pharmazeutische Chemie, Westfalische Wilhelms-Universitat, Munster, Germany. Source: Hogger, P Rohdewald, P Int-J-Clin-Pharmacol-Ther. 1999 August; 37(8): 377-85 0946-1965

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Comparison of tramadol and morphine via subcutaneous PCA following major orthopaedic surgery. Author(s): Department of Anaesthesiology, Hillbrow Hospital, University of The Witwatersrand, Johannesburg, South Africa. Source: Hopkins, D Shipton, E A Potgieter, D Van derMerwe, C A Boon, J De Wet, C Murphy, J Can-J-Anaesth. 1998 May; 45(5 Pt 1): 435-42 0832-610X

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Dose- and time-dependent action of morphine, tramadol and flupirtine as studied by radioelectroencephalography in the freely behaving rat. Author(s): Pro Science Private Research Institute GmbH, Linden, FRG. Source: Dimpfel, W Spuler, M Nickel, B Neuropsychobiology. 1989; 20(3): 164-8 0302282X

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Double-blind study with dipyrone versus tramadol and butylscopolamine in acute renal colic pain. Author(s): DIAS Institute (Institute for Drug Investigation, Auditing and Statistics), Kirchheim/Munchen, Germany. Source: Stankov, G Schmieder, G Zerle, G Schinzel, S Brune, K World-J-Urol. 1994; 12(3): 155-61 0724-4983

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Effect of tramadol and morphine on pain and gastrointestinal motor function in patients with chronic pancreatitis. Author(s): Gastrointestinal Clinic, Groote Schuur Hospital, University of Cape Town, South Africa. Source: Wilder Smith, C H Hill, L Osler, W O'Keefe, S Dig-Dis-Sci. 1999 June; 44(6): 110716 0163-2116

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Effects of morphine and tramadol on somatic and visceral sensory function and gastrointestinal motility after abdominal surgery. Author(s): Visceral Physiology Institute, Department of Pharmacology, Groote Schuur Hospital, University of Cape Town, South Africa. [email protected] Source: Wilder Smith, C H Hill, L Wilkins, J Denny, L Anesthesiology. 1999 September; 91(3): 639-47 0003-3022

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Effects of the analgesic agent tramadol in normal and arthritic rats: comparison with the effects of different opioids, including tolerance and cross-tolerance to morphine. Author(s): Unite de Recherche de Physiopharmacologie du Systeme Nerveux, I.N.S.E.R.M., U 161, Paris, France. Source: Kayser, V Besson, J M Guilbaud, G Eur-J-Pharmacol. 1991 March 19; 195(1): 3745 0014-2999

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Effects of tramadol and its enantiomers on Concanavalin-A induced-proliferation and NK activity of mouse splenocytes: involvement of serotonin. Author(s): Department of Pharmacology, University of Milan, Milano, Italy. [email protected] Source: Sacerdote, P Bianchi, M Gaspani, L Panerai, A E Int-J-Immunopharmacol. 1999 November; 21(11): 727-34 0192-0561

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Efficacy and side effects of tramadol versus oxycodone for patient-controlled analgesia after maxillofacial surgery. Author(s): Department of Anaesthesia, Toolo Hospital, Helsinki University Central Hospital, Finland. Source: Silvasti, M Tarkkila, P Tuominen, M Svartling, N Rosenberg, P H Eur-JAnaesthesiol. 1999 December; 16(12): 834-9 0265-0215

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Evaluation of the analgesic effects of epidurally administered morphine, alfentanil, butorphanol, tramadol, and U50488H in horses. Author(s): Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Minnesota, St Paul 55108, USA. Source: Natalini, C C Robinson, E P Am-J-Vet-Res. 2000 December; 61(12): 1579-86 00029645

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Evidence for a noradrenergic component in the antinociceptive effect of the analgesic agent tramadol in an animal model of clinical pain, the arthritic rat. Author(s): Unite de Recherche de Physiopharmacologie du Systeme Nerveux, U 161 I.N.S.E.R.M., Paris, France. Source: Kayser, V Besson, J M Guilbaud, G Eur-J-Pharmacol. 1992 November 24; 224(1): 83-8 0014-2999

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High-dose tramadol in comparison to low-dose morphine for cancer pain relief. Author(s): Department of Anesthesiology, University of Cologne, Germany. Source: Grond, S Radbruch, L Meuser, T Loick, G Sabatowski, R Lehmann, K A J-PainSymptom-Manage. 1999 September; 18(3): 174-9 0885-3924

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In vitro/in vivo characterization of a tramadol HCl depot system composed of monoolein and water. Author(s): Laboratoire de Pharmacie Galenique et de Biopharmacie, Institut de Pharmacie, Universite Libre de Bruxelles, Belgium. [email protected] Source: Malonne, H Fontaine, J Moes, A Biol-Pharm-Bull. 2000 May; 23(5): 627-31 09186158

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Increased nausea and dizziness when using tramadol for post-operative patientcontrolled analgesia (PCA) compared with morphine after intraoperative loading with morphine. Author(s): Department of Anaesthesiology, University of Hong Kong, Queen Mary Hospital, Hong Kong. Source: Ng, K F Tsui, S L Yang, J C Ho, E T Eur-J-Anaesthesiol. 1998 September; 15(5): 565-70 0265-0215

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Induction of 5-hydroxytryptamine release by tramadol, fenfluramine and reserpine. Author(s): Grunenthal, Abteilung Pharmakologie, Aachen, Germany. Source: Reimann, W Schneider, F Eur-J-Pharmacol. 1998 May 22; 349(2-3): 199-203 00142999

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Influence of tramadol on neurotransmitter systems of the rat brain. Author(s): Grunenthal GmbH, Department of Biochemical Pharmacology, Aachen, Germany. Source: Frink, M C Hennies, H H Englberger, W Haurand, M Wilffert, B Arzneimittelforschung. 1996 November; 46(11): 1029-36 0004-4172

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Intravenous tramadol compared to propacetamol for postoperative analgesia following thyroidectomy. Author(s): Department of Anaesthesia, Institut Jules Bordet, Rue H. Bordet 1, 1000 Brussels, Belgium. Source: Dejonckheere, M Desjeux, L Deneu, S Ewalenko, P Acta-Anaesthesiol-Belg. 2001; 52(1): 29-33 0001-5164

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Lack of interaction between tramadol and coumarins. Author(s): Centre for Human Drug Research, Leiden University, The Netherlands. Source: Boeijinga, J K van Meegen, E van den Ende, R Schook, C E Cohen, A F J-ClinPharmacol. 1998 October; 38(10): 966-70 0091-2700

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Lack of sensitization during place conditioning in rats is consistent with the low abuse potential of tramadol. Author(s): Grunenthal GmbH, Research and Development, Department of Pharmacology, Postfach 500444, 52088 Aachen, Germany. [email protected] Source: Tzschentke, T M Bruckmann, W Friderichs, E Neurosci-Lett. 2002 August 23; 329(1): 25-8 0304-3940

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Multicenter trial comparing tramadol and morphine for pain after abdominal surgery. Author(s): Servizio Anestesia e Rianimazione, Azienda Ospedaliera, Padova, Italy. Source: Gritti, G Verri, M Launo, C Palermo, S Novelli, G P Casali, R Paoletti, F Boanelli, A Tufano, R Leone, D Drugs-Exp-Clin-Res. 1998; 24(1): 9-16 0378-6501

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Oral tramadol and buprenorphine in tumour pain. An Italian multicentre trial. Author(s): Tumour Centre, Ospedale San Paolo, Savona, Italy. Source: Brema, F Pastorino, G Martini, M C Gottlieb, A Luzzani, M Libretti, A Sacca, L Cigolari, S Int-J-Clin-Pharmacol-Res. 1996; 16(4-5): 109-16 0251-1649

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Pain management in dental practice: tramadol vs. codeine combinations. Author(s): Department of Public Health Dentistry, University of Pittsburgh School of Dental Medicine, Pa. 15261, USA. Source: Moore, P A J-Am-Dent-Assoc. 1999 July; 130(7): 1075-9 0002-8177

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Perioperative antinociceptive effects of tramadol. A prospective, randomized, doubleblind comparison with morphine. Author(s): Department of Anaesthesia, King Saud University, College of Medicine, King Khalid University Hospital, Riyadh, Saudi Arabia. [email protected] Source: Naguib, M Seraj, M Attia, M Samarkandi, A H Seet, M Jaroudi, R Can-J-Anaesth. 1998 December; 45(12): 1168-75 0832-610X

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Pharmacokinetic properties of tramadol sustained release capsules. 2nd communication: investigation of relative bioavailability and food interaction. Author(s): Temmler Pharma GmbH, Marburg, Germany. Source: Raber, M Schulz, H U Schurer, M Bias Imhoff, U Momberger, H Arzneimittelforschung. 1999 July; 49(7): 588-93 0004-4172

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Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effects of main active metabolites of tramadol, (+)-O-desmethyltramadol and (-)-Odesmethyltramadol, in rats. Author(s): Department of Pharmacology, School of Medicine, University of Basque Country, Leioa, Bizkaia, Spain. Source: Valle, M Garrido, M J Pavon, J M Calvo, R Troconiz, I F J-Pharmacol-Exp-Ther. 2000 May; 293(2): 646-53 0022-3565

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Plasma glucose-lowering effect of tramadol in streptozotocin-induced diabetic rats. Author(s): Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan City, Taiwan. [email protected] Source: Cheng, J T Liu, I M Chi, T C Tzeng, T F Lu, F H Chang, C J Diabetes. 2001 December; 50(12): 2815-21 0012-1797

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Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Author(s): Department of Biochemical Pharmacology, Grunenthal GmbH, Aachen, Fed. Rep. of Germany. Source: Hennies, H H Friderichs, E Schneider, J Arzneimittelforschung. 1988 July; 38(7): 877-80 0004-4172

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The analgesic drug tramadol prevents the effect of surgery on natural killer cell activity and metastatic colonization in rats. Author(s): Department of Pharmacology, University of Milan, via Vanvitelli 32, 20129, Milan, Italy. Source: Gaspani, L Bianchi, M Limiroli, E Panerai, A E Sacerdote, P J-Neuroimmunol. 2002 August; 129(1-2): 18-24 0165-5728

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The antinociceptive effect of tramadol on a model of neuropathic pain in rats. Author(s): Ege University, Center for Drug R&D and Pharmacokinetic Applications, Bornova Izmir, Turkey. Source: Apaydin, S Uyar, M Karabay, N U Erhan, E Yegul, I Tuglular, I Life-Sci. 2000 March; 66(17): 1627-37 0024-3205

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The effects of tramadol and morphine on immune responses and pain after surgery in cancer patients. Author(s): Department of Pharmacology, University of Milano, Milan, Italy. [email protected] Source: Sacerdote, P Bianchi, M Gaspani, L Manfredi, B Maucione, A Terno, G Ammatuna, M Panerai, A E Anesth-Analg. 2000 June; 90(6): 1411-4 0003-2999

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Tramadol hydrochloride: analgesic efficacy compared with codeine, aspirin with codeine, and placebo after dental extraction. Author(s): Department of Dental Public Health, University of Pittsburgh, School of Dental Medicine, Pennsylvania 15261, USA. Source: Moore, P A Crout, R J Jackson, D L Schneider, L G Graves, R W Bakos, L J-ClinPharmacol. 1998 June; 38(6): 554-60 0091-2700

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Tramadol infusion for postthoracotomy pain relief: a placebo-controlled comparison with epidural morphine. Author(s): Department of Anesthesia, Groote Schuur Hospital, Cape Town, South Africa. Source: Bloch, Mark B Dyer, Robert A Heijke, Sylvia A James, Michael F Anesth-Analg. 2002 Mar; 94(3): 523-8; table of contents 0003-2999

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Tramadol inhibits norepinephrine transporter function at desipramine-binding sites in cultured bovine adrenal medullary cells. Author(s): Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan. Source: Sagata, Kenichiro Minami, Kouichiro Yanagihara, Nobuyuki Shiraishi, Munehiro Toyohira, Yumiko Ueno, Susumu Shigematsu, Akio Anesth-Analg. 2002 April; 94(4): 901-6, table of contents 0003-2999

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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 or morphine administered during operation: a study of immediate postoperative effects after abdominal hysterectomy. Author(s): Department of Anaesthesiology, Faculty of Medicine, University of Stellenbosch, Tygerberg. Source: Coetzee, J F van Loggerenberg, H Br-J-Anaesth. 1998 November; 81(5): 737-41 0007-0912

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Tramadol reduces the 5-HTP-induced head-twitch response in mice via the activation of mu and kappa opioid receptors. Author(s): National Institute on Drug Dependence, Peking University, Xue Yuan Road 38, Haidian District, Beijing 100083, PR China. Source: Sun, H L Zheng, J W Wang, K Liu, R K Liang, J H Life-Sci. 2003 January 31; 72(11): 1221-30 0024-3205

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Tramadol suppositories are less suitable for post-operative pain relief than rectal acetaminophen/codeine. Author(s): Department of Hospital Pharmacy, University Hospital Rotterdam-Dijkzigt, Rotterdam, The Nethelands. Source: Pluim, M A Wegener, J T Rupreht, J Vulto, A G Eur-J-Anaesthesiol. 1999 July; 16(7): 473-8 0265-0215

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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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Tramadol, a centrally acting opioid: anticonvulsant effect against maximal electroshock seizure in mice. Author(s): Department of Pharmacology, University College of Medical Sciences and GTB Hospital, Delhi. Source: Manocha, A Sharma, K K Mediratta, P K Indian-J-Physiol-Pharmacol. 1998 July; 42(3): 407-11 0019-5499

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Tramadol/acetaminophen combination tablets and codeine/acetaminophen combination capsules for the management of chronic pain: a comparative trial. Author(s): Indiana University School of Medicine, Evansville Center for Medical Education, USA. Source: Mullican, W S Lacy, J R Clin-Ther. 2001 September; 23(9): 1429-45 0149-2918

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Tramadol: pain relief by an opioid without depression of respiration. Author(s): Department of Anaesthetics, University of Wales College of Medicine, Heath Park, Cardiff. Source: Vickers, M D O'Flaherty, D Szekely, S M Read, M Yoshizumi, J Anaesthesia. 1992 April; 47(4): 291-6 0003-2409

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Tramadol-warfarin interaction. Author(s): Samford University McWhorter School of Pharmacy, Department of Pharmacy Practice, Birmingham, Alabama, USA. Source: Sabbe, J R Sims, P J Sims, M H Pharmacotherapy. 1998 Jul-August; 18(4): 871-3 0277-0008

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Treatment of severe pain from osteoarthritis with slow-release tramadol or dihydrocodeine in combination with NSAID's: a randomised study comparing analgesia, antinociception and gastrointestinal effects. Author(s): Visceral Physiology Institute, Groote Schuur Hospital, University of Cape Town, 7925, Cape Town, South Africa. [email protected] Source: Wilder Smith, C H Hill, L Spargo, K Kalla, A Pain. 2001 March; 91(1-2): 23-31 0304-3959

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Unexpected antinociceptive effect of the N-oxide (RWJ 38705) of tramadol hydrochloride. Author(s): R.W. Johnson Pharmaceutical Research Institute, Spring House, Pennsylvania, USA. Source: Raffa, R B Haslego, M L Maryanoff, C A Villani, F J Codd, E E Connelly, C D Martinez, R P Schupsky, J J Buben, J A Wu, W N Takacs, A N Mckown, L A JPharmacol-Exp-Ther. 1996 September; 278(3): 1098-104 0022-3565

Federal Resources on Nutrition In addition to the IBIDS, the United States Department of Health and Human Services (HHS) and the United States Department of Agriculture (USDA) provide many sources of information on general nutrition and health. Recommended resources include: •

healthfinder®, HHS’s gateway to health information, including diet and nutrition: http://www.healthfinder.gov/scripts/SearchContext.asp?topic=238&page=0

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The United States Department of Agriculture’s Web site dedicated to nutrition information: www.nutrition.gov

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The Food and Drug Administration’s Web site for federal food safety information: www.foodsafety.gov

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The National Action Plan on Overweight and Obesity sponsored by the United States Surgeon General: http://www.surgeongeneral.gov/topics/obesity/

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The Center for Food Safety and Applied Nutrition has an Internet site sponsored by the Food and Drug Administration and the Department of Health and Human Services: http://vm.cfsan.fda.gov/

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Center for Nutrition Policy and Promotion sponsored by the United States Department of Agriculture: http://www.usda.gov/cnpp/

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Food and Nutrition Information Center, National Agricultural Library sponsored by the United States Department of Agriculture: http://www.nal.usda.gov/fnic/

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Food and Nutrition Service sponsored by the United States Department of Agriculture: http://www.fns.usda.gov/fns/

Additional Web Resources A number of additional Web sites offer encyclopedic information covering food and nutrition. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=174&layer=&from=subcats

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Family Village: http://www.familyvillage.wisc.edu/med_nutrition.html

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Google: http://directory.google.com/Top/Health/Nutrition/

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Healthnotes: http://www.healthnotes.com/

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Open Directory Project: http://dmoz.org/Health/Nutrition/

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Yahoo.com: http://dir.yahoo.com/Health/Nutrition/

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WebMDHealth: http://my.webmd.com/nutrition

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

The following is a specific Web list relating to tramadol; 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: •

Vitamins Vitamin C Source: Prima Communications, Inc.www.personalhealthzone.com

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CHAPTER 3. ALTERNATIVE MEDICINE AND TRAMADOL Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to tramadol. At the conclusion of this chapter, we will provide additional sources.

National Center for Complementary and Alternative Medicine The National Center for Complementary and Alternative Medicine (NCCAM) of the National Institutes of Health (http://nccam.nih.gov/) has created a link to the National Library of Medicine’s databases to facilitate research for articles that specifically relate to tramadol and complementary medicine. To search the database, go to the following Web site: http://www.nlm.nih.gov/nccam/camonpubmed.html. Select “CAM on PubMed.” Enter “tramadol” (or synonyms) into the search box. Click “Go.” The following references provide information on particular aspects of complementary and alternative medicine that are related to tramadol: •

A nonsurgical approach to low back pain. Author(s): Jermyn RT. Source: J Am Osteopath Assoc. 2001 April; 101(4 Suppl Pt 2): S6-11. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11392208&dopt=Abstract

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A randomized double-blind pilot study comparing Doloteffin and Vioxx in the treatment of low back pain. Author(s): Chrubasik S, Model A, Black A, Pollak S. Source: Rheumatology (Oxford, England). 2003 January; 42(1): 141-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12509627&dopt=Abstract

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An East-West approach to the management of central post-stroke pain. Author(s): Yen HL, Chan W.

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Source: Cerebrovascular Diseases (Basel, Switzerland). 2003; 16(1): 27-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12766358&dopt=Abstract •

Analgesic effects of dihydrocodeine and tramadol when administered either in the morning or evening. Author(s): Hummel T, Kraetsch HG, Lotsch J, Hepper M, Liefhold J, Kobal G. Source: Chronobiology International. 1995 February; 12(1): 62-72. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7750159&dopt=Abstract

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Dose dependent time course of the analgesic effect of a sustained-release preparation of tramadol on experimental phasic and tonic pain. Author(s): Thurauf N, Fleischer WK, Liefhold J, Schmid O, Kobal G. Source: British Journal of Clinical Pharmacology. 1996 February; 41(2): 115-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8838437&dopt=Abstract

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Effectiveness of Harpagophytum extract WS 1531 in the treatment of exacerbation of low back pain: a randomized, placebo-controlled, double-blind study. Author(s): Chrubasik S, Junck H, Breitschwerdt H, Conradt C, Zappe H. Source: European Journal of Anaesthesiology. 1999 February; 16(2): 118-29. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10101629&dopt=Abstract

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Electrical stimulation of auricular acupuncture points is more effective than conventional manual auricular acupuncture in chronic cervical pain: a pilot study. Author(s): Sator-Katzenschlager SM, Szeles JC, Scharbert G, Michalek-Sauberer A, Kober A, Heinze G, Kozek-Langenecker SA. Source: Anesthesia and Analgesia. 2003 November; 97(5): 1469-73. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14570667&dopt=Abstract

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Management of adolescent chronic pelvic pain from endometriosis: a pain center perspective. Author(s): Greco CD. Source: Journal of Pediatric and Adolescent Gynecology. 2003 June; 16(3 Suppl): S17-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12742182&dopt=Abstract

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Meeting the therapeutic challenge of the patient with osteoarthritis. Author(s): Todd C. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2002 January-February; 42(1): 74-82. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833521&dopt=Abstract

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Postoperative analgesia and vomiting, with special reference to day-case surgery: a systematic review. Author(s): McQuay HJ, Moore RA. Source: Health Technology Assessment (Winchester, England). 1998; 2(12): 1-236. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10103349&dopt=Abstract

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Treatment of low back pain exacerbations with willow bark extract: a randomized double-blind study. Author(s): Chrubasik S, Eisenberg E, Balan E, Weinberger T, Luzzati R, Conradt C. Source: The American Journal of Medicine. 2000 July; 109(1): 9-14. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10936472&dopt=Abstract

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Treatment of tremors in complex regional pain syndrome. Author(s): Navani A, Rusy LM, Jacobson RD, Weisman SJ. Source: Journal of Pain and Symptom Management. 2003 April; 25(4): 386-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12691691&dopt=Abstract

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Update of ACR guidelines for osteoarthritis: role of the coxibs. Author(s): Schnitzer TJ; American College of Rheumatology. Source: Journal of Pain and Symptom Management. 2002 April; 23(4 Suppl): S24-30; Discussion S31-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11992747&dopt=Abstract

Additional Web Resources A number of additional Web sites offer encyclopedic information covering CAM and related topics. The following is a representative sample: •

Alternative Medicine Foundation, Inc.: http://www.herbmed.org/

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AOL: http://search.aol.com/cat.adp?id=169&layer=&from=subcats

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Chinese Medicine: http://www.newcenturynutrition.com/

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drkoop.com: http://www.drkoop.com/InteractiveMedicine/IndexC.html

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Family Village: http://www.familyvillage.wisc.edu/med_altn.htm

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Google: http://directory.google.com/Top/Health/Alternative/

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Healthnotes: http://www.healthnotes.com/

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MedWebPlus: http://medwebplus.com/subject/Alternative_and_Complementary_Medicine

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Open Directory Project: http://dmoz.org/Health/Alternative/

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HealthGate: http://www.tnp.com/

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WebMDHealth: http://my.webmd.com/drugs_and_herbs

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WholeHealthMD.com: http://www.wholehealthmd.com/reflib/0,1529,00.html

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Yahoo.com: http://dir.yahoo.com/Health/Alternative_Medicine/

The following is a specific Web list relating to tramadol; please note that any particular subject below may indicate either a therapeutic use, or a contraindication (potential danger), and does not reflect an official recommendation: •

General Overview Colds and Flus Source: Prima Communications, Inc.www.personalhealthzone.com Fibromyalgia Source: Integrative Medicine Communications; www.drkoop.com Osteoarthritis Source: Integrative Medicine Communications; www.drkoop.com

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Herbs and Supplements 5-htp Alternative names: 5-Hydroxytryptophan (5-HTP) Source: Integrative Medicine Communications; www.drkoop.com 5-hydroxytryptophan Source: Healthnotes, Inc.; www.healthnotes.com 5-hydroxytryptophan (5-htp) Alternative names: 5-HTP Source: Integrative Medicine Communications; www.drkoop.com Tramadol Source: Healthnotes, Inc.; www.healthnotes.com Tramadol Alternative names: Ultram Source: Prima Communications, Inc.www.personalhealthzone.com

General References A good place to find general background information on CAM is the National Library of Medicine. It has prepared within the MEDLINEplus system an information topic page dedicated to complementary and alternative medicine. To access this page, go to the MEDLINEplus site at http://www.nlm.nih.gov/medlineplus/alternativemedicine.html. This Web site provides a general overview of various topics and can lead to a number of general sources.

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CHAPTER 4. DISSERTATIONS ON TRAMADOL Overview In this chapter, we will give you a bibliography on recent dissertations relating to tramadol. 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 “tramadol” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tramadol, we have not necessarily excluded non-medical dissertations in this bibliography.

Dissertations on Tramadol 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 tramadol. 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: •

Tramadol: a Study on the Enantioselectivity of Its Pharmacokinetic Profile by Garcia Quetglas, Emilio; Dr from Universidad de Navarra (Spain), 2002, 238 pages http://wwwlib.umi.com/dissertations/fullcit/f831089

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 5. PATENTS ON TRAMADOL 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 “tramadol” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on tramadol, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Tramadol By performing a patent search focusing on tramadol, 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

5Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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will tell you how to obtain this information later in the chapter. The following is an example of the type of information that you can expect to obtain from a patent search on tramadol: •

Combination preparation containing tramadol and a calcium channel antagonist Inventor(s): Reimann; Wolfgang (Aachen, DE) Assignee(s): Gruenenthal GmbH (Aachen, DE) Patent Number: 5,929,122 Date filed: October 1, 1997 Abstract: A pharmaceutical combination preparation, particularly for the treatment of pain, which contains a combination of the pain killer tramadol with at least one calcium channel antagonist, and a method of treating pain by administering to a patient suffering therefrom an analgesically effective combination of tramadol and at least one calcium channel antagonist. Excerpt(s): The present invention relates to a pharmaceutical combination preparation, particularly for the treatment of pain, which contains a combination of the pain-killer tramadol and a calcium channel antagonist, and to a method of treating pain using such a combination preparation. Due to their strong analgesic effect, opioids are used for the alleviation of moderately severe to the most severe acute pain. However, one considerable disadvantage of the use of opioids is the severe side effects associated therewith. Thus they frequently have effects on the gastrointestinal tract, such as obstipation (?), and moreover give rise to respiratory depression, and, on repeated use, to dependency which can lead to misuse. Furthermore, the development of tolerance is a disadvantageous effect. It has been known for many years that the analgesic effect of opioids is enhanced by the simultaneous administration of organic calcium channel antagonists (Fortschr. Anaesth. 1987, 5). Calcium channel antagonists can be classified into those of the dihydropyridine, benzothiazepine and phenylalkylamine types. They are usually employed for the treatment of cardiovascular disease conditions such as high blood pressure, arrhythmia or angina pectoris. The mode of action of these substances act is based on the selective suppression of the Ca.sup.2+ flux in the Ca.sup.2+ channels of the heart and of the peripheral vascular system. Calcium channels with a high affinity for calcium channel antagonists have also been detected in the brain, so that a central effect of calcium channel antagonists appears probable. Web site: http://www.delphion.com/details?pn=US05929122__

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Composition comprising a tramadol material and acetaminophen and its use Inventor(s): Raffa; Robert B. (Norristown, PA), Vaught; Jeffrey L. (Perkosie, PA) Assignee(s): McNeilab, Inc. (Spring House, PA) Patent Number: 5,336,691 Date filed: November 10, 1992 Abstract: This invention relates to a composition comprising a tramadol material and acetaminophen, and its use. As used herein tramadol refers to various forms of tramadol. The compositions are pharmacologically useful in treating pain and tussive conditions. The compositions are also subject to less opioid side-effects such as abuse liability, tolerance, constipation and respiratory depression. Furthermore, where the

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components of the compositions are within certain ratios the pharmacological effects of the compositions are superadditive (synergistic). Excerpt(s): 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)-[(dimethylamino)-methyl]-1-(3-methoxyphenyl)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(I), 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), disclose 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(I), 183 (1978)), constipation (I. Arend et al., Arzneim. Forsch, (Drug Res.), 28(I), 199 (1978)), tolerance (L. Flohe et, al., Arzneim. Forsch, (Drug Res.), 28(I), 213 (1978)), and abuse liability ( T. Yanagita, Arzneim. Forsch, (Drug Res.), 28(I), 158 (1978)). When given at a dose of 50 mg by rapid i.v. injection, tramadol may produce certain side effects unique to tramadol including hot flushes and sweating. Despite these 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 as an analgesic. Opioids have for many years been used as analgesics to treat severe pain. They, however, produce undesirable side effects and as a result cannot be given repeatedly or at high doses. The side effect problems are well documented in the literature. See, for example, J. Jaffe and W. Martin in chapter 15, "The Pharmacological Basis of Therapeutics", editors L. Goodman and A. Gilman, 5th Edition, 245 (1975) 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. As alternatives to using opioids, non-opioids such as acetaminophen (APAP) and aspirin are used as analgesics. APAP, like aspirin, is not subject to the tolerance, addiction and toxicity of the opioid analgesics. However, APAP and aspirin are only useful in relieving pain of moderate intensity, whereas the opioid analgesics are useful in relieving more intense pain; See Woodbury, D. and Fingl, E. in "The Pharmacological Basis of Therapeutics", 5th Ed.; Goodman, L. and Gilman, A., Chapter 15, pages 325 (1975). Web site: http://www.delphion.com/details?pn=US05336691__ •

Controlled release formulation Inventor(s): Hahn; Udo (Nentershausen, DE), Leslie; Stewart T. (Cambridge, GB2), Malkowska; Sandra T. A. (Cambridgeshire, GB2), Miller; Ronald B. (Basel, CH), Prater; Derek A. (Cambridge, GB2), Smith; Kevin J. (Cambridge, GB2), Wimmer; Walter (Limburg, DE), Winkler; Horst (Linter, DE) Assignee(s): Euro-Celtique, S.A. (Luxembourg, LU) Patent Number: 5,591,452 Date filed: May 10, 1994 Abstract: A controlled release preparation for oral administration contains tramadol, or a pharmaceutically acceptable salt thereof, as active ingredient.

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Excerpt(s): The present invention relates to a controlled release preparation for oral administration, to processes for its preparation and to its medical use. In particular, the invention relates to a controlled release preparation comprising tramadol or a pharmaceutically acceptable salt thereof. Tramadol, which has the chemical name (.+-.)trans-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol, is an orally active opioid analgesic. Conventional release preparations in the form of capsules, drops and suppositories containing tramadol, or more particularly its hydrochloride salt, have been commercially available for many years for use in the treatment of moderate to severe pain. Such preparations, however, do not provide a controlled release of the tramadol. Moreover, despite tramadol's long-standing use, controlled release preparations for oral administration containing tramadol as active ingredient have not even previously been described in the literature. It is an object of the present invention to provide an oral controlled release tramadol preparation suitable for at least twelvehourly (e.g. up to twenty-four hourly) administration for the treatment of pain. Web site: http://www.delphion.com/details?pn=US05591452__ •

Controlled release oral dosage form Inventor(s): Chen; Chih-Ming (Davie, FL), Chou; Joseph (Coral Springs, FL), Sriwongjanya; Mongkol (Davie, FL), Weng; Timothy (Plantation, FL) Assignee(s): Andex Pharmaceuticals, Inc. (Fort Lauderdale, FL) Patent Number: 6,156,342 Date filed: May 26, 1998 Abstract: A controlled release dosage form for an analgesic that does not contain an expanding polymer and comprising a core containing the analgesic, preferably tramadol or it pharmaceutically acceptable deviates and a semipermeable membrane coating the core. Excerpt(s): The present invention relates to oral controlled release dosage formulations containing an analgesic. More specifically, the present invention relates to an oral dosage formulation in the form of a capsule, tablet or pellet comprising a water soluble analgesic such as tramadol or its pharmaceutically acceptable derivatives which are described in U.S. Pat. Nos. 5,516,803, 5,336,691 and 5,468,7442 and are incorporated herein by reference. In the prior art are extended release tablets which have an osmotically active drug core surrounded by a semipermeable membrane. These tablets function by allowing a fluid such as gastric or intestinal fluid to permeate the coating membrane and dissolve the active ingredient so it can be released through a passageway in the membrane. If the active ingredient is insoluble in the permeating fluid, a hydrogel is employed to push the active ingredient through the passageway. Some representative examples of these osmotic tablet systems can be found in U.S. Pat. Nos. 3,845,770, 3,916,899, 3,952,741, 4,034,758, 4,077,407 and 4,783,337. The basic osmotic device described in the above-cited patents has been refined over time in an effort to provide greater control of the release of the active ingredient. For example U.S. Pat. Nos. 4,777,049 and 4,851,229 describe an osmotic dosage form comprising a semipermeable wall surrounding a core. The core contains an active ingredient and a modulating agent wherein the modulating agent causes the active ingredient to be released through a passageway in the semipermeable membrane in a pulsed manner. Further refinements are described in U.S. Pat. Nos. 5,178,867, 4,587,117 and 4,522,625 which include modifications to the semipermeable membrane surrounding the active core or as

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described in U.S. Pat. Nos. 5,650,170 and 4,892,739 which include increasing the number of coatings surrounding the active core. Web site: http://www.delphion.com/details?pn=US06156342__ •

Controlled release tramadol preparation with a storage-stable release profile and process for their production Inventor(s): Bartholomaeus; Johannes Heinrich (Aachen, DE), Ziegler; Iris (RottRoetgen, DE) Assignee(s): Gruenenthal GmbH (Aachen, DE) Patent Number: 6,451,350 Date filed: January 18, 2000 Abstract: A process for producing an oral, controlled release preparation of tramadol or a physiologically compatible tramadol salt having a storage stable active substance release profile by coating the active substance preparation with an aqueous ethylcellulose dispersion which contains at least one physiologically compatible, lipophilic diester of a C.sub.6 -C.sub.40 aliphatic or aromatic dicarboxylic acid and a C.sub.1 -C.sub.8 aliphatic alcohol as plasticizer, and, during coating, drying the coating at conventional temperatures, with the result that a storage stable active substance release profile is obtained even without subsequent heat treatment. Optionally, in order to increase the active substance release profile without impairing the storage stability of the preparation, a heat treatment may be performed at temperatures of >35.degree. C. until a desired, increased active substance release profile is achieved. Excerpt(s): The present invention relates to preferably multi-particulate, oral tramadol preparations, having a controlled active substance release profile which is established in a storage-stable manner by an ethylcellulose coating containing plasticizer even without heat treatment. Multiparticulate, controlled release tramadol preparations having a controlled release coating of ethylcellulose are known in the prior art. DE-A-196 30 035 accordingly describes multiparticulate tramadol preparations in the form of pellets which are provided with a controlled release coating of ethylcellulose. To this end, accretion pellets are coated with one or more ethylcellulose membrane layers which are applied from solutions in organic solvents. This production method has the disadvantage that the organic solvents must be recovered on environmental grounds, thus rendering this process somewhat costly. It is moreover disadvantageous to use organic solvents in the production of pharmaceuticals. Where controlled release coatings of aqueous ethylcellulose dispersions are applied onto substrates, it is generally recognized by experts that, once produced, such coatings do not usually provide storage-stable active substance release profiles. Such ethylcellulose coatings are indeed known to have a tendency to "post-filming", i.e. active substance release is increasingly delayed over storage. In order to overcome this problem, elaborate heat treatment processes at elevated temperature and optionally defined atmospheric humidity are recommended in the prior art in order to achieve a storage-stable release profile within days rather than after several months' storage (EP-A-0 548 448, EP-A-0 630 646). Web site: http://www.delphion.com/details?pn=US06451350__

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Esters derived from substituted phennyl-cyclohexyl compounds Inventor(s): Chalaux Freixa; Maria (Barcelona, ES), De Ramon Amat; Elisabet (Barcelona, ES), Del Castillo Nieto; Juan Carlos (Barcelona, ES), Huguet Clotet; Joan (Sant Joan Despi, ES), Mourelle Mancini; Marisabel (Barcelona, ES) Assignee(s): Vita Invest, S.A. (Sant Joan Despi, ES) Patent Number: 6,455,585 Date filed: May 4, 2001 Abstract: New esters derived from substituted phenyl-cyclohexyl compounds, which are derived from Tramadol, process for obtaining them and their use for preparing a drug with analgesic properties. These new compounds of general formula (I) have a higher analgesic activity, a lower toxicity and a longer effective time period than Tramadol. Excerpt(s): The present invention relates to new esters derived from substituted phenylcyclohexyl compounds, which are derived from Tramadol. The obtained compounds have a higher analgesic activity, a lower toxicity and a longer effective time period than Tramadol. The treatment of pain is of great importance in the field of medicine. The pharmacological agents presently used for the treatment of pain can be primarily classified into two large groups: opioid compounds and non-steroidal antiinflammatories (NSAIs). The NSAIs are only useful in the case of light or moderate pain; severe pain has traditionally been treated with opiod compounds. However, these opioid compounds have several undesirable side effects, such as constipation, respiratory depression, tolerance and possibility of addiction. have been described in the Dutch patent NL 6610022. Web site: http://www.delphion.com/details?pn=US06455585__

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Formulation for intranasal administration Inventor(s): Alfonso; Mark (Easton, CT), Goldenheim; Paul (Wilton, CT), Sackler; Richard (Greenwich, CT) Assignee(s): Euro-Celtique, S.A. (Luxembourg, LU) Patent Number: 6,017,963 Date filed: November 14, 1995 Abstract: A dosage form for intranasal and/or inhalation administration of an analgesic having low opioid receptor binding activity to a warm blooded animal, that includes a pharmaceutically effective amount of the analgesic. A preferred analgesic is tramadol, a tramadol and/or a pharmaceutically acceptable salt, metabolite or derivative thereof. Methods of making and using the formulation according to the invention are also provided. Excerpt(s): The present invention relates to formulations and methods for the intranasal and inhalation administration of analgesics having low opioid receptor binding affinity. Pharmacologically active compounds are most commonly administered by the oral route. In particular, analgesics are preferably taken by mouth. However, this convenient route of administration is not always possible for certain patients. Contraindications to oral administration of analgesics can include nausea and/or emesis, oral or gastrointestinal surgery and dysphagia. In addition, rate of analgesia onset is slower and more variable due to first pass effects which compromise the apparent potency of some analgesics and complicate their use. The alternative of administration by injection, e.g.,

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parenteral, intramuscular or subcutaneous injection, is generally not preferred due to patient discomfort and the attendant increased costs associated with the production of and administration of injectable products. Another, less invasive form of administration is transmucosal administration. Transmucosal administration can be via oral, nasal and/or upper respiratory tract, rectal or vaginal mucosal surfaces, to name the more common non-oral transmucosal routes of administration. Transmucosal administration has the advantage that patients who are unable to swallow can be medicated without recourse to injection. Importantly, transmucosal administration may often provide a more rapid relief of pain, compared to oral administration, by providing direct access to the blood circulation and bypassing the gastrointestinal tract and portal vein circulation and liver metabolism. A particularly preferred route enterohepatic blood circulation. A particularly preferred route for transmucosal delivery is intranasal administration for absorption by the nasal mucosal surfaces and/or inhalation for absorption in the bronchial passages of the lungs. Web site: http://www.delphion.com/details?pn=US06017963__ •

Method of alleviating pain Inventor(s): Caruso; Frank S. (Colts Neck, NJ) Assignee(s): Algos Pharmaceutical Corporation (Neptune, NJ) Patent Number: 5,919,826 Date filed: August 1, 1997 Abstract: The analgesic effectiveness of an tramadol is significantly enhanced by administering tramadol with the administration of an analgesia-enhancer which is a nontoxic NMDA receptor blocker and/or a nontoxic substance that blocks at least one major intracellular consequence of NMDA receptor activation. Excerpt(s): This invention relates to a method of alleviating pain. More particularly, this invention is directed to a method of alleviating pain, e.g., arthritic pain, lumbosacral pain, musculo-skeletal pain, pain associated with a sore throat, etc., by administering to a mammal in need of relief from pain tramadol and, to enhance the analgesic effectiveness of the tramadol, a nontoxic antagonist for the N-methyl-D-aspartate (NMDA) receptor such as dextromethorphan, dextrorphan or ketamine. The compound cis-2-›(dimethylamino)methyl!-1-(3-methoxyphenyl)cyclohexanol, commonly known as tramadol, is an analgesic commercially available as the hydrochloride salt. The process by which tramadol may be made is described in U.S. Pat. No. 3,652,589 the contents of which are incorporated herein by reference. Tramadol is chemically unrelated to the opiates, e.g., morphine, codeine, hydrocodone and oxycodone. However, a number of adverse side effects associated with the administration of tramadol, e.g., dizziness, somnolence, nausea, constipation, sweating and pruritus, are similar to that of the opioids. Since tramadol causes significantly less respiratory depression than the opioids, any enhancement, or potentiation, of the analgesic activity of tramadol would allow the dosage level of the drug to be reduced below that of the standard dosage level without a reduction in analgesic response. Alternatively, potentiation of tramadol would allow the standard dosage level to be maintained but with an increase in analgesic response. Either way, the safety of tramadol-induced analgesia will have been considerably improved by a potentiation of its analgesic effectiveness. Dextromethorphan is the disomer of the codeine analog of levorphanol. Unlike the l-isomer, dextromethorphan is said to have no analgesic or addictive properties (Goodman and Gilman's, "The Pharmacological Basis of Therapeutics", 8th ed., McGraw-Hill, Inc. (1990), p. 518).

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Web site: http://www.delphion.com/details?pn=US05919826__ •

Methods of treating obsessive-compulsive spectrum disorders Inventor(s): Goldsmith; Toby D. (Gainesville, FL), Keck, Jr.; Paul E. (Cincinnati, OH), Shapira; Nathan A. (Gainesville, FL) Assignee(s): University of Cincinnati (Cincinnati, OH) Patent Number: 6,387,956 Date filed: March 24, 2000 Abstract: A method of treating an obsessive-compulsive spectrum disorder comprises the step of administering an effective amount of tramadol to an individual. Excerpt(s): This invention relates to methods of treating obsessive-compulsive spectrum disorders. More particularly, the invention relates to methods of treating obsessivecompulsive spectrum disorders comprising the step of administering an effective amount of tramadol to an individual. Although originally believed to be rare, it is now known that obsessive-compulsive disorder (OCD) is common, with estimated life time prevalence rates in the United States ranging from 1.9% to 3.3% (Shapira et al., Depression and Anxiety 6; 170-173 (1997).) The Diagnostic and Statistical Manual of Mental Disorders, fourth edition, (DSM-IV), includes as its diagnostic criteria for OCD that: the person exhibits either obsessions or compulsions; at some point during the course of the disorder the person has recognized that the obsessions or compulsions are excessive or unreasonable; the obsessions or compulsions caused marked stress, are time-consuming or significantly interfere with the person's normal routine, occupational/academic functioning, or usual social activities or relationships; if another axis I disorder is present, the content of the obsessions or compulsions is not restricted to it; and the disturbance is not due to the direct physiologic effects of a substance or a general medical condition. The DSM-IV sets four indicia of obsessions. First, the person has recurrent and/or persistent thoughts, impulses or images that are experienced at some time during the disturbance as intrusive and inappropriate and as causing marked anxiety or distress. Second, the thoughts, impulses or images are not simply excessive worries about real-life problems. Third, the person attempts to ignore or suppress such thoughts, impulses or images or to neutralize them through some other thought or action. Fourth, the person recognizes that the obsessional thoughts, impulses, or images are products of his or her own mind and are not imposed from without. Web site: http://www.delphion.com/details?pn=US06387956__

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Multilayer tablet for administering a fixed combination of tramadol and diclofenac Inventor(s): Bartholomaeus; Johannes (Aachen, DE), Ziegler; Iris (Rott-Roetgen, DE) Assignee(s): Gruenenthal GmbH (Aachen, DE) Patent Number: 6,558,701 Date filed: December 17, 2001 Abstract: A multilayer tablet for oral administration containing at least one Tramadol layer including Tramadol or a physiologically acceptable salt thereof; at least one diclofenac layer including diclofenac or a physiologically acceptable salt thereof, and at

Patents 75

least one separating layer which separates the tramadol layer(s) and the diclofenac layer(s) from each other. Excerpt(s): This application is a continuation of international patent application no. PCT/EP00/05385, filed Jun. 13, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. DE 199 27 688.9, filed Jun. 17, 1999. The present invention relates to a multilayer tablet containing the active substances Tramadol and Diclofenac and/or their in each case physiologically compatible salts, with the active substances being separated from one another by a separating layer. Tramadol is an analgesic used to treat severe and moderately severe pain, whose mode of action is not based on a pure opioid mechanism. Tramadol does not exhibit the characteristic side effects of an opioid. In some cases nausea is observed as an undesirable accompanying symptom. Web site: http://www.delphion.com/details?pn=US06558701__ •

Pharmaceutical compositions containing tramadol for migraine Inventor(s): Momberger; Helmut (Marburg, DE), Raber; Marc (Giessen, DE) Assignee(s): ASTA Medica AG (Dresden, DE) Patent Number: 6,376,550 Date filed: February 9, 1999 Abstract: A method for treating migraine is disclosed in which a composition consisting essentially of pharmacologically effective amounts of both an antiemetic compound and tramadol is administered to a patient in need thereof. Excerpt(s): The present invention relates to a new process for using pharmaceutical compositions containing tramadol, and an antiemetic-antinauseant substance for the treatment of migraines and migraine-like headaches. Migraine is a disease with recurring attacks of headaches, which last between 4 and 72 hours. Migraine attacks predominantly are unilateral, dull at the beginning and then pulsing headaches occur with moderate to severe intensity. Typical accompanying symptoms of migraines are hypersensitivity towards light and sound, pallor, nausea and vomiting and without neurological focal attack, as a prodromal stage. The (usual) migraine without aura is differentiated from the (classical) migraine with aura, which always commences with a characteristic scintillating scotoma. A complicated migraine exists if the visual disorders last for days or other neurological focal symptoms occur with the known special forms of the retinal, basilar, ophthal-moplegic, aphasic or hemiplegic migraine. Web site: http://www.delphion.com/details?pn=US06376550__

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Pharmaceutical compositions of O-desmethyl-N-mono-desmethyl-tramadol Inventor(s): Englberger; Werner (Stolberg, DE), Friderichs; Elmar (Stolberg, DE), Hennies; Hagen-Heinrich (Simmerath, DE), Koegel; Babette (Langerwehe, DE) Assignee(s): Gruenenthal GmbH (Aachen, DE) Patent Number: 6,593,373 Date filed: October 12, 2001

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Abstract: A method of producing pharmaceutical compositions using O-desmethyl-Nmono-desmethyl-tramadol for the treatment of pain and various related indications, pharmaceutical compositions containing O-desmethyl-N-mono-desmethyl-tramadol, and a method of treating pain, urinary incontinence, diarrhea or pruritus using Odesmethyl-N-mono-desmethyl-tramadol. Excerpt(s): This invention relates to the use of O-desmethyl-N-mono-desmethyltramadol for the production of pharmaceutical compositions for the treatment of pain and various related indications as well as pharmaceuticals comprising O-desmethyl-Nmono-desmethyl-tramadol. The treatment of pain conditions is of great importance in medicine. There is currently a world-wide need for additional pain therapy. The pressing requirement for a target-oriented treatment of pain conditions which is right for the patient which is to be understood as the successful and satisfactory treatment of pain for the patients is documented in the large number of scientific works which have recently and over the years appeared in the field of applied analgesics or on basic research on nociception. The underlying object of the present invention was to provide a substance useful in the treatment of pain and also related indications, as well as pharmaceutical compositions for such treatment. Web site: http://www.delphion.com/details?pn=US06593373__ •

Pharmaceutical drug dosage forms providing different release rates Inventor(s): Bardsley; Hazel Judith (Cambridge, GB), Gilbert; Julian Clive (Cambridge, GB), Richards; Andrew John McGlashan (Cambridge, GB) Assignee(s): Darwin Discovery Limited (GB) Patent Number: 6,056,968 Date filed: March 11, 1998 Abstract: A pharmaceutical dosage form comprises, in one portion thereof, a substantially single (+)-enantiomer of a chiral drug other than verapamil and, in another, separate portion thereof, a substantially single (-)-enantiomer of the drug wherein, in use, the different enantiomers are released at different rates from the dosage form. The dosage form is useful for administration of chiral drugs where both enantiomers have a valid pharmacological input, and where a clinical benefit may be realised by controlling the release rates of those enantiomers. Examples of such drugs include, in particular, tramadol and warfarin. Excerpt(s): This invention relates to the discovery of novel pharmaceutical dosage forms of chiral drugs. The separate enantiomers of some chiral drugs have different therapeutic properties, and/or mechanisms of action and yet in some cases it may still be desirable to dose both enantiomers together. However, where the pharmacokinetic properties of the separate enantiomers are different, for instance due to differences in the rates at which they are metabolised, the ratio of the different enantiomers changes with time after initial dosing, which can lead to reduced efficacy of the drug. The actual enantiomeric ratio at any one time may be dependent upon a number of factors, and may be further complicated if different dosage forms provide different enantiomeric ratios. Effects such as these have been observed with the different enantiomers of verapamil, for instance see Longstreth, J.A. Clin. Pharmacol. (1993) 18 (2nd Edition): 315-336 and Gupta et al., Eur. J. Pharm. Biopharm. (1996) 42(1): 74-81. According to the present invention, a pharmaceutical dosage form comprises, in one portion thereof, a substantially single (+)-enantiomer of a chiral drug other than verapamil and, in

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another, separate, portion thereof, a substantially single (-)-enantiomer of the drug, wherein, in use, the different enantiomers are released at different rates from the dosage form. Web site: http://www.delphion.com/details?pn=US06056968__ •

Process Inventor(s): Evans; Graham (Cambridge, GB) Assignee(s): Darwin Discovery, Ltd. (GB) Patent Number: 6,323,368 Date filed: November 30, 1999 Abstract: A process for preparing a substantially single enantiomer of tramadol, or a pharmaceutically-acceptable salt thereof, proceeds by means of a classical salt resolution using a substantially single enantiomer of O,O-di-p-toluoyltartaric acid as a resolving agent. Excerpt(s): The present invention relates to a process for the manufacture of single enantiomers of tramadol. In connection with our own interest in this area, we required an efficient and reliable method for the preparation of individual enantiomers of tramadol. Due to the ready availability of racemic tramadol a classical resolution process, involving separation of diastereomeric salts by selective crystallisation, appeared ideal for this purpose. Initially, literature procedures for the resolution of tramadol were investigated. In U.S. Pat. No. 5,723,668, it is reported that use of L-(+)tartaric acid as resolving agent facilitates a highly efficient resolution whereby 49% yield (with respect to racemic base) of a diastereomerically-pure salt of 1S, 2S-(-)-tramadol is obtained after a single crystallisation from ethanol solution, by filtration and washing with solvent. However, in our hands, these results could not be reproduced. Typically, following dissolution of racemic tramadol and L-(+)-tartaric acid, we observed crystallisation, but analysis of the isolated salt showed little or no diastereomeric enrichment. Web site: http://www.delphion.com/details?pn=US06323368__

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Process for the purification of methoxyphenyl)cyclohexanol hydrochloride

(RR-SS)-2-dimethylaminomethyl-1-(3-

Inventor(s): Brenner; Dov (Lod, IL), Kaspi; Joseph (Givatayim, IL), Lerman; Ori (Ramat Gan, IL) Assignee(s): Chemagis, Ltd. (Bnei Brak, IL) Patent Number: 5,874,620 Date filed: August 14, 1997 Abstract: The invention provides a process for the separation of (RR,SS) 2dimethylaminomethyl-1-(3-methoxyphenyl) cyclohexanol hydrochloride ›(RR,SS)Tramadol!, from a mixture consisting of (RR,SS) Tramadol and (RS,SR)-2dimethylaminomethyl-1-(3-methoxyphenyl) cyclohexanol ›(RS,SR)-Tramadol!, which process includes combining the mixture with an electrophilic reagent, the reagent selectively reacting with the hydroxyl group of (RS,SR)-Tramadol, leaving most of the

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(RR,SS) Tramadol intact, and precipitating the remaining, practically pure (RR,SS) Tramadol from the mixture. Excerpt(s): The present invention relates to a process for the purification of (RR,SS)-2dimethylaminomethyl-1-(3-methoxyphenyl)cyclohexanol hydrochloride, also known as trans Tramadol, from its (RS,SR) isomer and from other undesirable products. More particularly, the present invention relates to a process for the purification of the (RR,SS) isomer, based on the discovery that the hydroxyl group of the (RS,SR) isomer undergoes various chemical reactions faster than the same group of the (RR,SS) isomer. Thus, the invention is based on reacting a mixture of isomers with various chemical substances reacting predominantly with the (RS,SR) isomer, while the (RR,SS) isomer remains practically intact. The desired (RR,SS) isomer is then easily purified by recrystallization from an appropriate solvent. Tramadol is a well established pain killer, invented by Gruenenthal GmbH, Germany, used as a non-addictive analgesic and sold under different trade names such as Tramal, Ultram, Crispin and Tramundin. Web site: http://www.delphion.com/details?pn=US05874620__ •

Rapidly disintegrating medicinal form of tramadol or a tramadol salt Inventor(s): Bartholomaeus; Johannes Heinrich Antonious (Aachen, DE), Betzing; Juergen (Aachen, DE) Assignee(s): Gruenenthal GmbH (Aachen, DE) Patent Number: 5,776,492 Date filed: August 19, 1996 Abstract: Rapidly disintegrating, binder-free tablets of tramadol or a tramadol salt for oral administration comprising microcrystalline cellulose and tramadol or a pharmaceutically acceptable tramadol salt in a weight ratio of at least 2:1. Excerpt(s): This invention relates to binder-free tablets of tramadol or of a tramadol salt for oral application. In order to obtain the fastest possible, defined release of active ingredient for solid forms of medication such as tablets, a very rapid disintegration of the form of medication must be achieved in the release medium. Disintegration, namely the falling apart of the tablets into individual particles of granular material, is influenced by numerous factors: thus binders (granulating agents), lubricants and fillers, and the solubility of fillers in particular, can considerably reduce the rate of disintegration. Moreover, the size and shape of the particles, as well as the hardness of the tablets, which depends on the pressing force employed in their manufacture, have a strong influence on the rate of disintegration. In many cases, the time of disintegration increases significantly above a given tablet hardness. The rate of disintegration of tablets can be increased by the use of disintegrating agents. Disintegrating agents are substances which are capable of accelerating the disintegration of tablets in contact with water, buffer solutions or digestive juices. Examples of known disintegrating agents include starch, sodium carboxymethyl celluloses with a low degree of substitution, hydroxypropyl celluloses with a low degree of substitution, calcium carboxymethyl celluloses, alginic acid, cross-linked carboxyymethyl celluloses and cross-linked polyvinyl pyrrolidones. Web site: http://www.delphion.com/details?pn=US05776492__

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Remedies for frequent urination and urinary incontinence Inventor(s): Sasaki; Yasuo (Kameoka, JP) Assignee(s): Nippon Shinyaku Co., Ltd. (Kyoto, JP) Patent Number: 6,090,856 Date filed: January 3, 2000 Abstract: The object of this invention is to provide a novel medicinal use for tramadol the safety, among other properties, of which has already been established. This invention is directed to a therapeutic or prophylactic composition for urinary frequency and a therapeutic or prophylactic composition for urinary incontinence, both comprising tramadol or a salt thereof. The preferable salt of tramadol includes tramadol hydrochloride. Excerpt(s): This invention relates to a therapeutic or prophylactic composition for urinary frequency or a therapeutic or prophylactic composition for urinary incontinence, which comprises tramadol or a salt thereof as an active ingredient. Tramadol is an opioid non-narcotic analgesic drug having the chemical name of trans-(.+-.)-2[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol and has heretofore been used broadly in the form of hydrochloride for the management of intense to moderate pain. Urinary incontinence is a disease generally considered to occur when the intravesical pressure involuntarily exceeds the urethral closure pressure and is suspected to involve, as an etiologic factor, an increase in intravesical pressure (which chiefly causes urge urinary incontinence or urinary frequency) or a decrease in urethral closure pressure (which chiefly causes stress urinary incontinence). Web site: http://www.delphion.com/details?pn=US06090856__

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Sustained release drug formulation containing a tramadol salt Inventor(s): Bartholomaeus; Johannes H. A. (Aachen, DE) Assignee(s): Gruenenthal GmbH (Aachen, DE) Patent Number: 5,601,842 Date filed: January 16, 1996 Abstract: A drug formulation of tramadol or a tramadol salt in orally administrable tablet form containing at least one pharmaceutically acceptable matrixing agent is disclosed from which a non-moisture sensitive, physiologically acceptable tramadol salt is sustained released. Excerpt(s): This invention relates to drug formulations in form of tablets for oral administration from which a non-moisture sensitive, physiologically acceptable salt of tramadol is released in a sustained manner and which contain at least one pharmaceutically acceptable matrixing agent. Tramadolhydrochloride-(1RS;2RS)-2[(dimethylamino)methyl]-1-(3-methoxypheny l)cyclohexanol, hydrochloride--is an analgesic effective in severe and moderate severe pain. All drug formulations available on the market are immediate release forms which require administration 3 to 4 times per day in order to achieve good therapeutic effectiveness in relieving chronic pain. It would be a desirable relief to the patients if the frequency of administration could be reduced to once or twice daily. Several principles of sustained release formulations are known to a person skilled in the art. For example, U.S. Pat. No. 3,065,143, filed on Apr. 19, 1960, discloses a sustained release tablet containing at least one-third part by weight

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of the weight of the tablet of a pharmaceutically acceptable hydrophilic gum which rapidly absorbs water and swells at 37.degree. C. to form a soft mucilaginous gel barrier on the surface of the tablet when brought into contact with the aqueous fluids of the gastrointestinal tract which prevents rapid disintegration of the tablet and release of the medicament contained therein when taken orally, but allows slow disintegration of the tablet and release of medicament over a period of at least four hours. However, the examples show that the release of the medicament is influenced by the pH value. For the release mechanism it is further described that the soft mucilaginous gum gel barrier is worn away by the motion of the tablet in the gastrointestinal tract, and some of the admixed medicinal agent is carried away with it and released. At the same time the protective coating at the surface of the tablet is renewed. This means that the release of the medicament is also influenced by mechanical stress. Further it is described that the rate of release depends on the weight ratio of active ingredient to gum as well as on the content of hydrophilic gum in the tablet. Web site: http://www.delphion.com/details?pn=US05601842__ •

Synthesis and purification of (r*,r*)-2-[ methoxyphenyl) cyclohexanol hydrochloride

(dimethylamino)

methyl]-1-(3-

Inventor(s): Grayson; Neile A. (Glendale, MO), Halvachs; Robert E. (Belleville, IL), Jarvi; Esa T. (Ballwin, MO) Assignee(s): Mallinckrodt Inc. (St. Louis, MO) Patent Number: 6,399,829 Date filed: November 20, 2000 Abstract: (R*,R*)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (Tramadol) is synthesized in a Grignard reaction in the presence of an additive resulting in a higher trans:cis ratio of product than is obtained in the absence of the additive. The Grignard reaction between 3 bromoanisole and the appropriate Mannich base in the presence of an amine or ether additive gives the amine product in an improved trans/cis ratio. The base is converted to its hydrochloride and recrystallized from a low molecular weight nitrile such as acetonitrile until a greater than 98% trans/cis ratio is obtained. Recrystallization from isopropanol gives (R*,R*)2-[(dimethylamino)methyl]-1(3-metboxyphenyl)cyclohexanol hydrochloride free of the nitrile solvent. A hydrochloride of Tramadol can be synthesized without increasing a ratio of trans:cis by including a step in which HCl is added to Tramadol base in the presence of toluene. Excerpt(s): Methods of manufacture begin with a Grignard reaction which results in a mixture of cis and trans isomers. These are then separated by methods taught in the prior art. U.S. Pat. No. 5,652,589 teaches a method of heating the mixture under reflux with a mixture of anhydrous dioxane and water for one hour while stirring and filtering. The filter residue obtained includes the trans form of the hydrochloride of Tramadol. The filtrate is a mixture of about 20-30% cis form and 70-80% trans form. This filtrate can be further separated by cooling to yield crystals which are then pulverized and stirred with dichloromethane at room temperature. The cis isomer is not dissolved whereas the trans isomer goes into solution. This solution is filtered. The filtrate yields substantially pure trans isomer. The filter residue is dissolved in methanol and crystallized by adding ether. The resulting crystals are substantially pure cis isomer of Tramadol. U.S. Pat. No. 5,414,129, which is incorporated herein by reference, teaches a process for the improved purification and separation of the cis and trans isomers of Tramadol. This '129 patent lists the many problems with using dioxane in the preparation of a compound which is

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to be used as part of a drug. Included in this list are the following: dioxane has been listed as a category I carcinogen by OSHA (Kirk & Othmer, 3rd edition vol. 9, page 386) and it causes CNS depression and necrosis of the liver and kidneys (Kirk & Othmer, 3rd edition vol. 13, page 267). Therefore, the presence of dioxane as a residue is monitored and a limit of several parts per billion has been set. The '129 patent teaches a method which avoids the use of dioxane. Tramadol is first synthesized via a Grignard reaction to yield a mixture of cis and trans forms plus Grignard reaction side products. This mix of products is combined with a solution of hydrochloric acid in a low molecular weight alcohol or with gaseous hydrogen chloride in the presence of an organic solvent selected from medium molecular weight alcohols, ketones, esters and ethers or aromatic ethers, to effect the selective precipitation of the trans isomer (Tramadol). The '129 patent states that alternative solvents to dioxane which will effectively separate the cis and trans isomers were very hard to find, but those listed in the patent were found to be usable. In accordance with the present invention, a method is provided for forming a product comprising (R*,R*)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol (Tramadol) by a process selected from the group consisting of 1) synthesizing Tramadol in a sequence of steps including a Grignard reaction in the presence of an additive wherein the presence of said additive results in a higher trans:cis ratio of Tramadol than is obtained in the absence of said additive, 2) synthesizing a hydrochloride of Tramadol without increasing a ratio of trans:cis by performing a step consisting essentially of adding HCl to Tramadol base in the presence of toluene, and 3) synthesizing a hydrochloride of Tramadol while increasing a ratio of trans:cis by converting trans and cis forms of Tramadol to hydrochloride forms and recrystallizing said hydrochloride forms from a nitrile solvent. Web site: http://www.delphion.com/details?pn=US06399829__ •

Therapeutic use and formulation Inventor(s): Huckle; Richard Michael (Cambridge, GB) Assignee(s): Darwin Discovery, Ltd. (GB) Patent Number: 6,297,286 Date filed: November 8, 2000 Abstract: Substantially single-enantiomer(-)-tramadol, and its metabolites and structural and/or functional analogues, are useful for the prevention and/or treatment of one or more symptoms selected from nausea, vomiting, dizziness, blurred vision, drowsiness, somnolence, hallucinations, respiratory depression, constipation and euphoria. In particular, substantially single enantiomer (-)-tramadol, and its o-desmethyl metabolite, have been found to be potent anti-emetics. Excerpt(s): This invention relates to new therapeutic uses of tramadol and its structural and/or functional analogues, and to new formulations thereof. Tramadol has the chemical name (+/-)-trans (RR,SS)-2-[(di-methylamino)methyl]-1-(3-methoxyphenyl) cyclohexanol, and which is generally, and erroneously, referred to in literature as the cis(RS,SR) diastereomer, is a centrally acting, binary analgesic that is neither opiatederived, nor is a non-steroidal, anti-inflammatory drug (NSAID). It is used to control moderate pain in chronic pain settings, such as osteoarthritis and postoperative cases, and acute pain, such as dental pain. Used in therapy as a racemic mixture, the (+)enantiomer binds to the.mu.-opioid receptor, and both enantiomers inhibit 5hydroxytryptamine (serotonin) and noradrenaline (norepinephrine) reuptake. Tramadol's major active metabolite, O-desmethyltramadol (M1), shows higher affinity

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for the.mu.-opioid receptor and has at least twice the analgesic potency of the parent drug. Web site: http://www.delphion.com/details?pn=US06297286__ •

Tramadol multiple unit formulations Inventor(s): Kuhn; Dieter (Marburg, DE), Momberger; Helmut (Marburg, DE), Raber; Marc (Giessen, DE), Schmid; Wolfgang (Lohra, DE) Assignee(s): Asto-Medica AG (Radebeul, DE) Patent Number: 6,436,438 Date filed: July 8, 1999 Abstract: A multiple unit oral pharmaceutical dosage form having a plurality of pellets in a water soluble capsule or in a tablet compressed from the pellets, wherein each pellet contains (a) a substantially inert core, (b) an active ingredient layer over the inert core, and containing (i) a pharmacologically active particulate active ingredient, (ii) a nonembedding amount of a binder for adhering the active ingredient over the inert core, and optionally (iii) a pharmaceutically acceptable, inert adjuvant, such as colloidal silica, and (c) a coating over the active ingredient layer for retarding the release of the active ingredient from the active ingredient layer into an aqueous body fluid solvent in situ, the nonembedding amount of the binder is suitably from about 1% wt. to about 10% wt. based on the active ingredient layer, the binder in the active ingredient layer is suitably a mixture of ethylcellulose and shellac, in a weight proportion suitably of from about 1: about 9, to from about 9: about 1, the coating for retarding the release suitably contains from about 70% wt. to about 95% wt. based on the coating, of a substantially waterinsoluble, pharmacologically inert, particulate material, and a binder; the pharmacologically inert, particulate material is suitably talcum, and the binder in the active ingredient layer is suitably identical to the binder in the coating. Excerpt(s): The invention relates to oral, multiple unit formulations of delayed-release pellets which contain a pharmacologically active component coated by at least one pharmaceutically acceptable, release-delaying substance, and to a process for their preparation. Single unit controlled release tablet dosage forms of drugs have known disadvantages compared to the more desirable multiple unit dosage forms. In single dosage matrix tablets the active ingredient is dispersed as a solid in an inert, release delaying matrix. The embedding matrixing material that slows the release of the drug is usually an insoluble plastic (e.g. methyl acrylate-methacrylate, polyvinyl chloride, or polyethylene), a hydrophilic polymer (e.g. methylcellulose, hydroxypropylmethylcellulose, or sodium carboxyl methylcellulose), or fatty compounds (e.g. various waxes, such as carnauba wax, or glyceryl stearate). Such tablets pass undisintegrated through the gastrointestinal tract, and become ever smaller due to breakdown (erosion tablets), or wherein the active compound is released only in the intestine (enteric-coated tablets), in either case depleting the surface inward through the matrix by dissolution or diffusion through the matrix to the external solution. Multiple unit dosage forms are usually contained within a rapid dissolving capsule, or are compressed into a tablet, and soon after ingestion upon its dissolution fall apart into the multiple units, such as pellets. The sub-units or pellets have the desired slow release properties of the dosage form. In contrast to the matrixed formulations, the multiple unit pellets are each surrounded by a polymeric delay release film coating that provides the controlled, slowed release of the active ingredient from within the pellet. These coated dosage forms are generally referred to as "reservoir devices" when diffusion

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phenomena occur through the release slowing coat, or "encapsulated formulations" when the slow release coat slowly dissolves (see e.g. Remington's Pharmaceutical Sciences, Mack Publ. Co.). In the case of the single unit, matrixed delayed-release dosage forms, considerable variations can occur in the gastric residence times, and this can lead to an irregular passage through the gastrointestinal tract and thus to differing, fluctuating blood level values. Local irritation is also becomes of lesser concern also being reduced by the use of multiple unit pharmaceutical dosage forms. "Dose dumping" or the too rapid release of the active compound from delayed-release dosage forms (see e.g. H. Blume, "Biopharmazeutische Aspekte von Multiple Unit Dosage Forms; ein Vergleich mit Single Units" [Biopharmaceutical aspects of multiple unit dosage forms; a comparison with single units], published by Capsugel, Basel, and delivered at a symposium in November 1988 in Hamburg). Web site: http://www.delphion.com/details?pn=US06436438__ •

Tramadol, salts thereof and process for their preparation Inventor(s): Nikolopoulos; Aggelos (Cork, IE), Schickaneder; Helmut (Cork, IE) Assignee(s): Russinsky Limited (Cork, IE) Patent Number: 6,469,213 Date filed: January 14, 2000 Abstract: Cis-Tramadol hydrochloride is prepared by forming a Mannich hydrochloride, liberating the Mannich base, reacting the Mannich base with a Grignard reagent to form a base hydrate of cis-Tramadol which is used to form pure cis-Tramadol hydrochloride. Also claimed is the base hydrate of cis-Tramadol per se and its use as a medicament. Excerpt(s): The invention relates to a new, stable and pure Tramadol derivative, a specific process for preparing it and its use. The invention also relates to a process for producing Tramadol and salts thereof, especially Tramadol hydrochloride using the derivative. Tramadol is the compound cis(+/-)-2-[(dimethylamino)-methyl]-1-(3methoxyphenyl) cyclohexanol which, in the form of the hydrochloride salt is widely used as an analgesic. Tramadol hydrochloride assumes a special position among centrally acting;s analgesics since this active ingredient acts as a strong inhibitor of pain without the side effects which are known for opioids (T. Phannacol. Exptl. Ther. 267,331 (1993)). Web site: http://www.delphion.com/details?pn=US06469213__

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Use of (+)-tramadol, O-demethyltramadol or (+)-O-demethyl-tramadol, O-desmethylN-mono-desmethyl-tramadol or (+)- O-desmethyl-N-mono-desmethyltramadol Inventor(s): Christoph; Thomas (Aachen, DE), Friderichs; Elmar (Zehntweg, DE) Assignee(s): Gruenethal GmbH (Aachen, DE) Patent Number: 6,660,774 Date filed: April 5, 2002 Abstract: Method for the treatment of increased urinary urgency or urinary incontinence comprising administering (+)-tramadol, O-demethyltramadol, (+)-O-demethyltramadol, O-desmethyl-N-mono-desmethyltramadol, or (+)-O-desmethyl-N-mono-

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desmethyltramadol, as free bases and/or in the form of physiologically compatible salts, are disclosed. Excerpt(s): The invention relates to the use of (+)-tramadol or 0-demethyltramadol, in particular (+)-O-demethyltramadol, O-desmethyl-N-mono-desmethyltramadol, in particular (+)-O-desmethyl-N-mono-desmethyltramadol as free bases and/or in the form of physiologically compatible salts for the production of a pharmaceutical preparation for the treatment of increased urinary urgency or urinary incontinence and to corresponding pharmaceutical preparations and to a method for the treatment of increased urinary urgency or urinary incontinence. Urinary incontinence is the involuntary release of urine, which occurs in an uncontrolled manner when the pressure within the bladder exceeds the pressure required to seal the ureter. This may be caused, on the one hand, by increased internal bladder pressure (for example due to detrusor instability) resulting in urge incontinence and, on the other hand, by reduced sphincter pressure (for example after giving birth or surgical intervention) resulting in stress incontinence. The detrusor is the coarsely bundled, multilayer bladder wall musculature, contraction of which results in voiding of urine, while the sphincter is the muscle which closes the urethra. Mixed forms of these types of incontinence occur, as do so-called overflow incontinence (for example in cases of benign prostate hyperplasia) or reflex incontinence (for example after spinal cord damage). Further details in this connection may be found in Chutka, D. S. and Takahashi, P. Y., 1998, Drugs 560: 587595. Urinary urgency is the state of increased bladder muscle tension directed towards voiding of urine (micturition) as bladder capacity is approached (or exceeded). This tension acts as the micturition stimulus. Increased urinary urgency is taken in particular to mean the occurrence of premature or more frequent, sometimes even painful urinary urgency, going as far as urinary compulsion. This consequently results in distinctly more frequent micturition. Possible causes are bladder inflammation and neurogenic bladder dysfunction as well as vesical tuberculosis. However, not all causes have yet been explained. Web site: http://www.delphion.com/details?pn=US06660774__

Patent Applications on Tramadol 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 tramadol: •

Analgesic regimen Inventor(s): Kamin, Marc; (West Windsor, NJ), Olson, William; (Princeton, NJ) Correspondence: Audley A. Ciamporcero JR.; Johnson & Johnson; One Johnson & Johnson Plaza; New Brunswick; NJ; 08933-7003; US Patent Application Number: 20020055544 Date filed: October 26, 2001 Abstract: A regimen for the administration of tramadol for the treatment of analgesia is described. The regimen involves a slower initial titration rate of tramadol which results

6

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

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in a significantly lower percentage of discontinuations of therapy due to a lower incidence and severity of side effects. Excerpt(s): This invention relates to a dosing regimen for the administration of the analgesic tramadol. The dosing regimen achieves the desired analgesic effect while reducing or delaying the on-set of the side effects generally associated with the administration of tramadol. Tramadol, the chemical name for which is 2[(dimethylamino)methyl]-- 1-(3-methoxyphenyl)cyclohexanol, is a synthetic, centrallyacting analgesic that is effective for the treatment of moderate to moderately-severe chronic pain. It has been marketed under the trade name Tramal.TM. since 1977 in the dosage forms of capsules, injections, suppositories and drops. The compound can be employed as the free base or its pharmaceutically acceptable salts, stereo isomers and solvates. It is generally supplied in the form of its hydrochloride salt and over 400 million doses of tramadol have been administered since its introduction in Germany. Patients experiencing chronic pain require an analgesic therapeutic regimen that is both effective and well tolerated. The two traditional categories of analgesics, i.e. opioids and nonsteroidal anti-inflammatory drugs (NSAIDs), are both effective but are associated with potentially serious side effects. Concerns regarding tolerance and dependence minimize the chronic use of narcotics such as morphine and codeine for the treatment of chronic pain. Patients on chronic NSAID therapy risk severe gastrointestinal symptoms, including ulceration and bleeding which have been estimated to result in up to 20,000 deaths each year. An alternative to this dilemma is tramadol, a non-narcotic, nonNSAID analgesic which is indicated for the management of moderate to moderatelysevere pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Anticonvulsant containing composition for treating neuropathic pain Inventor(s): Caruso, Frank S.; (Colts Neck, NJ), Lyle, John W.; (Belmar, NJ), Minn, Fredrick L.; (Blue Bell, PA) Correspondence: Peter G. Dilworth, ESQ.; Dilworth & Barrese, Llp; 333 Earle Ovington Boulevard; Uniondale; NY; 11553; US Patent Application Number: 20010008889 Date filed: February 9, 2001 Abstract: The analgesic effectiveness of an tramadol is significantly enhanced by administering tramadol prior to, with or following the administration of an analgesia enhancer which is a nontoxic NMDA receptor blocker and/or a nontoxic substance that blocks at least one major intracellular consequence of NMDA receptor activation. Excerpt(s): This invention relates to a composition and method for alleviating neuropathic pain. More particularly, this invention is directed to a composition and method for alleviating neuropathic pain in which a neuropathic pain-alleviating amount of an anticonvulsant is combined with an anticonvulsant-potentiating amount of a nontoxic antagonist, or blocker, for the N-methyl-D-aspartate (NMDA) receptor or nontoxic substance that blocks a major intracellular consequence of NMDA receptor activation. Neuropathic pain is pain that is due to functional abnormalities of the nervous system. Fields, "Pain", McGraw-Hill, Inc. (1987), pp. 133 et seq. There are a variety of possible mechanisms by which nerve dysfunction can cause neuropathic pain: hyperactivity in primary afferent or central nervous system (CNS) nociceptive neurons, loss of central inhibitory connections, and increased activity in sympathetic efferents.

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Neuropathic pain typically occurs following injury to elements of the nervous system involved in nociception, such as peripheral nerve injury, in which the lesions deafferent the nociceptive pathway, the resultant pain sometimes being referred to deafferentation pain. Neuropathic pain is much more likely to occur with peripheral than with central nervous system damage. Examples of causes of painful nerve injury are: accidental trauma, tumors, cerval or lumbar spine disease, and surgical procedures. These injuries usually involve one or two peripheral nerves or nerve roots, and the pain is felt in the body region normally innervated by the damaged nerves. Additionally, there are also toxic, metabolic, and hereditary causes of painful polyneuropathies, e.g., alcohol abuse, diabetes mellitus. These tend to be symmetrical and are most severe on the distal limbs. In accordance with the present invention, a drug composition is provided which comprises a neuropathic pain-alleviating amount of at least one anticonvulsant in combination with an anticonvulsant-potentiati- ng amount of at least one nontoxic antagonist for the NMDA receptor or nontoxic substance that blocks a major intracellular consequence of NMDA receptor activation. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Compositions and methods for enhancing analgesic potency of tramadol and attenuating its adverse side effects Inventor(s): Barbier, Remi; (San Francisco, CA), Crain, Stanley M.; (State College, PA), Friedmann, Nadav; (Lafayette, CA), Remien, Mary; (San Francisco, CA), Shen, Ke-Fei; (Flushing, NY), Sherman, Barry; (Hillsborough, CA) Correspondence: Mcandrews Held & Malloy, Ltd; 500 West Madison Street; Suite 3400; Chicago; IL; 60661 Patent Application Number: 20030148941 Date filed: March 12, 2002 Abstract: The invention generally relates to compositions and methods with tramadol and an opioid antagonist to enhance analgesic potency and/or attenuate one or more adverse effects of tramadol, including adverse side effect(s) in humans such as nausea, vomiting, dizziness, headache, sedation (somnolence) or pruritis. This invention relates to compositions and methods for selectively enhancing the analgesic potency of tramadol and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of tramadol. The methods of the present invention comprise administering to a subject an analgesic or subanalgesic amount of tramadol and an amount of excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of tramadol and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of tramadol. Excerpt(s): This is a continuation-in-part of co-pending application Ser. No. 09/306,164 filed May 6, 1999, the content of which is hereby incorporated by reference in its entirety. Morphine or other bimodally-acting opioid agonists are administered to relieve severe pain due to the fact that they have analgesic effects mediated by their activation of inhibitory opioid receptors on nociceptive neurons (see North, Trends Neurosci., Vol. 9, pp. 114-117 (1986) and Crain and Shen, Trends Pharmacol. Sci., Vol. 11, pp. 77-81 (1990)). However, morphine and other bimodally-acting opioid agonists also activate opioid excitatory receptors on nociceptive neurons, which attenuate the analgesic potency of the opioids and result in the development of physical dependence and

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increased tolerance (see Shen and Crain, Brain Res., Vol. 597, pp. 74-83 (1992)), as well as hyperexcitability, hyperalgesia and other undesirable (excitatory) side effects. As a result, a long-standing need has existed to develop a method of both enhancing the analgesic (inhibitory) effects of bimodally-acting opioid agonists and blocking or preventing undesirable (excitatory) side effects caused by such opioid agonists. Tramadol is an orally active, clinically effective, centrally acting analgene compound with opioid and non-opioid activity. This synthetic analgesic has a novel mechanism of action involving a complementary and synergistic interaction between inhibition of neuronal monamine uptake and weak affinity for opioid receptors (Raffa et al., Rev. Contemp. Pharmacother. 6:485-497 (1995)). Tramadol is generally well tolerated, with dizziness, nausea, constipation, headache, somnolence (sedation), vomiting, pruritis, CNS stimulation, sezures, asthenia, dyspepsia, diarrhea, dry mouth and/or sweating as adverse side effects. Respiratory depression is uncommon (Lee et al., Drugs 46: 313-340 (1993); Vickers et al., Anaesthesia 47: 291-296 (1992)). Tramadol is marketed in the United States as ULTRAM.RTM. Data from a double-blind, crossover study suggest that oral tramadol 120 mg is equipotent to oral morphine 30 mg (Wilder et al., Ann. Oncol. 5: 141-146 (1994)). A need thus exists for compositions and methods that could enhance the analgesic potency of tramadol and/or block or prevent its adverse side effects, particularly its principal adverse effects in humans. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Controlled release pharmaceutical composition containing tramadol hydrochloride Inventor(s): Gattnar, Ondrej; (Bratislava, SK), Razus, L?apos;uboslav; (Hlohovec, SK), Sedlarova, Helena; (Hlohovec, SK), Varga, Ivan; (Hlohovec, SK), Zemanek, Marian; (Bratislava, SK) Correspondence: Oblon, Spivak, Mcclelland, Maier & Neustadt, P.C.; 1940 Duke Street; Alexandria; VA; 22314; US Patent Application Number: 20030175343 Date filed: May 5, 2003 Abstract: The invention solves a controlled release pharmaceutical composition containing tramadol hydrochloride, characterized in that it contains 100 to 200 mg of the active ingredient in admixture with micronized esters of glycerol with higher fatty acids, alkali salts of phosphoric acid, non-ionic vinylpyrrolidone polymers, substances from the group of salts of higher fatty acids with alkaline earth metals and silicon oxides and a method for the preparation of this composition. Excerpt(s): The invention belongs to the pharmaceutical field, it relates to the composition and the method of preparing of an oral therapeutic preparation in the form of controlled release tablets containing the active ingredient tramadol hydrochloride. Tramadol hydrochloride containing therapeutic compositions in the form of controlled release tablets are described in SK patent No. 280496, according to which a formulation is prepared by melting a mixture of the drug and a hydrophobic or hydrophilic carrier in high performance homogenization devices with heating and cooling facilities. The molten, homogenized mixture is cooled down; particle size of the agglomerates is adjusted while undercooling the mixture in order to obtain desirable physical parameters for mechanic dividing and adjustment of the particle size for further processing. As described in SK patent No. 280496, the meltable carriers include, e.g., waxes, hydrogenated vegetable oils and higher fatty acid esters with glycerol.

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Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Controlled release tramadol formulation Inventor(s): Hahn, Udo; (Nentershausen, DE), Leslie, Stewart Thomas; (Cambridge, GB), Malkowska, Sandra Therese Antoinette; (Cambridgeshire, GB), Miller, Ronald Brown; (Basle, CH), Prater, Derek Allan; (Cambridge, GB), Smith, Kevin John; (Cambridge, GB), Wimmer, Walter; (Limburg, DE), Winkler, Horst; (Linter, DE) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20010036477 Date filed: March 6, 2001 Abstract: A controlled release preparation for oral administration contains tramadol, or a pharmaceutically acceptable salt thereof, as active ingredient. Excerpt(s): The present invention relates to a controlled release preparation for oral administration, to processes for its preparation and to its medical use. In particular, the invention relates to a controlled release preparation comprising tramadol or a pharmaceutically acceptable salt thereof. Tramadol, which has the chemical name (.+-.)trans-2-[(dimethylamin- o)methyl]-1-(3-methoxyphenyl) cyclohexanol, is an orally active opioid analgesic. Conventional release preparations in the form of capsules, drops and suppositories containing tramadol, or more particularly its hydrochloride salt, have been commercially available for many years for use in the treatment of moderate to severe pain; Such preparations, however, do not provide a controlled release of the tramadol. Moreover, despite tramadol's long-standing use, controlled release preparations for oral administration containing tramadol as active ingredient have not even previously been described in the literature. It is an object of the present invention to provide an oral controlled release tramadol preparation suitable for at least twelvehourly (e.g. up to twenty-four hourly) administration for the treatment of pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Controlled release tramadol preparations with a storage-stable release profile and process for their production Inventor(s): Bartholomaeus, Johannes Heinrich; (Aachen, DE), Ziegler, Iris; (RottRoetgen, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030104061 Date filed: June 26, 2002 Abstract: A process for producing an oral, controlled release preparation of tramadol or a physiologically compatible tramadol salt having a storage stable active substance release profile by coating the active substance preparation with an aqueous ethylcellulose dispersion which contains at least one physiologically compatible, lipophilic diester of a C.sub.6-C.sub.40 aliphatic or aromatic dicarboxylic acid and a C.sub.6-C.sub.8 aliphatic alcohol as plasticizer, and, during coating, drying the coating at conventional temperatures, with the result that a storage stable active substance

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release profile is obtained even without subsequent heat treatment. Optionally, in order to increase the active substance release profile without impairing the storage stability of the preparation, a heat treatment may be performed at temperatures of >35.degree. C. until a desired, increased active substance release profile is achieved. Excerpt(s): The present invention relates to preferably multi-particulate, oral tramadol preparations, having a controlled active substance release profile which is established in a storage-stable manner by an ethylcellulose coating containing plasticizer even without heat treatment. Multiparticulate, controlled release tramadol preparations having a controlled release coating of ethylcellulose are known in the prior art. DE-A-196 30 035 accordingly describes multiparticulate tramadol preparations in the form of pellets which are provided with a controlled release coating of ethylcellulose. To this end, accretion pellets are coated with one or more ethylcellulose membrane layers which are applied from solutions in organic solvents. This production method has the disadvantage that the organic solvents must be recovered on environmental grounds, thus rendering this process somewhat costly. It is moreover disadvantageous to use organic solvents in the production of pharmaceuticals. Where controlled release coatings of aqueous ethylcellulose dispersions are applied onto substrates, it is generally recognized by experts that, once produced, such coatings do not usually provide storage-stable active substance release profiles. Such ethylcellulose coatings are indeed known to have a tendency to "post-filming", i.e. active substance release is increasingly delayed over storage. In order to overcome this problem, elaborate heat treatment processes at elevated temperature and optionally defined atmospheric humidity are recommended in the prior art in order to achieve a storage-stable release profile within days rather than after several months' storage (EP-A-0 548 448, EP-A-0 630 646). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Delivery of analgesics through an inhalation route Inventor(s): Rabinowitz, Joshua D.; (Mountain View, CA), Zaffaroni, Alejandro C.; (Atherton, CA) Correspondence: Richard R. Eckman; Morrison & Foerster Llp; 755 Page Mill Road; Palo Alto; CA; 94304-1018; US Patent Application Number: 20030017117 Date filed: May 16, 2002 Abstract: The present invention relates to the delivery of analgesics through an inhalation route. Specifically, it relates to aerosols containing acetaminophen, orphenadrine or tramadol that are used in inhalation therapy. In a composition aspect of the present invention, the aerosol comprises particles comprising at least 5 percent by weight of acetaminophen, orphenadrine or tramadol. In a method aspect of the present invention, one of acetaminophen, orphenadrine or tramadol is delivered to a mammal through an inhalation route. The method comprises: a) heating a composition, wherein the composition comprises at least 5 percent by weight of acetaminophen, orphenadrine or tramadol, to form a vapor; and, b) allowing the vapor to cool, thereby forming a condensation aerosol comprising particles, which is inhaled by the mammal. In a kit aspect of the present invention, a kit for delivering acetaminophen, orphenadrine or tramadol through an inhalation route to a mammal is provided which comprises: a) a composition comprising at least 5 percent by weight of acetaminophen, orphenadrine or tramadol; and, b) a device that forms an acetaminophen, orphenadrine or tramadol containing aerosol from the composition, for inhalation by the mammal.

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Excerpt(s): This application claims priority to U.S. provisional application Serial No. 60/294,203 entitled "Thermal Vapor Delivery of Drugs," filed May 24, 2001, Rabinowitz and Zaffaroni, the entire disclosure of which is hereby incorporated by reference. This application further claims priority to U.S. provisional application Serial No. 60/317,479 entitled "Aerosol Drug Delivery," filed Sep. 5, 2001, Rabinowitz and Zaffaroni, the entire disclosure of which is hereby incorporated by reference. The present invention relates to the delivery of analgesics through an inhalation route. Specifically, it relates to aerosols containing acetaminophen, orphenadrine or tramadol that are used in inhalation therapy. There are a number of compositions currently marketed as analgesics. The compositions contain at least one active ingredient that provides for the observed therapeutic effects. Among the active ingredients given in analgesic compositions are acetaminophen, orphenadrine and tramadol. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Developing a delivery system for multi-pharmaceutical active materials at various release rates Inventor(s): Baichwal, Anand; (Wappingers Falls, NY), Liu, Lirong; (Washington Township, NJ), Shlyankevich, Alex; (Ridgefield, CT) Correspondence: Hale And Dorr, Llp; 60 State Street; Boston; MA; 02109 Patent Application Number: 20020143065 Date filed: October 3, 2001 Abstract: The invention provides a novel pharmaceutical compositions useful for the delivery of more than one pharmaceutically active compound. More specifically, the invention provides a novel pharmaceutical compositions useful for the delivery of the (+) tramadol enantiomer and the (-) tramadol enantiomer. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/237,451, filed Oct. 3, 2000, and U.S. Provisional Application No. 60/239,362, filed Oct. 11, 2000. The invention relates to the fields of pharmacology and medicine. More specifically, the invention relates to a pharmaceutical delivery system suitable for use with more than one pharmaceutically active agent, particularly enantiomers of chiral drugs. The advantages of controlled release products are well known in the pharmaceutical field and include the ability to maintain a desired blood level of a medicament over a comparatively longer period of time while increasing patient compliance by reducing the number of administrations necessary to achieve the same. These advantages have been attained by a wide variety of methods. For example, different hydrogel have been described for use in controlled release medicines, some of which are synthetic, but most of which are semi-synthetic or of natural origin. A few contain both synthetic and non-synthetic material. However, some of the systems require special process and production equipment, and in addition some of these systems are susceptible to variable drug release. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Dosage forms which can be administered parenterally and comprise a suspension of the salt of tramadol and diclofenac Inventor(s): Bartholomaus, Johannes; (Aachen, DE), Kugelmann, Heinrich; (Aachen, DE) Correspondence: Clarence A. Green; Perman & Green, Llp; 425 Post Road; Fairfield; CT; 06824; US Patent Application Number: 20030203037 Date filed: May 21, 2003 Abstract: The invention relates to parenteral dosage forms of administration that comprise a suspension of the salt of the active substances tramadol and diclofenac. Excerpt(s): The present invention relates to dosage forms which can be administered parenterally and comprise a suspension of the salt of the active ingredients tramadol and diclofenac. The active pharmaceutical ingredient tramadol is frequently employed in the form of its hydrochloride --(1RS,2RS)-2-[(dimethylamino)m- ethyl]-1-(3methoxyphenyl)cyclohexanol hydrochloride--as analgesic for controlling moderate to severe pain. Satisfactory control of pain in some patients is possible only by parenteral administration of the analgesics, for example if the patient is unable or only poorly able, because of his physical incapacity, to take an analgesic orally. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Extended release composition containing Tramadol Inventor(s): Deboeck, Arthur M.; (Gurabo, PR), Sereno, Antonio; (Melsbroeck, BE), Vanderbist, Francis; (Meise, BE) Correspondence: Lowe Hauptman Gilman And Berner, Llp; 1700 Diagonal Road; Suite 300 /310; Alexandria; VA; 22314; US Patent Application Number: 20030143270 Date filed: April 11, 2002 Abstract: The present invention relates to a once daily extended release pharmaceutical preparation of Tramadol or its acceptable pharmaceutical salts.The preparation provides, effective blood concentration for a period of about 24 hours with reduced peak concentrations. It is characterized that effective Tramadol levels appear within the first hours after administration, the time to maximal Tramadol content T.sub.max is at least 10 hours and the peak Tramadol concentration is less than three times the concentration obtained after 24 hours of said administration. Excerpt(s): The present invention relates to a once daily extended release oral Tramadol pharmaceutical preparation which provides effective blood concentration for a period of about 24 hours with reduced peak Tramadol plasma concentrations, The formulation of the present invention provides peak Tramadol plasma concentrations that are less than twice the plasma concentration measured 24 hours after administration, while providing for effective Tramadol plasma concentration about 1 to 2 hours after administration. Tramadol is a centrally acting synthetic analgesic compound that is not derived from natural sources nor is it chemically related to opiates. Although its mode of action is not completely understood, at least two complementary mechanisms appear applicable: Binding to.mu.-opioid receptors and inhibition of reuptake of nor epinephrine and serotonin. Tramadol opioid activity derives from low affinity binding the parent compound to A-opioid receptors and higher affinity binding of the M1 metabolite. In

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animal models, M1 is up to 6 times more potent than Tramadol in producing analgesia and 200 times more potent in u-opioid binding. The contribution to human analgesia of Tramadol relative to M1 is unknown. Tramadol-induced antinociception is only partially antagonized by the opiate antagonist naloxone in animal test. In addition, Tramadol inhibits reuptake of nor-epinephrine and serotonin in-vitro after oral administration of immediate release dosage form the onset of analgesia is evident within 1 hour after administration and reaches a peak in.apprxeq.2 to 3 hours. Peak plasma concentrations are reached about 2 hours after administration, which correlates closely with the time to peak pain relief. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

FORMULATIONS FOR RESPIRATORY TRACT ADMINISTRATION Inventor(s): ALFONSO, MARK; (EASTON, CT), GOLDENHEIM, PAUL; (WILTON, CT), SACKLER, RICHARD; (GREENWICH, CT) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20010049391 Date filed: November 5, 1999 Abstract: A dosage form for intranasal and/or inhalation administration of an analgesic having low opioid receptor binding activity to a warm blooded animal, that includes a pharmaceutically effective amount of the analgesic. A preferred analgesic is tramadol, a tramadol and/or a pharmaceutically acceptable salt, metabolite or derivative thereof. Methods of making and using the formulation according to the invention are also provided. Excerpt(s): The present invention relates to formulations and methods for the intranasal and inhalation administration of analgesics having low opioid receptor binding affinity. Pharmacologically active compounds are most commonly administered by the oral route. In particular, analgesics are preferably taken by mouth. However, this convenient route of administration is not always possible for certain patients. Contraindications to oral administration of analgesics can include nausea and/or emesis, oral or gastrointestinal surgery and dysphagia. In addition, rate of analgesia onset is slower and more variable due to first pass effects which compromise the apparent potency of some analgesics and complicate their use. The alternative of administration by injection, e.g., parenteral, intramuscular or subcutaneous injection, is generally not preferred due to patient discomfort and the attendant increased costs associated with the production of and administration of injectable products. Another, less invasive form of administration is transmucosal administration. Transmucosal administration can be via oral, nasal and/or upper respiratory tract, rectal or vaginal mucosal surfaces, to name the more common non-oral transmucosal routes of administration. Transmucosal administration has the advantage that patients who are unable to swallow can be medicated without recourse to injection. Importantly, transmucosal administration may often provide a more rapid relief of pain, compared to oral administration, by providing direct access to the blood circulation and bypassing the gastrointestinal tract and portal vein circulation and liver metabolism. A particularly preferred route enterohepatic blood circulation. A particularly preferred route for transmucosal delivery is intranasal administration for absorption by the nasal mucosal surfaces and/or inhalation for absorption in the bronchial passages of the lungs. administration for absorption by the nasal mucosal surfaces and/or inhalation for absorption in the bronchial passages of the lungs.

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administration for absorption by the nasal mucosal surfaces and/or inhalation for absorption in the bronchial passages of the lungs. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method of delaying ejaculation Inventor(s): Bar-Or, David; (Englewood, CO) Correspondence: Sheridan Ross PC; 1560 Broadway; Suite 1200; Denver; CO; 80202 Patent Application Number: 20020132857 Date filed: March 15, 2002 Abstract: The invention provides a method of delaying ejaculation. The method comprises administering an effective amount of a tramadol material to a human male prior to sexual intercourse. The method is particularly useful for treating premature ejaculation. Excerpt(s): This application claims benefit of provisional application 60/276,806, filed Mar. 16, 2001, the entire disclosure of which is considered to be part of the disclosure of this application and is hereby incorporated by reference. The invention relates to a method of delaying ejaculation. In particular, the invention relates to a method of delaying ejaculation by the administration of a tramadol material. Premature ejaculation is a debilitating sexual dysfunction. This dysfunction can lead to an inability to enter into, or sustain, relationships and can cause psychological damage to sufferers. Premature ejaculation can also impair reproductive success. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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METHOD OF SIMULTANEOUSLY ENHANCING ANALGESIC POTENCY AND ATTENUATING ADVERSE SIDE EFFECTS CAUSED BY TRAMADOL AND OTHER BIMODALLY-ACTING OPIOID AGONISTS Inventor(s): CRAIN, STANLEY M.; (LEONIA, NJ), SHEN, KE-FEI; (FLUSHING, NY) Correspondence: Craig J Arnold Esq; Amster Rothstein & Ebenstein; 90 Park Avenue; New York; NY; 10016 Patent Application Number: 20010006967 Date filed: May 6, 1999 Abstract: This invention relates to a method for selectively enhancing the analgesic potency of a bimodally-acting opioid agonist such as tramadol and simultaneously attenuating anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects associated with the administration of the bimodally-acting opioid agonist. The method of the present invention comprises administering to a subject an analgesic or sub-analgesic amount of a bimodally-acting opioid agonist such as tramadol and an amount of an excitatory opioid receptor antagonist such as naltrexone or nalmefene effective to enhance the analgesic potency of the bimodally-acting opioid agonist and attenuate the anti-analgesia, hyperalgesia, hyperexcitability, physical dependence and/or tolerance effects of the bimodally-acting opioid agonist. Excerpt(s): This is a continuation-in-part of copending application Ser. No. 09/094,977, filed Jun. 16, 1998, which is a continuation of application Ser. No. 08/759,590, filed Dec.

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3, 1996, now U.S. Pat. No. 5,767,125, which is a continuation-in-part of application Ser. No. 08/276,966, filed Jul. 19, 1994, now U.S. Pat. No. 5,512,578, which is a continuationin-part of application Ser. No. 08/097,460, filed Jul. 27, 1993, now U.S. Pat. No. 5,472,943, which is a continuation-in-part of application Ser. No. 07/947,690, filed Sep. 19, 1992, now abandoned, the contents of which are hereby incorporated by reference in their entirety. This invention relates to a method of enhancing the analgesic (inhibitory) effects of bimodally-acting opioid agonists, including morphine, codeine and other clinically used opioid analgesics, while at the same time attenuating anti-analgesia, physical dependence, tolerance, hyperexcitability, hyperalgesia, and other undesirable (excitatory) side effects typically caused by chronic use of bimodally-acting opioid agonists. "Bimodally-acting opioid agonists" are opioid agonists that bind to and activate both inhibitory and excitatory opioid receptors on nociceptive neurons which mediate pain. Opioid analgesia results from activation by opioid agonists of inhibitory opioid receptors on neurons in the nociceptive (pain) pathways of the peripheral and central nervous systems. The undesirable side effects, including anti-analgesic actions, hyperexcitability and hyperalgesia, the development of physical dependence, and some types of tolerance result from sustained activation by bimodally-acting opioid agonists of excitatory opioid receptors on neurons in the nociceptive (pain) pathways of the peripheral and central nervous systems. In the instant invention, a very low dose of a selective excitatory opioid receptor antagonist, an opioid which binds to and acts as an antagonist to excitatory but not inhibitory opioid receptors on nociceptive neurons which mediate pain, is combined with a dose of a bimodally-acting opioid agonist so as to enhance the degree of analgesia (inhibitory effects) and attenuate the undesired side effects (excitatory effects). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Novel esters derived from (rr,ss)-2-hydroxybenzoate of 3-(2-dimethylaminomethyl-1hydroxycyclohexyl)phenyl Inventor(s): De Ramon Amat, Elisabet; (Barcelona, ES), Huguet Clotet, Juan; (Sant Joan Despi, ES), Mourelle Mancini, Marisabel; (Barcelona, ES) Correspondence: Steinberg & Raskin, P.C.; 1140 Avenue OF The Americas, 15th Floor; New York; NY; 10036-5803; US Patent Application Number: 20030100598 Date filed: June 27, 2002 Abstract: New esters derived from substituted phenyl-cyclohexyl compounds, which are derived from Tramadol, process for obtaining them and their use for preparing a drug with analgesic properties. These new compounds of general formula (I) have a higher analgesic activity, a lower toxicity and a longer effective time period than Tramadol. Excerpt(s): The present invention relates to new esters derived from substituted phenylcyclohexyl compounds, which are derived from Tramadol. The obtained compounds have a higher analgesic activity, a lower toxicity and a longer effective time period than Tramadol. The treatment of pain is of great importance in the field of medicine. The pharmacological agents presently used for the treatment of pain can be primarily classified into two large groups: opioid compounds and non-steroidal antiinflammatories (NSAIs). The NSAIs are only useful in the case of light or moderate pain; severe pain has traditionally been treated with opiod compounds. However, these opioid compounds have several undesirable side effects, such as constipation,

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respiratory depression, tolerance and possibility of addiction. have been described in the Dutch patent NL 6610022. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Oral administration forms for administering a fixed tramadol and diclofenac combination Inventor(s): Bartholomaeus, Johannes; (Aachen, DE), Ziegler, Iris; (Rott-Roetgen, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20020156133 Date filed: December 17, 2001 Abstract: An oral administration unit containing the active substances Tramadol and Diclofenac and/or physiologically acceptable salts thereof, in which both active substances are contained in the same administration unit as two separately formulated subunits. Excerpt(s): This application is a continuation of international patent application no. PCT/EP00/05386, filed Jun. 13, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. DE 199 27 689.7, filed Jun. 17, 1999. The present invention relates to an oral administration unit containing the active substances Tramadol and Diclofenac and/or their respective physiologically compatible salts, the two active substances being present in subunits separately formulated in each case, in the same administration unit. Tramadol is an analgesic used to treat severe and moderately severe pain, whose mode of action is not based on a pure opioid mechanism. Tramadol also does not exhibit the characteristic side effects of an opioid. In some cases nausea is observed as an undesirable accompanying symptom. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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O-substituted 6-methyltramadol derivatives Inventor(s): Buschmann, Helmut; (Aachen, DE), Friderichs, Elmar; (Stolberg, DE), Kaulartz, Dagmar; (Stolberg, DE), Koegel, Babette-Yvonne; (Langerwehe-Hamich, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030220389 Date filed: March 31, 2003 Abstract: The invention relates to O-substituted 6-methyl-tramadol derivatives, to methods for producing them, to medicaments containing these compounds, to the use of O-substituted 6-methyl-tramadol derivatives for producing medicaments for treating pain and other symptoms or diseases, and to methods of treatment using the medicaments. Excerpt(s): The present application is a continuation of International Patent Application No. PCT/EP01/11276, filed Sep. 28, 2001, designating the United States of America and published in German as WO 02/26694 A1, the entire disclosure of which is incorporated

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herein by reference. Priority is claimed based on Federal Republic of Germany Patent Application No. 100 49 483.8, filed Sep. 29, 2000. The present invention relates to Osubstituted 6-methyltramadol derivatives, processes for their production, medicaments containing these compounds, and the use of O-substituted 6-methyltramadol derivatives for the production of medicaments for treating pain, and methods for treating pain using the medicaments. The treatment of chronic and non-chronic pain conditions is very important in medicine. There is therefore a universal need for highly effective pain treatments. The urgent need for a patient-oriented and targeted treatment of chronic and non-chronic pain conditions, which is understood to include the successful and satisfactory treatment of pain on the part of the patient, is documented in the large number of scientific studies that have recently appeared in the field of applied analgesia and in basic research relating to nociception. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical tramadol salts Inventor(s): Kugelmann, Heinrich; (Aachen, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030158242 Date filed: February 28, 2002 Abstract: Disclosed are a compound of tramadol and a sugar substitute, pharmaceutical compositions and sustained-release formulations comprising the compound, and methods of treatment using the compound. The tramadol compound according to the present invention has reduced bitter taste of tramadol and is more acceptable to the patient. Excerpt(s): The present application is a continuation of international patent application no. PCT/EP00/07526, filed Aug. 3, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. 199 40 740.1, filed Aug. 31, 1999. The present invention relates to pharmaceutical salts of the active substance tramadol and at least one sugar substitute, to medicaments, or pharmaceutical compositions, containing these salts, to the use of these salts for the preparation of medicaments, and to forms of administration or pharmaceutical formulations, containing these salts. Tramadol hydrochloride--(1RS,2RS)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol hydrochloride--is suitable for the control of intense and moderately intense pain and for the treatment of urinary incontinence. U.S. Pat. No. 3,652,589 and WO98/46216 describe the use of other salts of the active substance tramadol with inorganic acids, e.g. sulfuric acid, nitric acid or phosphoric acid, and with organic acids, e.g. benzoic acid, salicylic acid or phthalic acid, for the preparation of a medicament for the control of pain or for the treatment of urinary incontinence. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for the separation of the cis trans diasteroisomers of tramadol Inventor(s): Evans, Graham; (Cambridge, GB) Correspondence: Saliwanchik Lloyd & Saliwanchik; A Professional Association; 2421 N.W. 41st Street; Suite A-1; Gainesville; FL; 326066669 Patent Application Number: 20030092773 Date filed: October 24, 2002 Abstract: A process for separating a mixture of trans (RR, SS) and cis (RS, SR) tramadol comprises a classical salt resolution using a chiral resolving agent selected from tartaric acid and derivatives thereof, and mandelic acid, provided that the resolving agent is not substantially single enantiomer di-O,O-toluoyltartaric acid. Excerpt(s): The present invention relates to a process for the separation of the diastereomers of tramadol. 2-[(dimethylamino)methyl]-1-(3methoxyphenyl)cyclohexanol, is a chiral compound which exists as a mixture of trans (RR,SS) and cis (RS,SR) diastereomers, referred to hereinafter as the trans and cis forms of tramadol, respectively. The trans diastereomer is used as a high-potency analgesic agent. There is some confusion in the literature as to the nomenclature of the trans and cis forms of tramadol, and further confusion arises as, generally, the name tramadol is used to refer to the substantially pure trans form of the compound. In the context of the present Application, however, the trans and cis forms of tramadol, and the enantiomers thereof, are depicted as 1a to 1d in Scheme 1 below. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Stabilized sustained release tramadol formulations Inventor(s): Chasin, Mark; (Manalapan, NJ), Goldenheim, Paul; (Wilton, CT), Huang, Hua-Pin; (Englewood Cliffs, NY), Oshlack, Benjamin; (New York, NY) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20020102302 Date filed: October 19, 2001 Abstract: A stabilized sustained release oral solid dosage form which includes an effective amount of tramadol or a pharmaceutically acceptable salt thereof dispersed in a matrix of a hydrophobic material comprising a wax-like substance which was melted or softened during the preparation of the matrix, is cured at a temperature from about 35.degree. C. to about 65.degree. C. for a time period from about 4 to about 72 hours, such that the formulation, when subjected to in-vitro dissolution after exposure to accelerated storage conditions of at least one month at 40.degree. C./75% RH, releases an amount of tramadol which does not vary at any given dissolution time point by more than about 20% of the total amount of tramadol released when compared to in-vitro dissolution conducted prior to subjecting the dosage form to the accelerated storage conditions. Excerpt(s): The present invention relates to sustained release matrix preparations containing tramadol or a pharmaceutically acceptable salt thereof as the therapeutically active agent. Sustained release preparations are known to those skilled in the art to achieve a slow release of a drug over an extended period of time, thereby extending the duration of drug action over that achieved by conventional delivery. Preferably such a

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preparation maintains a drug concentration in the blood within the therapeutic range for 12 hours or more. An important aspect of the manufacture, regulatory review and approval of all dosage forms concerns their stability over extended periods of time. The stability data obtained with regard to a particular dosage form directly affects its shelflife. The stability of a pharmaceutical dosage form is related to maintaining its physical, chemical, microbiological, therapeutic, and toxicological properties when stored, i.e., in a particular container and environment. Stability study requirements are covered, e.g., in the Good Manufacturing Practices (GMPs), the U.S.P., as well as in the regulatory requirements of the country where approval to market a dosage form is being sought. In the United States, a request to test, and eventually market, a drug or a drug formulation may be made via a New Drug Application (NDA), an Abbreviated New Drug Application (ANDA) or an Investigational New Drug Applications (IND). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Sustained-release form of administration containing tramadol saccharinate Inventor(s): Bartholomaeus, Johannes; (Aachen, DE), Kugelmann, Heinrich; (Aachen, DE), Ziegler, Iris; (Rott-Roetgen, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030035835 Date filed: February 28, 2002 Abstract: Disclosed herein is sustained-release formulations of tramadol comprising tramadol saccharinate coated with at least one sustained-release coating. The sustained release formulations may also contain tramadol in non-sustained release form, and other pharmaceutically acceptable excipients. Also disclosed are methods of preparation of and methods of treatment using the inventive formulations. Excerpt(s): The present application is a continuation of international patent application no. PCT/EP00/07527, filed Aug. 3, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on German patent application nos. 199 40 944.7, filed Aug. 31, 1999; 199 40 740.1, filed Aug. 31, 1999; and 100 23 699.5, filed May 16, 2000. The present invention relates to forms of administration of tramadol, retarded by a coating, which contain the active substance tramadol as tramadol saccharinate, optionally together with other auxiliary substances. The very readily water-soluble tramadol hydrochloride--(1RS,2RS)-2-[(dimethylamino)methyl]-1-(3-methoxyphenyl)cyclohexanol hydrochloride--is often used for the control of intense and moderately intense pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Sustained-release, oral pharamaceutical forms of formulation Inventor(s): Bartholomaeus, Johannes; (Aachen, DE), Ziegler, Iris; (Rott-Roetgen, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030044464 Date filed: February 28, 2002

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Abstract: A sustained-release, oral pharmaceutical formulation of tramadol comprising a compound formed in situ of tramadol or its salt and a pharmaceutically acceptable acidic substance. The compound formed in situ has a desired water solubility. Also provided are methods of treatment using the pharmaceutical formulations. Method for preparing such formulations are also provided. The preparation method comprises repeatedly mixing tramadol or its salt with the acidic substance, and moistening the mixture and formulating the mixture under an energy input, such as heat or pressure. Optionally, drying, repeated granulating, extrudation and pelleting may also be included. Excerpt(s): The present application is a continuation of international patent application no. PCT/EP00/07525, filed Aug. 3, 2000, designating the United States of America, the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application no. 199 40 944.7, filed Aug. 31, 1999. The present invention relates to partially sustained-release, oral pharmaceutical forms of administration in which the active substance, tramadol, is present at least partially as a compound formed in situ which has a water solubility of.ltoreq.100 mg/ml, and to processes for their preparation. The administration of pharmacological active substances in the form of sustained-release preparations represents a therapeutic improvement for many active substances, especially analgesics. Even for pharmacological substances with a relatively short half-life in vivo, retardation of release makes it possible to provide a preparation with a long-lasting action and also, through more constant blood levels, to avoid side effects and improve the patients' observance of dosage instructions. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Tramadol analogs and uses thereof Inventor(s): Currie, Mark; (Sterling, MA), Fang, Qun Kevin; (Wellesley, MA), Grover, Paul T.; (Franklin, MA), Jerussi, Thomas P.; (Framingham, MA), Senanayake, Chris Hugh; (Shrewsbury, MA) Correspondence: Heslin Rothenberg Farley & Mesiti PC; 5 Columbia Circle; Albany; NY; 12203; US Patent Application Number: 20030171440 Date filed: December 2, 2002 Abstract: Compounds of formula I are effective in treating disorders modulated by opiate receptor activity and/or monoamine activity. 1In formula I, R.sup.1 is selected from alkyl, aryl, alkylaryl, substituted alkyl, substituted aryl, and substituted alkylaryl; R.sup.2 is selected from hydrogen, hydroxy, cyano, haloalkyl, glycosyl, SO.sub.2R.sup.5, and OR.sup.5; R.sup.3 and R.sup.4 are independently selected from hydrogen and lower alkyl, or R.sup.3 and R.sup.4 taken together with nitrogen form a five- or six-membered heterocyclic or substituted heterocyclic ring; and R.sup.5 is selected from alkyl, aryl, alkylaryl, substituted alkyl, substituted aryl, and substituted alkylaryl. Excerpt(s): This application claims priority from U.S. provisional application, serial No. 60/325,275, filed Nov. 30, 2001, the entire disclosure of which is incorporated herein by reference. The invention relates to tramadol analogs that are useful for the treatment of CNS-related disorders including pain, anxiety, depression and attention deficit disorder. Opioids such as morphine are very effective for the treatment of pain, but can result in very serious adverse effects, including respiratory depression, and addiction and dependency. Less serious side effects include gastrointestinal inhibition effects and

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obstipation. As a result, the use of such drugs is limited by the possibility of adverse effects. There is, therefore, a need for effective analgesics, which are not associated with these adverse effects. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Treatment of functional gastrointestinal disorders Inventor(s): Fowler, David; (Cambridge, GB) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20030119916 Date filed: November 18, 2002 Abstract: Tramadol or a pharmaceutically acceptable salt thereof is used in the manufacture of a pharmaceutical preparation for the treatment of functional gastrointestinal disorders such as irritable bowel syndrome. Excerpt(s): The present invention relates to the treatment of functional gastrointestinal (GI) disorders, especially irritable bowel syndrome (IBS). In particular the present invention relates to pharmaceutical preparations containing tramadol for the treatment of such disorders and the use of tramadol in the manufacture of such preparations. Tramadol (2-[(Dimethylamino) methyl]-1-(3-methoxy phenyl) cyclohexanol is a nonnarcotic opioid analgesic which was first described in the 1960's (see UK Patent 997399). It was first marketed in Germany in 1977 and subsequently in various countries and by 1980 a total of 34 different tramadol formulations in immediate release oral and injectable form were on the market. In 1996 controlled release preparations containing tramadol were introduced, for example TRAMUNDIN RETARD capsules of Mundipharma GmbH, TRAMAL LONG 100 tablets of Grunenthal GmbH and ZYDOL SR tablets of G D Searle & Co. Ltd. The only medical indication for which the various tramadol products are used is the treatment of moderate to severe pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Use of (+)-tramadol, O-demethyltramadol or (+)-O-demethyl-tramadol, O-desmethylN-mono-desmethyl-tramadol or (+)- O-desmethyl-N-mono-desmethy- ltramadol for the treatment of urinary incontinence Inventor(s): Christoph, Thomas; (Aachen, DE), Friderichs, Elmar; (Zehntweg, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20030069314 Date filed: April 5, 2002 Abstract: Method for the treatment of increased urinary urgency or urinary incontinence using (+)-tramadol or O-demethyltramadol, in particular (+)-O-demethyltramadol, Odesmethyl-N-mono-desmethyltramadol, in particular (+)-O-desmethyl-N-monodesmethyltramadol as free bases and/or in the form of physiologically compatible salts are disclosed. Also disclosed are pharmaceutical compositions comprising (+)-tramadol or O-demethyltramadol.

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Excerpt(s): The present application is a continuation of international patent application no. PCT/EP00/09420, filed Sep. 20, 2000, designating the U.S.A., the entire disclosure of which is incorporated herein by reference. Priority is claimed based on Federal Republic of Germany patent application nos. 199 47 747.7, filed Oct. 5, 1999 and 200 02 943.6, filed Feb. 21, 2000. The invention relates to the use of (+)-tramadol or O-demethyltramadol, in particular (+)-O-demethyltramadol, O-desmethyl-N-mono-desmethyltramadol, in particular (+)-O-desmethyl-N-mono-desmethyltramadol as free bases and/or in the form of physiologically compatible salts for the production of a pharmaceutical preparation for the treatment of increased urinary urgency or urinary incontinence and to corresponding pharmaceutical preparations and to a method for the treatment of increased urinary urgency or urinary incontinence. Urinary incontinence is the involuntary release of urine, which occurs in an uncontrolled manner when the pressure within the bladder exceeds the pressure required to seal the ureter. This may be caused, on the one hand, by increased internal bladder pressure (for example due to detrusor instability) resulting in urge incontinence and, on the other hand, by reduced sphincter pressure (for example after giving birth or surgical intervention) resulting in stress incontinence. The detrusor is the coarsely bundled, multilayer bladder wall musculature, contraction of which results in voiding of urine, while the sphincter is the muscle which closes the urethra. Mixed forms of these types of incontinence occur, as do so-called overflow incontinence (for example in cases of benign prostate hyperplasia) or reflex incontinence (for example after spinal cord damage). Further details in this connection may be found in Chutka, D. S. and Takahashi, P. Y., 1998, Drugs 560: 587595. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Use of O-desmethyl-N-mono-desmethyl-tramadol Inventor(s): Englberger, Werner; (Stolberg, DE), Friderichs, Elmar; (Stolberg, DE), Hennies, Hagen-Heinrich; (Simmerath, DE), Koegel, Babette; (Langerwehe, DE) Correspondence: Crowell & Moring Llp; Intellectual Property Group; P.O. Box 14300; Washington; DC; 20044-4300; US Patent Application Number: 20020032239 Date filed: October 12, 2001 Abstract: A method of producing pharmaceutical compositions using O-desmethyl-Nmono-desmethyl-tramadol for the treatment of pain and various related indications, pharmaceutical compositions containing O-desmethyl-N-mono-desmethyl-tramadol, and a method of treating pain, urinary incontinence, diarrhea or pruritus using Odesmethyl-N-mono-desme- thyl-tramadol. Excerpt(s): This invention relates to the use of O-desmethyl-N-mono-desmethyl-tramadol for the production of pharmaceutical compositions for the treatment of pain and various related indications as well as pharmaceuticals comprising O-desmethyl-Nmono-desmethyl-tramadol. The treatment of pain conditions is of great importance in medicine. There is currently a world-wide need for additional pain therapy. The pressing requirement for a target-oriented treatment of pain conditions which is right for the patient which is to be understood as the successful and satisfactory treatment of pain for the patients is documented in the large number of scientific works which have recently and over the years appeared in the field of applied analgesics or on basic research on nociception. The underlying object of the present invention was to provide a

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substance useful in the treatment of pain and also related indications, as well as pharmaceutical compositions for such treatment. 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 tramadol, 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 “tramadol” (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 tramadol. You can also use this procedure to view pending patent applications concerning tramadol. 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 6. PERIODICALS AND NEWS ON TRAMADOL Overview In this chapter, we suggest a number of news sources and present various periodicals that cover tramadol.

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

Labopharm shares rise as U.S. tramadol trial ends Source: Reuters Industry Breifing Date: September 15, 2003

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Labopharm loss widens on Tramadol trial costs Source: Reuters Industry Breifing Date: August 08, 2003

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Tramadol abuse growing more common in Taiwan Source: Reuters Health eLine Date: January 22, 2003

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Once-daily tramadol looks good in phase III Source: Reuters Medical News Date: January 22, 2003

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Labopharm once-daily tramadol looks good in phase III Source: Reuters Industry Breifing Date: January 22, 2003

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Labopharm starts US phase III trials of Tramadol Source: Reuters Industry Breifing Date: January 13, 2003

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Ivax to begin sales of generic Ultram Source: Reuters Industry Breifing Date: July 05, 2002

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Ethypharm, Viatris to develop new oral formulation of tramadol Source: Reuters Industry Breifing Date: June 24, 2002

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Mylan, Mutual get FDA approval for generic tramadol Source: Reuters Industry Breifing Date: June 21, 2002

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Teva gets FDA OK for generic Ultram Source: Reuters Industry Breifing Date: June 20, 2002

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Caraco gets FDA approval for generic tramadol Source: Reuters Industry Breifing Date: June 20, 2002

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IVAX, Able in marketing agreement for tramadol Source: Reuters Industry Breifing Date: January 28, 2002

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Alpharma nearing FDA approval for generic versions of tramadol, lisinopril Source: Reuters Industry Breifing Date: January 24, 2002

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Extended-release tramadol shown effective for back pain Source: Reuters Medical News Date: January 14, 2002

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Biovail says extended-release tramadol effective in second phase III trial Source: Reuters Industry Breifing Date: January 14, 2002

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Tramadol equivalent to diclofenac for post-tonsillectomy pain control Source: Reuters Medical News Date: April 25, 2001

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Nutraceutix, Lehigh Valley Technologies to develop controlled-release tramadol Source: Reuters Industry Breifing Date: January 24, 2001

Periodicals and News

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Tramadol effective in treating chronic lower back pain Source: Reuters Medical News Date: April 24, 2000

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High-dose tramadol as effective as low-dose morphine for cancer pain Source: Reuters Medical News Date: October 04, 1999

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Tramadol reduces pain associated with diabetic neuropathy Source: Reuters Medical News Date: June 17, 1998

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Johnson And Johnson Sends 'Dear Doctor' Letter On Ultram Source: Reuters Medical News Date: April 05, 1996

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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 “tramadol” (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 “tramadol” (or synonyms). If you know the name of a company that is relevant to tramadol, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for

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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 “tramadol” (or synonyms).

Academic Periodicals covering Tramadol Numerous periodicals are currently indexed within the National Library of Medicine’s PubMed database that are known to publish articles relating to tramadol. In addition to these sources, you can search for articles covering tramadol 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 7. 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 tramadol. One such source is the United States Pharmacopeia. In 1820, eleven physicians met in Washington, D.C. to establish the first compendium of standard drugs for the United States. They called this compendium the U.S. Pharmacopeia (USP). Today, the USP is a nonprofit organization consisting of 800 volunteer scientists, eleven elected officials, and 400 representatives of state associations and colleges of medicine and pharmacy. The USP is located in Rockville, Maryland, and its home page is located at http://www.usp.org/. The USP currently provides standards for over 3,700 medications. The resulting USP DI Advice for the Patient can be accessed through the National Library of Medicine of the National Institutes of Health. The database is partially derived from lists of federally approved medications in the Food and Drug Administration’s (FDA) Drug Approvals database, located at http://www.fda.gov/cder/da/da.htm. While the FDA database is rather large and difficult to navigate, the Phamacopeia is both user-friendly and free to use. It covers more than 9,000 prescription and over-the-counter medications. To access this database, simply type the following hyperlink into your Web browser: http://www.nlm.nih.gov/medlineplus/druginformation.html. To view examples of a given medication (brand names, category, description, preparation, proper use, precautions, side effects, etc.), simply follow the hyperlinks indicated within the United States Pharmacopeia (USP). Below, we have compiled a list of medications associated with tramadol. 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 tramadol: Tramadol •

Systemic - U.S. Brands: Ultram http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202789.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 brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

111

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.

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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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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 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 “tramadol” (or synonyms) into the search box and click “Search.” The results will be presented in a tabular form, indicating the number of references in each database category. Results Summary Category Journal Articles Books / Periodicals / Audio Visual Consumer Health Meeting Abstracts Other Collections Total

Items Found 912 0 348 1 0 1261

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 “tramadol” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

10

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

11

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). 12 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 13 14

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

Other important documents in HSTAT include: the National Institutes of Health (NIH) Consensus Conference Reports and Technology Assessment Reports; the HIV/AIDS Treatment Information Service (ATIS) resource documents; the Substance Abuse and Mental Health Services Administration's Center for Substance Abuse Treatment (SAMHSA/CSAT) Treatment Improvement Protocols (TIP) and Center for Substance Abuse Prevention (SAMHSA/CSAP) Prevention Enhancement Protocols System (PEPS); the Public Health Service (PHS) Preventive Services Task Force's Guide to Clinical Preventive Services; the independent, nonfederal Task Force on Community Services’ Guide to Community Preventive Services; and the Health Technology Advisory Committee (HTAC) of the Minnesota Health Care Commission (MHCC) health technology evaluations.

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Coffee Break: Tutorials for 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/.

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/.

15 Adapted 16

from http://www.ncbi.nlm.nih.gov/Coffeebreak/Archive/FAQ.html.

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 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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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 tramadol 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 tramadol. 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 tramadol. 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 “tramadol”:

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•

Other guides Chronic Fatigue Syndrome http://www.nlm.nih.gov/medlineplus/chronicfatiguesyndrome.html Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.html Lupus http://www.nlm.nih.gov/medlineplus/lupus.html Osteoarthritis http://www.nlm.nih.gov/medlineplus/osteoarthritis.html Pancreatic Cancer http://www.nlm.nih.gov/medlineplus/pancreaticcancer.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The Combined Health Information Database (CHID) CHID Online is a reference tool that maintains a database directory of thousands of journal articles and patient education guidelines on tramadol. CHID offers summaries that describe the guidelines available, including contact information and pricing. CHID’s general Web site is http://chid.nih.gov/. To search this database, go to http://chid.nih.gov/detail/detail.html. In particular, you can use the advanced search options to look up pamphlets, reports, brochures, and information kits. The following was recently posted in this archive: •

Interstitial Cystitis and Pain Source: Rockville, MD: Interstitial Cystitis Association (ICA). 2003. [2 p.]. Contact: Available from Interstitial Cystitis Association (ICA). 110 North Washington Street, Suite 340, Rockville, MD 20850. (301) 610-5300. Fax (301) 610-5308. E-mail: [email protected]. Website: www.ichelp.org. PRICE: $1.00 for members; $1.25 for nonmembers; plus shipping and handling. Item number: RFIP01. Summary: This fact sheet reviews the treatment guidelines for the pain associated with interstitial cystitis (IC), a chronic, painful inflammatory condition of the bladder wall. Although there is no cure for IC, many treatment options are currently available, and there have been many recent advances in pain research and therapies. Leading pain specialists in the United States believe that nonmalignant pain, such as the pain caused by IC, is as serious and debilitating as malignant pain (that due to cancer) and should be treated just as aggressively. This aggressive treatment includes opiate therapy when more conservative approaches fail. The fact sheet reviews drugs used, including non opioid pain medications (aspirin, acetominophen, and nonsteroidal antiinflammatory drugs), tricyclic antidepressants, Pentosan polysulfate sodium (Elmiron), local anesthetics, anticonvulsants, benzodiazepines, antihistamines, tramadol (Ultram), and opioid pain medications. In each category, the fact sheet reviews the use of the drug and

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the potential side effects. The author notes that nonpharmacologic treatments for IC pain (diet modification, physical therapy, acupuncture, transcutaneous electric nerve stimulation, biofeedback, hypnosis, cognitive therapy) can play a valuable, complementary role in the treatment of IC pain. The fact sheet includes the contact information for the Interstitial Cystitis Association (ICA). 2 references. 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 tramadol. 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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to tramadol. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with tramadol. 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 tramadol. 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.

120 Tramadol

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 “tramadol” (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 “tramadol”. 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 “tramadol” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “tramadol” (or a synonym) into the search box, and click “Submit Query.”

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APPENDIX C. FINDING MEDICAL LIBRARIES Overview In this Appendix, we show you how to quickly find a medical library in your area.

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.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.

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•

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

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

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

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

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

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Massachusetts: St. Luke’s Hospital Health Sciences Library (St. Luke’s Hospital, Southcoast Health System, New Bedford), http://www.southcoast.org/library/

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Massachusetts: Treadwell Library Consumer Health Reference Center (Massachusetts General Hospital), http://www.mgh.harvard.edu/library/chrcindex.html

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

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

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

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

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Michigan: Patient Education Resouce Center - University of Michigan Cancer Center (University of Michigan Comprehensive Cancer Center, Ann Arbor), http://www.cancer.med.umich.edu/learn/leares.htm

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

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Montana: Center for Health Information (St. Patrick Hospital and Health Sciences Center, Missoula)

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National: Consumer Health Library Directory (Medical Library Association, Consumer and Patient Health Information Section), http://caphis.mlanet.org/directory/index.html

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National: National Network of Libraries of Medicine (National Library of Medicine) provides library services for health professionals in the United States who do not have access to a medical library, http://nnlm.gov/

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

Finding Medical Libraries

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

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

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

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New Jersey: Dr. Walter Phillips Health Sciences Library (Englewood Hospital and Medical Center, Englewood), http://www.englewoodhospital.com/links/index.htm

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New Jersey: Meland Foundation (Englewood Hospital and Medical Center, Englewood), http://www.geocities.com/ResearchTriangle/9360/

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New York: Choices in Health Information (New York Public Library) - NLM Consumer Pilot Project participant, http://www.nypl.org/branch/health/links.html

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New York: Health Information Center (Upstate Medical University, State University of New York, Syracuse), http://www.upstate.edu/library/hic/

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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

•

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

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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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TRAMADOL DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 5-Hydroxytryptophan: Precursor of serotonin used as antiepileptic and antidepressant. [NIH] Abdominal: Having to do with the abdomen, which is the part of the body between the chest and the hips that contains the pancreas, stomach, intestines, liver, gallbladder, and other organs. [NIH] Abdominal Pain: Sensation of discomfort, distress, or agony in the abdominal region. [NIH] Aberrant: Wandering or deviating from the usual or normal course. [EU] 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] Acupuncture Analgesia: Analgesia produced by the insertion of acupuncture needles at certain points in the body. These activate the small myelinated nerve fibers in the muscle which transmit impulses to the spinal cord and then activate three centers - the spinal cord, midbrain and pituitary hypothalamus - to produce analgesia. [NIH] Acupuncture Points: Designated locations along nerves or organ meridians for inserting acupuncture needles. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [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]

Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH] 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

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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] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Agoraphobia: Obsessive, persistent, intense fear of open places. [NIH] Alfentanil: A short-acting opioid anesthetic and analgesic derivative of fentanyl. It produces an early peak analgesic effect and fast recovery of consciousness. Alfentanil is effective as an anesthetic during surgery, for supplementation of analgesia during surgical procedures, and as an analgesic for critically ill patients. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allergen: An antigenic substance capable of producing immediate-type hypersensitivity (allergy). [EU] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] 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] Amitriptyline: Tricyclic antidepressant with anticholinergic and sedative properties. It appears to prevent the re-uptake of norepinephrine and serotonin at nerve terminals, thus potentiating the action of these neurotransmitters. Amitriptyline also appears to antaganize cholinergic and alpha-1 adrenergic responses to bioactive amines. [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]

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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] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Anaesthetic: 1. Pertaining to, characterized by, or producing anaesthesia. 2. A drug or agent that is used to abolish the sensation of pain. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Androgens: A class of sex hormones associated with the development and maintenance of the secondary male sex characteristics, sperm induction, and sexual differentiation. In addition to increasing virility and libido, they also increase nitrogen and water retention and stimulate skeletal growth. [NIH] Anesthesia: A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. [NIH] Anesthetics: Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. [NIH] 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] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Antiallergic: Counteracting allergy or allergic conditions. [EU] Anti-Anxiety Agents: Agents that alleviate anxiety, tension, and neurotic symptoms, promote sedation, and have a calming effect without affecting clarity of consciousness or neurologic conditions. Some are also effective as anticonvulsants, muscle relaxants, or anesthesia adjuvants. Adrenergic beta-antagonists are commonly used in the symptomatic treatment of anxiety but are not included here. [NIH] Antibacterial: A substance that destroys bacteria or suppresses their growth or reproduction. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH]

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Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticholinergic: An agent that blocks the parasympathetic nerves. Called also parasympatholytic. [EU] Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antiemetic: An agent that prevents or alleviates nausea and vomiting. Also antinauseant. [EU]

Antiepileptic: An agent that combats epilepsy. [EU] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Antihypertensive: An agent that reduces high blood pressure. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU]

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Antipyretic: An agent that relieves or reduces fever. Called also antifebrile, antithermic and febrifuge. [EU] Antispasmodic: An agent that relieves spasm. [EU] Antitussive: An agent that relieves or prevents cough. [EU] Anus: The opening of the rectum to the outside of the body. [NIH] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aqueous: Having to do with water. [NIH] Aqueous fluid: Clear, watery fluid that flows between and nourishes the lens and the cornea; secreted by the ciliary processes. [NIH] Aromatic: Having a spicy odour. [EU] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arteries: The vessels carrying blood away from the heart. [NIH] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Arthroscopy: Endoscopic examination, therapy and surgery of the joint. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Asthenia: Clinical sign or symptom manifested as debility, or lack or loss of strength and energy. [NIH] Astrocytes: The largest and most numerous neuroglial cells in the brain and spinal cord. Astrocytes (from "star" cells) are irregularly shaped with many long processes, including those with "end feet" which form the glial (limiting) membrane and directly and indirectly contribute to the blood brain barrier. They regulate the extracellular ionic and chemical environment, and "reactive astrocytes" (along with microglia) respond to injury. Astrocytes have high- affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitter, but their role in signaling (as in many other functions) is not well understood. [NIH] Asymptomatic: Having no signs or symptoms of disease. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Auditory: Pertaining to the sense of hearing. [EU]

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Aura: A subjective sensation or motor phenomenon that precedes and marks the of a paroxysmal attack, such as an epileptic attack on set. [EU] Auricular: Pertaining to an auricle or to the ear, and, formerly, to an atrium of the heart. [EU] Autodigestion: Autolysis; a condition found in disease of the stomach: the stomach wall is digested by the gastric juice. [NIH] Autonomic: Self-controlling; functionally independent. [EU] Autonomic Neuropathy: A disease of the nerves affecting mostly the internal organs such as the bladder muscles, the cardiovascular system, the digestive tract, and the genital organs. These nerves are not under a person's conscious control and function automatically. Also called visceral neuropathy. [NIH] Axilla: The underarm or armpit. [NIH] Axillary: Pertaining to the armpit area, including the lymph nodes that are located there. [NIH]

Axonal: Condition associated with metabolic derangement of the entire neuron and is manifest by degeneration of the distal portion of the nerve fiber. [NIH] Axons: Nerve fibers that are capable of rapidly conducting impulses away from the neuron cell body. [NIH] Back Pain: Acute or chronic pain located in the posterior regions of the trunk, including the thoracic, lumbar, sacral, or adjacent regions. [NIH] Bacteria: Unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. [NIH] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] 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] Basophil: A type of white blood cell. Basophils are granulocytes. [NIH] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Benzodiazepines: A two-ring heterocyclic compound consisting of a benzene ring fused to a diazepine ring. Permitted is any degree of hydrogenation, any substituents and any Hisomer. [NIH] Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to glycine in the liver and excreted as hippuric acid. [NIH] Bewilderment: Impairment or loss of will power. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from

Dictionary 135

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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [NIH] Biliary Tract: The gallbladder and its ducts. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biological Transport: The movement of materials (including biochemical substances and drugs) across cell membranes and epithelial layers, usually by passive diffusion. [NIH] 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] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Bloating: Fullness or swelling in the abdomen that often occurs after meals. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Platelets: Non-nucleated disk-shaped cells formed in the megakaryocyte and found in the blood of all mammals. They are mainly involved in blood coagulation. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Body Regions: Anatomical areas of the body. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH]

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Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Brachial: All the nerves from the arm are ripped from the spinal cord. [NIH] Brachial Plexus: The large network of nerve fibers which distributes the innervation of the upper extremity. The brachial plexus extends from the neck into the axilla. In humans, the nerves of the plexus usually originate from the lower cervical and the first thoracic spinal cord segments (C5-C8 and T1), but variations are not uncommon. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Breast reconstruction: Surgery to rebuild a breast's shape after a mastectomy. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchial: Pertaining to one or more bronchi. [EU] Buccal: Pertaining to or directed toward the cheek. In dental anatomy, used to refer to the buccal surface of a tooth. [EU] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [NIH] Caesarean section: A surgical incision through the abdominal and uterine walls in order to deliver a baby. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium 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] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsaicin: Cytotoxic alkaloid from various species of Capsicum (pepper, paprika), of the Solanaceae. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbamazepine: An anticonvulsant used to control grand mal and psychomotor or focal

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seizures. Its mode of action is not fully understood, but some of its actions resemble those of phenytoin; although there is little chemical resemblance between the two compounds, their three-dimensional structure is similar. [NIH] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogen: Any substance that causes cancer. [NIH] Cardiac: Having to do with the heart. [NIH] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Carotene: The general name for a group of pigments found in green, yellow, and leafy vegetables, and yellow fruits. The pigments are fat-soluble, unsaturated aliphatic hydrocarbons functioning as provitamins and are converted to vitamin A through enzymatic processes in the intestinal wall. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Caudal: Denoting a position more toward the cauda, or tail, than some specified point of reference; same as inferior, in human anatomy. [EU] 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 membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Cellobiose: A disaccharide consisting of two glucose units in beta (1-4) glycosidic linkage. Obtained from the partial hydrolysis of cellulose. [NIH]

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Cellulose: A polysaccharide with glucose units linked as in cellobiose. It is the chief constituent of plant fibers, cotton being the purest natural form of the substance. As a raw material, it forms the basis for many derivatives used in chromatography, ion exchange materials, explosives manufacturing, and pharmaceutical preparations. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Centrifugation: A method of separating organelles or large molecules that relies upon differential sedimentation through a preformed density gradient under the influence of a gravitational field generated in a centrifuge. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemoreceptor: A receptor adapted for excitation by chemical substances, e.g., olfactory and gustatory receptors, or a sense organ, as the carotid body or the aortic (supracardial) bodies, which is sensitive to chemical changes in the blood stream, especially reduced oxygen content, and reflexly increases both respiration and blood pressure. [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] Cholinergic: Resembling acetylcholine in pharmacological action; stimulated by or releasing acetylcholine or a related compound. [EU] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary processes: The extensions or projections of the ciliary body that secrete aqueous humor. [NIH] CIS: Cancer Information Service. The CIS is the National Cancer Institute's link to the public, interpreting and explaining research findings in a clear and understandable manner, and providing personalized responses to specific questions about cancer. Access the CIS by calling 1-800-4-CANCER, or by using the Web site at http://cis.nci.nih.gov. [NIH] Cisplatin: An inorganic and water-soluble platinum complex. After undergoing hydrolysis, it reacts with DNA to produce both intra and interstrand crosslinks. These crosslinks appear to impair replication and transcription of DNA. The cytotoxicity of cisplatin correlates with cellular arrest in the G2 phase of the cell cycle. [NIH]

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Citalopram: A selective neuronal serotonin reuptake inhibitor and a clinically effective antidepressant with tolerable side effects. The drug is also effective in reducing ethanol uptake in alcoholics and is used in depressed patients who also suffer from tardive dyskinesia (TD) in preference to tricyclic antidepressants, which aggravate this condition. [NIH]

Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] 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] Cognition: Intellectual or mental process whereby an organism becomes aware of or obtains knowledge. [NIH] Cognitive Therapy: A direct form of psychotherapy based on the interpretation of situations (cognitive structure of experiences) that determine how an individual feels and behaves. It is based on the premise that cognition, the process of acquiring knowledge and forming beliefs, is a primary determinant of mood and behavior. The therapy uses behavioral and verbal techniques to identify and correct negative thinking that is at the root of the aberrant behavior. [NIH] Colic: Paroxysms of pain. This condition usually occurs in the abdominal region but may occur in other body regions as well. [NIH] Colitis: Inflammation of the colon. [NIH] Collapse: 1. A state of extreme prostration and depression, with failure of circulation. 2. Abnormal falling in of the walls of any part of organ. [EU] Colloidal: Of the nature of a colloid. [EU] Colorectal: Having to do with the colon or the rectum. [NIH] Complement: A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed 'components of complement' and are designated by the symbols C1 through C9. C1 is a calcium-dependent complex of three distinct proteins C1q, C1r and C1s. The proteins of the alternative pathway (collectively referred to as the properdin system) and complement regulatory proteins are known by semisystematic or trivial names. Fragments resulting from proteolytic cleavage of complement proteins are designated with lower-case letter suffixes, e.g., C3a. Inactivated fragments may be designated with the suffix

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'i', e.g. C3bi. Activated components or complexes with biological activity are designated by a bar over the symbol e.g. C1 or C4b,2a. The classic pathway is activated by the binding of C1 to classic pathway activators, primarily antigen-antibody complexes containing IgM, IgG1, IgG3; C1q binds to a single IgM molecule or two adjacent IgG molecules. The alternative pathway can be activated by IgA immune complexes and also by nonimmunologic materials including bacterial endotoxins, microbial polysaccharides, and cell walls. Activation of the classic pathway triggers an enzymatic cascade involving C1, C4, C2 and C3; activation of the alternative pathway triggers a cascade involving C3 and factors B, D and P. Both result in the cleavage of C5 and the formation of the membrane attack complex. Complement activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complete remission: The disappearance of all signs of cancer. Also called a complete response. [NIH] Compress: A plug used to occludate an orifice in the control of bleeding, or to mop up secretions; an absorbent pad. [NIH] Compulsion: In psychology, an irresistible urge, sometimes amounting to obsession to perform a particular act which usually is carried out against the performer's will or better judgment. [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] Concomitant: Accompanying; accessory; joined with another. [EU] Cone: One of the special retinal receptor elements which are presumed to be primarily concerned with perception of light and color stimuli when the eye is adapted to light. [NIH] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a

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fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Consciousness: Sense of awareness of self and of the environment. [NIH] Constipation: Infrequent or difficult evacuation of feces. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Convulsive: Relating or referring to spasm; affected with spasm; characterized by a spasm or spasms. [NIH] Cornea: The transparent part of the eye that covers the iris and the pupil and allows light to enter the inside. [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 Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Cortical: Pertaining to or of the nature of a cortex or bark. [EU] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees,

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and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Coumarin: A fluorescent dye. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Curare: Plant extracts from several species, including Strychnos toxifera, S. castelnaei, S. crevauxii, and Chondodendron tomentosum, that produce paralysis of skeletal muscle and are used adjunctively with general anesthesia. These extracts are toxic and must be used with the administration of artificial respiration. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Curettage: Removal of tissue with a curette, a spoon-shaped instrument with a sharp edge. [NIH]

Curette: A spoon-shaped instrument with a sharp edge. [NIH] Cutaneous: Having to do with the skin. [NIH] Cystitis: Inflammation of the urinary bladder. [EU] Cystoscope: A thin, lighted instrument used to look inside the bladder and remove tissue samples or small tumors. [NIH] 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] Cytotoxic: Cell-killing. [NIH] Cytotoxic chemotherapy: Anticancer drugs that kill cells, especially cancer cells. [NIH] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Decarboxylation: The removal of a carboxyl group, usually in the form of carbon dioxide, from a chemical compound. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

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Dendrites: Extensions of the nerve cell body. They are short and branched and receive stimuli from other neurons. [NIH] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Desipramine: A tricyclic dibenzazepine compound that potentiates neurotransmission. Desipramine selectively blocks reuptake of norepinephrine from the neural synapse, and also appears to impair serotonin transport. This compound also possesses minor anticholingeric activity, through its affinity to muscarinic receptors. [NIH] Detoxification: Treatment designed to free an addict from his drug habit. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [NIH] Dextroamphetamine: The d-form of amphetamine. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. [NIH] Dextromethorphan: The d-isomer of the codeine analog of levorphanol. Dextromethorphan shows high affinity binding to several regions of the brain, including the medullary cough center. This compound is a NMDA receptor antagonist (receptors, N-methyl-D-aspartate) and acts as a non-competitive channel blocker. It is used widely as an antitussive agent, and is also used to study the involvement of glutamate receptors in neurotoxicity. [NIH] Dextrorphan: Dextro form of levorphanol. It acts as a noncompetitive NMDA receptor antagonist, among other effects, and has been proposed as a neuroprotective agent. It is also a metabolite of dextromethorphan. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diarrhea: Passage of excessively liquid or excessively frequent stools. [NIH] Diclofenac: A non-steroidal anti-inflammatory agent (NSAID) with antipyretic and analgesic actions. It is primarily available as the sodium salt, diclofenac sodium. [NIH] Diclofenac Sodium: The sodium form of diclofenac. It is used for its analgesic and antiinflammatory properties. [NIH] Diffusion: The tendency of a gas or solute to pass from a point of higher pressure or concentration to a point of lower pressure or concentration and to distribute itself throughout the available space; a major mechanism of biological transport. [NIH] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH] Digestive tract: The organs through which food passes when food is eaten. These organs are the mouth, esophagus, stomach, small and large intestines, and rectum. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place,

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or identity. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Distention: The state of being distended or enlarged; the act of distending. [EU] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] 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] Double-blinded: A clinical trial in which neither the medical staff nor the person knows which of several possible therapies the person is receiving. [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] Dyes: Chemical substances that are used to stain and color other materials. The coloring may or may not be permanent. Dyes can also be used as therapeutic agents and test reagents in medicine and scientific research. [NIH] Dyskinesia: Impairment of the power of voluntary movement, resulting in fragmentary or incomplete movements. [EU] Dysmenorrhea: Painful menstruation. [NIH] Dyspepsia: Impaired digestion, especially after eating. [NIH]

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Dysphagia: Difficulty in swallowing. [EU] 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] Ejaculation: The release of semen through the penis during orgasm. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] 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 chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current. [NIH]

Electroplating: Coating with a metal or alloy by electrolysis. [NIH] Electroshock: Induction of a stress reaction in experimental subjects by means of an electrical shock; applies to either convulsive or non-convulsive states. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Emesis: Vomiting; an act of vomiting. Also used as a word termination, as in haematemesis. [EU]

Emetics: Agents that cause vomiting. They may act directly on the gastrointestinal tract, bringing about emesis through local irritant effects, or indirectly, through their effects on the chemoreceptor trigger zone in the postremal area near the medulla. [NIH] Emollient: Softening or soothing; called also malactic. [EU] Encapsulated: Confined to a specific, localized area and surrounded by a thin layer of tissue. [NIH]

Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Enhancer: Transcriptional element in the virus genome. [NIH] Enteric-coated: A term designating a special coating applied to tablets or capsules which prevents release and absorption of their contents until they reach the intestines. [EU]

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Enterohepatic: Of or involving the intestine and liver. [EU] Enterohepatic Circulation: Recycling through liver by excretion in bile, reabsorption from intestines into portal circulation, passage back into liver, and re-excretion in bile. [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] Epidural: The space between the wall of the spinal canal and the covering of the spinal cord. An epidural injection is given into this space. [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] Erectile: The inability to get or maintain an erection for satisfactory sexual intercourse. Also called impotence. [NIH] Erection: The condition of being made rigid and elevated; as erectile tissue when filled with blood. [EU] Erythema: Redness of the skin produced by congestion of the capillaries. This condition may result from a variety of causes. [NIH] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Euphoria: An exaggerated feeling of physical and emotional well-being not consonant with apparent stimuli or events; usually of psychologic origin, but also seen in organic brain disease and toxic states. [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] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams, salves, etc. [NIH] Excitatory: When cortical neurons are excited, their output increases and each new input they receive while they are still excited raises their output markedly. [NIH] Exocytosis: Cellular release of material within membrane-limited vesicles by fusion of the vesicles with the cell membrane. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU]

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Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extracorporeal: Situated or occurring outside the body. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Extremity: A limb; an arm or leg (membrum); sometimes applied specifically to a hand or foot. [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 reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [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] Fenfluramine: A centrally active drug that apparently both blocks serotonin uptake and provokes transport-mediated serotonin release. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Fertilizers: Substances or mixtures that are added to the soil to supply nutrients or to make available nutrients already present in the soil, in order to increase plant growth and productivity. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fixation: 1. The act or operation of holding, suturing, or fastening in a fixed position. 2. The condition of being held in a fixed position. 3. In psychiatry, a term with two related but distinct meanings : (1) arrest of development at a particular stage, which like regression (return to an earlier stage), if temporary is a normal reaction to setbacks and difficulties but if protracted or frequent is a cause of developmental failures and emotional problems, and (2) a close and suffocating attachment to another person, especially a childhood figure, such as one's mother or father. Both meanings are derived from psychoanalytic theory and refer to 'fixation' of libidinal energy either in a specific erogenous zone, hence fixation at the oral, anal, or phallic stage, or in a specific object, hence mother or father fixation. 4. The use of a fixative (q.v.) to preserve histological or cytological specimens. 5. In chemistry, the process whereby a substance is removed from the gaseous or solution phase and localized, as in carbon dioxide fixation or nitrogen fixation. 6. In ophthalmology, direction of the gaze so that the visual image of the object falls on the fovea centralis. 7. In film processing, the chemical removal of all undeveloped salts of the film emulsion, leaving only the developed silver to form a permanent image. [EU] Flame Ionization: Pyrolysis of organic compounds at the temperature of a hydrogen-air flame to produce ionic intermediates which can be collected and the resulting ion current

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measured by gas chromatography. [NIH] Flatus: Gas passed through the rectum. [NIH] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Fluoxetine: The first highly specific serotonin uptake inhibitor. It is used as an antidepressant and often has a more acceptable side-effects profile than traditional antidepressants. [NIH] Flurbiprofen: An anti-inflammatory analgesic and antipyretic of the phenylalkynoic acid series. It has been shown to reduce bone resorption in periodontal disease by inhibiting carbonic anhydrase. [NIH] Foot Care: Taking special steps to avoid foot problems such as sores, cuts, bunions, and calluses. Good care includes daily examination of the feet, toes, and toenails and choosing shoes and socks or stockings that fit well. People with diabetes have to take special care of their feet because nerve damage and reduced blood flow sometimes mean they will have less feeling in their feet than normal. They may not notice cuts and other problems as soon as they should. [NIH] Foot Ulcer: Lesion on the surface of the skin of the foot, usually accompanied by inflammation. The lesion may become infected or necrotic and is frequently associated with diabetes or leprosy. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fungi: A kingdom of eukaryotic, heterotrophic organisms that live as saprobes or parasites, including mushrooms, yeasts, smuts, molds, etc. They reproduce either sexually or asexually, and have life cycles that range from simple to complex. Filamentous fungi refer to those that grow as multicelluar colonies (mushrooms and molds). [NIH] Fungistatic: Inhibiting the growth of fungi. [EU] 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] Gastric: Having to do with the stomach. [NIH] Gastric Emptying: The evacuation of food from the stomach into the duodenum. [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]

Genital: Pertaining to the genitalia. [EU] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH]

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Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glucocorticoids: A group of corticosteroids that affect carbohydrate metabolism (gluconeogenesis, liver glycogen deposition, elevation of blood sugar), inhibit corticotropin secretion, and possess pronounced anti-inflammatory activity. They also play a role in fat and protein metabolism, maintenance of arterial blood pressure, alteration of the connective tissue response to injury, reduction in the number of circulating lymphocytes, and functioning of the central nervous system. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Glucuronic Acid: Derivatives of uronic acid found throughout the plant and animal kingdoms. They detoxify drugs and toxins by conjugating with them to form glucuronides in the liver which are more water-soluble metabolites that can be easily eliminated from the body. [NIH] Glucuronides: Glycosides of glucuronic acid formed by the reaction of uridine diphosphate glucuronic acid with certain endogenous and exogenous substances. Their formation is important for the detoxification of drugs, steroid excretion and bilirubin metabolism to a more water-soluble compound that can be eliminated in the urine and bile. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glycerol: A trihydroxy sugar alcohol that is an intermediate in carbohydrate and lipid metabolism. It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent. [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] Glycopyrrolate: A muscarinic antagonist used as an antispasmodic, in some disorders of the gastrointestinal tract, and to reduce salivation with some anesthetics. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Groin: The external junctural region between the lower part of the abdomen and the thigh. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Gynaecological: Pertaining to gynaecology. [EU] Haematemesis: The vomiting of blood. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Haptens: Small antigenic determinants capable of eliciting an immune response only when coupled to a carrier. Haptens bind to antibodies but by themselves cannot elicit an antibody response. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage;

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craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [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] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hemostasis: The process which spontaneously arrests the flow of blood from vessels carrying blood under pressure. It is accomplished by contraction of the vessels, adhesion and aggregation of formed blood elements, and the process of blood or plasma coagulation. [NIH]

Hepatic: Refers to the liver. [NIH] Hereditary: Of, relating to, or denoting factors that can be transmitted genetically from one generation to another. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Hernia: Protrusion of a loop or knuckle of an organ or tissue through an abnormal opening. [NIH]

Herniorrhaphy: An operation to repair a hernia. [NIH] Heterogeneity: The property of one or more samples or populations which implies that they are not identical in respect of some or all of their parameters, e. g. heterogeneity of variance. [NIH]

Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Histamine Release: The secretion of histamine from mast cell and basophil granules by exocytosis. This can be initiated by a number of factors, all of which involve binding of IgE, cross-linked by antigen, to the mast cell or basophil's Fc receptors. Once released, histamine binds to a number of different target cell receptors and exerts a wide variety of effects. [NIH] Histidine: An essential amino acid important in a number of metabolic processes. It is required for the production of histamine. [NIH] Homologous: Corresponding in structure, position, origin, etc., as (a) the feathers of a bird and the scales of a fish, (b) antigen and its specific antibody, (c) allelic chromosomes. [EU] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin

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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] Hydrogel: A network of cross-linked hydrophilic macromolecules used in biomedical applications. [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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydrophilic: Readily absorbing moisture; hygroscopic; having strongly polar groups that readily interact with water. [EU] Hydrophobic: Not readily absorbing water, or being adversely affected by water, as a hydrophobic colloid. [EU] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypospadias: A developmental anomaly in the male in which the urethra opens on the underside of the penis or on the perineum. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Hysterectomy: Excision of the uterus. [NIH] Hysterosalpingography: Radiography of the uterus and fallopian tubes after the injection of a contrast medium. [NIH] Ibuprofen: A nonsteroidal anti-inflammatory agent with analgesic properties used in the 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] Idiopathic: Describes a disease of unknown cause. [NIH] Imipramine: The prototypical tricyclic antidepressant. It has been used in major depression, dysthymia, bipolar depression, attention-deficit disorders, agoraphobia, and panic disorders. It has less sedative effect than some other members of this therapeutic group.

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[NIH]

Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunization: Deliberate stimulation of the host's immune response. Active immunization involves administration of antigens or immunologic adjuvants. Passive immunization involves administration of immune sera or lymphocytes or their extracts (e.g., transfer factor, immune RNA) or transplantation of immunocompetent cell producing tissue (thymus or bone marrow). [NIH] Immunology: The study of the body's immune system. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] Impotence: The inability to perform sexual intercourse. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] 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] Incision: A cut made in the body during surgery. [NIH] Incontinence: Inability to control the flow of urine from the bladder (urinary incontinence) or the escape of stool from the rectum (fecal incontinence). [NIH] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

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] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inguinal: Pertaining to the inguen, or groin. [EU] Inhalation: The drawing of air or other substances into the lungs. [EU]

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Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Inpatients: Persons admitted to health facilities which provide board and room, for the purpose of observation, care, diagnosis or treatment. [NIH] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intervertebral: Situated between two contiguous vertebrae. [EU] Intervertebral Disk Displacement: An intervertebral disk in which the nucleus pulposus has protruded through surrounding fibrocartilage. This occurs most frequently in the lower lumbar region. [NIH] Intestinal: Having to do with the intestines. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intrathecal: Describes the fluid-filled space between the thin layers of tissue that cover the brain and spinal cord. Drugs can be injected into the fluid or a sample of the fluid can be removed for testing. [NIH] Intravenous: IV. Into a vein. [NIH] Intravesical: Within the bladder. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [EU] Intubation: Introduction of a tube into a hollow organ to restore or maintain patency if obstructed. It is differentiated from catheterization in that the insertion of a catheter is usually performed for the introducing or withdrawing of fluids from the body. [NIH] Invasive: 1. Having the quality of invasiveness. 2. Involving puncture or incision of the skin or insertion of an instrument or foreign material into the body; said of diagnostic techniques. [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]

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Irritable Bowel Syndrome: A disorder that comes and goes. Nerves that control the muscles in the GI tract are too active. The GI tract becomes sensitive to food, stool, gas, and stress. Causes abdominal pain, bloating, and constipation or diarrhea. Also called spastic colon or mucous colitis. [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] Ketamine: A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (receptors, NMethyl-D-Aspartate) and may interact with sigma receptors. [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] Kidney Pelvis: The flattened, funnel-shaped expansion connecting the ureter to the kidney calices. [NIH] Large Intestine: The part of the intestine that goes from the cecum to the rectum. The large intestine absorbs water from stool and changes it from a liquid to a solid form. The large intestine is 5 feet long and includes the appendix, cecum, colon, and rectum. Also called colon. [NIH] Laryngeal: Having to do with the larynx. [NIH] Larynx: An irregularly shaped, musculocartilaginous tubular structure, lined with mucous membrane, located at the top of the trachea and below the root of the tongue and the hyoid bone. It is the essential sphincter guarding the entrance into the trachea and functioning secondarily as the organ of voice. [NIH] Laxative: An agent that acts to promote evacuation of the bowel; a cathartic or purgative. [EU]

Lens: The transparent, double convex (outward curve on both sides) structure suspended between the aqueous and vitreous; helps to focus light on the retina. [NIH] Leprosy: A chronic granulomatous infection caused by Mycobacterium leprae. The granulomatous lesions are manifested in the skin, the mucous membranes, and the peripheral nerves. Two polar or principal types are lepromatous and tuberculoid. [NIH] Lesion: An area of abnormal tissue change. [NIH] Levo: It is an experimental treatment for heroin addiction that was developed by German scientists around 1948 as an analgesic. Like methadone, it binds with opioid receptors, but it is longer acting. [NIH] Levorphanol: A narcotic analgesic that may be habit-forming. It is nearly as effective orally as by injection. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Lidocaine: A local anesthetic and cardiac depressant used as an antiarrhythmia agent. Its actions are more intense and its effects more prolonged than those of procaine but its duration of action is shorter than that of bupivacaine or prilocaine. [NIH] Ligament: A band of fibrous tissue that connects bones or cartilages, serving to support and strengthen joints. [EU]

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Lipid: Fat. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lithotripsy: The destruction of a calculus of the kidney, ureter, bladder, or gallbladder by physical forces, including crushing with a lithotriptor through a catheter. Focused percutaneous ultrasound and focused hydraulic shock waves may be used without surgery. Lithotripsy does not include the dissolving of stones by acids or litholysis. Lithotripsy by laser is laser lithotripsy. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] 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] Lubricants: Oily or slippery substances. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lupus: A form of cutaneous tuberculosis. It is seen predominantly in women and typically involves the nasal, buccal, and conjunctival mucosa. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lysine: An essential amino acid. It is often added to animal feed. [NIH] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mania: Excitement of psychotic proportions manifested by mental and physical hyperactivity, disorganization of behaviour, and elevation of mood. [EU] Mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible). [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Mediator: An object or substance by which something is mediated, such as (1) a structure of the nervous system that transmits impulses eliciting a specific response; (2) a chemical substance (transmitter substance) that induces activity in an excitable tissue, such as nerve or muscle; or (3) a substance released from cells as the result of the interaction of antigen with antibody or by the action of antigen with a sensitized lymphocyte. [EU] Medical Staff: Professional medical personnel who provide care to patients in an organized facility, institution or agency. [NIH] Medicament: A medicinal substance or agent. [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] Membrane: A very thin layer of tissue that covers a surface. [NIH]

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Meninges: The three membranes that cover and protect the brain and spinal cord. [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] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Meta-Analysis: A quantitative method of combining the results of independent studies (usually drawn from the published literature) and synthesizing summaries and conclusions which may be used to evaluate therapeutic effectiveness, plan new studies, etc., with application chiefly in the areas of research and medicine. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Metastasis: The spread of cancer from one part of the body to another. Tumors formed from cells that have spread are called "secondary tumors" and contain cells that are like those in the original (primary) tumor. The plural is metastases. [NIH] Metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another. [NIH] Methacrylate: A vinyl monomer. [NIH] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methylcellulose: Methylester of cellulose. Methylcellulose is used as an emulsifying and suspending agent in cosmetics, pharmaceutics and the chemical industry. It is used therapeutically as a bulk laxative. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] Metoclopramide: A dopamine D2 antagonist that is used as an antiemetic. [NIH] Mexiletine: Antiarrhythmic agent pharmacologically similar to lidocaine. It may have some anticonvulsant properties. [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] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microbiological: Pertaining to microbiology : the science that deals with microorganisms, including algae, bacteria, fungi, protozoa and viruses. [EU] Microbiology: The study of microorganisms such as fungi, bacteria, algae, archaea, and viruses. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] Microsomal: Of or pertaining to microsomes : vesicular fragments of endoplasmic reticulum formed after disruption and centrifugation of cells. [EU] Micturition: The passage of urine; urination. [EU]

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Mineralocorticoids: A group of corticosteroids primarily associated with the regulation of water and electrolyte balance. This is accomplished through the effect on ion transport in renal tubules, resulting in retention of sodium and loss of potassium. Mineralocorticoid secretion is itself regulated by plasma volume, serum potassium, and angiotensin II. [NIH] Mitochondrial Swelling: Increase in volume of mitochondria due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecular Structure: The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. [NIH] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Monoamine Oxidase: An enzyme that catalyzes the oxidative deamination of naturally occurring monoamines. It is a flavin-containing enzyme that is localized in mitochondrial membranes, whether in nerve terminals, the liver, or other organs. Monoamine oxidase is important in regulating the metabolic degradation of catecholamines and serotonin in neural or target tissues. Hepatic monoamine oxidase has a crucial defensive role in inactivating circulating monoamines or those, such as tyramine, that originate in the gut and are absorbed into the portal circulation. (From Goodman and Gilman's, The Pharmacological Basis of Therapeutics, 8th ed, p415) EC 1.4.3.4. [NIH] Monotherapy: A therapy which uses only one drug. [EU] 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] Motility: The ability to move spontaneously. [EU] Motion Sickness: Sickness caused by motion, as sea sickness, train sickness, car sickness, and air sickness. [NIH] Motor nerve: An efferent nerve conveying an impulse that excites muscular contraction. [NIH]

Mucilaginous: Pertaining to or secreting mucus. [NIH] Mucosa: A mucous membrane, or tunica mucosa. [EU] Mucus: The viscous secretion of mucous membranes. It contains mucin, white blood cells, water, inorganic salts, and exfoliated cells. [NIH] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Muscle relaxant: An agent that specifically aids in reducing muscle tension, as those acting at the polysynaptic neurons of motor nerves (e.g. meprobamate) or at the myoneural

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junction (curare and related compounds). [EU] Muscle tension: A force in a material tending to produce extension; the state of being stretched. [NIH] Musculature: The muscular apparatus of the body, or of any part of it. [EU] Musculoskeletal System: Themuscles, bones, and cartilage of the body. [NIH] 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] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Nalbuphine: A narcotic used as a pain medication. It appears to be an agonist at kappa opioid receptors and an antagonist or partial agonist at mu opioid receptors. [NIH] Naloxone: A specific opiate antagonist that has no agonist activity. It is a competitive antagonist at mu, delta, and kappa opioid receptors. [NIH] Naltrexone: Derivative of noroxymorphone that is the N-cyclopropylmethyl congener of naloxone. It is a narcotic antagonist that is effective orally, longer lasting and more potent than naloxone, and has been proposed for the treatment of heroin addiction. The FDA has approved naltrexone for the treatment of alcohol dependence. [NIH] 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] Nasal Cavity: The proximal portion of the respiratory passages on either side of the nasal septum, lined with ciliated mucosa, extending from the nares to the pharynx. [NIH] Nasal Mucosa: The mucous membrane lining the nasal cavity. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action

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toward a goal he believes will satisfy the impulse. [NIH] Neoplasm: A new growth of benign or malignant tissue. [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] Nerve Fibers: Slender processes of neurons, especially the prolonged axons that conduct nerve impulses. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neural: 1. Pertaining to a nerve or to the nerves. 2. Situated in the region of the spinal axis, as the neutral arch. [EU] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] Neuroleptic: A term coined to refer to the effects on cognition and behaviour of antipsychotic drugs, which produce a state of apathy, lack of initiative, and limited range of emotion and in psychotic patients cause a reduction in confusion and agitation and normalization of psychomotor activity. [EU] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease. [NIH] Neurosurgery: A surgical specialty concerned with the treatment of diseases and disorders of the brain, spinal cord, and peripheral and sympathetic nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Neurotransmitters: Endogenous signaling molecules that alter the behavior of neurons or effector cells. Neurotransmitter is used here in its most general sense, including not only messengers that act directly to regulate ion channels, but also those that act through second messenger systems, and those that act at a distance from their site of release. Included are neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not acting at synapses. [NIH] Nitric acid: A toxic, corrosive, colorless liquid used to make fertilizers, dyes, explosives, and other chemicals. [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] Nonmalignant: Not cancerous. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Nortriptyline: A metabolite of amitryptyline that is also used as an antidepressive agent. Nortriptyline is used in major depression, dysthymia, and atypical depressions. [NIH]

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Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] 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] Obsession: A recurrent, persistent thought, image, or impulse that is unwanted and distressing (ego-dystonic) and comes involuntarily to mind despite attempts to ignore or suppress it. Common obsessions involve thoughts of violence, contamination, and selfdoubt. [EU] Obsessional: Neurosis characterized by the repetitive intrusion into the mind, against volition, of ideas, numinations and phobias, often associated with compulsive actions. [NIH] Obstipation: Intractable constipation. [EU] Odour: A volatile emanation that is perceived by the sense of smell. [EU] 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] Ondansetron: A competitive serotonin type 3 receptor antagonist. It is effective in the treatment of nausea and vomiting caused by cytotoxic chemotherapy drugs, including cisplatin, and it has reported anxiolytic and neuroleptic properties. [NIH] On-line: A sexually-reproducing population derived from a common parentage. [NIH] Ophthalmic: Pertaining to the eye. [EU] 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] Opsin: A protein formed, together with retinene, by the chemical breakdown of metarhodopsin. [NIH] Optic Nerve: The 2nd cranial nerve. The optic nerve conveys visual information from the retina to the brain. The nerve carries the axons of the retinal ganglion cells which sort at the optic chiasm and continue via the optic tracts to the brain. The largest projection is to the lateral geniculate nuclei; other important targets include the superior colliculi and the suprachiasmatic nuclei. Though known as the second cranial nerve, it is considered part of the central nervous system. [NIH] Optic Nerve Diseases: Conditions which produce injury or dysfunction of the second cranial or optic nerve, which is generally considered a component of the central nervous system. Damage to optic nerve fibers may occur at or near their origin in the retina, at the optic disk, or in the nerve, optic chiasm, optic tract, or lateral geniculate nuclei. Clinical manifestations may include decreased visual acuity and contrast sensitivity, impaired color vision, and an afferent pupillary defect. [NIH] Orgasm: The crisis of sexual excitement in either humans or animals. [NIH] Orphenadrine: A muscarinic antagonist used to treat drug-induced parkinsonism and to relieve pain from muscle spasm. [NIH] Orthopaedic: Pertaining to the correction of deformities of the musculoskeletal system; pertaining to orthopaedics. [EU]

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Osmosis: Tendency of fluids (e.g., water) to move from the less concentrated to the more concentrated side of a semipermeable membrane. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] Osteoarthritis: A progressive, degenerative joint disease, the most common form of arthritis, especially in older persons. The disease is thought to result not from the aging process but from biochemical changes and biomechanical stresses affecting articular cartilage. In the foreign literature it is often called osteoarthrosis deformans. [NIH] Outpatient: A patient who is not an inmate of a hospital but receives diagnosis or treatment in a clinic or dispensary connected with the hospital. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxides: Binary compounds of oxygen containing the anion O(2-). The anion combines with metals to form alkaline oxides and non-metals to form acidic oxides. [NIH] Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Paediatric: Of or relating to the care and medical treatment of children; belonging to or concerned with paediatrics. [EU] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pallor: A clinical manifestation consisting of an unnatural paleness of the skin. [NIH] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatitis: Acute or chronic inflammation of the pancreas, which may be asymptomatic or symptomatic, and which is due to autodigestion of a pancreatic tissue by its own enzymes. It is caused most often by alcoholism or biliary tract disease; less commonly it may be associated with hyperlipaemia, hyperparathyroidism, abdominal trauma (accidental or operative injury), vasculitis, or uraemia. [EU] Panic: A state of extreme acute, intense anxiety and unreasoning fear accompanied by disorganization of personality function. [NIH]

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Panic Disorder: A type of anxiety disorder characterized by unexpected panic attacks that last minutes or, rarely, hours. Panic attacks begin with intense apprehension, fear or terror and, often, a feeling of impending doom. Symptoms experienced during a panic attack include dyspnea or sensations of being smothered; dizziness, loss of balance or faintness; choking sensations; palpitations or accelerated heart rate; shakiness; sweating; nausea or other form of abdominal distress; depersonalization or derealization; paresthesias; hot flashes or chills; chest discomfort or pain; fear of dying and fear of not being in control of oneself or going crazy. Agoraphobia may also develop. Similar to other anxiety disorders, it may be inherited as an autosomal dominant trait. [NIH] Paramedic: An emergency medical technician (EMT) who received further training for the delivery of some aspects of advanced life support (ALS) care. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Parkinsonism: A group of neurological disorders characterized by hypokinesia, tremor, and muscular rigidity. [EU] Paroxetine: A serotonin uptake inhibitor that is effective in the treatment of depression. [NIH]

Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Partial remission: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial response. [NIH] Particle: A tiny mass of material. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Patient Education: The teaching or training of patients concerning their own health needs. [NIH]

Patient Selection: Criteria and standards used for the determination of the appropriateness of the inclusion of patients with specific conditions in proposed treatment plans and the criteria used for the inclusion of subjects in various clinical trials and other research protocols. [NIH] Pelvic: Pertaining to the pelvis. [EU] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Penis: The external reproductive organ of males. It is composed of a mass of erectile tissue enclosed in three cylindrical fibrous compartments. Two of the three compartments, the corpus cavernosa, are placed side-by-side along the upper part of the organ. The third compartment below, the corpus spongiosum, houses the urethra. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Perineum: The area between the anus and the sex organs. [NIH]

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Periodontal disease: Disease involving the supporting structures of the teeth (as the gums and periodontal membranes). [NIH] Perioperative: Around the time of surgery; usually lasts from the time of going into the hospital or doctor's office for surgery until the time the patient goes home. [NIH] Peripheral Nerves: The nerves outside of the brain and spinal cord, including the autonomic, cranial, and spinal nerves. Peripheral nerves contain non-neuronal cells and connective tissue as well as axons. The connective tissue layers include, from the outside to the inside, the epineurium, the perineurium, and the endoneurium. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or formulation of the finished dosage form. [NIH] 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] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Phenprocoumon: 3-(1-Phenylpropyl)-4-hydroxycoumarin. Long acting oral anticoagulant. It may cause diarrhea. [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phobias: An exaggerated and invariably pathological dread of some specific type of stimulus or situation. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physical Therapy: The restoration of function and the prevention of disability following disease or injury with the use of light, heat, cold, water, electricity, ultrasound, and exercise. [NIH]

Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Pigments: Any normal or abnormal coloring matter in plants, animals, or micro-organisms. [NIH]

Pilot study: The initial study examining a new method or treatment. [NIH] Piroxicam: 4-Hydroxy-2-methyl-N-2-pyridyl-2H-1,2-benzothiazine-3-carboxamide 1,1dioxide. A non-steroidal anti-inflammatory agent that is well established in the treatment of rheumatoid arthritis and osteoarthritis. Its usefulness has also been demonstrated in the treatment of musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily. The drug has also been shown to be

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effective if administered rectally. Gastrointestinal complaints are the most frequently reported side effects. [NIH] Pituitary Gland: A small, unpaired gland situated in the sella turcica tissue. It is connected to the hypothalamus by a short stalk. [NIH] Plants: Multicellular, eukaryotic life forms of the kingdom Plantae. They are characterized by a mainly photosynthetic mode of nutrition; essentially unlimited growth at localized regions of cell divisions (meristems); cellulose within cells providing rigidity; the absence of organs of locomotion; absense of nervous and sensory systems; and an alteration of haploid and diploid generations. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plexus: A network or tangle; a general term for a network of lymphatic vessels, nerves, or veins. [EU] Podiatry: A specialty concerned with the diagnosis and treatment of foot disorders and injuries and anatomic defects of the foot. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polyethylene: A vinyl polymer made from ethylene. It can be branched or linear. Branched or low-density polyethylene is tough and pliable but not to the same degree as linear polyethylene. Linear or high-density polyethylene has a greater hardness and tensile strength. Polyethylene is used in a variety of products, including implants and prostheses. [NIH]

Polymers: Compounds formed by the joining of smaller, usually repeating, units linked by covalent bonds. These compounds often form large macromolecules (e.g., polypeptides, proteins, plastics). [NIH] Polyneuropathies: Diseases of multiple peripheral nerves. The various forms are categorized by the type of nerve affected (e.g., sensory, motor, or autonomic), by the distribution of nerve injury (e.g., distal vs. proximal), by nerve component primarily affected (e.g., demyelinating vs. axonal), by etiology, or by pattern of inheritance. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Posterior: Situated in back of, or in the back part of, or affecting the back or dorsal surface of the body. In lower animals, it refers to the caudal end of the body. [EU] Postoperative: After surgery. [NIH] Postoperative Period: The period following a surgical operation. [NIH] Potentiates: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiating: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Potentiation: An overall effect of two drugs taken together which is greater than the sum of the effects of each drug taken alone. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government

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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] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Premedication: Preliminary administration of a drug preceding a diagnostic, therapeutic, or surgical procedure. The commonest types of premedication are antibiotics (antibiotic prophylaxis) and anti-anxiety agents. It does not include preanesthetic medication. [NIH] Prevalence: The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propofol: A widely used anesthetic. [NIH] Propoxyphene: A narcotic analgesic structurally related to methadone. Only the dextroisomer has an analgesic effect; the levo-isomer appears to exert an antitussive effect. [NIH] Prostate: A gland in males that surrounds the neck of the bladder and the urethra. It secretes a substance that liquifies coagulated semen. It is situated in the pelvic cavity behind the lower part of the pubic symphysis, above the deep layer of the triangular ligament, and rests upon the rectum. [NIH] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [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] Protozoa: A subkingdom consisting of unicellular organisms that are the simplest in the animal kingdom. Most are free living. They range in size from submicroscopic to macroscopic. Protozoa are divided into seven phyla: Sarcomastigophora, Labyrinthomorpha, Apicomplexa, Microspora, Ascetospora, Myxozoa, and Ciliophora. [NIH] Proximal: Nearest; closer to any point of reference; opposed to distal. [EU] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to

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obtain relief. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychology: The science dealing with the study of mental processes and behavior in man and animals. [NIH] Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychotherapy: A generic term for the treatment of mental illness or emotional disturbances primarily by verbal or nonverbal communication. [NIH] Psychotomimetic: Psychosis miming. [NIH] 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] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] 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] Receptors, Serotonin: Cell-surface proteins that bind serotonin and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action. [NIH] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large intestine and ends at the anus. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refraction: A test to determine the best eyeglasses or contact lenses to correct a refractive error (myopia, hyperopia, or astigmatism). [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of

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treatment. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Reserpine: An alkaloid found in the roots of Rauwolfia serpentina and R. vomitoria. Reserpine inhibits the uptake of norepinephrine into storage vesicles resulting in depletion of catecholamines and serotonin from central and peripheral axon terminals. It has been used as an antihypertensive and an antipsychotic as well as a research tool, but its adverse effects limit its clinical use. [NIH] Resolving: The ability of the eye or of a lens to make small objects that are close together, separately visible; thus revealing the structure of an object. [NIH] Resorption: The loss of substance through physiologic or pathologic means, such as loss of dentin and cementum of a tooth, or of the alveolar process of the mandible or maxilla. [EU] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which contains more carbon dioxide than the air taken in (Blakiston's Gould Medical Dictionary, 4th ed.). This does not include tissue respiration (= oxygen consumption) or cell respiration (= cell respiration). [NIH] Restless legs: Legs characterized by or showing inability to remain at rest. [EU] Restoration: Broad term applied to any inlay, crown, bridge or complete denture which restores or replaces loss of teeth or oral tissues. [NIH] Retina: The ten-layered nervous tissue membrane of the eye. It is continuous with the optic nerve and receives images of external objects and transmits visual impulses to the brain. Its outer surface is in contact with the choroid and the inner surface with the vitreous body. The outer-most layer is pigmented, whereas the inner nine layers are transparent. [NIH] Retinal: 1. Pertaining to the retina. 2. The aldehyde of retinol, derived by the oxidative enzymatic splitting of absorbed dietary carotene, and having vitamin A activity. In the retina, retinal combines with opsins to form visual pigments. One isomer, 11-cis retinal combines with opsin in the rods (scotopsin) to form rhodopsin, or visual purple. Another, all-trans retinal (trans-r.); visual yellow; xanthopsin) results from the bleaching of rhodopsin by light, in which the 11-cis form is converted to the all-trans form. Retinal also combines with opsins in the cones (photopsins) to form the three pigments responsible for colour vision. Called also retinal, and retinene1. [EU] Retinol: Vitamin A. It is essential for proper vision and healthy skin and mucous membranes. Retinol is being studied for cancer prevention; it belongs to the family of drugs called retinoids. [NIH] Rheumatic Diseases: Disorders of connective tissue, especially the joints and related structures, characterized by inflammation, degeneration, or metabolic derangement. [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]

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Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Rods: One type of specialized light-sensitive cells (photoreceptors) in the retina that provide side vision and the ability to see objects in dim light (night vision). [NIH] Salicylate: Non-steroidal anti-inflammatory drugs. [NIH] Salicylic: A tuberculosis drug. [NIH] Salivation: 1. The secretion of saliva. 2. Ptyalism (= excessive flow of saliva). [EU] 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] Scotoma: A localized defect in the visual field bordered by an area of normal vision. This occurs with a variety of eye diseases (e.g., retinal diseases and glaucoma), optic nerve diseases, and other conditions. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Semen: The thick, yellowish-white, viscid fluid secretion of male reproductive organs discharged upon ejaculation. In addition to reproductive organ secretions, it contains spermatozoa and their nutrient plasma. [NIH] Sensibility: The ability to receive, feel and appreciate sensations and impressions; the quality of being sensitive; the extend to which a method gives results that are free from false negatives. [NIH] Sensitization: 1. Administration of antigen to induce a primary immune response; priming; immunization. 2. Exposure to allergen that results in the development of hypersensitivity. 3. The coating of erythrocytes with antibody so that they are subject to lysis by complement in the presence of homologous antigen, the first stage of a complement fixation test. [EU] 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] Serotonin Syndrome: An adverse drug interaction characterized by altered mental status, autonomic dysfunction, and neuromuscular abnormalities. It is most frequently caused by

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use of both serotonin reuptake inhibitors and monoamine oxidase inhibitors, leading to excess serotonin availability in the CNS at the serotonin 1A receptor. [NIH] Sertraline: A selective serotonin uptake inhibitor that is used in the treatment of depression. [NIH]

Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] Shivering: Involuntary contraction or twitching of the muscles. It is a physiologic method of heat production in man and other mammals. [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] Signs and Symptoms: Clinical manifestations that can be either objective when observed by a physician, or subjective when perceived by the patient. [NIH] Silicon: A trace element that constitutes about 27.6% of the earth's crust in the form of silicon dioxide. It does not occur free in nature. Silicon has the atomic symbol Si, atomic number 14, and atomic weight 28.09. [NIH] Silicon Dioxide: Silica. Transparent, tasteless crystals found in nature as agate, amethyst, chalcedony, cristobalite, flint, sand, quartz, and tridymite. The compound is insoluble in water or acids except hydrofluoric acid. [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Sneezing: Sudden, forceful, involuntary expulsion of air from the nose and mouth caused by irritation to the mucous membranes of the upper respiratory tract. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] 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] Soma: The body as distinct from the mind; all the body tissue except the germ cells; all the axial body. [NIH] Somatic: 1. Pertaining to or characteristic of the soma or body. 2. Pertaining to the body wall in contrast to the viscera. [EU] Somnolence: Sleepiness; also unnatural drowsiness. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH]

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Spastic: 1. Of the nature of or characterized by spasms. 2. Hypertonic, so that the muscles are stiff and the movements awkward. 3. A person exhibiting spasticity, such as occurs in spastic paralysis or in cerebral palsy. [EU] Spatial disorientation: Loss of orientation in space where person does not know which way is up. [NIH] Specialist: In medicine, one who concentrates on 1 special branch of medical science. [NIH] Species: A taxonomic category subordinate to a genus (or subgenus) and superior to a subspecies or variety, composed of individuals possessing common characters distinguishing them from other categories of individuals of the same taxonomic level. In taxonomic nomenclature, species are designated by the genus name followed by a Latin or Latinized adjective or noun. [EU] Specificity: Degree of selectivity shown by an antibody with respect to the number and types of antigens with which the antibody combines, as well as with respect to the rates and the extents of these reactions. [NIH] Spectrum: A charted band of wavelengths of electromagnetic vibrations obtained by refraction and diffraction. By extension, a measurable range of activity, such as the range of bacteria affected by an antibiotic (antibacterial s.) or the complete range of manifestations of a disease. [EU] Sphincter: A ringlike band of muscle fibres that constricts a passage or closes a natural orifice; called also musculus sphincter. [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] Spinal Nerves: The 31 paired peripheral nerves formed by the union of the dorsal and ventral spinal roots from each spinal cord segment. The spinal nerve plexuses and the spinal roots are also included. [NIH] Splenic Vein: Vein formed by the union (at the hilus of the spleen) of several small veins from the stomach, pancreas, spleen and mesentery. [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] Steady state: Dynamic equilibrium. [EU] Sterilization: The destroying of all forms of life, especially microorganisms, by heat, chemical, or other means. [NIH] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH]

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Stool: The waste matter discharged in a bowel movement; feces. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stress incontinence: An involuntary loss of urine that occurs at the same time that internal abdominal pressure is increased, such as with laughing, sneezing, coughing, or physical activity. [NIH] Stress urinary: Leakage of urine caused by actions--such as coughing, laughing, sneezing, running, or lifting--that place pressure on the bladder from inside the body. Stress urinary incontinence can result from either a fallen bladder or weak sphincter muscles. [NIH] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [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] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [EU] Subclinical: Without clinical manifestations; said of the early stage(s) of an infection or other disease or abnormality before symptoms and signs become apparent or detectable by clinical examination or laboratory tests, or of a very mild form of an infection or other disease or abnormality. [EU] Subcutaneous: Beneath the skin. [NIH] Substance P: An eleven-amino acid neurotransmitter that appears in both the central and peripheral nervous systems. It is involved in transmission of pain, causes rapid contractions of the gastrointestinal smooth muscle, and modulates inflammatory and immune responses. [NIH]

Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sulfuric acid: A strong acid that, when concentrated is extemely corrosive to the skin and mucous membranes. It is used in making fertilizers, dyes, electroplating, and industrial explosives. [NIH] Sulindac: A sulfinylindene derivative whose sulfinyl moiety is converted in vivo to an active anti-inflammatory analgesic that undergoes enterohepatic circulation to maintain constant blood levels without causing gastrointestinal side effects. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Suppositories: A small cone-shaped medicament having cocoa butter or gelatin at its basis and usually intended for the treatment of local conditions in the rectum. [NIH] Suppression: A conscious exclusion of disapproved desire contrary with repression, in which the process of exclusion is not conscious. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects

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similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symphysis: A secondary cartilaginous joint. [NIH] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatology: 1. That branch of medicine with treats of symptoms; the systematic discussion of symptoms. 2. The combined symptoms of a disease. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Talcum: A native magnesium silicate. [NIH] Tardive: Marked by lateness, late; said of a disease in which the characteristic lesion is late in appearing. [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thoracic: Having to do with the chest. [NIH] Thorax: A part of the trunk between the neck and the abdomen; the chest. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] Tonic: 1. Producing and restoring the normal tone. 2. Characterized by continuous tension. 3. A term formerly used for a class of medicinal preparations believed to have the power of restoring normal tone to tissue. [EU] Topical: On the surface of the body. [NIH] Tourniquet: A device, band or elastic tube applied temporarily to press upon an artery to stop bleeding; a device to compress a blood vessel in order to stop bleeding. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Transcutaneous: Transdermal. [EU] Transcutaneous Electric Nerve Stimulation: Electrical stimulation of nerves and/or muscles to relieve pain; it is used less frequently to produce anesthesia. The optimal placements of electrodes or "trigger points" may correspond with acupuncture analgesia points. TENS is sometimes referred to as acupuncture-like when using a low frequency stimulus. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is

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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] Transurethral: Performed through the urethra. [EU] Transurethral Resection of Prostate: Resection of the prostate using a cystoscope passed through the urethra. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tricyclic: Containing three fused rings or closed chains in the molecular structure. [EU] Trigger zone: Dolorogenic zone (= producing or causing pain). [EU] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Tuberculosis: Any of the infectious diseases of man and other animals caused by species of Mycobacterium. [NIH] Tumour: 1. Swelling, one of the cardinal signs of inflammations; morbid enlargement. 2. A new growth of tissue in which the multiplication of cells is uncontrolled and progressive; called also neoplasm. [EU] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ulcer: A localized necrotic lesion of the skin or a mucous surface. [NIH] Ulceration: 1. The formation or development of an ulcer. 2. An ulcer. [EU] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uraemia: 1. An excess in the blood of urea, creatinine, and other nitrogenous end products of protein and amino acids metabolism; more correctly referred to as azotemia. 2. In current usage the entire constellation of signs and symptoms of chronic renal failure, including nausea, vomiting anorexia, a metallic taste in the mouth, a uraemic odour of the breath, pruritus, uraemic frost on the skin, neuromuscular disorders, pain and twitching in the muscles, hypertension, edema, mental confusion, and acid-base and electrolyte imbalances. [EU]

Ureter: One of a pair of thick-walled tubes that transports urine from the kidney pelvis to the bladder. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Urge urinary incontinence: Urinary leakage when the bladder contracts unexpectedly by itself. [NIH] Uridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety. [NIH] Uridine Diphosphate Glucuronic Acid: A nucleoside diphosphate sugar which serves as a source of glucuronic acid for polysaccharide biosynthesis. It may also be epimerized to UDP iduronic acid, which donates iduronic acid to polysaccharides. In animals, UDP glucuronic acid is used for formation of many glucosiduronides with various aglycones. [NIH]

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Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary urgency: Inability to delay urination. [NIH] Urine: Fluid containing water and waste products. Urine is made by the kidneys, stored in the bladder, and leaves the body through the urethra. [NIH] Urticaria: A vascular reaction of the skin characterized by erythema and wheal formation due to localized increase of vascular permeability. The causative mechanism may be allergy, infection, or stress. [NIH] 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] Vaccine: A substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms, such as bacteria or viruses. [NIH] Vagina: The muscular canal extending from the uterus to the exterior of the body. Also called the birth canal. [NIH] Vaginal: Of or having to do with the vagina, the birth canal. [NIH] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasculitis: Inflammation of a blood vessel. [NIH] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Viscera: Any of the large interior organs in any one of the three great cavities of the body, especially in the abdomen. [NIH] Visceral: , from viscus a viscus) pertaining to a viscus. [EU] Visual field: The entire area that can be seen when the eye is forward, including peripheral vision. [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

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together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Volition: Voluntary activity without external compulsion. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [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] Xenograft: The cells of one species transplanted to another species. [NIH]

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INDEX 5 5-Hydroxytryptophan, 64, 129 A Abdominal, 7, 16, 17, 20, 30, 37, 41, 46, 54, 56, 57, 129, 136, 139, 154, 161, 162, 171 Abdominal Pain, 129, 154 Aberrant, 129, 139 Acetaminophen, 4, 5, 9, 14, 30, 44, 46, 47, 52, 57, 58, 68, 69, 89, 90, 129 Acupuncture Analgesia, 129, 172 Acupuncture Points, 62, 129 Acute renal, 19, 54, 129 Adjustment, 87, 129 Adjuvant, 4, 37, 82, 129, 148 Adrenal Cortex, 129, 141 Adrenal Medulla, 57, 129, 137, 146, 159 Adrenergic, 129, 130, 131, 132, 144, 146, 171 Adverse Effect, 86, 87, 99, 129, 167, 169 Aerosol, 89, 90, 129 Afferent, 85, 129, 160 Affinity, 10, 68, 72, 81, 87, 91, 92, 129, 130, 133, 143, 155, 169 Age of Onset, 130, 173 Agonist, 32, 69, 93, 94, 130, 136, 144, 158 Agoraphobia, 130, 151, 162 Alfentanil, 55, 130 Algorithms, 130, 135 Alimentary, 130, 162 Alkaline, 87, 130, 136, 161 Alkaloid, 130, 136, 157, 167 Allergen, 130, 168 Allylamine, 130 Alpha-1, 130 Alternative medicine, 105, 130 Amine, 69, 80, 130, 150 Amitriptyline, 3, 5, 9, 130 Ammonia, 130 Amphetamine, 6, 131, 143 Anaesthetic, 15, 131 Analog, 73, 131, 143 Anatomical, 131, 133, 135, 141, 152 Androgens, 129, 131, 141 Anesthetics, 118, 131, 146, 149 Angina, 68, 131 Angina Pectoris, 68, 131 Animal model, 55, 92, 131 Antiallergic, 131, 142

Anti-Anxiety Agents, 131, 165 Antibacterial, 131, 170 Antibiotic, 131, 165, 170 Antibiotic Prophylaxis, 131, 165 Antibody, 130, 132, 139, 149, 150, 152, 155, 168, 170 Anticholinergic, 130, 132 Anticoagulant, 132, 163, 175 Anticonvulsant, 5, 58, 85, 132, 136, 156 Antidepressant, 28, 53, 129, 130, 132, 139, 148, 151 Antiemetic, 75, 132, 156 Antiepileptic, 129, 132 Antigen, 130, 132, 140, 150, 151, 152, 155, 168 Antihypertensive, 132, 167 Anti-Inflammatory Agents, 132, 133, 137, 142, 154 Antineoplastic, 132, 142 Antineoplastic Agents, 132 Antioxidant, 5, 132 Antipsychotic, 132, 159, 167 Antipyretic, 129, 133, 143, 148, 154 Antispasmodic, 133, 149, 160 Antitussive, 56, 133, 143, 160, 165 Anus, 133, 136, 162, 166 Anxiety, 31, 74, 99, 131, 133, 161, 162 Anxiolytic, 133, 160 Aqueous, 71, 80, 82, 88, 89, 133, 134, 138, 154 Aqueous fluid, 80, 133 Aromatic, 71, 81, 88, 133 Arrhythmia, 68, 133, 174 Arteries, 133, 135, 141, 156, 158 Arterioles, 133, 135, 136, 158 Arthroscopy, 33, 45, 133 Articular, 133, 161 Aspartate, 73, 85, 133, 143, 154 Aspirin, 5, 45, 57, 69, 118, 133 Assay, 12, 18, 24, 133 Asthenia, 87, 133 Astrocytes, 133, 157 Asymptomatic, 133, 161 Atrial, 133, 175 Atrial Fibrillation, 133, 175 Atrium, 133, 134 Attenuated, 6, 133 Atypical, 35, 133, 159

178 Tramadol

Auditory, 20, 24, 133 Aura, 75, 134 Auricular, 62, 134 Autodigestion, 134, 161 Autonomic, 5, 132, 134, 159, 163, 164, 168, 171 Autonomic Neuropathy, 5, 134 Axilla, 134, 136 Axillary, 44, 134 Axonal, 134, 164 Axons, 134, 159, 160, 163 B Back Pain, 4, 15, 53, 104, 105, 134 Bacteria, 131, 132, 134, 135, 140, 145, 147, 156, 170, 174 Bactericidal, 134, 146 Base, 77, 80, 81, 83, 85, 134, 143, 146, 154, 173 Basophil, 134, 150 Benign, 84, 101, 134, 149, 159 Benzene, 134 Benzodiazepines, 118, 134 Benzoic Acid, 96, 134 Bewilderment, 134, 140 Bile, 19, 134, 135, 146, 148, 149, 155, 170 Bile Acids, 134, 170 Bile Acids and Salts, 134 Bile Ducts, 135 Biliary, 31, 135, 161 Biliary Tract, 135, 161 Bilirubin, 135, 149 Binding Sites, 57, 135 Bioavailability, 13, 33, 34, 56, 135 Biochemical, 55, 56, 135, 161, 168 Biological Transport, 135, 143 Biotechnology, 7, 105, 113, 135 Biotransformation, 16, 135 Bladder, 84, 101, 118, 134, 135, 142, 152, 153, 155, 159, 165, 171, 173, 174 Bloating, 135, 154 Blood Coagulation, 135, 136 Blood Platelets, 135, 168 Blood pressure, 68, 132, 135, 137, 138, 149, 151, 157, 169 Blood vessel, 135, 136, 137, 138, 145, 162, 169, 171, 172, 174 Body Fluids, 135, 144, 169 Body Regions, 135, 139 Bowel, 135, 136, 153, 154, 171 Bowel Movement, 136, 171 Brachial, 44, 136 Brachial Plexus, 44, 136

Branch, 125, 136, 162, 170, 172 Breakdown, 82, 136, 143, 148, 160 Breast reconstruction, 14, 53, 136 Bronchi, 136, 146 Bronchial, 73, 92, 136, 150 Buccal, 136, 155 Bupivacaine, 8, 13, 14, 33, 136, 154 Buprenorphine, 6, 19, 31, 56, 136 Butorphanol, 6, 55, 136 C Caesarean section, 38, 41, 136 Calcium, 4, 68, 78, 136, 139, 174 Calcium channel blocker, 4, 136, 174 Calcium Channel Blockers, 4, 136 Capillary, 10, 12, 18, 22, 40, 136, 174 Capsaicin, 4, 5, 136 Capsules, 8, 13, 33, 34, 47, 56, 58, 70, 85, 88, 100, 136, 144, 145, 148 Carbamazepine, 3, 136 Carbohydrate, 137, 141, 149, 164 Carbon Dioxide, 26, 137, 142, 147, 167 Carcinogen, 81, 137 Cardiac, 130, 133, 137, 146, 154, 158, 170 Cardiovascular, 5, 30, 68, 131, 134, 137, 168 Cardiovascular disease, 5, 68, 137 Cardiovascular System, 134, 137 Carotene, 137, 167 Case report, 23, 137, 139 Catecholamine, 20, 137, 144 Catheterization, 137, 153 Caudal, 8, 13, 14, 35, 53, 137, 164 Celecoxib, 30, 137 Cell membrane, 135, 136, 137, 146 Cell Respiration, 137, 167 Cellobiose, 137, 138 Cellulose, 78, 137, 138, 156, 164 Central Nervous System, 85, 94, 131, 134, 138, 143, 148, 149, 150, 156, 157, 160, 162, 168 Central Nervous System Infections, 138, 150 Centrifugation, 138, 156 Cerebral, 39, 138, 141, 146, 166, 170 Cerebrovascular, 62, 136, 137, 138 Cerebrum, 138 Cervical, 62, 136, 138 Cervix, 138 Character, 131, 138, 142 Chemoreceptor, 132, 138, 145 Cholesterol, 134, 135, 138, 141, 170 Cholinergic, 130, 132, 138

Index 179

Ciliary, 133, 138 Ciliary processes, 133, 138 CIS, 25, 73, 80, 81, 83, 97, 138, 167 Cisplatin, 138, 160 Citalopram, 23, 139 Clinical study, 139, 141 Clinical trial, 6, 47, 58, 113, 139, 141, 144, 157, 162, 166 Cloning, 135, 139 Coagulation, 135, 139, 150, 175 Codeine, 8, 11, 15, 32, 40, 45, 46, 47, 52, 53, 56, 57, 58, 69, 73, 85, 94, 139, 143, 151, 160, 161 Cognition, 139, 159 Cognitive Therapy, 119, 139 Colic, 19, 27, 31, 54, 139 Colitis, 139, 154 Collapse, 136, 139 Colloidal, 82, 139, 145 Colorectal, 53, 139 Complement, 139, 140, 168 Complementary and alternative medicine, 61, 64, 140 Complementary medicine, 61, 140 Complete remission, 140, 167 Compress, 140, 172 Compulsion, 84, 140, 175 Computational Biology, 113, 140 Concentric, 57, 140 Concomitant, 4, 140 Cone, 140, 171 Confusion, 97, 140, 143, 159, 173 Conjugated, 134, 135, 140, 142 Conjugation, 135, 140 Connective Tissue, 141, 148, 149, 155, 163, 167 Consciousness, 130, 131, 141, 144 Constipation, 4, 68, 69, 72, 73, 81, 87, 94, 132, 141, 154, 160 Constriction, 141, 174 Constriction, Pathologic, 141, 174 Contraindications, ii, 72, 92, 141 Controlled clinical trial, 10, 45, 141 Controlled study, 36, 44, 45, 141 Convulsions, 132, 141 Convulsive, 141, 145 Cornea, 133, 141 Coronary, 131, 137, 141, 156, 158 Coronary Circulation, 131, 141 Coronary heart disease, 137, 141 Coronary Thrombosis, 141, 156, 158 Cortical, 141, 146, 168

Corticosteroid, 5, 141 Coumarin, 142 Cranial, 142, 149, 160, 163 Craniocerebral Trauma, 142, 150 Curare, 142, 158 Curative, 142, 172 Curettage, 32, 142 Curette, 142 Cutaneous, 142, 155 Cystitis, 118, 142 Cystoscope, 142, 173 Cytochrome, 25, 142 Cytotoxic, 136, 142, 160 Cytotoxic chemotherapy, 142, 160 D Databases, Bibliographic, 113, 142 Decarboxylation, 142, 150 Degenerative, 142, 161 Demethylation, 35, 142 Dendrites, 143, 159 Density, 138, 143, 164 Desipramine, 3, 57, 143 Detoxification, 29, 143, 149 Deuterium, 143, 151 Dextroamphetamine, 131, 143, 156 Dextromethorphan, 16, 73, 143 Dextrorphan, 73, 143 Diabetes Mellitus, 86, 143, 149 Diagnostic procedure, 67, 105, 143 Dialyzer, 143, 150 Diarrhea, 76, 87, 101, 143, 154, 163 Diclofenac, 36, 74, 75, 91, 95, 104, 143 Diclofenac Sodium, 143 Diffusion, 82, 135, 143 Digestion, 130, 134, 135, 143, 144, 153, 155, 170 Digestive tract, 134, 143 Direct, iii, 18, 73, 74, 92, 107, 139, 143, 144, 166 Disinfectant, 143, 146 Disorientation, 140, 143 Dissociation, 129, 144, 153 Distal, 86, 134, 144, 164, 165 Distention, 53, 144 Dizziness, 25, 55, 73, 81, 86, 87, 144, 162 Dopamine, 4, 131, 132, 143, 144, 156, 157 Dosage Forms, 76, 82, 85, 91, 98, 144 Double-blinded, 10, 41, 144 Drug Interactions, 108, 144 Drug Tolerance, 144, 172 Duct, 19, 137, 144 Duodenum, 134, 144, 148, 170

180 Tramadol

Dyes, 144, 159, 171 Dyskinesia, 132, 139, 144 Dysmenorrhea, 144, 163 Dyspepsia, 87, 144 Dysphagia, 72, 92, 145 E Efficacy, 5, 8, 9, 10, 11, 12, 14, 15, 21, 22, 25, 32, 35, 36, 37, 41, 44, 45, 52, 53, 54, 57, 76, 145 Ejaculation, 93, 145, 168 Elective, 41, 145 Electrolyte, 141, 145, 157, 169, 173 Electrons, 132, 134, 145, 153, 161, 166 Electrophoresis, 10, 12, 18, 22, 40, 145 Electroplating, 145, 171 Electroshock, 58, 145 Emboli, 145, 175 Embolism, 145, 166, 175 Embolization, 145, 175 Embryo, 145, 152 Emesis, 29, 72, 92, 145 Emetics, 81, 145 Emollient, 145, 149, 160 Encapsulated, 83, 145 Endometrial, 145 Endometriosis, 62, 145 Endometrium, 145 Enhancer, 73, 85, 145 Enteric-coated, 82, 145 Enterohepatic, 73, 92, 146, 171 Enterohepatic Circulation, 146, 171 Environmental Health, 57, 112, 114, 146 Enzymatic, 136, 137, 140, 146, 150, 167 Enzyme, 146, 155, 157, 174 Epidural, 7, 14, 22, 23, 27, 33, 35, 37, 38, 41, 45, 52, 57, 146 Epinephrine, 91, 129, 144, 146, 159, 173 Erectile, 5, 146, 162 Erection, 146 Erythema, 146, 174 Erythrocytes, 146, 168 Esophagus, 143, 146, 166, 170 Ethanol, 34, 77, 139, 146 Ether, 80, 146 Euphoria, 81, 146 Evacuation, 141, 146, 148, 154 Evoke, 146, 170 Excipients, 98, 146 Excitatory, 86, 93, 94, 146, 149 Exocytosis, 146, 150 Exogenous, 135, 146, 149, 173 Expiration, 147, 167

Extracellular, 133, 141, 147, 169 Extracorporeal, 37, 147 Extraction, 13, 18, 29, 45, 49, 57, 147 Extrapyramidal, 132, 144, 147 Extremity, 136, 147 F Fallopian Tubes, 147, 151 Family Planning, 113, 147 Fat, 135, 137, 141, 145, 147, 149, 155, 167 Fatigue, 118, 147, 150, 162 Fatty acids, 87, 147 Feces, 141, 147, 171 Fenfluramine, 55, 147 Fentanyl, 6, 37, 41, 42, 45, 130, 147 Fertilizers, 147, 159, 171 Filtration, 77, 147 Fixation, 147, 168 Flame Ionization, 18, 147 Flatus, 148 Fluorescence, 12, 18, 148 Fluoxetine, 3, 29, 39, 148 Flurbiprofen, 23, 148 Foot Care, 5, 148 Foot Ulcer, 5, 148 Forearm, 135, 148 Fungi, 140, 148, 156 Fungistatic, 134, 148 G Gallbladder, 129, 135, 148, 155 Ganglia, 132, 148, 159, 163, 171 Gas, 18, 37, 130, 137, 143, 148, 151, 154, 159, 171 Gastric, 8, 70, 83, 134, 144, 148, 150, 151 Gastric Emptying, 8, 148 Gastrointestinal tract, 68, 73, 80, 82, 92, 145, 146, 148, 149, 168 Gelatin, 148, 149, 171 Gene, 36, 135, 148 Genital, 134, 148 Genotype, 17, 25, 36, 148 Gland, 129, 149, 155, 161, 164, 165, 168, 170 Glucocorticoids, 129, 141, 149 Glucose, 56, 137, 138, 143, 149, 153 Glucose Intolerance, 143, 149 Glucuronic Acid, 149, 173 Glucuronides, 18, 149 Glutamate, 143, 149 Glycerol, 87, 149 Glycine, 134, 135, 149 Glycopyrrolate, 5, 149 Governing Board, 149, 165

Index 181

Groin, 149, 152 Growth, 131, 147, 148, 149, 155, 159, 164, 173 Gynaecological, 11, 149 H Haematemesis, 145, 149 Half-Life, 99, 149, 163 Haptens, 130, 149 Headache, 42, 86, 87, 149, 150 Headache Disorders, 150 Heart attack, 137, 150 Heart failure, 150, 155 Heme, 135, 142, 150 Hemodialysis, 34, 143, 150 Hemodynamics, 20, 150 Hemorrhage, 142, 149, 150, 171 Hemostasis, 150, 168 Hepatic, 23, 150, 157 Hereditary, 86, 150 Heredity, 148, 150 Hernia, 150 Herniorrhaphy, 13, 14, 53, 150 Heterogeneity, 130, 150 Histamine, 12, 132, 150 Histamine Release, 12, 150 Histidine, 150 Homologous, 150, 168 Hormonal, 142, 150 Hormone, 141, 146, 150, 153, 167 Hydrochloric Acid, 81, 151 Hydrocodone, 6, 9, 46, 47, 52, 57, 58, 69, 73, 151 Hydrogel, 70, 90, 151 Hydrogen, 81, 99, 130, 134, 137, 143, 147, 151, 157, 161, 165 Hydrolysis, 135, 137, 138, 151 Hydrophilic, 80, 82, 87, 151 Hydrophobic, 87, 97, 151 Hyperalgesia, 86, 87, 93, 94, 151 Hyperplasia, 84, 101, 151 Hypersensitivity, 75, 130, 151, 167, 168 Hypertension, 136, 137, 150, 151, 155, 173 Hypertrophy, 151 Hypospadias, 13, 14, 151 Hypoxia, 26, 151 Hysterectomy, 21, 32, 46, 57, 151 Hysterosalpingography, 32, 151 I Ibuprofen, 3, 151, 154 Id, 59, 63, 119, 124, 126, 151 Idiopathic, 25, 151 Imipramine, 3, 5, 8, 151

Immune response, 42, 57, 129, 132, 142, 149, 152, 168, 171, 174 Immune system, 152, 174 Immunization, 152, 168 Immunology, 129, 152 Impairment, 7, 134, 144, 152 Impotence, 146, 152 In situ, 82, 99, 152 In vitro, 25, 55, 152 In vivo, 55, 99, 152, 171 Incision, 136, 152, 153 Incontinence, 76, 79, 83, 84, 96, 100, 101, 152, 171 Indicative, 152, 162, 174 Induction, 38, 55, 131, 132, 145, 152, 154 Infarction, 152 Infection, 138, 152, 154, 155, 159, 167, 171, 174 Inflammation, 84, 132, 133, 138, 139, 142, 148, 152, 161, 167, 174 Infusion, 13, 17, 27, 41, 45, 57, 152 Ingestion, 23, 82, 152, 156, 164 Inguinal, 14, 53, 152 Inhalation, 72, 89, 90, 92, 129, 152, 164 Innervation, 136, 153 Inorganic, 96, 138, 153, 157 Inotropic, 144, 153 Inpatients, 17, 153 Insulin, 5, 153, 173 Insulin-dependent diabetes mellitus, 153 Intermittent, 27, 153 Interstitial, 118, 153 Intervertebral, 21, 153, 155 Intervertebral Disk Displacement, 153, 155 Intestinal, 70, 137, 153 Intestine, 82, 135, 144, 146, 151, 153, 154 Intoxication, 39, 153, 175 Intracellular, 73, 85, 136, 152, 153, 166 Intramuscular, 13, 73, 92, 153, 162 Intrathecal, 19, 153 Intravenous, 8, 10, 11, 14, 17, 23, 27, 37, 43, 49, 53, 55, 152, 153, 162 Intravesical, 79, 153 Intrinsic, 130, 153 Intubation, 42, 137, 153 Invasive, 73, 92, 153 Involuntary, 84, 101, 153, 158, 166, 169, 171 Ionization, 40, 153 Ions, 134, 144, 145, 151, 153, 157 Irritable Bowel Syndrome, 100, 154

182 Tramadol

J Joint, 4, 133, 154, 161, 170, 172 K Kb, 112, 154 Ketamine, 7, 73, 154 Ketoprofen, 10, 154 Ketorolac, 17, 28, 41, 154 Kidney Pelvis, 154, 173 L Large Intestine, 143, 153, 154, 166 Laryngeal, 8, 52, 154 Larynx, 154 Laxative, 154, 156 Lens, 133, 154, 167 Leprosy, 148, 154 Lesion, 148, 154, 172, 173 Levo, 36, 154, 165 Levorphanol, 73, 143, 154 Library Services, 124, 154 Lidocaine, 26, 29, 41, 42, 43, 154, 156 Ligament, 154, 165, 170 Lipid, 149, 153, 155 Lipophilic, 71, 88, 155 Lisinopril, 104, 155 Lithotripsy, 37, 155 Liver, 24, 25, 73, 81, 92, 129, 134, 135, 142, 146, 147, 148, 149, 150, 155, 157 Localized, 4, 145, 147, 152, 155, 157, 164, 168, 173, 174 Low Back Pain, 4, 22, 61, 62, 63, 155 Lubricants, 78, 155 Lumbar, 86, 134, 153, 155 Lupus, 118, 155 Lymph, 134, 138, 155 Lymph node, 134, 138, 155 Lysine, 33, 155 M Malignant, 6, 17, 40, 118, 132, 155, 159 Mania, 29, 48, 155 Mastectomy, 136, 155 Mediate, 94, 144, 155 Mediator, 155, 168 Medical Staff, 144, 155 Medicament, 80, 83, 90, 96, 155, 171 MEDLINE, 113, 155 Medullary, 143, 155 Membrane, 70, 71, 89, 133, 137, 140, 143, 145, 146, 154, 155, 157, 158, 161, 167 Meninges, 138, 142, 156 Meperidine, 6, 9, 20, 27, 38, 47, 156 Mesenteric, 156, 164 Meta-Analysis, 14, 40, 156

Metabolite, 16, 18, 22, 24, 34, 36, 41, 72, 81, 91, 92, 135, 143, 156, 159 Metastasis, 156 Metastatic, 57, 156 Methacrylate, 82, 156 Methanol, 80, 156 Methylcellulose, 82, 156 Methylphenidate, 6, 156 Metoclopramide, 29, 156 Mexiletine, 4, 156 MI, 127, 156 Microbe, 156, 172 Microbiological, 98, 156 Microbiology, 133, 156 Microorganism, 156, 174 Microsomal, 24, 156 Micturition, 84, 156 Mineralocorticoids, 129, 141, 157 Mitochondrial Swelling, 157, 158 Modeling, 56, 157 Modification, 119, 157 Molecular, 80, 81, 113, 115, 135, 140, 157, 166, 173 Molecular Structure, 157, 173 Molecule, 132, 134, 135, 140, 144, 151, 157, 161, 166 Monitor, 9, 157, 160 Monoamine, 32, 99, 131, 143, 157, 169 Monoamine Oxidase, 131, 143, 157, 169 Monotherapy, 48, 157 Motility, 20, 54, 157, 168 Motion Sickness, 157, 158 Motor nerve, 157 Mucilaginous, 80, 157 Mucosa, 155, 157, 158 Mucus, 157 Multicenter study, 21, 157 Muscle relaxant, 5, 131, 157 Muscle tension, 84, 157, 158 Musculature, 84, 101, 158, 170 Musculoskeletal System, 158, 160 Myocardial infarction, 141, 156, 158, 175 Myocardial Ischemia, 131, 158 Myocardium, 131, 156, 158 N Nalbuphine, 6, 11, 42, 52, 158 Naloxone, 15, 20, 53, 92, 158 Naltrexone, 86, 93, 158 Narcolepsy, 143, 156, 158 Narcosis, 158 Narcotic, 12, 79, 85, 100, 136, 147, 151, 154, 156, 157, 158, 161, 165, 172

Index 183

Nasal Cavity, 158 Nasal Mucosa, 73, 92, 158 Nausea, 25, 27, 33, 40, 42, 55, 72, 73, 75, 81, 86, 87, 92, 95, 132, 144, 158, 160, 162, 173 NCI, 1, 111, 138, 158 Necrosis, 81, 152, 156, 158 Need, 3, 73, 75, 76, 87, 96, 100, 101, 120, 158, 172 Neoplasm, 159, 173 Nerve Fibers, 129, 136, 159, 160 Nervous System, 37, 85, 94, 129, 131, 138, 155, 159, 163, 171, 172 Neural, 129, 143, 157, 159 Neurogenic, 84, 159 Neuroleptic, 132, 159, 160 Neuromuscular, 159, 168, 173 Neuronal, 87, 139, 158, 159, 163 Neurons, 85, 86, 94, 143, 146, 148, 157, 159, 171 Neuropathy, 3, 5, 19, 29, 44, 105, 134, 159 Neurosurgery, 37, 159 Neurotoxicity, 143, 159 Neurotransmitters, 130, 159 Nitric acid, 96, 159 Nitrogen, 18, 99, 130, 131, 147, 159, 173 Nonmalignant, 118, 159 Norepinephrine, 4, 57, 81, 129, 130, 143, 144, 159, 167 Nortriptyline, 3, 159 Nuclear, 140, 145, 158, 160 Nucleic acid, 159, 160 O Obsession, 140, 160 Obsessional, 74, 160 Obstipation, 68, 100, 160 Odour, 133, 160, 173 Ointments, 144, 160 Ondansetron, 12, 31, 42, 43, 160 On-line, 40, 127, 160 Ophthalmic, 12, 160 Opium, 157, 160 Opsin, 160, 167 Optic Nerve, 160, 167, 168 Optic Nerve Diseases, 160, 168 Orgasm, 145, 160 Orphenadrine, 89, 90, 160 Orthopaedic, 16, 28, 54, 160 Osmosis, 161 Osmotic, 70, 157, 161 Osteoarthritis, 4, 8, 21, 35, 44, 47, 48, 58, 62, 63, 64, 81, 118, 154, 161, 163 Outpatient, 6, 32, 37, 47, 161

Overdose, 23, 39, 41, 43, 161 Oxidation, 132, 135, 142, 161 Oxidation-Reduction, 135, 161 Oxides, 87, 161 Oxycodone, 6, 15, 21, 54, 69, 73, 161 Oxygen Consumption, 161, 167 P Paediatric, 8, 12, 14, 161 Palliative, 43, 161, 172 Pallor, 75, 161 Pancreas, 129, 153, 161, 170 Pancreatic, 118, 161 Pancreatitis, 20, 54, 161 Panic, 151, 161, 162 Panic Disorder, 151, 162 Paramedic, 23, 162 Parenteral, 32, 73, 91, 92, 162 Parkinsonism, 132, 160, 162 Paroxetine, 3, 39, 162 Paroxysmal, 131, 134, 150, 162 Partial remission, 162, 167 Particle, 87, 162 Pathologic, 141, 151, 162, 167 Patient Compliance, 90, 162 Patient Education, 118, 122, 124, 127, 162 Patient Selection, 4, 162 Pelvic, 62, 145, 162, 165 Pemoline, 6, 162 Penis, 145, 151, 162 Percutaneous, 155, 162 Perfusion, 151, 162 Perineum, 151, 162 Periodontal disease, 148, 163 Perioperative, 33, 48, 56, 163 Peripheral Nerves, 86, 154, 163, 164, 170 Peripheral Nervous System, 163, 171 Pharmaceutical Preparations, 84, 100, 101, 138, 146, 148, 163 Pharmaceutical Solutions, 144, 163 Pharmacodynamic, 7, 23, 56, 163 Pharmacokinetic, 18, 22, 33, 34, 56, 57, 65, 76, 163 Pharmacologic, 4, 5, 131, 149, 163, 172 Phenprocoumon, 26, 28, 163 Phenyl, 72, 94, 100, 156, 163 Phobias, 160, 163 Phosphorus, 136, 163 Physical Therapy, 119, 163 Physiologic, 74, 130, 149, 163, 166, 167, 169 Pigments, 137, 163, 167 Pilot study, 31, 34, 61, 62, 163 Piroxicam, 44, 163

184 Tramadol

Pituitary Gland, 141, 164 Plants, 130, 137, 149, 159, 163, 164 Plasma, 13, 18, 20, 22, 24, 29, 39, 49, 56, 91, 137, 148, 149, 150, 157, 164, 168 Plexus, 136, 164 Podiatry, 5, 164 Poisoning, 153, 158, 164 Polyethylene, 82, 164 Polymers, 87, 164, 165 Polyneuropathies, 86, 164 Polysaccharide, 132, 138, 164, 173 Portal Vein, 73, 92, 164 Posterior, 134, 161, 164 Postoperative, 6, 7, 8, 11, 12, 13, 14, 19, 21, 22, 23, 25, 26, 27, 28, 31, 32, 33, 34, 36, 37, 38, 40, 41, 42, 44, 46, 52, 53, 55, 57, 63, 81, 156, 163, 164 Postoperative Period, 26, 44, 164 Potentiates, 143, 164 Potentiating, 85, 130, 164 Potentiation, 73, 164 Practice Guidelines, 114, 164 Precipitation, 81, 165 Precursor, 129, 144, 146, 159, 165, 173 Premedication, 33, 165 Prevalence, 74, 165 Procaine, 154, 165 Progression, 131, 165 Progressive, 144, 149, 158, 161, 165, 173 Projection, 159, 160, 165 Prophylaxis, 165, 175 Propofol, 38, 42, 43, 165 Propoxyphene, 6, 165 Prostate, 84, 101, 165, 173 Protective Agents, 136, 165 Protein S, 135, 165 Proteins, 132, 137, 139, 157, 159, 164, 165, 166, 169 Protons, 151, 165, 166 Protozoa, 140, 156, 165 Proximal, 144, 158, 164, 165 Pruritus, 73, 76, 101, 165, 173 Psychic, 166, 168 Psychology, 140, 144, 166 Psychomotor, 6, 136, 159, 166 Psychotherapy, 139, 166 Psychotomimetic, 131, 143, 166 Public Policy, 113, 166 Pulmonary, 135, 166, 175 Pulmonary Artery, 135, 166 Pulmonary Embolism, 166, 175 Pulse, 157, 166

R Race, 10, 77, 81, 166 Radiation, 131, 148, 166 Radioactive, 149, 151, 153, 160, 166 Reagent, 77, 83, 151, 166 Receptor, 10, 31, 56, 72, 73, 81, 85, 86, 92, 93, 94, 99, 132, 138, 140, 143, 144, 160, 166, 168, 169 Receptors, Serotonin, 166, 168 Rectal, 46, 58, 73, 92, 166 Rectum, 133, 136, 139, 143, 148, 152, 154, 165, 166, 171 Refer, 1, 97, 136, 139, 144, 147, 148, 159, 166 Reflex, 20, 84, 101, 166 Reflux, 80, 166 Refraction, 166, 170 Refractory, 15, 31, 48, 53, 166 Regimen, 84, 85, 145, 162, 166 Relaxant, 167 Remission, 37, 167 Reserpine, 55, 167 Resolving, 77, 97, 167 Resorption, 148, 167 Respiration, 20, 58, 137, 138, 142, 157, 167 Restless legs, 48, 167 Restoration, 163, 167 Retina, 154, 160, 167, 168 Retinal, 75, 140, 160, 167, 168 Retinol, 167 Rheumatic Diseases, 4, 167 Rheumatism, 44, 151, 167 Rheumatoid, 154, 163, 167 Rheumatoid arthritis, 154, 163, 167 Risk factor, 23, 168 Rods, 167, 168 S Salicylate, 33, 168 Salicylic, 96, 168 Salivation, 149, 168 Schizoid, 168, 175 Schizophrenia, 168, 175 Schizotypal Personality Disorder, 168, 175 Scotoma, 75, 168 Screening, 139, 168 Secretion, 142, 149, 150, 153, 157, 168 Sedative, 130, 139, 151, 168 Seizures, 25, 39, 43, 137, 162, 168 Semen, 145, 165, 168 Sensibility, 131, 151, 168 Sensitization, 36, 56, 168

Index 185

Serotonin, 3, 4, 28, 35, 39, 54, 81, 91, 129, 130, 132, 139, 143, 147, 148, 157, 160, 162, 166, 167, 168, 169, 173 Serotonin Syndrome, 35, 168 Sertraline, 35, 169 Serum, 18, 37, 39, 41, 139, 157, 169 Shivering, 9, 17, 30, 35, 46, 47, 169 Shock, 145, 155, 169, 173 Signs and Symptoms, 167, 169, 173 Silicon, 87, 169 Silicon Dioxide, 169 Skeletal, 73, 131, 142, 169 Skeleton, 154, 169 Smooth muscle, 130, 136, 150, 157, 169, 171 Sneezing, 169, 171 Sodium, 19, 78, 82, 118, 143, 157, 169 Solvent, 77, 78, 80, 81, 82, 134, 146, 149, 156, 161, 163, 169 Soma, 169 Somatic, 20, 54, 163, 169 Somnolence, 73, 81, 86, 87, 169 Spasm, 133, 141, 160, 169 Spastic, 154, 170 Spatial disorientation, 144, 170 Specialist, 52, 119, 170 Species, 136, 142, 146, 166, 170, 173, 174, 175 Specificity, 130, 170 Spectrum, 74, 170 Sphincter, 19, 84, 101, 154, 170, 171 Spinal cord, 53, 84, 101, 129, 133, 136, 138, 146, 153, 156, 159, 163, 166, 170, 171 Spinal Nerves, 163, 170 Splenic Vein, 164, 170 Sprains and Strains, 155, 170 Steady state, 34, 170 Sterilization, 7, 170 Steroid, 134, 149, 170 Stimulant, 131, 143, 150, 156, 162, 170 Stimulus, 6, 84, 153, 163, 166, 170, 172 Stomach, 129, 134, 143, 146, 148, 151, 158, 166, 170 Stool, 4, 152, 154, 171 Stress, 74, 79, 80, 84, 101, 137, 145, 154, 158, 167, 171, 174 Stress incontinence, 84, 101, 171 Stress urinary, 79, 171 Stroke, 61, 112, 137, 171 Stromal, 145, 171 Stupor, 158, 171 Subarachnoid, 149, 171

Subclinical, 152, 168, 171 Subcutaneous, 16, 54, 73, 92, 162, 171 Substance P, 71, 88, 156, 168, 171 Suction, 147, 171 Sulfuric acid, 96, 171 Sulindac, 3, 171 Supplementation, 41, 130, 171 Suppositories, 34, 46, 58, 70, 85, 88, 148, 171 Suppression, 68, 142, 171 Sympathetic Nervous System, 159, 171 Sympathomimetic, 131, 143, 144, 146, 159, 171 Symphysis, 165, 172 Symptomatic, 5, 131, 161, 172 Symptomatology, 39, 172 Synergistic, 69, 87, 172 Systemic, 4, 108, 135, 146, 150, 152, 172, 175 T Talcum, 82, 172 Tardive, 132, 139, 172 Therapeutics, 9, 12, 30, 40, 41, 47, 69, 73, 108, 157, 172 Thoracic, 134, 136, 172 Thorax, 155, 172 Thrombosis, 165, 171, 172 Tolerance, 53, 54, 68, 69, 72, 85, 86, 87, 93, 94, 95, 136, 149, 172 Tonic, 18, 62, 172 Topical, 4, 5, 146, 172 Tourniquet, 41, 172 Toxic, iv, 86, 134, 141, 142, 146, 156, 159, 172 Toxicity, 69, 72, 94, 144, 172 Toxicology, 6, 9, 25, 37, 41, 42, 52, 69, 114, 172 Trace element, 169, 172 Transcutaneous, 4, 119, 172 Transcutaneous Electric Nerve Stimulation, 119, 172 Transfection, 135, 172 Transmitter, 133, 144, 155, 159, 173 Transurethral, 19, 173 Transurethral Resection of Prostate, 19, 173 Trauma, 86, 158, 161, 173 Tricyclic, 3, 5, 43, 118, 130, 139, 143, 151, 173 Trigger zone, 132, 145, 173 Tryptophan, 168, 173 Tuberculosis, 84, 155, 168, 173

186 Tramadol

Tumour, 31, 56, 173 Type 2 diabetes, 5, 173 Tyrosine, 144, 173 U Ulcer, 173 Ulceration, 85, 173 Unconscious, 131, 151, 173 Uraemia, 161, 173 Ureter, 84, 101, 154, 155, 173 Urethra, 84, 101, 151, 162, 165, 173, 174 Urge urinary incontinence, 79, 173 Uridine Diphosphate, 149, 173 Uridine Diphosphate Glucuronic Acid, 149, 173 Urinary, 76, 79, 83, 84, 96, 100, 101, 142, 152, 171, 173, 174 Urinary urgency, 83, 84, 100, 101, 174 Urine, 10, 12, 18, 40, 84, 101, 135, 149, 152, 156, 171, 173, 174 Urticaria, 14, 174 Uterus, 138, 145, 147, 151, 174 V Vaccine, 129, 174 Vagina, 138, 174 Vaginal, 73, 92, 174

Vascular, 68, 130, 136, 150, 152, 174 Vasculitis, 161, 174 Vasoconstriction, 46, 146, 174 Vasodilator, 144, 150, 174 Vein, 153, 160, 164, 170, 174 Venous, 165, 174, 175 Venous Thrombosis, 174, 175 Venules, 135, 136, 174 Verapamil, 76, 174 Vertebrae, 153, 170, 174 Vesicular, 156, 174 Veterinary Medicine, 55, 113, 174 Virulence, 133, 172, 174 Virus, 138, 145, 174 Viscera, 169, 174 Visceral, 20, 54, 58, 134, 174 Visual field, 168, 174 Vitro, 92, 97, 174 Vivo, 175 Volition, 153, 160, 175 W Warfarin, 36, 48, 58, 76, 175 Withdrawal, 10, 31, 35, 47, 49, 156, 175 X Xenograft, 131, 175

Index 187

188 Tramadol

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Capital Punishment: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

Malepattern Baldness: A Medical Dictionary, Bibliography, And Annotated Research Guide To Internet References

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