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

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

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OXYCODONE 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., 1960Oxycodone: 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: 0-597-84145-4 1. Oxycodone-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 Oxycodone. 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 OXYCODONE ............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Oxycodone..................................................................................... 4 E-Journals: PubMed Central ....................................................................................................... 10 The National Library of Medicine: PubMed ................................................................................ 10 CHAPTER 2. NUTRITION AND OXYCODONE ................................................................................... 31 Overview...................................................................................................................................... 31 Finding Nutrition Studies on Oxycodone ................................................................................... 31 Federal Resources on Nutrition ................................................................................................... 36 Additional Web Resources ........................................................................................................... 37 CHAPTER 3. ALTERNATIVE MEDICINE AND OXYCODONE ............................................................. 39 Overview...................................................................................................................................... 39 National Center for Complementary and Alternative Medicine.................................................. 39 Additional Web Resources ........................................................................................................... 40 General References ....................................................................................................................... 41 CHAPTER 4. PATENTS ON OXYCODONE.......................................................................................... 43 Overview...................................................................................................................................... 43 Patents on Oxycodone.................................................................................................................. 43 Patent Applications on Oxycodone.............................................................................................. 50 Keeping Current .......................................................................................................................... 56 CHAPTER 5. PERIODICALS AND NEWS ON OXYCODONE ............................................................... 57 Overview...................................................................................................................................... 57 News Services and Press Releases................................................................................................ 57 Academic Periodicals covering Oxycodone.................................................................................. 58 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 61 Overview...................................................................................................................................... 61 U.S. Pharmacopeia....................................................................................................................... 61 Commercial Databases ................................................................................................................. 62 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 67 Overview...................................................................................................................................... 67 NIH Guidelines............................................................................................................................ 67 NIH Databases............................................................................................................................. 69 Other Commercial Databases....................................................................................................... 71 APPENDIX B. PATIENT RESOURCES ................................................................................................. 73 Overview...................................................................................................................................... 73 Patient Guideline Sources............................................................................................................ 73 Finding Associations.................................................................................................................... 75 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 77 Overview...................................................................................................................................... 77 Preparation................................................................................................................................... 77 Finding a Local Medical Library.................................................................................................. 77 Medical Libraries in the U.S. and Canada ................................................................................... 77 ONLINE GLOSSARIES.................................................................................................................. 83 Online Dictionary Directories ..................................................................................................... 83 OXYCODONE DICTIONARY ...................................................................................................... 85 INDEX .............................................................................................................................................. 113

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

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

Around-the-Clock, Controlled-Release Oxycodone Therapy for Osteoarthritis-Related Pain Source: Archives of Internal Medicine. 160(6): 853-860. March 27, 2000. Summary: This journal article provides health professionals with information on a study that evaluated the effects of controlled-release oxycodone (OxyContin tablets) treatment on pain and function and its safety versus placebo and in long term use in patients who had moderate to severe osteoarthritis (OA). The study population consisted of 135 patients experiencing persistent OA related pain for at least 1 month who were randomized to double blind treatment with placebo or 10 milligrams or 20 milligrams of controlled-release oxycodone every 12 hours for 14 days. One hundred six patients enrolled in an open label, 6 month extension trial. Treatment for an additional 12 months was optional. Results indicate that the use of 20 milligrams of controlled-release

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oxycodone was superior to placebo in reducing pain intensity and the interference of pain with mood, sleep, and enjoyment of life. During long term treatment, the mean dose remained stable at approximately 40 milligrams per day after titration, and pain intensity was stable. Fifty-eight patients completed 6 months of treatment, 41 completed 12 months, and 15 completed 18 months. Common opioid side effects were reported, several of which decreased in duration as therapy continued. The article concludes that around the clock controlled-release oxycodone therapy seemed to be an effective and safe treatment modality for patients who had chronic, moderate to severe pain associated with OA. 34 references. (AA-M).

Federally Funded Research on Oxycodone The U.S. Government supports a variety of research studies relating to Oxycodone. These studies are tracked by the Office of Extramural Research at the National Institutes of Health.2 CRISP (Computerized Retrieval of Information on Scientific Projects) is a searchable database of federally funded biomedical research projects conducted at universities, hospitals, and other institutions. Search the CRISP Web site at http://crisp.cit.nih.gov/crisp/crisp_query.generate_screen. You will have the option to perform targeted searches by various criteria, including geography, date, and topics related to Oxycodone. 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 Oxycodone. The following is typical of the type of information found when searching the CRISP database for Oxycodone: •

Project Title: ANALGESIA OF SC-65872, OXYCODONE/ACETAMINOPHEN, OR IBUPR Principal Investigator & Institution: Brennan, Timothy J.; Associate Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2001 Summary: This study is designed to compare the analgesic efficacy and safety of orally administered SC-65872, a novel compound that exhibits potent anti-inflammatory and analgesic activity via selective inhibition of one form of the enzyme cyclooxygenase, to oxycodone/acetaminophen, ibuprofen and placebo in patients with moderate to severe pain after general surgery. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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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

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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Summary: Until recently, little attention had been paid to characterizing behavioral effects of opioids in normal volunteers (i.e., volunteers with no history of drug or alcohol dependence) using the rigorous testing methodologies that had been employed in the studies with abusers. For the past three years, we have employed an abuse liability/behavioral toxicology testing methodology to examine the effects of a number of different opioids that are typically given to patients for postoperative pain. This application will have four series of studies that are logical continuations of studies from the previous grant period. In the first series of studies, we will focus on opioids that are typically given to patients who are recovering from outpatient surgery. These patients might be at home or at work, engaging in different activities that may or may not be adversely affected by the opioids. It is vitally important to understand the behavioral toxicology of these opioids, yet rigorous toxicology studies (employing multiple measures of behavior and examining a range of doses that might be used by patients) have not been conducted to date. Therefore, we plan to continue our opioid characterization studies in normal volunteers, focusing on four oral drugs commonly used in outpatient settings: hydrocodone, oxycodone, propoxyphene, and tramadol. In the second series of studies, we will follow up on a study from the previous granting period in which some of morphine's subjective effects were attenuated by a painful stimulus. In four studies, we will use a cumulative dosing procedure recently developed in our laboratory to examine the degree to which a painful stimulus modulates the subjective and psychomotor effects of morphine, meperidine, butorphanol and nalbuphine. We will study different opioids at different doses and at different levels of painful stimulation in order to better understand how pain, which frequently accompanies opioid administration in patients, modulates behavioral effects of opioids. In the third series of studies, we will again follow up on a previous study from our laboratory in which we demonstrated that a painful stimulus modulated the reinforcing effects of an opioid, fentanyl. We propose to utilize a patient controlled analgesia (PCA) methodology to examine the degree to which four different opioids- morphine, meperidine, nalbuphine and butorphanol- maintain self-administration, and the degree to which self-administration is modulated by a painful stimulus. In the fourth series of studies, the effects of psychomotor stimulants alone and in combination with an opioid will be examined. Psychomotor stimulants are often given as adjuncts to opioids in patients suffering from chronic malignant pain to offset the sedating and impairing effects of high-dose opioid therapy. We will study buprenorphine in combination with three psychomotor stimulants- d-amphetamine, methylphenidate, and pemoline- to determine the relative pharmacodynamic profiles and which combination(s) produces the most analgesia with the least degree of troublesome side effects (including marked sedation and psychomotor/cognitive impairment). Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: CHANGES IN HOMICIDE AND DRUG OVERDOSE IN NEW YORK CITY Principal Investigator & Institution: Tardiff, Kenneth J.; Professor; Psychiatry; Weill Medical College of Cornell Univ New York, Ny 10021 Timing: Fiscal Year 2002; Project Start 30-SEP-1990; Project End 30-JUN-2007 Summary: (provided by applicant): We are applying for a continuation grant for the study of changes in homicide and accidental fatal drug overdoses. Continuing our long term collaboration with the New York City Medical Examiner, we will collect and analyze data from 2000 to 2006 on an estimated 30,000 fatal injuries, which added to our data base of 40,000 fatalities over 10 years, will allow us to analyze 70,000 fatalities over

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a 17 year period from 1990-2006. Our data set is unique in that it contains information on types of fatal injuries, time and place of injury and death, characteristics and residence of the victim, and toxicology results for a wide range of illicit drugs and alcohol. This will enable us to extend our surveillance of homicide and overdose mortality in NYC and to test etiologic hypotheses regarding these two causes of death. Our aims are: 1) To determine the incidence, temporal trends, and correlates of homicide, accidental drug overdoses and other fatal accidents with a focus on identifying the emerging role of newer drugs such as ecstasy and oxycodone. 2) To determine neighborhood-level determinants of homicide (e.g., drug use, policing, concentrated disadvantages) and to assess how they are related to changes in the frequency of homicide over timw and place. 3) To determine the association between individual drug use, age of decedents, neighborhood factors (e.g., economic disadvantage, level of illicit drug use), and the risk of becoming a homicide case using fatal accidents as controls. 4) To determine neighborhood-level determinants of drug overdose and to assess how these are related to changes in fatal drug overdose over time and place. There have been significant changes in the use of illicit drugs, the frequency of homicide and of fatal drug overdoses in NYC over the past decade. Although there are many theories as to why these changes have occurred, few scientific studies have been able to address the key hypotheses regarding these changes. Some of the questions that can be addressed in this proposal include: Have arrests for "quality of life" crimes restored public order and lowered the frequency of homicide ad changed drug-dealing? Has individual use of certain illicit drugs increased the risk for homicide and fatal drug overdose? We intend our findings to be helpful to public health and law enforcement practice. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISCRIMINATIVE STIMULUS EFFECTS OF OPIOID WITHDRAWAL Principal Investigator & Institution: France, Charles P.; Professor; Pharmacology; University of Texas Hlth Sci Ctr San Ant 7703 Floyd Curl Dr San Antonio, Tx 78229 Timing: Fiscal Year 2003; Project Start 01-MAY-1995; Project End 30-JUN-2008 Summary: (provided by applicant): Opioid abuse remains a significant public health problem despite continued research and the availability of new drugs for treatment. In addition to the ongoing problem of heroin abuse is a growing concern about the recreational use of potent, efficacious opioid analgesics such as oxycodone. This is a competing continuation of a grant that has developed novel drug discrimination procedures for studying opioid dependence and withdrawal; those procedures have been used in concert with other measures of opioid activity to examine a range of pharmacologic and behavioral parameters that contribute to the abuse and dependence liability of morphine and related opioids. Studies proposed in this renewal exploit these discrimination procedures to focus on the neuropharmacology of opioid dependence and withdrawal as well as the role of opioid withdrawal in drug taking. AIM I characterizes the neuropharmacology of opioid withdrawal in rhesus monkeys by examining monoaminergic drugs for their ability to modulate discriminative stimulus and other effects (directly observable and HPA activation) of opioid withdrawal in monkeys. These studies build upon published data from this laboratory showing that dopamine uptake blockers attenuate discriminative stimulus and not other indices of withdrawal. AIM II combines a well-established drug discrimination procedure with i.v. self administration in monkeys to examine the effects of withdrawal on self administration of cocaine and mu agonists that vary in efficacy. AIM III provides a comprehensive set of descriptive data from rhesus monkeys on the behavioral pharmacology of several prescription opioids that are believed to be increasingly

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abused, including oxycodone, oxymorphone, hydrocodone and hydromorphone. While it is assumed that these opioids have exclusively morphine-like actions, there are limited data available to support that view. The four opioids will be compared to morphine using measures of drug discrimination, antinociception, and respiration. Finally, studies under AIM IV investigate the relationship between opioid tolerance and dependence, on the one hand, and constitutive activity and inverse agonism at opioid receptors, on the other hand, using drug discrimination procedures in pigeons with varying degrees of morphine tolerance and dependence. These studies should provide insight to the lasting neurobiological changes that can occur as a consequence of chronic drug treatment. Collectively these studies will apply drug discrimination and other procedures to important question regarding opioid dependence, withdrawal and abuse and will provide information that will facilitate the development of new therapeutics for opioid abuse. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: DISTINCTION AMONG EIGHT OPIATE DRUGS IN URINE BY GAS CHROMATOGRAPHIC Principal Investigator & Institution: Nowatzke, William; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001 Summary: Opiates are commonly abused substances, and forensic urine drug-testing for them involves an immunoassay screen and gas chromatographic/mass spectrometric (GC/MS) confirmation. There are also medical reasons to test urine for opiates, and confirmation procedures other than GC/MS are often used for medical drug-testing which are more compatible with the demands of clinical services and which identify a wider range of opiates than those in standard forensic batteries. One such procedure involves thin-layer chromatographic (TLC) analysis of opiate derivatives and can distinguish eight clinically encountered opiates, including morphine, acetylmorphine, hydromorphone, oxymorphone, codeine, dihydrocodeine, hydrocodone, and oxycodone. Medical drug-testing results are sometimes challenged by patients, causing physicians to request additional confirmation of the identified opiates. To our knowledge, no previous report examines all opiates specified above in a single GC/MS pr ocedure, but we find that they can be distinguished by GC/MS analyses of trimethylsilyl (TMS) ether derivatives, the mass spectra of which contain prominent molecular ions. Inclusion of deuterium-labeled internal standards permits quantitation of each of the eight opiates in urine. The GC/MS assay is linear over a concentration range which spans the TLC cutoff level, and coefficients of variation of 10% or less at concentrations below the TLC cutoff are achieved by for all opiates specified above except for oxymorphone and oxycodone, which exhibit coefficients of variation of 1819%. This procedure has proved useful as a third-stage identification step for medical drug-testing specimens in which results from prior immunoassay and TLC analyses were challenged. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: HERB-OPIOID INTERACTIONS Principal Investigator & Institution: Shen, Danny D.; Member; Fred Hutchinson Cancer Research Center Box 19024, 1100 Fairview Ave N Seattle, Wa 98109 Timing: Fiscal Year 2001; Project Start 10-SEP-2001; Project End 31-MAY-2004

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Summary: (provided by applicant):Extract of SJW; Hypericum perforatum, has gained widespread popularity as an over-the-counter, natural antidepressant. Until recently, SJW was thought to be well tolerated and relatively safe. Within the past year, adverse metabolic interactions have been reported between SJW and several narrow therapeutic index drugs, notably cyclosporine indinavir, and digoxin. The interactions are now recognized to involve induction of two drug disposition mechanisms: cytochrome P450 3A4 enzyme and the active efflux pump, P-glycoprotein, both leading to profound reductions in blood or plasma drug concentration that compromises the therapeutic efficacy of the affected drug. Natural and synthetic opioids are the first-line agents for the palliative treatment of severe pain that results from cancer and cancer treatment. It is well recognized that depression is a co-morbid condition of severe and poorly controlled cancer-related pain. Given the widespread recognition of St. Johns wort as a "mood enhancer" and natural antidepressant, cancer pain patients receiving opioid analgesics may well turn to this herbal preparation for relief of depressive symptoms. The overall objective of this research proposal is to investigate if significant interactions occur between two widely used opioid analgesics - oxycodone and fentanyl and St. John wort extract through laboratory-based studies in healthy volunteers. The studies will assess the potential clinical significance of the interactions with respect to opioid analgesia efficacy and side effects, and provide scientific insights into the pharmacokinetic mechanisms underlying any observed interactions. The oxycodone arm of the study is designed to 1) investigate the induction of CYP3A4-mediated Ndemethylation which is the major detoxification pathway for oxycodone, and 2) resolve the inductive effects of SJW on intestinal and hepatic CYP3A4 through intravenous and oral administrations of a CYP3A-specific, in vivo catalytic probe -midazolam. The fentanyl arm of the study will 1) assess the effects of SJW on the brain uptake and efflux kinetics of fentanyl through pharmacokinetic-pharmacodynamic (PK-PD) modeling of miotic response over time during and following intravenous infusion of the opioid, and 2) to evaluate the changes in analgesia and side effects of fentanyl upon pretreatment with SJW that may have resulted from induction of Pgp at the BBB. A third arm of the study will assess whether SJW has analgesic properties of its own, or is capable of promoting opioid analgesia. Overall, the proposed research will provide a definitive assessment of the potential and clinical significance of adverse interactions between SJW and opioids in the context of cancer pain therapy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: HYPERALGESIA IN METHADONE PATIENTS: CAN IT BE TREATED? Principal Investigator & Institution: Compton, Margaret A.; None; University of California Los Angeles 10920 Wilshire Blvd., Suite 1200 Los Angeles, Ca 90024 Timing: Fiscal Year 2002; Project Start 01-SEP-2002; Project End 31-MAY-2007 Summary: (provided by applicant): Addressing the under-treatment of clinical pain has become a national priority, with a central goal being to identify effective interventions for those subgroups of patients most at risk for suffering unrelieved pain (NIH Program Announcement PA-01 -115). In fact, the under-treatment of pain was recently ruled a form of patient abuse with a California court awarding one million dollars in damages to the family of such a patient. Novel data accumulated by our investigative group has shown that patients maintained on the mu-opioid agonist, methadone, for the treatment of addiction, are significantly hyperalgesic to cold-pressor experimental pain as compared to normal controls. This diminished pain tolerance, in addition to the contextual prohibitions associated with providing known opioid addicts with opioid

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analgesics, makes them a population uniquely vulnerable to the under treatment of pain. Unfortunately, little is known about how to best manage the pain suffered by the over 120,000 methadone-maintained (MM) patients in this country, in part because the hyperalgesia they suffer appears to be akin to neuropathic pain and opioid-induced. In the proposed series of studies, the Principal Investigator (a first-time RO1 applicant) will build upon her previous studies validating and characterizing hyperalgesia in MM samples to explore it's underlying mechanism from a pharmacological perspective. Utilizing slightly different double-blind, placebo-controlled designs, the proposed work will evaluate the ability of three classes of medication (N-methyl-D-aspartate (NMDA)antagonists, adjuvant anticonvulsant analgesics, and novel opioid analgesics) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states suffered by MM patients. Specifically, in a sample of MM patients, (1) dextromethorphan, which interferes with the development of opioid-induced hyperalgesia, (2) gabapentin, which has proven efficacy in treating neuropathic pain, and (3) oxycodone, which has novel opioid activity, will each be evaluated for its ability to ameliorate or diminish the opioid-induced hyperalgesia in these patients as reflected by changes on pain threshold and tolerance to both cold-pressor and electrical pain, at peak and through methadone blood levels. The results of this work will not only provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, but also direction for the medical management of pain complicated by opioid-induced hyperalgesia. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: PRECRIPTION OPIOID EFFECTS IN DRUG AND NON-DRUG ABUSERS Principal Investigator & Institution: Comer, Sandra D.; Associate Professor; New York State Psychiatric Institute 1051 Riverside Dr New York, Ny 10032 Timing: Fiscal Year 2003; Project Start 20-SEP-2003; Project End 31-MAY-2008 Summary: (provided by investigator): Prescription opioid abuse is becoming an increasingly widespread and serious public health concern. The 2001 National Household Survey on Drug Abuse report revealed that the number of first-time users of prescription opioid medications for non-medical reasons reached 2.0 million in the year 2000, a number that has quintupled since 1984, and the 2002 Drug Abuse Warning Network (DAWN) report showed that the number of emergency department mentions of several prescription opioid medications more than doubled between 1994 and 2001. Despite these trends, little experimental research has been directed towards understanding who may be abusing these medications, and under what conditions. The current application will examine the reinforcing, subjective, performance, and physiological effects of two commonly prescribed opioid medications (oxycodone, codeine) in two separate studies. Because it is not clear who is abusing prescription opioids, the medication effects will be compared in drug abusers and non-drug abusers. And because it is not clear under what conditions these medications are used, the effects of oxycodone and codeine will be examined in the presence and absence of experimentally-induced pain. For each study, one between- [drug use history (drug abusers, non-drug abusers)] and two within-subjects variables [pain condition (pain, no pain); medication dose (placebo, low, high dose)] will be examined. Because previous studies have shown sex differences in response to opioid medications, we will attempt to enroll equivalent numbers of men and women in each study so that we can conduct exploratory analyses of sex differences in response to oxycodone and codeine. The results of these studies will yield important information about who may be abusing

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prescription opioid medications, and will provide a better understanding of several important variables that may influence the propensity to abuse these medications. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

E-Journals: PubMed Central3 PubMed Central (PMC) is a digital archive of life sciences journal literature developed and managed by the National Center for Biotechnology Information (NCBI) at the U.S. National Library of Medicine (NLM).4 Access to this growing archive of e-journals is free and unrestricted.5 To search, go to http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Pmc, and type “Oxycodone” (or synonyms) into the search box. This search gives you access to full-text articles. The following is a sample of items found for Oxycodone in the PubMed Central database: •

Drug advisory: oxycodone hydrochloride (OxyContin). by Wooltorton E.; 2001 Sep 4; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=81427

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Oxycodone, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Oxycodone” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Oxycodone (hyperlinks lead to article summaries): •

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A clinical study on the use of codeine, oxycodone, dextropropoxyphene, buprenorphine, and pentazocine in cancer pain. Author(s): De Conno F, Ripamonti C, Sbanotto A, Barletta L, Zecca E, Martini C, Ventafridda V. Source: Journal of Pain and Symptom Management. 1991 October; 6(7): 423-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1940486&dopt=Abstract Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

With PubMed Central, NCBI is taking the lead in preservation and maintenance of open access to electronic literature, just as NLM has done for decades with printed biomedical literature. PubMed Central aims to become a world-class library of the digital age. 5 The value of PubMed Central, in addition to its role as an archive, lies in the availability of data from diverse sources stored in a common format in a single repository. Many journals already have online publishing operations, and there is a growing tendency to publish material online only, to the exclusion of print. 6 PubMed was developed by the National Center for Biotechnology Information (NCBI) at the National Library of Medicine (NLM) at the National Institutes of Health (NIH). The PubMed database was developed in conjunction with publishers of biomedical literature as a search tool for accessing literature citations and linking to full-text journal articles at Web sites of participating publishers. Publishers that participate in PubMed supply NLM with their citations electronically prior to or at the time of publication.

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A comparison of analgesic effectiveness of oral butorphanol/acetaminophen, oxycodone/acetaminophen and placebo in hospitalized postsurgical patients. Author(s): Young RE. Source: J Med. 1979; 10(6): 417-28. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=299451&dopt=Abstract

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A comparison of ketorolac tromethamine/oxycodone versus patient-controlled analgesia with morphine in anterior cruciate ligament reconstruction patients. Author(s): Popp JE, Sanko WA, Sinha AK, Kaeding CC. Source: Arthroscopy : the Journal of Arthroscopic & Related Surgery : Official Publication of the Arthroscopy Association of North America and the International Arthroscopy Association. 1998 November-December; 14(8): 816-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9848591&dopt=Abstract

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A comparison of oral transmucosal fentanyl citrate and oral oxycodone for pediatric outpatient wound care. Author(s): Sharar SR, Carrougher GJ, Selzer K, O'Donnell F, Vavilala MS, Lee LA. Source: The Journal of Burn Care & Rehabilitation. 2002 January-February; 23(1): 27-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11803309&dopt=Abstract

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A comparison of pethidine, piritramide and oxycodone in patients with pain following cholecystectomy. Author(s): Takki S, Tammisto T. Source: Der Anaesthesist. 1973 April; 22(4): 162-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=4705927&dopt=Abstract

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A fatal drug interaction between oxycodone and clonazepam. Author(s): Burrows DL, Hagardorn AN, Harlan GC, Wallen ED, Ferslew KE. Source: J Forensic Sci. 2003 May; 48(3): 683-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12762549&dopt=Abstract

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A pharmacokinetic/pharmacodynamic study of controlled-release oxycodone. Author(s): Benziger DP, Miotto J, Grandy RP, Thomas GB, Swanton RE, Fitzmartin RD. Source: Journal of Pain and Symptom Management. 1997 February; 13(2): 75-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9095564&dopt=Abstract

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A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty. Author(s): Cheville A, Chen A, Oster G, McGarry L, Narcessian E. Source: The Journal of Bone and Joint Surgery. American Volume. 2001 April; 83-A(4): 572-6. Erratum In: J Bone Joint Surg Am 2001 June; 83-A(6): 915. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11315787&dopt=Abstract

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A review of oxycodone's clinical pharmacokinetics and pharmacodynamics. Author(s): Poyhia R, Vainio A, Kalso E. Source: Journal of Pain and Symptom Management. 1993 February; 8(2): 63-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8492004&dopt=Abstract

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A study of deaths involving oxycodone. Author(s): Drummer OH, Syrjanen ML, Phelan M, Cordner SM. Source: J Forensic Sci. 1994 July; 39(4): 1069-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8064265&dopt=Abstract

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Additive analgesic effects of oxycodone and ibuprofen in the oral surgery model. Author(s): Dionne RA. Source: Journal of Oral and Maxillofacial Surgery : Official Journal of the American Association of Oral and Maxillofacial Surgeons. 1999 June; 57(6): 673-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10368091&dopt=Abstract

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Advancement of opioid analgesia with controlled-release oxycodone. Author(s): Levy MH. Source: European Journal of Pain (London, England). 2001; 5 Suppl A: 113-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11798230&dopt=Abstract

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Adverse drug reactions to oxycodone and hydrocodone in CYP2D6 ultrarapid metabolizers. Author(s): de Leon J, Dinsmore L, Wedlund P. Source: Journal of Clinical Psychopharmacology. 2003 August; 23(4): 420-1. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12920424&dopt=Abstract

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Analgesic efficacy of controlled-release oxycodone in postoperative pain. Author(s): Sunshine A, Olson NZ, Colon A, Rivera J, Kaiko RF, Fitzmartin RD, Reder RF, Goldenheim PD. Source: Journal of Clinical Pharmacology. 1996 July; 36(7): 595-603. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8844441&dopt=Abstract

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Analgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone. Author(s): Beaver WT, Wallenstein SL, Rogers A, Houde RW. Source: The Journal of Pharmacology and Experimental Therapeutics. 1978 October; 207(1): 92-100. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=359779&dopt=Abstract

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Analgesic studies of codeine and oxycodone in patients with cancer. II. Comparisons of intramuscular oxycodone with intramuscular morphine and codeine. Author(s): Beaver WT, Wallenstein SL, Rogers A, Houde RW. Source: The Journal of Pharmacology and Experimental Therapeutics. 1978 October; 207(1): 101-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=359778&dopt=Abstract

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Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Author(s): Roth SH, Fleischmann RM, Burch FX, Dietz F, Bockow B, Rapoport RJ, Rutstein J, Lacouture PG. Source: Archives of Internal Medicine. 2000 March 27; 160(6): 853-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10737286&dopt=Abstract

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Attenuation of morphine-induced delirium in palliative care by substitution with infusion of oxycodone. Author(s): Maddocks I, Somogyi A, Abbott F, Hayball P, Parker D. Source: Journal of Pain and Symptom Management. 1996 September; 12(3): 182-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8803381&dopt=Abstract

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Atypical withdrawal syndrome (organic delusional syndrome) secondary to oxycodone detoxification. Author(s): Fishbain DA, Goldberg M, Rosomoff RS, Rosomoff H. Source: Journal of Clinical Psychopharmacology. 1988 December; 8(6): 441-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3235702&dopt=Abstract

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Bromfenac sodium, acetaminophen/oxycodone, ibuprofen, and placebo for relief of postoperative pain. Author(s): Johnson GH, Van Wagoner JD, Brown J, Cooper SA. Source: Clinical Therapeutics. 1997 May-June; 19(3): 507-19. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9220215&dopt=Abstract

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Buprenorphine as premedication and as analgesic during and after light isofluraneN2O-O2 anaesthesia. A comparison with oxycodone plus fentanyl. Author(s): Korttila K, Hovorka J. Source: Acta Anaesthesiologica Scandinavica. 1987 November; 31(8): 673-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3324612&dopt=Abstract

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Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control? Author(s): Salzman RT, Roberts MS, Wild J, Fabian C, Reder RF, Goldenheim PD. Source: Journal of Pain and Symptom Management. 1999 October; 18(4): 271-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10534967&dopt=Abstract

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Capillary electrophoresis and capillary electrophoresis-ion trap multiple-stage mass spectrometry for the differentiation and identification of oxycodone and its major metabolites in human urine. Author(s): Wey AB, Thormann W. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2002 April 25; 770(1-2): 191-205. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12013227&dopt=Abstract

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Characterization and validation of a pharmacokinetic model for controlled-release oxycodone. Author(s): Mandema JW, Kaiko RF, Oshlack B, Reder RF, Stanski DR. Source: British Journal of Clinical Pharmacology. 1996 December; 42(6): 747-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8971431&dopt=Abstract

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Codeine and oxycodone use in patients with chronic rheumatic disease pain. Author(s): Ytterberg SR, Mahowald ML, Woods SR. Source: Arthritis and Rheumatism. 1998 September; 41(9): 1603-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9751092&dopt=Abstract

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Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of moderate or severe acute low back pain. Author(s): Palangio M, Morris E, Doyle RT Jr, Dornseif BE, Valente TJ. Source: Clinical Therapeutics. 2002 January; 24(1): 87-99. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833838&dopt=Abstract

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

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Comparative clinical efficacy and safety of a novel controlled-release oxycodone formulation and controlled-release hydromorphone in the treatment of cancer pain. Author(s): Hagen NA, Babul N. Source: Cancer. 1997 April 1; 79(7): 1428-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9083166&dopt=Abstract

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Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration. Author(s): Leow KP, Smith MT, Watt JA, Williams BE, Cramond T. Source: Therapeutic Drug Monitoring. 1992 December; 14(6): 479-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1485370&dopt=Abstract

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Comparison of analgesic efficacy of oxycodone and morphine in postoperative intravenous patient-controlled analgesia. Author(s): Silvasti M, Rosenberg P, Seppala T, Svartling N, Pitkanen M. Source: Acta Anaesthesiologica Scandinavica. 1998 May; 42(5): 576-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9605375&dopt=Abstract

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Comparison of controlled-release and immediate-release oxycodone tablets in patients with cancer pain. Author(s): Kaplan R, Parris WC, Citron ML, Zhukovsky D, Reder RF, Buckley BJ, Kaiko RF. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 October; 16(10): 3230-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9779696&dopt=Abstract

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Comparison of epidural morphine and oxycodone for pain after abdominal surgery. Author(s): Backlund M, Lindgren L, Kajimoto Y, Rosenberg PH. Source: Journal of Clinical Anesthesia. 1997 February; 9(1): 30-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9051543&dopt=Abstract

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Comparison of i.m. lysine acetylsalicylate and oxycodone in the treatment of pain after operation. Author(s): Korttila K, Pentti OM, Auvinen J. Source: British Journal of Anaesthesia. 1980 June; 52(6): 613-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7000106&dopt=Abstract

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Comparison of intravenous diclofenac, indomethacin and oxycodone as postoperative analgesics in patients undergoing knee surgery. Author(s): Laitinen J, Nuutinen L, Kiiskila EL, Freudenthal Y, Ranta P, Karvonen J. Source: European Journal of Anaesthesiology. 1992 January; 9(1): 29-34. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1735396&dopt=Abstract

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Comparison of lysine acetylsalicylate and oxycodone in postoperative pain following upper abdominal surgery. Author(s): Tammisto T, Tigerstedt I, Korttila K. Source: Ann Chir Gynaecol. 1980; 69(6): 287-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6782930&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 the analgesic dose-effect relationships of nefopam and oxycodone in postoperative pain. Author(s): Tigerstedt I, Tammisto T, Leander P. Source: Acta Anaesthesiologica Scandinavica. 1979 December; 23(6): 555-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=397711&dopt=Abstract

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Comparison of the analgesic effects of intrabursal oxycodone and bupivacaine after acromioplasty. Author(s): Muittari PA, Nelimarkka O, Seppala T, Kanto JH, Kirvela OA. Source: Journal of Clinical Anesthesia. 1999 February; 11(1): 11-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10396713&dopt=Abstract

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Comparison of the pharmacokinetics of oxycodone administered in three Percocet formulations. Author(s): Gammaitoni AR, Davis MW. Source: Journal of Clinical Pharmacology. 2002 February; 42(2): 192-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11831542&dopt=Abstract

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Controlled-release oxycodone and morphine in cancer related pain. Author(s): Heiskanen T, Kalso E. Source: Pain. 1997 October; 73(1): 37-45. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9414055&dopt=Abstract

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Controlled-release oxycodone hydrochloride (OxyContin). Author(s): Heidrich DE. Source: Clinical Nurse Specialist Cns. 2001 September; 15(5): 207-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11855610&dopt=Abstract

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Controlled-release oxycodone relieves neuropathic pain: a randomized controlled trial in painful diabetic neuropathy. Author(s): Watson CP, Moulin D, Watt-Watson J, Gordon A, Eisenhoffer J. Source: Pain. 2003 September; 105(1-2): 71-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14499422&dopt=Abstract

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Conversion ratio and cost of oxycodone. Author(s): Kwarcinski M. Source: Am J Hosp Palliat Care. 2001 May-June; 18(3): 159-60. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11406890&dopt=Abstract

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Conversion to oral controlled-release oxycodone from intravenous opioid analgesic in the postoperative setting. Author(s): Ginsberg B, Sinatra RS, Adler LJ, Crews JC, Hord AH, Laurito CE, Ashburn MA. Source: Pain Medicine (Malden, Mass.). 2003 March; 4(1): 31-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873276&dopt=Abstract

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Determination of oxycodone in human plasma by high-performance liquid chromatography with electrochemical detection. Author(s): Schneider JJ, Triggs EJ, Bourne DW, Stephens ID, Haviland AM. Source: Journal of Chromatography. 1984 June 8; 308: 359-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6746828&dopt=Abstract

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Determination of oxycodone in plasma and identification of a major metabolite. Author(s): Weinstein SH, Gaylord JC. Source: Journal of Pharmaceutical Sciences. 1979 April; 68(4): 527-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=35601&dopt=Abstract

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Determination of the serum protein binding of oxycodone and morphine using ultrafiltration. Author(s): Leow KP, Wright AW, Cramond T, Smith MT. Source: Therapeutic Drug Monitoring. 1993 October; 15(5): 440-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8249052&dopt=Abstract

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Diclofenac and oxycodone in treatment of postoperative pain: a double-blind trial. Author(s): Nuutinen LS, Wuolijoki E, Pentikainen IT. Source: Acta Anaesthesiologica Scandinavica. 1986 November; 30(8): 620-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3544648&dopt=Abstract

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Differential effects of food on the bioavailability of controlled-release oxycodone tablets and immediate-release oxycodone solution. Author(s): Benziger DP, Kaiko RF, Miotto JB, Fitzmartin RD, Reder RF, Chasin M. Source: Journal of Pharmaceutical Sciences. 1996 April; 85(4): 407-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8901078&dopt=Abstract

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Dose-ranging study of oxycodone for chronic pain in advanced cancer. Author(s): Glare PA, Walsh TD. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1993 May; 11(5): 973-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8487060&dopt=Abstract

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Double-blind comparisons of zomepirac and oxycodone with APC in cancer pain. Author(s): Stambaugh JE Jr, Tejada F, Trudnowski RJ. Source: Journal of Clinical Pharmacology. 1980 April; 20(4 Pt 2): 261-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6991543&dopt=Abstract

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Double-blind, randomized comparison of the analgesic and pharmacokinetic profiles of controlled- and immediate-release oral oxycodone in cancer pain patients. Author(s): Stambaugh JE, Reder RF, Stambaugh MD, Stambaugh H, Davis M. Source: Journal of Clinical Pharmacology. 2001 May; 41(5): 500-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11361046&dopt=Abstract

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Dyskinesia after discountinuation of compound analgesic containing oxycodone. Author(s): Gardos G. Source: Lancet. 1977 April 2; 1(8014): 759-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=66559&dopt=Abstract

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Effectiveness and safety of new oxycodone/acetaminophen formulations with reduced acetaminophen for the treatment of low back pain. Author(s): Gammaitoni AR, Galer BS, Lacouture P, Domingos J, Schlagheck T. Source: Pain Medicine (Malden, Mass.). 2003 March; 4(1): 21-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12873275&dopt=Abstract

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Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Author(s): Heiskanen T, Olkkola KT, Kalso E. Source: Clinical Pharmacology and Therapeutics. 1998 December; 64(6): 603-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9871425&dopt=Abstract

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Efficacy and safety of controlled-release versus immediate-release oxycodone: randomized, double-blind evaluation in patients with chronic back pain. Author(s): Hale ME, Fleischmann R, Salzman R, Wild J, Iwan T, Swanton RE, Kaiko RF, Lacouture PG. Source: The Clinical Journal of Pain. 1999 September; 15(3): 179-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10524470&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 of controlled-release oxycodone. Author(s): Comerford T. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1999 February; 17(2): 738. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10080625&dopt=Abstract

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Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Author(s): Watson CP, Babul N. Source: Neurology. 1998 June; 50(6): 1837-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9633737&dopt=Abstract

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Evaluation of oxycodone and acetaminophen in treatment of postoperative dental pain. Author(s): Cooper SA, Precheur H, Rauch D, Rosenheck A, Ladov M, Engel J. Source: Oral Surg Oral Med Oral Pathol. 1980 December; 50(6): 496-501. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7005804&dopt=Abstract

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Federal reports say oxycodone abuse is on the rise. Author(s): Young D. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2001 July 1; 58(13): 1175, 1178-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11449872&dopt=Abstract

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

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GC-MS confirmation of codeine, morphine, 6-acetylmorphine, hydrocodone, hydromorphone, oxycodone, and oxymorphone in urine. Author(s): Meatherall R. Source: Journal of Analytical Toxicology. 1999 May-June; 23(3): 177-86. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10369327&dopt=Abstract

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Granulomatous glomerulonephritis in intravenous drug users: a report of three cases in oxycodone addicts. Author(s): Segal A, Dowling JP, Ireton HJ, Rhodes HC, Thomas GW, Kerr PG, Spagnolo DV. Source: Human Pathology. 1998 November; 29(11): 1246-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9824102&dopt=Abstract

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Hallucinations during morphine but not during oxycodone treatment. Author(s): Kalso E, Vainio A. Source: Lancet. 1988 October 15; 2(8616): 912. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2902362&dopt=Abstract

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Intravenous indomethacin or oxycodone in prevention of post-operative pain. Author(s): Mattila MA, Ahlstrom-Bengs E, Pekkola P. Source: British Medical Journal (Clinical Research Ed.). 1983 October 8; 287(6398): 1026. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=6412936&dopt=Abstract

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Intravenous morphine and oxycodone for pain after abdominal surgery. Author(s): Kalso E, Poyhia R, Onnela P, Linko K, Tigerstedt I, Tammisto T. Source: Acta Anaesthesiologica Scandinavica. 1991 October; 35(7): 642-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1785245&dopt=Abstract

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Ketamine and oxycodone in the management of postoperative pain. Author(s): Levanen J. Source: Military Medicine. 2000 June; 165(6): 450-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10870361&dopt=Abstract

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Ketoprofen, acetaminophen plus oxycodone, and acetaminophen in the relief of postoperative pain. Author(s): Sunshine A, Olson NZ, Zighelboim I, De Castro A. Source: Clinical Pharmacology and Therapeutics. 1993 November; 54(5): 546-55. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8222498&dopt=Abstract

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Lack of interaction between levofloxacin and oxycodone: pharmacokinetics and drug disposition. Author(s): Grant EM, Zhong M, Fitzgerald JF, Nicolau DP, Nightingale C, Quintiliani R. Source: Journal of Clinical Pharmacology. 2001 February; 41(2): 206-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11210403&dopt=Abstract

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Liposolubility and protein binding of oxycodone in vitro. Author(s): Poyhia R, Seppala T. Source: Pharmacology & Toxicology. 1994 January; 74(1): 23-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8159633&dopt=Abstract

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Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Author(s): Citron ML, Kaplan R, Parris WC, Croghan MK, Herbst LH, Rosenbluth RJ, Reder RF, Slagle NS, Buckley BJ, Kaiko RF. Source: Cancer Investigation. 1998; 16(8): 562-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9844616&dopt=Abstract

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Minimal interaction between gatifloxacin and oxycodone. Author(s): Grant EM, Nicolau DR, Nightingale C, Quintiliani R. Source: Journal of Clinical Pharmacology. 2002 August; 42(8): 928-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12162476&dopt=Abstract

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Morphine and oxycodone hydrochloride in the management of cancer pain. Author(s): Kalso E, Vainio A. Source: Clinical Pharmacology and Therapeutics. 1990 May; 47(5): 639-46. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2188774&dopt=Abstract

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Morphine and oxycodone in the management of cancer pain: plasma levels determined by chemical and radioreceptor assays. Author(s): Kalso E, Vainio A, Mattila MJ, Rosenberg PH, Seppala T. Source: Pharmacology & Toxicology. 1990 October; 67(4): 322-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2077525&dopt=Abstract

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Morphine or oxycodone in cancer pain? Author(s): Heiskanen TE, Ruismaki PM, Seppala TA, Kalso EA. Source: Acta Oncologica (Stockholm, Sweden). 2000; 39(8): 941-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11207001&dopt=Abstract

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Musical hallucinations induced by oxycodone. Author(s): Moore TA. Source: The American Journal of Geriatric Psychiatry : Official Journal of the American Association for Geriatric Psychiatry. 2003 July-August; 11(4): 470. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12837679&dopt=Abstract

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Nanogram level quantitation of oxycodone in human plasma by capillary gas chromatography using nitrogen-phosphorus selective detection. Author(s): Kapil RP, Padovani PK, King SY, Lam GN. Source: Journal of Chromatography. 1992 June 10; 577(2): 283-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1400759&dopt=Abstract

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Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy. Author(s): Davis MP, Varga J, Dickerson D, Walsh D, LeGrand SB, Lagman R. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 2003 February; 11(2): 84-92. Epub 2002 August 23. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12560936&dopt=Abstract

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Oxycodone in a patient reporting toxicities with multiple trials of opioids. Author(s): Mercadante S. Source: Palliative Medicine. 1998 November; 12(6): 466-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10621869&dopt=Abstract

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Oxycodone involvement in drug abuse deaths: a DAWN-based classification scheme applied to an oxycodone postmortem database containing over 1000 cases. Author(s): Cone EJ, Fant RV, Rohay JM, Caplan YH, Ballina M, Reder RF, Spyker D, Haddox JD. Source: Journal of Analytical Toxicology. 2003 March; 27(2): 57-67; Discussion 67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669998&dopt=Abstract

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Oxycodone-induced pulmonary edema. Author(s): Turturro MA, O'Toole KS. Source: The American Journal of Emergency Medicine. 1991 March; 9(2): 201-3. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1994955&dopt=Abstract

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Oxycontin: the concept of a “ghost pill” and the postmortem tissue distribution of oxycodone in 36 cases. Author(s): Anderson DT, Fritz KL, Muto JJ. Source: Journal of Analytical Toxicology. 2002 October; 26(7): 448-59. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422999&dopt=Abstract

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Patient-controlled analgesia with oxycodone in the treatment of postcraniotomy pain. Author(s): Tanskanen P, Kytta J, Randell T. Source: Acta Anaesthesiologica Scandinavica. 1999 January; 43(1): 42-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9926187&dopt=Abstract

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Patient-reported utilization patterns of fentanyl transdermal system and oxycodone hydrochloride controlled-release among patients with chronic nonmalignant pain. Author(s): Ackerman SJ, Mordin M, Reblando J, Xu X, Schein J, Vallow S, Brennan M. Source: J Manag Care Pharm. 2003 May-June; 9(3): 223-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14613465&dopt=Abstract

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Pharmacogenomics as molecular autopsy for postmortem forensic toxicology: genotyping cytochrome P450 2D6 for oxycodone cases. Author(s): Jannetto PJ, Wong SH, Gock SB, Laleli-Sahin E, Schur BC, Jentzen JM. Source: Journal of Analytical Toxicology. 2002 October; 26(7): 438-47. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12422998&dopt=Abstract

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Pharmacokinetic comparison of intravenous and intranasal administration of oxycodone. Author(s): Takala A, Kaasalainen V, Seppala T, Kalso E, Olkkola KT. Source: Acta Anaesthesiologica Scandinavica. 1997 February; 41(2): 309-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9062618&dopt=Abstract

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Pharmacokinetic-pharmacodynamic relationships of controlled-release oxycodone. Author(s): Kaiko RF, Benziger DP, Fitzmartin RD, Burke BE, Reder RF, Goldenheim PD. Source: Clinical Pharmacology and Therapeutics. 1996 January; 59(1): 52-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8549034&dopt=Abstract

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Pharmacokinetics and pharmacodynamics of oxycodone when given intravenously and rectally to adult patients with cancer pain. Author(s): Leow KP, Cramond T, Smith MT. Source: Anesthesia and Analgesia. 1995 February; 80(2): 296-302. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7818116&dopt=Abstract

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Pharmacokinetics and ventilatory effects of intravenous oxycodone in postoperative children. Author(s): Kalso E. Source: British Journal of Clinical Pharmacology. 1995 February; 39(2): 214-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7742170&dopt=Abstract

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Pharmacokinetics and ventilatory effects of intravenous oxycodone in postoperative children. Author(s): Olkkola KT, Hamunen K, Seppala T, Maunuksela EL. Source: British Journal of Clinical Pharmacology. 1994 July; 38(1): 71-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7605420&dopt=Abstract

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Pharmacokinetics and ventilatory effects of oxycodone before and after liver transplantation. Author(s): Tallgren M, Olkkola KT, Seppala T, Hockerstedt K, Lindgren L. Source: Clinical Pharmacology and Therapeutics. 1997 June; 61(6): 655-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9209248&dopt=Abstract

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

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Postoperative analgesia with controlled-release oxycodone for outpatient anterior cruciate ligament surgery. Author(s): Reuben SS, Connelly NR, Maciolek H. Source: Anesthesia and Analgesia. 1999 June; 88(6): 1286-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10357331&dopt=Abstract

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Preoperative administration of controlled-release oxycodone for the management of pain after ambulatory laparoscopic tubal ligation surgery. Author(s): Reuben SS, Steinberg RB, Maciolek H, Joshi W. Source: Journal of Clinical Anesthesia. 2002 May; 14(3): 223-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12031758&dopt=Abstract

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Problems with the use of oxycodone compound in patients with chronic pain. Author(s): Maruta T, Swanson DW. Source: Pain. 1981 December; 11(3): 389-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7329703&dopt=Abstract

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Psychomotor, respiratory and neuroendocrinological effects of a mu-opioid receptor agonist (oxycodone) in healthy volunteers. Author(s): Saarialho-Kere U, Mattila MJ, Seppala T. Source: Pharmacology & Toxicology. 1989 October; 65(4): 252-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2555803&dopt=Abstract

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

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Quantitation of oxycodone in human plasma using high-performance liquid chromatography with electrochemical detection. Author(s): Smith MT, Watt JA, Mapp GP, Cramond T. Source: Therapeutic Drug Monitoring. 1991 March; 13(2): 126-30. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2053119&dopt=Abstract

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Quantitative GLC determination of oxycodone in human plasma. Author(s): Renzi NL Jr, Tam JN. Source: Journal of Pharmaceutical Sciences. 1979 January; 68(1): 43-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=758463&dopt=Abstract

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Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. Author(s): Bruera E, Belzile M, Pituskin E, Fainsinger R, Darke A, Harsanyi Z, Babul N, Ford I. Source: Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. 1998 October; 16(10): 3222-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9779695&dopt=Abstract

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Randomized, double-blind, placebo-controlled comparison of the analgesic efficacy of oxycodone 10 mg/acetaminophen 325 mg versus controlled-release oxycodone 20 mg in postsurgical pain. Author(s): Gammaitoni AR, Galer BS, Bulloch S, Lacouture P, Caruso F, Ma T, Schlagheck T. Source: Journal of Clinical Pharmacology. 2003 March; 43(3): 296-304. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12638399&dopt=Abstract

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Re: The relative potentcy between high-dose oral oxycodone and intravenous morphine. Author(s): Miller A. Source: Journal of Pain and Symptom Management. 2000 May; 19(5): 326-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10928851&dopt=Abstract

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Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model. Author(s): Curtis GB, Johnson GH, Clark P, Taylor R, Brown J, O'Callaghan R, Shi M, Lacouture PG. Source: European Journal of Clinical Pharmacology. 1999 August; 55(6): 425-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10492054&dopt=Abstract

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Relative variability in bioavailability of oral controlled-release formulations of oxycodone and morphine. Author(s): Colucci RD, Swanton RE, Thomas GB, Kaiko RF. Source: American Journal of Therapeutics. 2001 July-August; 8(4): 231-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11441321&dopt=Abstract

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Safety and efficacy of controlled-release oxycodone: a systematic literature review. Author(s): Rischitelli DG, Karbowicz SH. Source: Pharmacotherapy. 2002 July; 22(7): 898-904. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126222&dopt=Abstract

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Severe chronic renal failure in association with oxycodone addiction: a new form of fibrillary glomerulopathy. Author(s): Hill P, Dwyer K, Kay T, Murphy B. Source: Human Pathology. 2002 August; 33(8): 783-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12203209&dopt=Abstract

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Sevoflurane versus halothane: effect of oxycodone premedication on emergence behaviour in children. Author(s): Murray DJ, Cole JW, Shrock CD, Snider RJ, Martini JA. Source: Paediatric Anaesthesia. 2002 May; 12(4): 308-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11982836&dopt=Abstract

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Single dose oxycodone and oxycodone plus paracetamol (acetominophen) for acute postoperative pain. Author(s): Edwards JE, Moore RA, McQuay HJ. Source: Cochrane Database Syst Rev. 2000; (4): Cd002763. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11034756&dopt=Abstract

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Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer. Author(s): Leow KP, Smith MT, Williams B, Cramond T. Source: Clinical Pharmacology and Therapeutics. 1992 November; 52(5): 487-95. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1424423&dopt=Abstract

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Solid-phase extraction method with high-performance liquid chromatography and electrochemical detection for the quantitative analysis of oxycodone in human plasma. Author(s): Wright AW, Lawrence JA, Iu M, Cramond T, Smith MT. Source: J Chromatogr B Biomed Sci Appl. 1998 August 7; 712(1-2): 169-75. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9698239&dopt=Abstract

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Steady-state bioavailability of controlled-release oxycodone in normal subjects. Author(s): Reder RF, Oshlack B, Miotto JB, Benziger DD, Kaiko RF. Source: Clinical Therapeutics. 1996 January-February; 18(1): 95-105. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8851456&dopt=Abstract

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Successful treatment of the idiopathic restless legs syndrome in a randomized double-blind trial of oxycodone versus placebo. Author(s): Walters AS, Wagner ML, Hening WA, Grasing K, Mills R, Chokroverty S, Kavey N. Source: Sleep. 1993 June; 16(4): 327-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8341893&dopt=Abstract

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The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery. Author(s): Daniels SE, Desjardins PJ, Talwalker S, Recker DP, Verburg KM. Source: The Journal of the American Dental Association. 2002 May; 133(5): 611-21; Quiz 625. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12036167&dopt=Abstract

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The combination of ibuprofen and oxycodone/acetaminophen in the management of chronic cancer pain. Author(s): Stambaugh JE Jr, Drew J. Source: Clinical Pharmacology and Therapeutics. 1988 December; 44(6): 665-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=2461823&dopt=Abstract

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The effect of buprenorphine and oxycodone on the intracholedochal passage pressure. Author(s): Tigerstedt I, Turunen M, Tammisto T, Hastbacka J. Source: Acta Anaesthesiologica Scandinavica. 1981 April; 25(2): 99-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=7324833&dopt=Abstract

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The effect of sedation on weaning following coronary artery bypass grafting: propofol versus oxycodone-thiopental. Author(s): Leino K, Nunes S, Valta P, Pikanen O, Vanakoski J, Takala J. Source: Acta Anaesthesiologica Scandinavica. 2000 April; 44(4): 369-77. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10757567&dopt=Abstract

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The effects of the genetic absence and inhibition of CYP2D6 on the metabolism of codeine and its derivatives, hydrocodone and oxycodone. Author(s): Lurcott G. Source: Anesthesia Progress. 1998 Fall; 45(4): 154-6. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10483388&dopt=Abstract

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The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Author(s): Poyhia R, Seppala T, Olkkola KT, Kalso E. Source: British Journal of Clinical Pharmacology. 1992 June; 33(6): 617-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1389934&dopt=Abstract

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The pharmacokinetics of oxycodone after intravenous injection in adults. Author(s): Poyhia R, Olkkola KT, Seppala T, Kalso E. Source: British Journal of Clinical Pharmacology. 1991 October; 32(4): 516-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1958450&dopt=Abstract

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The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. Author(s): Kirvela M, Lindgren L, Seppala T, Olkkola KT. Source: Journal of Clinical Anesthesia. 1996 February; 8(1): 13-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8695073&dopt=Abstract

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The relative potency between high dose oral oxycodone and intravenous morphine: a case illustration. Author(s): Zhukovsky DS, Walsh D, Doona M. Source: Journal of Pain and Symptom Management. 1999 July; 18(1): 53-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10439573&dopt=Abstract

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The safety and efficacy of intrabursal oxycodone and bupivacaine in analgesia after shoulder surgery. Author(s): Muittari P, Kirvela O. Source: Regional Anesthesia and Pain Medicine. 1998 September-October; 23(5): 474-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9773700&dopt=Abstract

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The simultaneous determination of codeine, morphine, hydrocodone, hydromorphone, 6-acetylmorphine, and oxycodone in hair and oral fluid. Author(s): Jones J, Tomlinson K, Moore C. Source: Journal of Analytical Toxicology. 2002 April; 26(3): 171-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11991534&dopt=Abstract

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The underutilization of oxycodone. Author(s): Rogers AG. Source: Journal of Pain and Symptom Management. 1991 October; 6(7): 452. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1940492&dopt=Abstract

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The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study. Author(s): Parris WC, Johnson BW Jr, Croghan MK, Moore MR, Khojasteh A, Reder RF, Kaiko RF, Buckley BJ. Source: Journal of Pain and Symptom Management. 1998 October; 16(4): 205-11. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9803047&dopt=Abstract

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The use of intermittent subcutaneous injections of oxycodone for opioid rotation in patients with cancer pain. Author(s): Gagnon B, Bielech M, Watanabe S, Walker P, Hanson J, Bruera E. Source: Supportive Care in Cancer : Official Journal of the Multinational Association of Supportive Care in Cancer. 1999 July; 7(4): 265-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10423053&dopt=Abstract

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The use of oxycodone in cancer-related pain: a literature review. Author(s): Cairns R. Source: International Journal of Palliative Nursing. 2001 November; 7(11): 522-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11775926&dopt=Abstract

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Time course of changes in breathing pattern in morphine- and oxycodone-induced respiratory depression. Author(s): Leino K, Mildh L, Lertola K, Seppala T, Kirvela O. Source: Anaesthesia. 1999 September; 54(9): 835-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10460553&dopt=Abstract

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Tourette syndrome: successful treatment with clonidine and oxycodone. Author(s): Sandyk R. Source: Journal of Neurology. 1986 June; 233(3): 178-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=3459810&dopt=Abstract

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Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial. Author(s): Caldwell JR, Hale ME, Boyd RE, Hague JM, Iwan T, Shi M, Lacouture PG. Source: The Journal of Rheumatology. 1999 April; 26(4): 862-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10229408&dopt=Abstract

•

Visual hallucination and tremor induced by sertraline and oxycodone in a bone marrow transplant patient. Author(s): Rosebraugh CJ, Flockhart DA, Yasuda SU, Woosley RL. Source: Journal of Clinical Pharmacology. 2001 February; 41(2): 224-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11210406&dopt=Abstract

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

Finding Nutrition Studies on Oxycodone The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.7 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Oxycodone” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

7 Adapted from http://ods.od.nih.gov. IBIDS is produced by the Office of Dietary Supplements (ODS) at the National Institutes of Health to assist the public, healthcare providers, educators, and researchers in locating credible, scientific information on dietary supplements. IBIDS was developed and will be maintained through an interagency partnership with the Food and Nutrition Information Center of the National Agricultural Library, U.S. Department of Agriculture.

32

Oxycodone

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

A comparison of ketorolac tromethamine/oxycodone versus patient-controlled analgesia with morphine in anterior cruciate ligament reconstruction patients. Author(s): Department of Surgery, The Ohio State University, Columbus, USA. Source: Popp, J E Sanko, W A Sinha, A K Kaeding, C C Arthroscopy. 1998 NovDecember; 14(8): 816-9 0749-8063

•

A comparison of oral transmucosal fentanyl citrate and oral oxycodone for pediatric outpatient wound care. Author(s): Department of Anesthesiology, University of Washington School of Medicine and Harborview Medical Center, Seattle, Washington 98104, USA. Source: Sharar, S R Carrougher, G J Selzer, K O'Donnell, F Vavilala, M S Lee, L A J-BurnCare-Rehabil. 2002 Jan-February; 23(1): 27-31 0273-8481

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A randomized trial of controlled-release oxycodone during inpatient rehabilitation following unilateral total knee arthroplasty. Author(s): Kessler Institute for Rehabilitation, East Orange, New Jersey, USA. [email protected] Source: Cheville, A Chen, A Oster, G McGarry, L Narcessian, E J-Bone-Joint-Surg-Am. 2001 April; 83-A(4): 572-6 0021-9355

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Additive analgesic effects of oxycodone and ibuprofen in the oral surgery model. Author(s): Pain and Neurosensory Mechanisms Branch, National Institute of Dental and Craniofacial Research, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD 20892, USA. [email protected] Source: Dionne, R A J-Oral-Maxillofac-Surg. 1999 June; 57(6): 673-8 0278-2391

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Advancement of opioid analgesia with controlled-release oxycodone. Author(s): Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA. [email protected] Source: Levy, M H Eur-J-Pain. 2001; 5 Suppl A: 113-6 1090-3801

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Around-the-clock, controlled-release oxycodone therapy for osteoarthritis-related pain: placebo-controlled trial and long-term evaluation. Author(s): Arthritis Center Ltd, Phoenix, Ariz, USA. Source: Roth, S H Fleischmann, R M Burch, F X Dietz, F Bockow, B Rapoport, R J Rutstein, J Lacouture, P G Arch-Intern-Med. 2000 March 27; 160(6): 853-60 0003-9926

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Can a controlled-release oral dose form of oxycodone be used as readily as an immediate-release form for the purpose of titrating to stable pain control? Author(s): Regional Oncology Hematology Associates, Kissimmee, Florida, USA. Source: Salzman, R T Roberts, M S Wild, J Fabian, C Reder, R F Goldenheim, P D J-PainSymptom-Manage. 1999 October; 18(4): 271-9 0885-3924

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Co-administration of sub-antinociceptive doses of oxycodone and morphine produces marked antinociceptive synergy with reduced CNS side-effects in rats. Author(s): School of Pharmacy, The University of Queensland, St Lucia, Brisbane, Australia. Source: Ross, F B Wallis, S C Smith, M T Pain. 2000 February; 84(2-3): 421-8 0304-3959

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Codeine and oxycodone use in patients with chronic rheumatic disease pain. Author(s): Minneapolis Veterans Affairs Medical Center, and the University of Minnesota, 55417, USA. Source: Ytterberg, S R Mahowald, M L Woods, S R Arthritis-Rheum. 1998 September; 41(9): 1603-12 0004-3591

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Combination hydrocodone and ibuprofen versus combination oxycodone and acetaminophen in the treatment of postoperative obstetric or gynecologic pain. Author(s): Medical Affairs Department, Knoll Pharmaceutical Company, Mount Olive, New Jersey 07828-1234, USA. [email protected] Source: Palangio, M Wideman, G L Keffer, M Landau, C J Morris, E Doyle, R T Jiang, J G Damask, M de Padova, A Clin-Ther. 2000 May; 22(5): 600-12 0149-2918

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Comparative oxycodone pharmacokinetics in humans after intravenous, oral, and rectal administration. Author(s): Department of Surgery, University of Queensland, Royal Brisbane Hospital, Herston, Australia. Source: Leow, K P Smith, M T Watt, J A Williams, B E Cramond, T Ther-Drug-Monit. 1992 December; 14(6): 479-84 0163-4356

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Comparison of analgesic efficacy of oxycodone and morphine in postoperative intravenous patient-controlled analgesia. Author(s): Department of Anaesthesia, Helsinki University Central Hospital, Finland. Source: Silvasti, M Rosenberg, P Seppala, T Svartling, N Pitkanen, M Acta-AnaesthesiolScand. 1998 May; 42(5): 576-80 0001-5172

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Comparison of controlled-release and immediate-release oxycodone tablets in patients with cancer pain. Author(s): Department of Anesthesiology Pain Service, Montefiore Medical Center, Bronx, NY, USA. Source: Kaplan, R Parris, W C Citron, M L Zhukovsky, D Reder, R F Buckley, B J Kaiko, R F J-Clin-Oncol. 1998 October; 16(10): 3230-7 0732-183X

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Comparison of the analgesic effects of intrabursal oxycodone and bupivacaine after acromioplasty. Author(s): Department of Anesthesiology, Turku University Hospital, Finland. Source: Muittari, P A Nelimarkka, O Seppala, T Kanto, J H Kirvela, O A J-Clin-Anesth. 1999 February; 11(1): 11-6 0952-8180

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Comparison of the pharmacokinetics of oxycodone administered in three Percocet formulations. Author(s): Endo Pharmaceuticals, Inc., Chadds Ford, Pennsylvania 19317, USA. Source: Gammaitoni, Arnold R Davis, Matthew W J-Clin-Pharmacol. 2002 February; 42(2): 192-7 0091-2700

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Controlled-release oxycodone hydrochloride (OxyContin). Source: Heidrich D, E Clin-Nurse-Spec. 2001 September; 15(5): 207-9 0887-6274

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Dose-ranging study of oxycodone for chronic pain in advanced cancer. Author(s): Palliative Care Program, Cleveland Clinic Foundation, OH 44195. Source: Glare, P A Walsh, T D J-Clin-Oncol. 1993 May; 11(5): 973-8 0732-183X

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Double-blind, randomized comparison of the analgesic and pharmacokinetic profiles of controlled- and immediate-release oral oxycodone in cancer pain patients. Author(s): Oncology and Hematology Associates, Woodbury, New Jersey, USA. Source: Stambaugh, J E Reder, R F Stambaugh, M D Stambaugh, H Davis, M J-ClinPharmacol. 2001 May; 41(5): 500-6 0091-2700

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Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Author(s): Department of Anaesthesia, Helsinki University Central Hospital, Finland. [email protected]

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Oxycodone

Source: Heiskanen, T Olkkola, K T Kalso, E Clin-Pharmacol-Ther. 1998 December; 64(6): 603-11 0009-9236 •

Efficacy and safety of controlled-release versus immediate-release oxycodone: randomized, double-blind evaluation in patients with chronic back pain. Author(s): Park Place Therapeutic Center, Plantation, Florida 33324, USA. Source: Hale, M E Fleischmann, R Salzman, R Wild, J Iwan, T Swanton, R E Kaiko, R F Lacouture, P G Clin-J-Pain. 1999 September; 15(3): 179-83 0749-8047

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Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Author(s): Department of Medicine, University of Toronto, Ontario, Canada. Source: Watson, C P Babul, N Neurology. 1998 June; 50(6): 1837-41 0028-3878

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Ketamine and oxycodone in the management of postoperative pain. Author(s): Department of Anesthesiology, Military Central Hospital, Helsinki, Finland. Source: Levanen, J Mil-Med. 2000 June; 165(6): 450-5 0026-4075

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Long-term administration of controlled-release oxycodone tablets for the treatment of cancer pain. Author(s): ProHealth Care Associates, LLP Lake Success, New York, USA. Source: Citron, M L Kaplan, R Parris, W C Croghan, M K Herbst, L H Rosenbluth, R J Reder, R F Slagle, N S Buckley, B J Kaiko, R F Cancer-Invest. 1998; 16(8): 562-71 07357907

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Morphine or oxycodone in cancer pain? Author(s): Pain Relief Unit, Helsinki University Hospital, Finland. [email protected] Source: Heiskanen, T E Ruismaki, P M Seppala, T A Kalso, E A Acta-Oncol. 2000; 39(8): 941-7 0284-186X

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Oxycodone and oxycontin. Source: Anonymous Med-Lett-Drugs-Ther. 2001 September 17; 43(1113): 80-1 0025-732X

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Oxycodone/ibuprofen. Source: Anonymous Drugs-R-D. 2002; 3(1): 56-7 1174-5886

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Patient-controlled analgesia with oxycodone in the treatment of postcraniotomy pain. Author(s): Department of Anaesthesia, Helsinki University Central Hospital, Finland. Source: Tanskanen, P Kytta, J Randell, T Acta-Anaesthesiol-Scand. 1999 January; 43(1): 42-5 0001-5172

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Postoperative analgesia with controlled-release oxycodone for outpatient anterior cruciate ligament surgery. Author(s): Acute Pain Service, Baystate Medical Center and Tufts University School of Medicine, Springfield, Massachusetts 01199, USA. [email protected] Source: Reuben, S S Connelly, N R Maciolek, H Anesth-Analg. 1999 June; 88(6): 1286-91 0003-2999

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Preoperative administration of controlled-release oxycodone for the management of pain after ambulatory laparoscopic tubal ligation surgery. Author(s): Department of Anesthesiology, Baystate Medical Center, Springfield, MA 01199, USA. [email protected] Source: Reuben, S S Steinberg, R B Maciolek, H Joshi, W J-Clin-Anesth. 2002 May; 14(3): 223-7 0952-8180

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Randomized, double-blind, cross-over trial comparing safety and efficacy of oral controlled-release oxycodone with controlled-release morphine in patients with cancer pain. Author(s): Grey Nuns Community Hospital and Health Centre, Cross Cancer Institute, Division of Palliative Care Medicine, University of Alberta, Edmonton, Canada. [email protected] Source: Bruera, E Belzile, M Pituskin, E Fainsinger, R Darke, A Harsanyi, Z Babul, N Ford, I J-Clin-Oncol. 1998 October; 16(10): 3222-9 0732-183X

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Relative potency of controlled-release oxycodone and controlled-release morphine in a postoperative pain model. Author(s): Alta View Hospital, Sandy, Utah 84094, USA. Source: Curtis, G B Johnson, G H Clark, P Taylor, R Brown, J O'Callaghan, R Shi, M Lacouture, P G Eur-J-Clin-Pharmacol. 1999 August; 55(6): 425-9 0031-6970

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Severe chronic renal failure in association with oxycodone addiction: a new form of fibrillary glomerulopathy. Author(s): Department of Anatomical Pathology, St. Vincent's Hospital, Fitzroy, Victoria, Australia. Source: Hill, P Dwyer, K Kay, T Murphy, B Hum-Pathol. 2002 August; 33(8): 783-7 00468177

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Sevoflurane versus halothane: effect of oxycodone premedication on emergence behaviour in children. Author(s): Department of Anesthesiology, Washington University at St Louis Children's Hospital, St Louis, MO 63110, USA. Source: Murray, David J Cole, Jennifer W Shrock, Charles D Snider, Rebecca J Martini, John A Paediatr-Anaesth. 2002 May; 12(4): 308-12 1155-5645

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Single dose oxycodone and oxycodone plus paracetamol (acetominophen) for acute postoperative pain. Author(s): Pain Research Unit, Nuffield Department of Anaesthetics, Churchill Hospital, Old Road, Oxford, UK, OX3 7LJ. [email protected] Source: Edwards, J E Moore, R A McQuay, H J Cochrane-Database-Syst-Revolume 2000; (4): CD002763 1469-493X

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Stability indicating HPLC method for the estimation of oxycodone and lidocaine in rectal gel. Author(s): Pharmacy Department, Repatriation General Hospital, Daw Park, Adelaide SA 5041, Australia. [email protected] Source: Gebauer, M G McClure, A F Vlahakis, T L Int-J-Pharm. 2001 July 31; 223(1-2): 4954 0378-5173

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The analgesic efficacy of valdecoxib vs. oxycodone/acetaminophen after oral surgery. Author(s): Clinical Site Operations, SCIREX Corp., Austin, Texas, USA. Source: Daniels, Stephen E Desjardins, Paul J Talwalker, Sheela Recker, David P Verburg, Kenneth M J-Am-Dent-Assoc. 2002 May; 133(5): 611-21; quiz 625 0002-8177

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The effect of sedation on weaning following coronary artery bypass grafting: propofol versus oxycodone-thiopental. Author(s): Department of Anaesthesiology, Turku University Hospital, Finland. Source: Leino, K Nunes, S Valta, P Pikanen, O Vanakoski, J Takala, J Acta-AnaesthesiolScand. 2000 April; 44(4): 369-77 0001-5172

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Oxycodone

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The influence of pharmacogenetics on opioid analgesia: studies with codeine and oxycodone in the Sprague-Dawley/Dark Agouti rat model. Author(s): Department of Clinical and Experimental Pharmacology, University of Adelaide, Australia. Source: Cleary, J Mikus, G Somogyi, A Bochner, F J-Pharmacol-Exp-Ther. 1994 December; 271(3): 1528-34 0022-3565

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The relative potency between high dose oral oxycodone and intravenous morphine: a case illustration. Author(s): Department of Medical Oncology, Cleveland Clinic Foundation, OH 44195, USA. Source: Zhukovsky, D S Walsh, D Doona, M J-Pain-Symptom-Manage. 1999 July; 18(1): 53-5 0885-3924

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The safety and efficacy of intrabursal oxycodone and bupivacaine in analgesia after shoulder surgery. Author(s): Department of Anesthesiology, Turku University Hospital, Finland. Source: Muittari, P Kirvela, O Reg-Anesth-Pain-Med. 1998 Sep-October; 23(5): 474-8 1098-7339

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The use of controlled-release oxycodone for the treatment of chronic cancer pain: a randomized, double-blind study. Author(s): Department of Anesthesiology, Vanderbilt University Medical Center, Nashville, Tennessee, USA. Source: Parris, W C Johnson, B W Croghan, M K Moore, M R Khojasteh, A Reder, R F Kaiko, R F Buckley, B J J-Pain-Symptom-Manage. 1998 October; 16(4): 205-11 0885-3924

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The use of intermittent subcutaneous injections of oxycodone for opioid rotation in patients with cancer pain. Author(s): Palliative Care Program, Grey Nuns Community Hospital & Health Centre, Edmonton, Alberta, Canada. Source: Gagnon, B Bielech, M Watanabe, S Walker, P Hanson, J Bruera, E Support-CareCancer. 1999 July; 7(4): 265-70 0941-4355

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The use of oxycodone in cancer-related pain: a literature review. Author(s): Oncology Unit, Western General Hospital, Edinburgh, UK. Source: Cairns, R Int-J-Palliat-Nurs. 2001 November; 7(11): 522-7 1357-6321

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Treatment of osteoarthritis pain with controlled release oxycodone or fixed combination oxycodone plus acetaminophen added to nonsteroidal antiinflammatory drugs: a double blind, randomized, multicenter, placebo controlled trial. Author(s): Gainesville Clinical Research Center, Florida 32605, USA. Source: Caldwell, J R Hale, M E Boyd, R E Hague, J M Iwan, T Shi, M Lacouture, P G JRheumatol. 1999 April; 26(4): 862-9 0315-162X

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

Nutrition

37

•

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. ALTERNATIVE MEDICINE AND OXYCODONE Overview In this chapter, we will begin by introducing you to official information sources on complementary and alternative medicine (CAM) relating to Oxycodone. 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 Oxycodone 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 “Oxycodone” (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 Oxycodone: •

Chronic opioid therapy for nonmalignant pain in patients with a history of substance abuse: report of 20 cases. Author(s): Dunbar SA, Katz NP. Source: Journal of Pain and Symptom Management. 1996 March; 11(3): 163-71. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8851374&dopt=Abstract

•

Drug dependence studies and regulations: an overview of the past and present. Author(s): Harris LS. Source: Nihon Shinkei Seishin Yakurigaku Zasshi. 2001 November; 21(5): 171-4. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11797422&dopt=Abstract

•

Failure of transcutaneous electrical nerve stimulation and indomethacin to reduce opiate requirement following cholecystectomy. Author(s): Laitinen J, Nuutinen L.

40

Oxycodone

Source: Acta Anaesthesiologica Scandinavica. 1991 November; 35(8): 700-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=1763589&dopt=Abstract •

Oxycodone involvement in drug abuse deaths: a DAWN-based classification scheme applied to an oxycodone postmortem database containing over 1000 cases. Author(s): Cone EJ, Fant RV, Rohay JM, Caplan YH, Ballina M, Reder RF, Spyker D, Haddox JD. Source: Journal of Analytical Toxicology. 2003 March; 27(2): 57-67; Discussion 67. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12669998&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 Oxycodone; 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 Kidney Stones Source: Healthnotes, Inc.; www.healthnotes.com Restless Legs Syndrome Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 41

•

Herbs and Supplements Endocet Source: Healthnotes, Inc.; www.healthnotes.com Oxycodone Source: Healthnotes, Inc.; www.healthnotes.com Percocet Source: Healthnotes, Inc.; www.healthnotes.com Percodan Source: Healthnotes, Inc.; www.healthnotes.com Roxicet Source: Healthnotes, Inc.; www.healthnotes.com Roxiprin Source: Healthnotes, Inc.; www.healthnotes.com

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

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CHAPTER 4. PATENTS ON OXYCODONE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “Oxycodone” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Oxycodone, we have not necessarily excluded nonmedical patents in this bibliography.

Patents on Oxycodone By performing a patent search focusing on Oxycodone, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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Oxycodone

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

Analgesic composition containing a mixture of 6-chloro-.alpha.-methyl-carbazole-2acetic acid plus an opiate as the active agent Inventor(s): Baruth, Jr.; Herman W. (Wayne, NJ), Berger; Leo (Montclair, NJ), Corraz; Alfred J. (Wayne, NJ), Sepinwall; Jerry (Pine Brook, NJ) Assignee(s): Hoffmann-La Roche Inc. (Nutley, NJ) Patent Number: 4,610,989 Date filed: July 31, 1985 Abstract: A method of producing analgesia by administering an opiate alkaloid such as morphine, codeine, oxycodone or a pharmaceutically acceptable acid addition salt thereof together with a carbazole compound, 6-chloro-.alpha.-methyl-carbazole-2-acetic acid, or a salt thereof with a pharmaceutically acceptable base and composition therefor. Excerpt(s): Relief of pain is one of the important goals in medicine. One method for alleviating pain is administration of analgesic drugs which act to decrease the awareness of the sensation of pain by elevating the pain threshold. Opiate alkaloids, for example, morphine, codeine and oxycodone, are among the more potent analgesic drugs available in the treatment of pain. Although the primary action of opiate alkaloids is analgesia, there are serious side-effects associated with these compounds such as respiratory depression and addiction. In an effort to maintain the maximum analgesic effect of opiate alkaloids and to minimize the side effects of these compounds, there has been a search for a compound which would potentiate the action of the opiate alkaloid, and thereby, reduce the amount of opiate used. Web site: http://www.delphion.com/details?pn=US04610989__

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Analgesic mixture of oxycodone and ibuprofen Inventor(s): Baker; Geraldine L. (Minneapolis, MN), Schmidt; William K. (Wilmington, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 4,569,937 Date filed: February 11, 1985 Abstract: Pharmaceutical compositions of narcotic analgesics and ibuprofen have been found to exhibit unexpectedly enhanced analgesic activity by applying an analysis model which considers data characterizing the analgesic effect of both the pure components as well as the fixed dose ratio combinations. This synergism enables the use of lower doses of either or both drugs with a concomitant reduction in risk of possible side effects. Excerpt(s): This invention relates to pharmaceutical compositions of narcotic analgesics and ibuprofen having analgesic activity in mammals, and to methods of use of the compositions to alleviate pain in mammals. More active analgesic combinations are in constant demand because they offer the attractive possibility of relieving pain with reduced dosages thereby diminishing the expected side effects and toxicity that would result from the otherwise required higher dosages. U.S. Pat. No. 4,464,376, issued to A.

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Sunshine et al., on Aug. 7, 1984 describes analgesic and antiinflammatory compositions which comprise caffeine together with a selected non-narcotic/non-steroidal antiinflammatory drug (NSAID) or a selected narcotic analgesic or both. This patent discloses that the analgesic effect of the combination of a selected NSAID and a selected narcotic analgesic is greater than for either alone which analgesic effect is further enhanced by the addition of caffeine. Sunshine provides no evidence or suggestion of other than an additive analgesic effect for the combinations. Web site: http://www.delphion.com/details?pn=US04569937__ •

Composition comprising a tramadol material and any of codeine, oxycodone or hydrocodone and their use Inventor(s): Raffa; Robert B. (Norristown, PA), Vaught; Jeffrey L. (Perkasie, PA) Assignee(s): McNeil Lab, Inc. (Spring House, PA) Patent Number: 5,468,744 Date filed: June 30, 1994 Abstract: This invention relates to compositions comprising a tramadol material selected from the group consisting of tramadol, its stereoisomers and its pharmaceutically acceptable salts and either codeine or oxycodone, and their use in treating pain. When the components, i.e., tramadol materials and either of codeine or oxycodone, of the composition are within certain ratios of pharmacological effects of the compositions are superaddditive (synergistic). Excerpt(s): This case is related to, but does not derive benefit under 35 U.S.C. 120 from application Ser. Nos. 07/974,863 and 07/974,865. U.S. Pat. No. 3,652,589 discloses a class of analgesic cycloalkanol-substituted phenol esters having a basic amine group in the cycloalkyl ring. The compound (1RS, 2RS) trans-2-[(dimethylamino)-methyl]-1-(3methoxyphenyl)cyclohexanol, commonly known as tramadol, is specifically disclosed therein. A series of articles pertaining to the pharmacology, toxicology and clinical studies of tramadol are found in Arzneim, Forsch (Drug Res.), 28(l), 114 (1978). Driessen et al., Arch. Pharmacol., 341, R104 (1990) disclose that tramadol produces its analgesic effect through a mechanism that is neither fully opioid-like nor non-opioid-like. The Abstracts of the VI th World Congress on Pain, Apr. 1-6 (1990) discloses that tramadol hydrochloride is an orally active pure agonist opioid analgesic. However, clinical experience indicates that tramadol lacks many of the typical-side effects of opioid agonists, e.g., respiratory depression (W. Vogel et al., Arzneim, Forsch, (Drug Res.), 28(l), 183 (1978)), constipation (I. Arend et al., Arzneim, Forsch, (Drug Res.), 28(l), 199 (1978)), tolerance (L. Flohe et al., Arzneim, Forsch, (Drug Res.), 28(l), 213 (1978)), and abuse liability (T. Yanagita, Arzneim, Forsch. (Drug Res.), 28(l), 158 (1978)). When given at a dose of 50 mg by rapid i.v. injection, tramadol may however, produce certain side effects unique to tramadol including hot flushes and sweating. Despite theses side effects, tramadol's combination of non-opioid and opioid activity makes tramadol a very unique drug. Tramadol is currently being marketed by Grunenthal GMBH in Germany as an analgesic. Opioids have for many years been used as analgesics to treat severe pain. However, they produce undesirable side effects which place limitations on their use. The side effect problems are well documented in the literature. See, Jaffe, J. in "Goodman and Gilman's The Pharmacological Basis of Therapeutics", 8th edition; Gilman et al.; Peragamon Press, New York, 1990; Chapter 22, pages 522-573, wherein it is disclosed that morphine and its congeners, e.g., codeine, hydrocodone and

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oxycodone, are opioid agonist analgesics that exhibit side effects such as respiratory depression, constipation, tolerance and abuse liability. Web site: http://www.delphion.com/details?pn=US05468744__ •

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

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Fluoro analogs of hydrocodone and oxycodone useful as analgesics, narcotic antagonists or both Inventor(s): Boswell, Jr.; George A. (Wilmington, DE), Henderson; Rosetta M. (Wilmington, DE) Assignee(s): E. I. Du Pont de Nemours and Company (Wilmington, DE) Patent Number: 4,241,065 Date filed: July 2, 1979 Abstract: 6-Fluoro analogs of hydrocodone and oxycodone are analgesics and/or narcotic antagonists. Exemplary are 17-cyclopropylmethyl-4,5-epoxy-6,6-difluoro-3methoxymorphinan and 17-cyclopropylmethyl-6,7-didehydro-4,5-epoxy-6-fluoro-3methoxy- and -3-acetoxymorphinan. Excerpt(s): This invention relates to fluorine analogs of hydrocodone and oxycodone and their analgesic and/or narcotic antagonist properties in mammals. Morphine and codeine analgesics exhibit toxic properties or have addictive action. Considerable effort

Patents 47

has been made to find derivatives that are free from these qualities and still have analgesic effects. Compounds which are narcotic antagonists are also useful in medicine, such as treatment of addicts. and pharmaceutically acceptable salts of the compound. Web site: http://www.delphion.com/details?pn=US04241065__ •

Preparation of opiates, intermediates and uses of salts Inventor(s): Dung; Jen-Sen (Boothwyn, PA), Mudryk; Bogdan (East Windsor, NJ), Sapino; Chester (Sewell, NJ), Sebastian; Alice (Deptford, NJ) Assignee(s): Johnson Matthey Public Limited Company (London, GB) Patent Number: 6,090,943 Date filed: June 30, 1998 Abstract: A process for the preparation of thebaine, its salts such as the bitartrate, and analogues thereof, together with a novel intermediate useful in said process are disclosed. Thebaine bitartrate is itself useful in the preparation of oxycodone; analogues are useful in the preparation of analogous 14-hydroxymorphinones. Excerpt(s): This invention relates to a process for the preparation of thebaine and analogues thereof, and to a novel intermediate useful in such a process. In particular, the invention relates to the preparation of thebaine from N-methyl morphinans, its isolation as a salt and the use of the salt in the preparation of N-methyl-14-hydroxymorphinones. Unfortunately, thebaine is expensive and is not always readily available in industriallyrequired quantities. Sohar et al, U.S. Pat. No. 3,894,026, disclose a method for producing thebaine, but the starting material is salutaridinol, which is itself not readily available. Therefore, it is desirable to prepare thebaine or its analogues, directly or through known intermediates, from more readily available morphinans such as codeine and morphine. Codeine is the corresponding 6-OH monoenolether analogue of thebaine. Web site: http://www.delphion.com/details?pn=US06090943__

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Preparation of oxycodone from codeine Inventor(s): Christodoulou; Aris P (New York, NY), Huang; Bao-Shan (Edison, NJ), Ji; Ben-Yi (Brooklyn, NY), Lu; Yansong (Edison, NJ) Assignee(s): Penick Corporation (Newark, NJ) Patent Number: 6,008,355 Date filed: July 16, 1998 Abstract: A process is provided for preparing oxycodone from codeine comprising either:(A) the steps of(1) oxidizing codeine so as to form codeinone;(2) converting codeinone to oxycodone in a two-step-one-pot reaction: first reacting codeinone with hydrogen peroxide in water in the presence of an acid at from about 15.degree. to about 70.degree. C. to form 14-hydroxycodeinone and then catalytically hydrogenating 14hydroxycodeinone in its original reaction mixture to form oxycodone; or(B) the steps of(1) oxydizing codeine so as to form codeinone;(2) reacting codeinone with an acylating agent so as to form codeinone dienol acylate;(3) oxidizing codeinone dienol acylate with an oxidation agent in water or a solubilizing solvent mixture in the presence of an acid at from about 15.degree. to about 70.degree. C. to form 14-hydroxycodeinone;(4) hydrogenating 14-hydroxycodeinone in its original reaction mixture to form oxycodone.

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Excerpt(s): This invention relates in general to process for the conversion of normorphinone and its derivatives, which can be synthesized from morphine, to the corresponding 14-hydroxynormorphinone and its derivatives including oxycodone, oxymorphone, noroxymorphone, and naltrexone. Noroxymorphone is a key intermediate for the production of important narcotic analgesics and antagonists. In another aspect, the invention is directed to certain novel intermediates. 14-Hydroxysubstituted morphine derivatives are important narcotic analgesics and/or antagonists. These drugs include oxycodone, oxymorphone, nalbuphine, naloxone, naltrexone, and nalmefene. They are readily synthesized from thebaine, which is a minor component of gum opium. As the supply of thebaine is limited and the demand is increasing, therefore, the price of thebaine is high. As a result, many alternative approaches have been made for the preparation of 14-hydroxymorphine derivatives. The reported efforts for preparing these narcotics bearing a 14-hydroxy group from readily abundant starting materials morphine or codeine (a minor component of gum opium, which may also be synthesized by methylation of morphine) are summarized as the following: (1) the conversion of codeine to thebaine through dihydrocodeinone (5.4% yield, H. Rapoport, et al., J. Am. Chem. Soc., vol. 89, 1967, p. 1942 and H. Rapoport, et al., J. Org. Chem., vol. 15, 1950, p. 1 103), codeinone (20% yield, I. Seki, Chem. Pharm. Bull., vol. 18, 1970, p. 671 and H. Rapoport, et al., J. Am. Chem. Soc., vol. 77, 1955, p. 490) or 6-methyl ether of codeine (using manganese dioxide, 67% yield, R. B. Barber, et al., J. Med. Chem., vol. 18, 1975, p. 1074); (2) the oxidation of codeinone pyrrolidinyl di-enamine to 1 4hydroxycodeinone (30-40% yield, I. Seki, Chem. Pharm. Bull., vol. 18, 1970, p. 671); (3) the direct allylic oxidation of codeine to the corresponding 14-hydroxy derivatives with manganese dioxide (I. Brown, et al., J. Chem. Soc., 1960, p. 4139), and selenium dioxide plus t-butyl hydrogen peroxide (M. A. Schwartz, et al., J. Med. Chem., vol. 24,1981, p. 1525); and (4) the six-step transformation of codeine to noroxycodone (52% yield) and noroxymorphone (43% yield) using photochemically generated singlet oxygen (M. A. Schwartz, et al., J. Med. Chem. vol. 24, 1981, p. 1525); and (5) the preparation of noroxymorphone from morphine through an intermediate with carbamate protection on the nitrogen atom (17-position) or a carbonate protecton at the 3 position and the carbamate protection at the 17 position of normorphinone dienol acetate with MCPBA in the substantial absence of water (37% yield, Wallace, U.S. Pat. No. 5,112,975). These processes suffer from either low yields, long steps, not amenable to scale-up, or involve the use of environmentally unfriendly heavy metals. Web site: http://www.delphion.com/details?pn=US06008355__ •

Prevention of analgesic abuse Inventor(s): Gordon; Maxwell (Syracuse, NY), Pachter; Irwin J. (Fayetteville, NY) Assignee(s): Bristol-Myers Company (New York, NY) Patent Number: 4,457,933 Date filed: December 11, 1981 Abstract: This invention concerns a method for decreasing both the oral and parenteral abuse potential of strong analgetic agents such as oxycodone, propoxyphene and pentazocine by combining an analgesic dose of the analgetic agents with naloxone in specific, relatively narrow ranges. Oxycodone-naloxone compositions having a ratio of 2.5-5:1 parts by weight and pentazocine-naloxone compositions having a ratio of 16-50:1 parts by weight are preferred.

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Excerpt(s): The potential for abuse, by both the oral and parenteral routes, of strong analgetic agents such as oxycodone, propoxyphene and pentazocine, is greatly decreased by combining an effective analgesic dose thereof with naloxone in specific, relatively narrow ranges of ratios by weight. It is known that strong analgetic agents such as oxycodone, propoxyphene or pentazocine can cause physical and psychic (mental) dependence in laboratory animals and man. This potential for abuse restricts the use of these agents as analgetics to a considerable extent. The present invention is concerned with a method of decreasing both the oral and parenteral abuse potential of strong analgetic agents, such as oxycodone, propoxyphene or pentazocine, by administration of the analgetic agent in combination with naloxone, thereby permitting more extensive analgesic use. U.S. Pat. No. 3,773,955 issued Nov. 20, 1973 to I. J. Pachter and M. Gordon describes orally effective analgetic compositions which, upon parenteral administration, do not produce analgesia, euphoria or physical dependence, and thereby prevent parenteral abuse of the analgetic agents. Examples of such compositions, in parts by weight, include 1 part of naloxone per 2 to 20 parts of oxycodone, 1 part of naloxone per 12 to 120 parts of dextropropoxyphene (propoxyphene) and 1 part of naloxone per 8 to 80 parts of pentazocine. Reference is also made to oral unit dosage forms of analgesics containing from 0.1 mg to about 10 mg of naloxone per analgetic oral dose. This reference is not concerned with the prevention of oral abuse of analgetic agents. Web site: http://www.delphion.com/details?pn=US04457933__ •

Synergistic analgesic combination of oxycodone and rofecoxib Inventor(s): Burch; Ronald M. (Wilton, CT), Goldenheim; Paul D. (Wilton, CT), Sackler; Richard S. (Greenwich, CT) Assignee(s): Euro-Celtique S.A. (Luxembourg, LU) Patent Number: 6,552,031 Date filed: September 17, 1998 Abstract: Disclosed is a pharmaceutical composition, comprising a combination of a dose of rofecoxib or a pharmaceutically acceptable salt thereof and a dose of oxcodone or a pharmaceutically acceptable salt thereof, said combination in an amount sufficient to provide an analgesic effect in a human patient. Also disclosed is a method of effectively treating pain in humans or other mammals, comprising administering to the patient a combination of a dose of rofecoxib or a pharmaceutically acceptable salt thereof and a dose of oxycodone or a pharmaceutically acceptable salt thereof such that the dosing interval of the rofecoxib overlaps with the dosing interval of the oxycodone, said combination in an amount sufficient to provide an analgesic effect in a human patient. Excerpt(s): The invention relates to analgesic pharmaceutical compositions containing an opioid analgesic and a cyclooxygenase-2 (COX-2) inhibitor. The invention also relates to methods of treating pain comprising administering such pharmaceutical compositions to human patients. There is a continuing need for analgesic medications able to provide high efficacy pain relief while reducing the possibility of undesirable effects. Non-steroidal anti-inflammatory drugs ("NSAID'S"), including compounds such as ibuprofen, ketoprofen and diclofenac, have anti-inflammatory actions and are effective on pain associated with the release of prostaglandins and other mediators of inflammation. For example, diclofenac is considered to be extremely potent and effective as an analgesic and anti-inflammatory agent. Diclofenac is approved in the United States

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for the long-term symptomatic treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. It is also considered to be useful for the short-term treatment of acute musculoskeletal injury, acute painful shoulder, postoperative pain and dysmenorrhea. However, NSAID'S such as diclofenac produce side effects in about 20% of patients that require cessation of medication. Side effects include, for example, gastrointestinal bleeding and the abnormal elevation of liver enzymes. The opioids are a group of drugs, both natural and synthetic, that are employed primarily as centrallyacting analgesics and are opium or morphine-like in their properties (Gilman et al., 1980, GOODMAN AND GILMAN'S. THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, Chapter 24:494-534, Pub. Pergamon Press; hereby incorporated by reference). The opioids include morphine and morphine-like homologs, including, e.g., the semisynthetic derivatives codeine (methylmorphine) and hydrocodone (dihydrocodeinone) among many other such derivatives. Morphine and related opioids exhibit agonist activity at central nervous system or CNS (referring to the brain and spinal cord).mu. (mu) opioid receptors as well as showing affinity for the.delta. and.kappa. opioid receptors, to produce a range of effects including analgesia, drowsiness, changes in mood and mental clouding. In addition to potent analgesic effects, the morphine-related opioids may also cause a number of undesirable effects, including, for example, respiratory depression, nausea, vomiting, dizziness, mental clouding, dysphoria, pruritus, constipation, increased biliary tract pressure, urinary retention and hypotension. The development of tolerance to the opioid drugs and the risk of chemical dependence and abuse for these drugs is another undesirable effect. Web site: http://www.delphion.com/details?pn=US06552031__

Patent Applications on Oxycodone As of December 2000, U.S. patent applications are open to public viewing.9 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to Oxycodone: •

Analgesic combination of oxycodone and meloxicam Inventor(s): Burch, Ronald M.; (Wilton, CT), Goldenheim, Paul D.; (Wilton, CT), Sackler, Richard S.; (Greenwich, CT) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20020099049 Date filed: January 25, 2002 Abstract: Disclosed is a pharmaceutical composition, comprising a combination of a dose of meloxicam or a pharmaceutically acceptable salt thereof and a dose of oxycodone or a pharmaceutically acceptable salt thereof, said combination in an amount sufficient to provide an analgesic effect in a human patient. Also disclosed is a method of effectively treating pain in humans or other mammals, comprising administering to the patient a combination of a dose of meloxicam or a pharmaceutically acceptable salt thereof and a dose of oxycodone or a pharmaceutically acceptable salt thereof such that the dosing interval of the meloxicam overlaps with the dosing interval of the

9

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

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oxycodone, said combination in an amount sufficient to provide an analgesic effect in a human patient. Excerpt(s): The invention relates to analgesic pharmaceutical compositions containing an opioid analgesic and a cyclooxygenase-2 (COX-2) inhibitor. The invention also relates to methods of treating pain comprising administering such pharmaceutical compositions to human patients. There is a continuing need for analgesic medications able to provide high efficacy pain relief while reducing the possibility of undesirable effects. Non-steroidal anti-inflammatory drugs ("NSAID'S"), including compounds such as ibuprofen, ketoprofen and diclofenac, have anti-inflammatory actions and are effective on pain associated with the release of prostaglandins and other mediators of inflammation. For example, diclofenac is considered to be extremely potent and effective as an analgesic and anti-inflammatory agent. Diclofenac is approved in the United States for the long-term symptomatic treatment of rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. It is also considered to be useful for the short-term treatment of acute musculoskeletal injury, acute painful shoulder, postoperative pain and dysmenorrhea. However, NSAID'S such as diclofenac produce side effects in about 20% of patients that require cessation of medication. Side effects include, for example, gastrointestinal bleeding and the abnormal elevation of liver enzymes. The opioids are a group of drugs, both natural and synthetic, that are employed primarily as centrallyacting analgesics and are opium or morphine-like in their properties (Gilman et al., 1980, GOODMAN AND GILMAN'S. THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, Chapter 24:494-534, Pub. Pergamon Press; hereby incorporated by reference). The opioids include morphine and morphine-like homologs, including, e.g., the semisynthetic derivatives codeine (methylmorphine) and hydrocodone (dihydrocodeinone) among many other such derivatives. Morphine and related opioids exhibit agonist activity at central nervous system or CNS (referring to the brain and spinal cord).mu. (mu) opioid receptors as well as showing affinity for the.delta. and.kappa. opioid receptors, to produce a range of effects including analgesia, drowsiness, changes in mood and mental clouding. In addition to potent analgesic effects, the morphine-related opioids may also cause a number of undesirable effects, including, for example, respiratory depression, nausea, vomiting, dizziness, mental clouding, dysphoria, pruritus, constipation, increased biliary tract pressure, urinary retention and hypotension. The development of tolerance to the opioid drugs and the risk of chemical dependence and abuse for these drugs is another undesirable effect. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Combination sustained release-immediate release oral dosage forms with an opioid analgesic and a non-opioid analgesic Inventor(s): Jim, Fai; (Franklin Square, NY), Kao, Huaihung; (Syosset, NY), Zeng, Yadi; (Fort Lee, NJ) Correspondence: Kramer Levin Naftalis & Frankel Llp; 919 Third Avenue; New York; NY; 10022; US Patent Application Number: 20030092724 Date filed: September 17, 2002 Abstract: The present invention relates to new and useful oral tablet compositions which include an immediate release portion having an opioid analgesic and a non-opioid analgesic, providing for a rapid onset of therapeutic effect, and a sustained release portion of an opioid analgesic and a non-opioid analgesic, providing for a relatively

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longer duration of therapeutic effect. A multilayer oral dosage form containing a sustained release layer, which includes oxycodone and APAP, hydrocodone and APAP, or oxymorphone and APAP, and an immediate release layer containing the same active ingredients as the sustained release layer, is also disclosed. Also disclosed are oral tablet compositions, containing a sustained release core, which includes oxycodone and APAP, hydrocodone and APAP, or oxymorphone and APAP, and an immediate release coating containing the same active ingredients as the sustained release core, are also disclosed. In addition, methods of making and using such oral tablet compositions are disclosed. Excerpt(s): This application claims priority to U.S. Provisional Application Serial No. 60/322,667, filed Sep. 17, 2001 and U.S. Provisional Application Serial No. 60/323,546, filed Sep. 19, 2001, the specifications of which are incorporated by reference into this application in their entirety. The present invention relates to new and useful oral tablet compositions that include an immediate release portion having a combination of an opioid analgesic and a non-opioid analgesic, which will provide a rapid onset of therapeutic effect, and a sustained release portion with a combination of an opioid analgesic and a non-opioid analgesic, which will provide for a longer duration of therapeutic effect. Sustained release oral dosage forms of therapeutically active substances are well known in the pharmaceutical arts. These dosage forms provide a relatively long duration of action as the active agent is gradually released in the gastrointestinal tract. However, they may not provide a sufficiently early onset of therapeutic effect as is commonly seen with some immediate release dosage forms. On the other hand, though immediate release dosage forms may provide early onset of activities, the duration of therapeutic effect may be relatively short, which might require repeated dosing every few hours or so. Unless the dosing of the immediate release dosage form is carefully monitored, maintaining a constant plasma level of active agents without wide fluctuations is often difficult. Hence, an orally administered tablet formulation which provides a favorable dissolution profile which may lead to a relatively constant plasma level of active agents and which provides both an early onset and a long duration of therapeutic effect would be highly desirable. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Controlled release oxycodone compositions Inventor(s): Chasin, Mark; (Manalpan, NJ), Francis Kaiko, Robert; (Weston, CT), Minogue, John Joseph; (Mount Vernon, NY), Oshlack, Benjamin; (New York, NY) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20010008639 Date filed: February 16, 2001 Abstract: A method for substantially reducing the range in daily dosages required to control pain in approximately 90% of patients is disclosed whereby an oral solid controlled release dosage formulation having from about 10 to about 40 mg of oxycodone or a salt thereof is administered to a patient. The formulation provides a mean maximum plasma concentration of oxycodone from about 6 to about 60 ng/ml from a mean of about 2 to about 4.5 hours after administration, and a mean minimum plasma concentration from about 3 to about 30 ng/ml from about 10 to about 14 hours after repeated "q12h" (i.e., every 12 hour) administration through steady-state conditions. Another embodiment is directed to a method for substantially reducing the

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range in daily dosages required to control pain in substantially all patients by administering an oral solid controlled release dosage formulation comprising up to about 160 mg of oxycodone or a salt thereof, such that a mean maximum plasma concentration of oxycodone up to about 240 ng/ml from a mean of up to about 2 to about 4.5 hours after administration, and a mean minimum plasma concentration up to about 120 ng/ml from about 10 to about 14 hours after repeated "q12h" (i.e., every 12 hour) administration through steady-state conditions are achieved. Controlled release oxycodone formulations for achieving the above are also disclosed. Excerpt(s): This application is a continuation of Ser. No. 08/081,302, filed Jun. 18, 1993, which is a continuation-in-part of Ser. No. 07/800,549, filed Nov. 27, 1991, now U.S. Pat. No. 5,266,331, hereby incorporated by reference. Surveys of daily dosages of opioid analgesics required to control pain suggest that an approximately eight-fold range in daily dosages is required to control pain in approximately 90% of patients. This extraordinary wide range in the appropriate dosage makes the titration process particularly time consuming and resource consuming, as well as leaving the patient without acceptable pain control for an unacceptably long duration. An opioid analgesic treatment which acceptably controls pain over a substantially narrower daily dosage range would, therefore, substantially improve the efficiency and quality of pain management. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Haptens, immunogens and antibodies to oxycodone and its metabolites Inventor(s): Benchikh, El Ouard; (Co. Antrim, IE), Fitzgerald, Stephen Peter; (Co. Antrim, GB), Lamont, John Victor; (Co.Antrim, IE), Lowry, Andrew Philip; (Co. Antrim, IE), McConnell, Robert Ivan; (Co.Antrim, IE) Correspondence: Oliff & Berridge, Plc; P.O. Box 19928; Alexandria; VA; 22320; US Patent Application Number: 20030157565 Date filed: December 20, 2002 Abstract: Novel haptens, which can be conjugated to form immunogens, are of formula I, II or III 1wherein R is a divalent alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, and X is a functional group. Excerpt(s): The present invention relates to novel hapten derivatives of oxycodone, and their use in the preparation of immunogens. Specific binding reactions, such as antibody-antigen reactions, have been used extensively in immunoassays to detect and/or quantify a variety of drugs or other compounds of interest in biological fluids. Such immunoassays have been developed for the determination of antigens such as proteins, as well as small molecules (haptens). Haptens are by definition molecules too small to stimulate the production of antibodies when administered to an animal; that is, haptens by themselves are not immunogenic. However, it is well known that a hapten can be made immunogenic by conjugating it to an appropriate carrier material, which will elicit an immunogenic response when injected into a host animal. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Method for preparing oxycodone Inventor(s): Chiu, Fang-Ting; (Chesterfield, VA), Lo, Young S.; (Chester, VA) Correspondence: Boehringer Ingelheim Corporation; 900 Ridgebury Road; P O Box 368; Ridgefield; CT; 06877; US Patent Application Number: 20010005754 Date filed: February 26, 2001 Abstract: A method for the preparation of oxycodone, and salts thereof, from codeine comprising oxidation of codeine to codeinone, formation of an dienolsilyl ether congener of codeinone in strong amine base, oxidation of the dienolsilyl ether congener using peracetic acid, and hydrogenation of the resulting 14-hydroxycodeinone product. Excerpt(s): The present invention relates to an improved method for preparing oxycodone. More particularly, the present invention sets forth a method for preparing oxycodone in high yields that does not require the employment, or synthesis, of thebaine in the reaction scheme. The analgesic activity of Papaver somniferum has been known since antiquity. It has long been understood that the milky juice derived from the unripe seed capsules of this poppy plant possesses potent pharmacological properties. The dried and powdered form of the juice is referred to as opium. Opium comprises about 10% of the juice obtained from the unripe seed capsules of Papaver somniferum. Early in the nineteenth century it was recognized that opium contains numerous alkaloid compounds. The first of these alkaloids to be isolated was morphine, described by Serturner in 1805. The isolation of other alkaloids, including codeine (Robiquet 1832), papaverine (Merck 1848), thebaine, oripavine and noscapine followed in short order. By the middle of the nineteenth century, the use of pure alkaloids rather than crude opium preparations was established medical practice. It is now known that opium contains more than twenty distinct alkaloids. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Pharmaceutical combinations of oxycodone and naloxone Inventor(s): Breder, Christopher D.; (Greenwich, CT), Colucci, Robert D.; (Newtown, CT), Howard, Stephen A.; (Danbury, CT), Oshlack, Benjamin; (New York, NY), Wright, Curtis; (Norwalk, CT) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20030069263 Date filed: July 18, 2002 Abstract: Disclosed in certain embodiments is a pharmaceutical composition comprising from 10 to 40 mg of oxycodone or a pharmaceutically acceptable salt thereof and 0.65 to 0.90 mg naloxone or a pharmaceutically acceptable salt thereof. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/306,301, filed Jul. 18, 2001, hereby incorporated by reference. Oxycodone formulations are sometimes the subject of abuse. A particular dose of oxycodone may be more potent when administered parenterally as compared to the same dose administered orally. One mode of abuse of oral oxycodone formulations involves putting the active agent in solution and injecting it. Opioid antagonists have been combined with certain opioid agonists in order to deter the parenteral abuse of these

Patents 55

drugs. In the prior art, the combination of immediate release pentazocine and naloxone has been utilized in tablets available in the United States, commercially available as Talwin.RTM.Nx from Sanofi-Winthrop. Talwin.RTM.Nx contains immediate release pentazocine hydrochloride equivalent to 50 mg base and naloxone hydrochloride equivalent to 0.5 mg base. A fixed combination therapy comprising tilidine (50 mg) and naloxone (4 mg) has been available in Germany for the management of pain since 1978 (Valoron.RTM.N, Goedecke). A fixed combination of buprenorphine and naloxone was introduced in 1991 in New Zealand (Temgesic Nx, Reckitt & Colman) for the treatment of pain. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Sustained release oxycodone formulations with no fed/fast effect Inventor(s): Chasin, Mark; (Manalapan, NJ), Oshlack, Benjamin; (New York, NY) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20010031278 Date filed: April 5, 2001 Abstract: A solid controlled release, oral dosage form, the dosage form comprising a therapeutically effective amount of oxycodone or a salt thereof together with a sustained release carrier which causes the formulation to preferentially release the drug in low pH (e.g., gastric fluid) is bioavailable and does not exhibit a fed/fast effect. Excerpt(s): The present invention relates to solid, controlled release oral dosage forms for use in the treatment of moderate to severe pain, which do not exhibit a altered absorption of active ingredient in the presence of food. It has been previously known in the art that controlled release oxycodone formulations could be prepared via sustained release coated bead or sustained release matrix formulations. For example, U.S. Pat. No. 5,266,331, assigned to the assignee of the present invention and hereby incorporated by reference in its entirety, teaches controlled release oxycodone formulations prepared utilizing a suitable sustained release matrix. The preparations described in the '331 patent preferably exhibit an in-vitro dissolution rate of the dosage form, when measured by the USP Paddle Method at 100 rpm in 900 ml aqueous buffer (pH between 1.6 and 7.2) at 37.degree. C., which is between 12.5 and 42.5% (by wt) oxycodone released after 1 hour, between 25 and 55% (by wt) released after 2 hours, between 45 and 75% (by wt) released after 4 hours and between 55 and 85% (by wt) released after 6 hours, the invitro release rate being independent of pH between pH 1.6 and 7.2 and chosen such that the peak plasma level of oxycodone obtained in vivo occurs between 2 and 4 hours after administration of the dosage form. It further known that suitable sustained release oxycodone formulations are prepared using sustained release coated spheroid formulations, as described in U.S. Pat. No. 5,508,042 (Oshlack et al.) assigned to the assignee of the present invention and hereby incorporated by reference in its entirety. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Keeping Current In order to stay informed about patents and patent applications dealing with Oxycodone, 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 “Oxycodone” (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 Oxycodone. You can also use this procedure to view pending patent applications concerning Oxycodone. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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CHAPTER 5. PERIODICALS AND NEWS ON OXYCODONE Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Oxycodone.

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

Oxycodone reduces moderate to severe pain of diabetic neuropathy Source: Reuters Industry Breifing Date: March 31, 2003

•

Controlled-Release Oxycodone Alternative To Hydromorphone For Cancer Pain Source: Reuters Medical News Date: April 09, 1997

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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 “Oxycodone” (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 “Oxycodone” (or synonyms). If you know the name of a company that is relevant to Oxycodone, you can go to any stock trading Web site (such as http://www.etrade.com/) and search for the company name there. News items across various news sources are reported on indicated hyperlinks. Google offers a similar service at http://news.google.com/. BBC Covering news from a more European perspective, the British Broadcasting Corporation (BBC) allows the public free access to their news archive located at http://www.bbc.co.uk/. Search by “Oxycodone” (or synonyms).

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

Periodicals and News

59

these sources, you can search for articles covering Oxycodone that have been published by any of the periodicals listed in previous chapters. To find the latest studies published, go to http://www.ncbi.nlm.nih.gov/pubmed, type the name of the periodical into the search box, and click “Go.” If you want complete details about the historical contents of a journal, you can also visit the following Web site: http://www.ncbi.nlm.nih.gov/entrez/jrbrowser.cgi. Here, type in the name of the journal or its abbreviation, and you will receive an index of published articles. At http://locatorplus.gov/, you can retrieve more indexing information on medical periodicals (e.g. the name of the publisher). Select the button “Search LOCATORplus.” Then type in the name of the journal and select the advanced search option “Journal Title Search.”

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CHAPTER 6. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

U.S. Pharmacopeia Because of historical investments by various organizations and the emergence of the Internet, it has become rather simple to learn about the medications recommended for Oxycodone. 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 Oxycodone. 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 Oxycodone: Narcotic Analgesics and Acetaminophen •

Systemic - U.S. Brands: Allay; Anexsia 5/500; Anexsia 7.5/650; Anolor DH 5; Bancap-HC; Capital with Codeine; Co-Gesic; Darvocet-N 100; Darvocet-N 50; DHCplus; Dolacet; Dolagesic; Duocet; E-Lor; Endocet; EZ III; Hycomed; HycoPap; Hydrocet; Hydrogesic; HY-PHEN; Lorcet 10/650; L http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202392.html

Narcotic Analgesics and Aspirin •

Systemic - U.S. Brands: Damason-P; Darvon Compound-65; Empirin with Codeine No.3; Empirin with Codeine No.4; Endodan; Lortab ASA; Panasal 5/500; PC-Cap; Percodan; Percodan-Demi; Propoxyphene Compound-65; Roxiprin; Synalgos-DC; Talwin Compound http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202393.html

Narcotic Analgesics for Pain Relief •

Systemic - U.S. Brands: Astramorph PF; Buprenex; Cotanal-65; Darvon; DarvonN; Demerol; Dilaudid; Dilaudid-5; Dilaudid-HP; Dolophine; Duramorph; Hydrostat IR; Kadian; Levo-Dromoran; M S Contin; Methadose; MS/L; MS/L Concentrate; MS/S; MSIR; Nubain; Numorphan; OMS Concentrate; http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202390.html

Commercial Databases In addition to the medications listed in the USP above, a number of commercial sites are available by subscription to physicians and their institutions. Or, you may be able to access these sources from your local medical library.

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html.

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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

67

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 Institute10: •

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/

10

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.11 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:12 •

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

11 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). 12 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 Gateway13 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.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Oxycodone” (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 481 1 744 4 1 1231

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 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.17 Simply search by “Oxycodone” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

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). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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 Biologists18 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.19 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.20 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/.

18 Adapted 19

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. 20 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 Oxycodone 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 Oxycodone. 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 Oxycodone. 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 “Oxycodone”:

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Oxycodone

•

Other guides Interstitial Cystitis http://www.nlm.nih.gov/medlineplus/interstitialcystitis.html Prescription Drug Abuse http://www.nlm.nih.gov/medlineplus/prescriptiondrugabuse.html Restless Legs http://www.nlm.nih.gov/medlineplus/restlesslegs.html

You may also choose to use the search utility provided by MEDLINEplus at the following Web address: http://www.nlm.nih.gov/medlineplus/. Simply type a keyword into the search box and click “Search.” This utility is similar to the NIH search utility, with the exception that it only includes materials that are linked within the MEDLINEplus system (mostly patient-oriented information). It also has the disadvantage of generating unstructured results. We recommend, therefore, that you use this method only if you have a very targeted search. The NIH Search Utility The NIH search utility allows you to search for documents on over 100 selected Web sites that comprise the NIH-WEB-SPACE. Each of these servers is “crawled” and indexed on an ongoing basis. Your search will produce a list of various documents, all of which will relate in some way to Oxycodone. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

AOL: http://search.aol.com/cat.adp?id=168&layer=&from=subcats

•

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

•

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

•

Med Help International: http://www.medhelp.org/HealthTopics/A.html

•

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

•

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

•

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

Patient Resources

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Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Oxycodone. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with Oxycodone. 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 Oxycodone. For more information, see the NHIC’s Web site at http://www.health.gov/NHIC/ or contact an information specialist by calling 1-800-336-4797. Directory of Health Organizations The Directory of Health Organizations, provided by the National Library of Medicine Specialized Information Services, is a comprehensive source of information on associations. The Directory of Health Organizations database can be accessed via the Internet at http://www.sis.nlm.nih.gov/Dir/DirMain.html. It is composed of two parts: DIRLINE and Health Hotlines. The DIRLINE database comprises some 10,000 records of organizations, research centers, and government institutes and associations that primarily focus on health and biomedicine. To access DIRLINE directly, go to the following Web site: http://dirline.nlm.nih.gov/. Simply type in “Oxycodone” (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 “Oxycodone”. 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 “Oxycodone” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Oxycodone” (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.21

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

21

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)22: •

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/

22

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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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

•

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

•

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

•

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

•

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

•

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

•

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

•

New York: Health Sciences Library (Long Island Jewish Medical Center, New Hyde Park), http://www.lij.edu/library/library.html

•

New York: ViaHealth Medical Library (Rochester General Hospital), http://www.nyam.org/library/

•

Ohio: Consumer Health Library (Akron General Medical Center, Medical & Consumer Health Library), http://www.akrongeneral.org/hwlibrary.htm

•

Oklahoma: The Health Information Center at Saint Francis Hospital (Saint Francis Health System, Tulsa), http://www.sfh-tulsa.com/services/healthinfo.asp

•

Oregon: Planetree Health Resource Center (Mid-Columbia Medical Center, The Dalles), http://www.mcmc.net/phrc/

•

Pennsylvania: Community Health Information Library (Milton S. Hershey Medical Center, Hershey), http://www.hmc.psu.edu/commhealth/

•

Pennsylvania: Community Health Resource Library (Geisinger Medical Center, Danville), http://www.geisinger.edu/education/commlib.shtml

•

Pennsylvania: HealthInfo Library (Moses Taylor Hospital, Scranton), http://www.mth.org/healthwellness.html

•

Pennsylvania: Hopwood Library (University of Pittsburgh, Health Sciences Library System, Pittsburgh), http://www.hsls.pitt.edu/guides/chi/hopwood/index_html

•

Pennsylvania: Koop Community Health Information Center (College of Physicians of Philadelphia), http://www.collphyphil.org/kooppg1.shtml

•

Pennsylvania: Learning Resources Center - Medical Library (Susquehanna Health System, Williamsport), http://www.shscares.org/services/lrc/index.asp

•

Pennsylvania: Medical Library (UPMC Health System, Pittsburgh), http://www.upmc.edu/passavant/library.htm

•

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

•

Texas: Houston HealthWays (Houston Academy of Medicine-Texas Medical Center Library), http://hhw.library.tmc.edu/

•

Washington: Community Health Library (Kittitas Valley Community Hospital), http://www.kvch.com/

•

Washington: Southwest Washington Medical Center Library (Southwest Washington Medical Center, Vancouver), http://www.swmedicalcenter.com/body.cfm?id=72

83

ONLINE GLOSSARIES The Internet provides access to a number of free-to-use medical dictionaries. The National Library of Medicine has compiled the following list of online dictionaries: •

ADAM Medical Encyclopedia (A.D.A.M., Inc.), comprehensive medical reference: http://www.nlm.nih.gov/medlineplus/encyclopedia.html

•

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

•

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

•

Multilingual Glossary of Technical and Popular Medical Terms in Eight European Languages (European Commission) - Danish, Dutch, English, French, German, Italian, Portuguese, and Spanish: http://allserv.rug.ac.be/~rvdstich/eugloss/welcome.html

•

On-line Medical Dictionary (CancerWEB): http://cancerweb.ncl.ac.uk/omd/

•

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

•

Technology Glossary (National Library of Medicine) - Health Care Technology: http://www.nlm.nih.gov/nichsr/ta101/ta10108.htm

Beyond these, MEDLINEplus contains a very patient-friendly encyclopedia covering every aspect of medicine (licensed from A.D.A.M., Inc.). The ADAM Medical Encyclopedia can be accessed at http://www.nlm.nih.gov/medlineplus/encyclopedia.html. ADAM is also available on commercial Web sites such as drkoop.com (http://www.drkoop.com/) and Web MD (http://my.webmd.com/adam/asset/adam_disease_articles/a_to_z/a).

Online Dictionary Directories The following are additional online directories compiled by the National Library of Medicine, including a number of specialized medical dictionaries: •

Medical Dictionaries: Medical & Biological (World Health Organization): http://www.who.int/hlt/virtuallibrary/English/diction.htm#Medical

•

MEL-Michigan Electronic Library List of Online Health and Medical Dictionaries (Michigan Electronic Library): http://mel.lib.mi.us/health/health-dictionaries.html

•

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

•

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

85

OXYCODONE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. 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] Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] Acetaminophen: Analgesic antipyretic derivative of acetanilide. It has weak antiinflammatory properties and is used as a common analgesic, but may cause liver, blood cell, and kidney damage. [NIH] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] 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] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Aldehydes: Organic compounds containing a carbonyl group in the form -CHO. [NIH] Alertness: A state of readiness to detect and respond to certain specified small changes occurring at random intervals in the environment. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] 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]

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Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. Alternative medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Amine: An organic compound containing nitrogen; any member of a group of chemical compounds formed from ammonia by replacement of one or more of the hydrogen atoms by organic (hydrocarbon) radicals. The amines are distinguished as primary, secondary, and tertiary, according to whether one, two, or three hydrogen atoms are replaced. The amines include allylamine, amylamine, ethylamine, methylamine, phenylamine, propylamine, and many other compounds. [EU] Amino Acid Sequence: The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining protein conformation. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amnestic: Nominal aphasia; a difficulty in finding the right name for an object. [NIH] Amphetamine: A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is dextroamphetamine. [NIH] Anaesthesia: Loss of feeling or sensation. Although the term is used for loss of tactile sensibility, or of any of the other senses, it is applied especially to loss of the sensation of pain, as it is induced to permit performance of surgery or other painful procedures. [EU] Analgesic: An agent that alleviates pain without causing loss of consciousness. [EU] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] 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] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another

Dictionary 87

living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cruciate Ligament: A strong ligament of the knee that originates from the posteromedial portion of the lateral condyle of the femur, passes anteriorly and inferiorly between the condyles, and attaches to the depression in front of the intercondylar eminence of the tibia. [NIH] 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] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antibiotic Prophylaxis: Use of antibiotics before, during, or after a diagnostic, therapeutic, or surgical procedure to prevent infectious complications. [NIH] Antibodies: Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the antigen that induced their synthesis in cells of the lymphoid series (especially plasma cells), or with an antigen closely related to it. [NIH] Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticonvulsant: An agent that prevents or relieves convulsions. [EU] Antidepressant: A drug used to treat depression. [NIH] Antigen: Any substance which is capable, under appropriate conditions, of inducing a specific immune response and of reacting with the products of that response, that is, with specific antibody or specifically sensitized T-lymphocytes, or both. Antigens may be soluble substances, such as toxins and foreign proteins, or particulate, such as bacteria and tissue cells; however, only the portion of the protein or polysaccharide molecule known as the antigenic determinant (q.v.) combines with antibody or a specific receptor on a lymphocyte. Abbreviated Ag. [EU] Anti-infective: An agent that so acts. [EU] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] 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] Anxiolytic: An anxiolytic or antianxiety agent. [EU] Aorta: The main trunk of the systemic arteries. [NIH] Aqueous: Having to do with water. [NIH] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal

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phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [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] Arthroplasty: Surgical reconstruction of a joint to relieve pain or restore motion. [NIH] Articular: Of or pertaining to a joint. [EU] Aspartate: A synthetic amino acid. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Attenuated: Strain with weakened or reduced virulence. [NIH] Autacoids: A chemically diverse group of substances produced by various tissues in the body that cause slow contraction of smooth muscle; they have other intense but varied pharmacologic activities. [NIH] Autopsy: Postmortem examination of the 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] Bacterial Infections: Infections by bacteria, general or unspecified. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] 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 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] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Bioavailable: The ability of a drug or other substance to be absorbed and used by the body. Orally bioavailable means that a drug or other substance that is taken by mouth can be absorbed and used by the body. [NIH] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and

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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] 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] Body Fluids: Liquid components of living organisms. [NIH] Bone Marrow: The soft tissue filling the cavities of bones. Bone marrow exists in two types, yellow and red. Yellow marrow is found in the large cavities of large bones and consists mostly of fat cells and a few primitive blood cells. Red marrow is a hematopoietic tissue and is the site of production of erythrocytes and granular leukocytes. Bone marrow is made up of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bupivacaine: A widely used local anesthetic agent. [NIH] Buprenorphine: A derivative of the opioid alkaloid thebaine that is a more potent and longer lasting analgesic than morphine. It appears to act as a partial agonist at mu and kappa opioid receptors and as an antagonist at delta receptors. The lack of delta-agonist activity has been suggested to account for the observation that buprenorphine tolerance may not develop with chronic use. [NIH] Butorphanol: A synthetic morphinan analgesic with narcotic antagonist action. It is used in the management of severe pain. [NIH] Caffeine: A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine's most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. It also relaxes smooth muscle, stimulates cardiac muscle, stimulates diuresis, and appears to be useful in the treatment of some types of headache. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable

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to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Carbon Dioxide: A colorless, odorless gas that can be formed by the body and is necessary for the respiration cycle of plants and animals. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiorespiratory: Relating to the heart and lungs and their function. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Case series: A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment. [NIH] Catecholamine: A group of chemical substances manufactured by the adrenal medulla and secreted during physiological stress. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] 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 Division: The fission of a cell. [NIH] Cell Respiration: The metabolic process of all living cells (animal and plant) in which oxygen is used to provide a source of energy for the cell. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebellar: Pertaining to the cerebellum. [EU] Cerebellar Diseases: Diseases that affect the structure or function of the cerebellum. Cardinal manifestations of cerebellar dysfunction include dysmetria, gait ataxia, and muscle hypotonia. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cholecystectomy: Surgical removal of the gallbladder. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other

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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] Clonazepam: An anticonvulsant used for several types of seizures, including myotonic or atonic seizures, photosensitive epilepsy, and absence seizures, although tolerance may develop. It is seldom effective in generalized tonic-clonic or partial seizures. The mechanism of action appears to involve the enhancement of gaba receptor responses. [NIH] Clonic: Pertaining to or of the nature of clonus. [EU] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coal: A natural fuel formed by partial decomposition of vegetable matter under certain environmental conditions. [NIH] Coca: Any of several South American shrubs of the Erythroxylon genus (and family) that yield cocaine; the leaves are chewed with alum for CNS stimulation. [NIH] Cocaine: An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. [NIH] Codeine: An opioid analgesic related to morphine but with less potent analgesic properties and mild sedative effects. It also acts centrally to suppress cough. [NIH] Colloidal: Of the nature of a colloid. [EU] Combination Therapy: Association of 3 drugs to treat AIDS (AZT + DDC or DDI + protease inhibitor). [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 '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

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activation also results in the formation of many biologically active complement fragments that act as anaphylatoxins, opsonins, or chemotactic factors. [EU] Complementary and alternative medicine: CAM. Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices are not considered standard medical approaches. CAM includes dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Complementary medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used to enhance or complement the standard treatments. Complementary medicine includes the taking of dietary supplements, megadose vitamins, and herbal preparations; the drinking of special teas; and practices such as massage therapy, magnet therapy, spiritual healing, and meditation. [NIH] Computational Biology: A field of biology concerned with the development of techniques 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] Concomitant: Accompanying; accessory; joined with another. [EU] Conjugated: Acting or operating as if joined; simultaneous. [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] 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] 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] 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 Artery Bypass: Surgical therapy of ischemic coronary artery disease achieved by grafting a section of saphenous vein, internal mammary artery, or other substitute between the aorta and the obstructed coronary artery distal to the obstructive lesion. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyclic: Pertaining to or occurring in a cycle or cycles; the term is applied to chemical compounds that contain a ring of atoms in the nucleus. [EU] Cyclosporine: A drug used to help reduce the risk of rejection of organ and bone marrow transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] 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

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of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delirium: (DSM III-R) an acute, reversible organic mental disorder characterized by reduced ability to maintain attention to external stimuli and disorganized thinking as manifested by rambling, irrelevant, or incoherent speech; there are also a reduced level of consciousness, sensory misperceptions, disturbance of the sleep-wakefulness cycle and level of psychomotor activity, disorientation to time, place, or person, and memory impairment. Delirium may be caused by a large number of conditions resulting in derangement of cerebral metabolism, including systemic infection, poisoning, drug intoxication or withdrawal, seizures or head trauma, and metabolic disturbances such as hypoxia, hypoglycaemia, fluid, electrolyte, or acid-base imbalances, or hepatic or renal failure. Called also acute confusional state and acute brain syndrome. [EU] Demethylation: Process that releases substantial amounts of carbon dioxide in the liver. [NIH]

Dental Caries: Localized destruction of the tooth surface initiated by decalcification of the enamel followed by enzymatic lysis of organic structures and leading to cavity formation. If left unchecked, the cavity may penetrate the enamel and dentin and reach the pulp. The three most prominent theories used to explain the etiology of the disase are that acids produced by bacteria lead to decalcification; that micro-organisms destroy the enamel protein; or that keratolytic micro-organisms produce chelates that lead to decalcification. [NIH]

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]

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Diagnostic procedure: A method used to identify a disease. [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] Dilatation: The act of dilating. [NIH] Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Discrimination: The act of qualitative and/or quantitative differentiation between two or more stimuli. [NIH] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Disorientation: The loss of proper bearings, or a state of mental confusion as to time, place, or identity. [EU] Disposition: A tendency either physical or mental toward certain diseases. [EU] Dissociation: 1. The act of separating or state of being separated. 2. The separation of a molecule into two or more fragments (atoms, molecules, ions, or free radicals) produced by the absorption of light or thermal energy or by solvation. 3. In psychology, a defense mechanism in which a group of mental processes are segregated from the rest of a person's mental activity in order to avoid emotional distress, as in the dissociative disorders (q.v.), or in which an idea or object is segregated from its emotional significance; in the first sense it is roughly equivalent to splitting, in the second, to isolation. 4. A defect of mental integration in which one or more groups of mental processes become separated off from normal consciousness and, thus separated, function as a unitary whole. [EU] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] 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]

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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] Dysmenorrhea: Painful menstruation. [NIH] Dysphoria: Disquiet; restlessness; malaise. [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] 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]

Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [NIH] Endoscopic: A technique where a lateral-view endoscope is passed orally to the duodenum for visualization of the ampulla of Vater. [NIH] End-stage renal: Total chronic kidney failure. When the kidneys fail, the body retains fluid and harmful wastes build up. A person with ESRD needs treatment to replace the work of the failed kidneys. [NIH] Enhancer: Transcriptional element in the virus genome. [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]

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] Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [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

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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] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Expiration: The act of breathing out, or expelling air from the lungs. [EU] Extracellular: Outside a cell or cells. [EU] Extraction: The process or act of pulling or drawing out. [EU] Extrapyramidal: Outside of the pyramidal tracts. [EU] Exudate: Material, such as fluid, cells, or cellular debris, which has escaped from blood vessels and has been deposited in tissues or on tissue surfaces, usually as a result of inflammation. An exudate, in contrast to a transudate, is characterized by a high content of protein, cells, or solid materials derived from cells. [EU] 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] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fentanyl: A narcotic opioid drug that is used in the treatment of pain. [NIH] Flatus: Gas passed through the rectum. [NIH] Fluorine: A nonmetallic, diatomic gas that is a trace element and member of the halogen family. It is used in dentistry as flouride to prevent dental caries. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Food Technology: The application of knowledge to the food industry. [NIH] GABA: The most common inhibitory neurotransmitter in the central nervous system. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH]

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Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [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]

Genetics: The biological science that deals with the phenomena and mechanisms of heredity. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glutamate: Excitatory neurotransmitter of the brain. [NIH] Glutathione Peroxidase: An enzyme catalyzing the oxidation of 2 moles of glutathione in the presence of hydrogen peroxide to yield oxidized glutathione and water. EC 1.11.1.9. [NIH]

Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] Grafting: The operation of transfer of tissue from one site to another. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Hallucination: A sense perception without a source in the external world; a perception of an external stimulus object in the absence of such an object. [EU] 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; 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] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodiafiltration: The combination of hemodialysis and hemofiltration either simultaneously or sequentially. Convective transport (hemofiltration) may be better for removal of larger molecular weight substances and diffusive transport (hemodialysis) for smaller molecular weight solutes. [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.

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The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemofiltration: Extracorporeal ultrafiltration technique without hemodialysis for treatment of fluid overload and electrolyte disturbances affecting renal, cardiac, or pulmonary function. [NIH] Hepatic: Refers to the liver. [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]

Homicide: The killing of one person by another. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Host: Any animal that receives a transplanted graft. [NIH] Hydrocodone: Narcotic analgesic related to codeine, but more potent and more addicting by weight. It is used also as cough suppressant. [NIH] Hydrogen: The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight 1. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are protons. Besides the common H1 isotope, hydrogen exists as the stable isotope deuterium and the unstable, radioactive isotope tritium. [NIH] Hydrogen Peroxide: A strong oxidizing agent used in aqueous solution as a ripening agent, bleach, and topical anti-infective. It is relatively unstable and solutions deteriorate over time unless stabilized by the addition of acetanilide or similar organic materials. [NIH] Hydromorphone: An opioid analgesic made from morphine and used mainly as an analgesic. It has a shorter duration of action than morphine. [NIH] Hyperalgesia: Excessive sensitiveness or sensibility to pain. [EU] Hypersensitivity: Altered reactivity to an antigen, which can result in pathologic reactions upon subsequent exposure to that particular antigen. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypotension: Abnormally low blood pressure. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] 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] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

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Immunoassay: Immunochemical assay or detection of a substance by serologic or immunologic methods. Usually the substance being studied serves as antigen both in antibody production and in measurement of antibody by the test substance. [NIH] Immunogenic: Producing immunity; evoking an immune response. [EU] Immunologic: The ability of the antibody-forming system to recall a previous experience with an antigen and to respond to a second exposure with the prompt production of large amounts of antibody. [NIH] Immunology: The study of the body's immune system. [NIH] 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 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] Indinavir: A potent and specific HIV protease inhibitor that appears to have good oral bioavailability. [NIH] Indomethacin: A non-steroidal anti-inflammatory agent (NSAID) that inhibits the enzyme cyclooxygenase necessary for the formation of prostaglandins and other autacoids. It also inhibits the motility of polymorphonuclear leukocytes. [NIH] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] Infection: 1. Invasion and multiplication of microorganisms in body tissues, which may be clinically unapparent or result in local cellular injury due to competitive metabolism, toxins, intracellular replication, or antigen-antibody response. The infection may remain localized, subclinical, and temporary if the body's defensive mechanisms are effective. A local infection may persist and spread by extension to become an acute, subacute, or chronic clinical infection or disease state. A local infection may also become systemic when the microorganisms gain access to the lymphatic or vascular system. 2. An infectious disease. [EU]

Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [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] Inhalation: The drawing of air or other substances into the lungs. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU]

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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] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] Intrinsic: Situated entirely within or pertaining exclusively to a part. [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] Isoflurane: A stable, non-explosive inhalation anesthetic, relatively free from significant side effects. [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] 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] Ketorolac Tromethamine: A pyrrolizine carboxylic acid derivative structurally related to indomethacin. It is a non-steroidal anti-inflammatory agent used for analgesia for postoperative pain and inhibits cyclooxygenase activity. [NIH] Kinetics: The study of rate dynamics in chemical or physical systems. [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] Lesion: An area of abnormal tissue change. [NIH] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [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] Levofloxacin: A substance used to treat bacterial infections. It belongs to the family of drugs called quinolone antibiotics. [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.

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[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] Ligation: Application of a ligature to tie a vessel or strangulate a part. [NIH] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver Transplantation: The transference of a part of or an entire liver from one human or animal to another. [NIH] Low Back Pain: Acute or chronic pain in the lumbar or sacral regions, which may be associated with musculo-ligamentous sprains and strains; intervertebral disk displacement; and other conditions. [NIH] Lumbar: Pertaining to the loins, the part of the back between the thorax and the pelvis. [EU] Lymphocyte: A white blood cell. Lymphocytes have a number of roles in the immune system, including the production of antibodies and other substances that fight infection and diseases. [NIH] Lymphoid: Referring to lymphocytes, a type of white blood cell. Also refers to tissue in which lymphocytes develop. [NIH] Lysine: An essential amino acid. It is often added to animal feed. [NIH] Malaise: A vague feeling of bodily discomfort. [EU] Malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body. [NIH] Mammary: Pertaining to the mamma, or breast. [EU] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Medullary: Pertaining to the marrow or to any medulla; resembling marrow. [EU] Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures. [NIH] Memory: Complex mental function having four distinct phases: (1) memorizing or learning, (2) retention, (3) recall, and (4) recognition. Clinically, it is usually subdivided into immediate, recent, and remote memory. [NIH] Meninges: The three membranes that cover and protect the brain and spinal cord. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Health: The state wherein the person is well adjusted. [NIH] Meperidine: 1-Methyl-4-phenyl-4-piperidinecarboxylic acid ethyl ester. A narcotic analgesic that can be used for the relief of most types of moderate to severe pain, including postoperative pain and the pain of labor. Prolonged use may lead to dependence of the morphine type; withdrawal symptoms appear more rapidly than with morphine and are of shorter duration. [NIH]

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Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] Methylphenidate: A central nervous system stimulant used most commonly in the treatment of attention-deficit disorders in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [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] Midazolam: A short-acting compound, water-soluble at pH less than 4 and lipid-soluble at physiological pH. It is a hypnotic-sedative drug with anxiolytic and amnestic properties. It is used for sedation in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. Because of its short duration and cardiorespiratory stability, it is particularly useful in poor-risk, elderly, and cardiac patients. [NIH]

Miosis: Pupillary constriction. This may result from congenital absence of the dilatator pupillary muscle, defective sympathetic innervation, or irritation of the conjunctiva or cornea. [NIH] Miotic: 1. Pertaining to, characterized by, or producing miosis : contraction of the pupil. 2. An agent that causes the pupil to contract. 3. Meiotic: characterized by cell division. [EU] 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] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monoamine: Enzyme that breaks down dopamine in the astrocytes and microglia. [NIH] Morphine: The principal alkaloid in opium and the prototype opiate analgesic and narcotic. Morphine has widespread effects in the central nervous system and on smooth muscle. [NIH] Morphine Derivatives: Analogs or derivatives of morphine. [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] 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]

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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] Narcotic Antagonists: Agents inhibiting the effect of narcotics on the central nervous system. [NIH] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuralgia: Intense or aching pain that occurs along the course or distribution of a peripheral or cranial nerve. [NIH] Neurogenic: Loss of bladder control caused by damage to the nerves controlling the bladder. [NIH] 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] Neuropharmacology: The branch of pharmacology dealing especially with the action of drugs upon various parts of the nervous system. [NIH] Neurotoxicity: The tendency of some treatments to cause damage to the nervous system. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] 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

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transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Noscapine: A naturally occurring opium alkaloid that is a centrally acting antitussive agent. [NIH]

Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Nucleus: A body of specialized protoplasm found in nearly all cells and containing the chromosomes. [NIH] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Opium: The air-dried exudate from the unripe seed capsule of the opium poppy, Papaver somniferum, or its variant, P. album. It contains a number of alkaloids, but only a few morphine, codeine, and papaverine - have clinical significance. Opium has been used as an analgesic, antitussive, antidiarrheal, and antispasmodic. [NIH] Osteoarthritis: 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] Ovaries: The pair of female reproductive glands in which the ova, or eggs, are formed. The ovaries are located in the pelvis, one on each side of the uterus. [NIH] Overdose: An accidental or deliberate dose of a medication or street drug that is in excess of what is normally used. [NIH] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxycodone: Semisynthetic derivative of codeine that acts as a narcotic analgesic more potent and addicting than codeine. [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Pain Threshold: Amount of stimulation required before the sensation of pain is experienced. [NIH]

Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Papaverine: An alkaloid found in opium but not closely related to the other opium alkaloids in its structure or pharmacological actions. It is a direct-acting smooth muscle relaxant used

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in the treatment of impotence and as a vasodilator, especially for cerebral vasodilation. The mechanism of its pharmacological actions is not clear, but it apparently can inhibit phosphodiesterases and it may have direct actions on calcium channels. [NIH] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pemoline: A central nervous system stimulant used in fatigue and depressive states and to treat hyperkinetic disorders in children. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Peracetic Acid: A liquid that functions as a strong oxidizing agent. It has an acrid odor and is used as a disinfectant. [NIH] Perception: The ability quickly and accurately to recognize similarities and differences among presented objects, whether these be pairs of words, pairs of number series, or multiple sets of these or other symbols such as geometric figures. [NIH] 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] 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] Pharmacogenetics: A branch of genetics which deals with the genetic components of variability in individual responses to and metabolism (biotransformation) of drugs. [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] Phenyl: Ingredient used in cold and flu remedies. [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] 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]

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]

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Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasma cells: A type of white blood cell that produces antibodies. [NIH] Poisoning: A condition or physical state produced by the ingestion, injection or inhalation of, or exposure to a deleterious agent. [NIH] Polysaccharide: A type of carbohydrate. It contains sugar molecules that are linked together chemically. [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] Postherpetic Neuralgia: Variety of neuralgia associated with migraine in which pain is felt in or behind the eye. [NIH] Postoperative: After surgery. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] 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] Probe: An instrument used in exploring cavities, or in the detection and dilatation of strictures, or in demonstrating the potency of channels; an elongated instrument for exploring or sounding body cavities. [NIH] Procaine: A local anesthetic of the ester type that has a slow onset and a short duration of action. It is mainly used for infiltration anesthesia, peripheral nerve block, and spinal block. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1016). [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] 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] Prostaglandins: A group of compounds derived from unsaturated 20-carbon fatty acids, primarily arachidonic acid, via the cyclooxygenase pathway. They are extremely potent mediators of a diverse group of physiological processes. [NIH] Prostaglandins A: (13E,15S)-15-Hydroxy-9-oxoprosta-10,13-dien-1-oic acid (PGA(1)); (5Z,13E,15S)-15-hydroxy-9-oxoprosta-5,10,13-trien-1-oic acid (PGA(2)); (5Z,13E,15S,17Z)-15hydroxy-9-oxoprosta-5,10,13,17-tetraen-1-oic acid (PGA(3)). A group of naturally occurring secondary prostaglandins derived from PGE. PGA(1) and PGA(2) as well as their 19hydroxy derivatives are found in many organs and tissues. [NIH] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs.

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They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [NIH] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protein Binding: The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific proteinbinding measures are often used as assays in diagnostic assessments. [NIH] Protein 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] Pruritus: An intense itching sensation that produces the urge to rub or scratch the skin to obtain relief. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [EU]

Psychomotor: Pertaining to motor effects of cerebral or psychic activity. [EU] Psychotomimetic: Psychosis miming. [NIH] Public Health: Branch of medicine concerned with the prevention and control of disease and disability, and the promotion of physical and mental health of the population on the international, national, state, or municipal level. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Edema: An accumulation of an excessive amount of watery fluid in the lungs, may be caused by acute exposure to dangerous concentrations of irritant gasses. [NIH] Pupil: The aperture in the iris through which light passes. [NIH] Quality of Life: A generic concept reflecting concern with the modification and enhancement of life attributes, e.g., physical, political, moral and social environment. [NIH] 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] Rectal: By or having to do with the rectum. The rectum is the last 8 to 10 inches of the large

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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] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relaxant: 1. Lessening or reducing tension. 2. An agent that lessens tension. [EU] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Respiration: The act of breathing with the lungs, consisting of inspiration, or the taking into the lungs of the ambient air, and of expiration, or the expelling of the modified air which 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] 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] Saphenous: Applied to certain structures in the leg, e. g. nerve vein. [NIH] Saphenous Vein: The vein which drains the foot and leg. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Selenium: An element with the atomic symbol Se, atomic number 34, and atomic weight 78.96. It is an essential micronutrient for mammals and other animals but is toxic in large amounts. Selenium protects intracellular structures against oxidative damage. It is an essential component of glutathione peroxidase. [NIH] Self Administration: Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. [NIH] Semisynthetic: Produced by chemical manipulation of naturally occurring substances. [EU]

Dictionary 109

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] Serologic: Analysis of a person's serum, especially specific immune or lytic serums. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] 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] 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] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Soft tissue: Refers to muscle, fat, fibrous tissue, blood vessels, or other supporting tissue of the body. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [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] Spinal cord: The main trunk or bundle of nerves running down the spine through holes in the spinal bone (the vertebrae) from the brain to the level of the lower back. [NIH] Spondylitis: Inflammation of the vertebrae. [EU]

110 Oxycodone

Sprains and Strains: A collective term for muscle and ligament injuries without dislocation or fracture. A sprain is a joint injury in which some of the fibers of a supporting ligament are ruptured but the continuity of the ligament remains intact. A strain is an overstretching or overexertion of some part of the musculature. [NIH] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH] Stomach: An organ of digestion situated in the left upper quadrant of the abdomen between the termination of the esophagus and the beginning of the duodenum. [NIH] Stress: Forcibly exerted influence; pressure. Any condition or situation that causes strain or tension. Stress may be either physical or psychologic, or both. [NIH] Stupor: Partial or nearly complete unconsciousness, manifested by the subject's responding only to vigorous stimulation. Also, in psychiatry, a disorder marked by reduced responsiveness. [EU] 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]

Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Symptomatic: Having to do with symptoms, which are signs of a condition or disease. [NIH] Symptomatic treatment: Therapy that eases symptoms without addressing the cause of disease. [NIH] Synergistic: Acting together; enhancing the effect of another force or agent. [EU] Systemic: Affecting the entire body. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] 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] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tissue Distribution: Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios. [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.

Dictionary 111

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] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxins: Specific, characterizable, poisonous chemicals, often proteins, with specific biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Trace element: Substance or element essential to plant or animal life, but present in extremely small amounts. [NIH] Tramadol: A narcotic analgesic proposed for severe pain. It may be habituating. [NIH] Transcutaneous: Transdermal. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Trauma: Any injury, wound, or shock, must frequently physical or structural shock, producing a disturbance. [NIH] Tremor: Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of Parkinson disease. [NIH] Tubal ligation: An operation to tie the fallopian tubes closed. This procedure prevents pregnancy by blocking the passage of eggs from the ovaries to the uterus. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Ultrafiltration: The separation of particles from a suspension by passage through a filter with very fine pores. In ultrafiltration the separation is accomplished by convective transport; in dialysis separation relies instead upon differential diffusion. Ultrafiltration occurs naturally and is a laboratory procedure. Artificial ultrafiltration of the blood is referred to as hemofiltration or hemodiafiltration (if combined with hemodialysis). [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

112 Oxycodone

Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] Urinate: To release urine from the bladder to the outside. [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] 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] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Vertebrae: A bony unit of the segmented spinal column. [NIH] 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] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Wakefulness: A state in which there is an enhanced potential for sensitivity and an efficient responsiveness to external stimuli. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

Withdrawal: 1. A pathological retreat from interpersonal contact and social involvement, as may occur in schizophrenia, depression, or schizoid avoidant and schizotypal personality disorders. 2. (DSM III-R) A substance-specific organic brain syndrome that follows the cessation of use or reduction in intake of a psychoactive substance that had been regularly used to induce a state of intoxication. [EU]

113

INDEX A Abdominal, 15, 20, 85, 104 Acceptor, 85, 104 Acetaminophen, 4, 11, 13, 14, 18, 19, 20, 25, 27, 29, 33, 35, 36, 62, 85 Adenosine, 85, 89, 105 Adjuvant, 9, 85 Adrenergic, 85, 87, 94, 95, 110 Adverse Effect, 85, 109 Affinity, 50, 51, 85, 93, 109 Agonist, 8, 24, 45, 50, 51, 85, 89, 94, 102, 103 Aldehydes, 46, 85 Alertness, 85, 89 Algorithms, 85, 89 Alimentary, 85, 100, 105 Alkaloid, 44, 54, 85, 89, 91, 102, 104 Allylamine, 86 Alternative medicine, 58, 86 Amine, 45, 54, 86 Amino Acid Sequence, 86, 87 Amino Acids, 86, 105, 107 Ammonia, 86 Amnestic, 86, 102 Amphetamine, 5, 86, 93 Anaesthesia, 13, 15, 26, 29, 33, 34, 86, 99 Analog, 86, 93 Analogous, 47, 86, 111 Anatomical, 35, 86, 99 Anesthesia, 4, 15, 16, 23, 24, 27, 28, 86, 87, 102, 106 Anions, 86, 100 Antagonism, 86, 89 Anterior Cruciate Ligament, 11, 24, 32, 34, 87 Anti-Anxiety Agents, 87, 106 Antibiotic, 87, 106 Antibiotic Prophylaxis, 87, 106 Antibodies, 53, 87, 97, 101, 106 Antibody, 53, 85, 87, 91, 97, 99, 109 Anticonvulsant, 9, 87, 91 Antidepressant, 8, 87 Antigen, 53, 85, 87, 91, 98, 99 Anti-infective, 87, 98 Anti-inflammatory, 4, 49, 51, 85, 87, 94, 98, 99, 100 Anti-Inflammatory Agents, 87, 100 Antipyretic, 85, 87, 94, 100

Antispasmodic, 87, 104 Antitussive, 87, 93, 104, 106 Anus, 87, 100, 108 Anxiolytic, 87, 102 Aorta, 87, 92 Aqueous, 55, 87, 88, 98 Arachidonic Acid, 87, 106 Arteries, 87, 88, 89, 92, 102 Arterioles, 88, 90 Arthroplasty, 11, 32, 88 Articular, 88, 104 Aspartate, 9, 88, 93 Assay, 7, 88, 99 Attenuated, 5, 88 Autacoids, 88, 99 Autopsy, 23, 88 B Back Pain, 18, 34, 88 Bacteria, 87, 88, 93, 96, 102, 112 Bacterial Infections, 88, 100 Base, 5, 44, 54, 55, 88, 93, 100, 110 Benzene, 46, 88 Bile, 88, 96, 101 Bile Ducts, 88 Biliary, 50, 51, 88 Biliary Tract, 50, 51, 88 Bioavailability, 17, 25, 26, 88, 99 Bioavailable, 55, 88 Biochemical, 88, 104, 109 Biotechnology, 10, 58, 69, 88 Biotransformation, 89, 105 Bladder, 89, 103, 111, 112 Blood pressure, 89, 98, 109 Body Fluids, 89, 109 Bone Marrow, 29, 88, 89, 92 Branch, 32, 81, 89, 103, 105, 107, 109, 110 Breakdown, 89, 94, 96 Bupivacaine, 16, 28, 33, 36, 89, 101 Buprenorphine, 5, 10, 13, 27, 55, 89 Butorphanol, 5, 11, 89 C Caffeine, 45, 89 Calcium, 89, 91, 105 Calcium Channels, 89, 105 Capillary, 14, 21, 90, 112 Capsules, 54, 90, 94 Carbon Dioxide, 90, 93, 108 Carcinogenic, 88, 90

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Cardiac, 86, 89, 90, 95, 98, 101, 102 Cardiorespiratory, 90, 102 Cardiovascular, 86, 90, 109 Case report, 90, 91 Case series, 90, 91 Catecholamine, 90, 94 Cations, 90, 100 Cell, 85, 88, 89, 90, 91, 96, 100, 102, 103, 105, 107, 108, 111, 112 Cell Division, 88, 90, 102, 105 Cell Respiration, 90, 108 Central Nervous System, 50, 51, 86, 88, 89, 90, 91, 93, 96, 97, 102, 103, 105, 109 Cerebellar, 90, 111 Cerebellar Diseases, 90, 111 Cerebral, 90, 92, 93, 95, 96, 105, 107 Cholecystectomy, 11, 39, 90 Chronic, 4, 5, 7, 14, 17, 18, 22, 24, 26, 27, 28, 32, 33, 34, 35, 36, 39, 88, 89, 90, 95, 99, 101 Chronic renal, 26, 35, 90 Clinical study, 10, 90 Clinical trial, 4, 69, 91, 92, 107 Clonazepam, 11, 91 Clonic, 91 Cloning, 89, 91 Coal, 88, 91 Coca, 91 Cocaine, 6, 91 Codeine, 7, 9, 10, 12, 13, 14, 19, 27, 28, 32, 36, 44, 45, 46, 47, 48, 50, 51, 54, 62, 91, 93, 98, 104 Colloidal, 91, 95 Combination Therapy, 55, 91 Complement, 91, 92 Complementary and alternative medicine, 39, 41, 92 Complementary medicine, 39, 92 Computational Biology, 69, 92 Concomitant, 44, 92 Conjugated, 53, 92, 93 Connective Tissue, 89, 92, 108 Consciousness, 86, 87, 92, 93, 94 Constipation, 45, 50, 51, 92 Contraindications, ii, 92 Convulsions, 87, 92, 98 Coronary, 27, 35, 92, 102 Coronary Artery Bypass, 27, 35, 92 Coronary Thrombosis, 92, 102 Curative, 92, 110 Cyclic, 46, 89, 92 Cyclosporine, 8, 92

Cytochrome, 8, 23, 92 D Databases, Bibliographic, 69, 93 Degenerative, 93, 104 Delirium, 13, 93 Demethylation, 8, 93 Dental Caries, 93, 96 Detoxification, 8, 13, 93 Deuterium, 7, 93, 98 Dextroamphetamine, 86, 93, 102 Dextromethorphan, 9, 93 Diagnostic procedure, 43, 58, 94 Diclofenac, 15, 17, 49, 51, 94 Diclofenac Sodium, 94 Diffusion, 94, 99, 111 Digestion, 85, 88, 94, 101, 110 Dilatation, 94, 106, 112 Direct, iii, 48, 61, 94, 104, 108 Discrimination, 6, 94 Disinfectant, 94, 105 Disorientation, 93, 94 Disposition, 8, 20, 94 Dissociation, 85, 94 Distal, 92, 94 Diuresis, 89, 94 Dizziness, 50, 51, 94 Dopamine, 6, 86, 91, 93, 94, 102 Dosage Forms, 49, 51, 52, 55, 94 Drug Interactions, 62, 95 Drug Tolerance, 95, 110 Dysmenorrhea, 50, 51, 95 Dysphoria, 50, 51, 95 E Efficacy, 4, 6, 8, 9, 12, 14, 15, 18, 19, 25, 26, 27, 28, 33, 34, 35, 36, 49, 51, 95 Electrolyte, 93, 95, 98, 109 Electrons, 88, 95, 100, 104 Electrophoresis, 14, 95 Embryo, 95, 99 Endoscopic, 95, 102 End-stage renal, 90, 95 Enhancer, 8, 95 Environmental Health, 68, 70, 95 Enzyme, 4, 8, 95, 97, 99, 102, 107, 112 Epidural, 15, 95 Epinephrine, 85, 94, 95, 103, 111 Erythrocytes, 89, 95 Ether, 7, 48, 54, 95 Euphoria, 49, 95 Evacuation, 92, 96 Evoke, 96, 110 Exogenous, 89, 96, 107

Index 115

Expiration, 96, 108 Extracellular, 92, 96, 109 Extraction, 26, 96 Extrapyramidal, 94, 96 Exudate, 96, 104 F Fallopian Tubes, 96, 111 Family Planning, 69, 96 Fat, 87, 89, 96, 101, 108, 109 Fatigue, 96, 105 Fatty acids, 96, 106 Feces, 92, 96 Femur, 87, 96 Fentanyl, 5, 8, 11, 13, 22, 32, 96 Flatus, 96 Fluorine, 46, 96 Fold, 53, 96 Food Technology, 96, 102 G GABA, 91, 96 Gallbladder, 85, 88, 90, 96 Gas, 7, 19, 21, 86, 90, 94, 96, 98, 103 Gasoline, 88, 96 Gastric, 55, 94, 96 Gastrointestinal, 50, 51, 52, 95, 97, 109, 110 Gastrointestinal tract, 52, 97, 109 Gene, 89, 97 Genetics, 97, 105 Gland, 97, 104, 110 Glomerular, 97, 108 Glomeruli, 97 Glomerulonephritis, 19, 97 Glutamate, 93, 97 Glutathione Peroxidase, 97, 108 Glycoprotein, 8, 97 Governing Board, 97, 106 Graft, 97, 98 Grafting, 27, 35, 92, 97 Growth, 86, 97, 101, 105 H Hallucination, 29, 97 Haptens, 53, 85, 97 Headache, 89, 97, 98 Heme, 93, 97 Hemodiafiltration, 97, 111 Hemodialysis, 97, 98, 111 Hemofiltration, 97, 98, 111 Hepatic, 8, 93, 98 Heterogeneity, 85, 98 Homicide, 5, 98 Hormone, 95, 98, 108 Host, 53, 98, 112

Hydrocodone, 5, 7, 12, 14, 19, 24, 27, 28, 33, 45, 46, 50, 51, 52, 98 Hydrogen, 47, 48, 85, 86, 88, 93, 97, 98, 102, 104, 107 Hydrogen Peroxide, 47, 48, 97, 98 Hydromorphone, 7, 14, 19, 28, 57, 98 Hyperalgesia, 9, 98 Hypersensitivity, 98, 108 Hypnotic, 98, 102 Hypoglycaemia, 93, 98 Hypotension, 50, 51, 92, 98 Hypoxia, 93, 98 I Ibuprofen, 4, 12, 13, 14, 27, 32, 33, 34, 44, 49, 51, 98, 100 Id, 37, 40, 74, 80, 82, 98 Idiopathic, 27, 98 Immune response, 85, 87, 97, 98, 99, 110, 112 Immunity, 98, 99 Immunoassay, 7, 99 Immunogenic, 53, 99 Immunologic, 99 Immunology, 85, 99 Impairment, 5, 93, 99 Impotence, 99, 105 In vitro, 20, 99 In vivo, 8, 55, 99 Indinavir, 8, 99 Indomethacin, 15, 20, 39, 99, 100 Induction, 8, 99 Infarction, 92, 99, 102 Infection, 93, 99, 101, 103, 108, 112 Infiltration, 97, 99, 106 Inflammation, 49, 51, 87, 96, 99, 107, 108, 109 Infusion, 8, 13, 99 Inhalation, 99, 100, 102, 106 Inotropic, 94, 99 Insight, 7, 9, 99 Intermittent, 29, 36, 99 Intervertebral, 100, 101 Intervertebral Disk Displacement, 100, 101 Intestinal, 8, 100 Intestines, 85, 96, 97, 100 Intoxication, 93, 100, 112 Intracellular, 89, 99, 100, 108 Intramuscular, 12, 13, 27, 100, 105 Intravenous, 8, 14, 15, 17, 19, 20, 23, 25, 28, 33, 36, 99, 100, 105 Intrinsic, 85, 100

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Ions, 7, 88, 90, 94, 95, 98, 100 Isoflurane, 13, 100 J Joint, 11, 32, 88, 100, 104, 110 K Kb, 68, 100 Ketoprofen, 20, 49, 51, 100 Ketorolac, 11, 32, 100 Ketorolac Tromethamine, 11, 32, 100 Kinetics, 8, 90, 100 L Large Intestine, 100, 108 Lesion, 92, 100 Leukocytes, 89, 99, 100 Levo, 62, 100, 106 Levofloxacin, 20, 100 Levorphanol, 93, 100 Library Services, 80, 100 Lidocaine, 35, 101 Ligament, 87, 101, 110 Ligation, 101 Lipid, 101, 102 Liver, 23, 24, 50, 51, 85, 87, 88, 93, 96, 98, 101 Liver Transplantation, 23, 101 Low Back Pain, 14, 18, 101 Lumbar, 88, 100, 101 Lymphocyte, 87, 101 Lymphoid, 87, 101 Lysine, 15, 101 M Malaise, 95, 101 Malignant, 5, 101 Mammary, 92, 101 Mediate, 94, 101 MEDLINE, 69, 101 Medullary, 93, 101 Membranes, 90, 101, 110 Memory, 93, 101 Meninges, 90, 101 Menstruation, 95, 101 Mental Health, iv, 4, 68, 70, 101, 107 Meperidine, 5, 101 Metabolite, 17, 89, 102 Methylene Chloride, 46, 102 Methylphenidate, 5, 102 MI, 83, 102 Microbe, 102, 111 Microorganism, 102, 112 Midazolam, 8, 102 Miosis, 102 Miotic, 8, 102

Modeling, 8, 102 Modification, 102, 107 Molecular, 7, 23, 69, 71, 89, 92, 97, 102 Molecule, 87, 88, 91, 94, 102, 104, 107 Monoamine, 86, 93, 102 Morphine Derivatives, 48, 102 Motility, 99, 102, 109 Motion Sickness, 102, 103 Myocardium, 102 N Nalbuphine, 5, 48, 102 Naloxone, 48, 49, 54, 55, 103 Naltrexone, 48, 103 Narcolepsy, 93, 102, 103 Narcosis, 103 Narcotic, 44, 46, 48, 62, 89, 96, 98, 100, 101, 102, 103, 104, 106, 111 Narcotic Antagonists, 46, 47, 103 Nausea, 50, 51, 94, 103 Necrosis, 99, 102, 103 Need, 3, 49, 51, 75, 90, 103, 110 Nerve, 39, 85, 86, 103, 106, 108, 110, 111 Nervous System, 86, 90, 103, 110 Neuralgia, 103, 106 Neurogenic, 103, 112 Neurons, 91, 103 Neuropathy, 16, 57, 103 Neuropharmacology, 6, 103 Neurotoxicity, 93, 103 Nitrogen, 21, 48, 85, 86, 103 Nonmalignant, 22, 39, 103 Norepinephrine, 85, 94, 103 Noscapine, 54, 104 Nucleic acid, 103, 104 Nucleus, 92, 93, 100, 104, 107 O Ointments, 94, 104 Opium, 48, 50, 51, 54, 102, 104 Osteoarthritis, 3, 13, 29, 32, 36, 50, 51, 100, 104 Outpatient, 5, 11, 24, 32, 34, 104 Ovaries, 96, 104, 111 Overdose, 6, 104 Oxidation, 47, 48, 54, 85, 89, 93, 97, 104 Oxygen Consumption, 104, 108 P Pain Threshold, 9, 44, 104 Palliative, 8, 13, 22, 29, 33, 35, 36, 104, 110 Pancreas, 85, 104 Papaverine, 54, 104 Parenteral, 48, 49, 54, 105 Patch, 105, 111

Index 117

Pathologic, 92, 98, 105, 112 Pemoline, 5, 105 Peptide, 105, 107 Peracetic Acid, 54, 105 Perception, 97, 105, 108 Perfusion, 98, 105, 110 Pharmaceutical Solutions, 94, 105 Pharmacodynamic, 5, 8, 11, 23, 105 Pharmacogenetics, 36, 105 Pharmacokinetic, 8, 11, 14, 18, 23, 33, 105 Pharmacologic, 6, 9, 86, 88, 105, 110, 111, 112 Phenyl, 101, 105 Phosphorus, 21, 89, 105 Physiologic, 85, 101, 105, 107, 111 Plants, 85, 90, 91, 104, 105, 111 Plasma, 8, 17, 21, 24, 25, 26, 52, 55, 87, 106, 110 Plasma cells, 87, 106 Poisoning, 93, 100, 103, 106 Polysaccharide, 87, 106 Posterior, 88, 104, 106 Postherpetic Neuralgia, 19, 34, 106 Postoperative, 5, 12, 13, 14, 15, 16, 17, 19, 20, 23, 24, 25, 26, 33, 34, 35, 50, 51, 100, 101, 106 Potentiate, 44, 106 Practice Guidelines, 70, 106 Precursor, 88, 94, 103, 106, 111 Premedication, 13, 26, 35, 106 Probe, 8, 106 Procaine, 101, 106 Progressive, 90, 95, 97, 103, 104, 106, 108 Propofol, 27, 35, 106 Propoxyphene, 5, 48, 49, 62, 106 Prostaglandins, 49, 51, 88, 99, 106 Prostaglandins A, 49, 51, 99, 106 Prostaglandins D, 106 Protease, 91, 99, 107 Protein Binding, 17, 20, 107, 110 Protein S, 89, 107 Proteins, 53, 86, 87, 91, 102, 103, 105, 106, 107, 109, 111 Protons, 98, 107 Pruritus, 50, 51, 107 Psychic, 49, 107, 108 Psychogenic, 107, 112 Psychomotor, 5, 24, 93, 107 Psychotomimetic, 86, 93, 107 Public Health, 6, 9, 70, 107 Public Policy, 69, 107 Publishing, 10, 107

Pulmonary, 22, 89, 98, 107 Pulmonary Edema, 22, 107 Pupil, 102, 107 Q Quality of Life, 6, 107 R Radioactive, 98, 107 Randomized, 3, 11, 16, 18, 19, 25, 27, 28, 29, 32, 33, 34, 35, 36, 95, 107 Reagent, 46, 107 Receptor, 24, 87, 91, 93, 94, 107, 109 Rectal, 14, 33, 35, 107 Rectum, 87, 96, 100, 107, 108 Refer, 1, 91, 94, 108 Regimen, 95, 108 Relaxant, 104, 108 Renal failure, 93, 108 Respiration, 7, 90, 108 Restless legs, 27, 108 Rheumatism, 14, 98, 108 Rheumatoid, 50, 51, 100, 108 Rheumatoid arthritis, 50, 51, 100, 108 S Saphenous, 92, 108 Saphenous Vein, 92, 108 Schizoid, 108, 112 Schizophrenia, 108, 112 Schizotypal Personality Disorder, 108, 112 Screening, 91, 108 Sedative, 91, 102, 108 Seizures, 91, 93, 108 Selenium, 48, 108 Self Administration, 6, 108 Semisynthetic, 50, 51, 104, 108 Sensibility, 86, 98, 109 Serologic, 99, 109 Serotonin, 109 Sertraline, 29, 109 Serum, 17, 91, 109 Side effect, 4, 5, 8, 18, 44, 45, 50, 51, 61, 85, 100, 109, 111 Skull, 109, 110 Smooth muscle, 86, 88, 89, 102, 104, 109, 110 Social Environment, 107, 109 Sodium, 13, 94, 109 Soft tissue, 89, 109 Solvent, 47, 88, 102, 105, 109 Spatial disorientation, 94, 109 Specialist, 16, 75, 109 Species, 95, 109, 111, 112 Specificity, 85, 90, 109, 110

118 Oxycodone

Spinal cord, 50, 51, 90, 95, 101, 103, 109 Spondylitis, 50, 51, 109 Sprains and Strains, 101, 110 Stimulant, 86, 89, 93, 102, 105, 110 Stimulus, 5, 6, 97, 110 Stomach, 85, 96, 97, 98, 100, 103, 110 Stress, 90, 103, 108, 110 Stupor, 103, 110 Subcutaneous, 29, 36, 105, 110 Substance P, 102, 110 Sympathomimetic, 86, 93, 94, 95, 104, 110 Symptomatic, 50, 51, 87, 110 Symptomatic treatment, 50, 51, 87, 110 Synergistic, 45, 49, 110 Systemic, 62, 87, 89, 93, 95, 99, 110 T Temporal, 6, 110 Therapeutics, 7, 12, 13, 14, 18, 20, 21, 23, 25, 26, 27, 45, 63, 110 Thoracic, 88, 110 Tissue, 22, 87, 88, 89, 90, 92, 95, 96, 97, 98, 99, 100, 101, 102, 103, 105, 108, 109, 110, 111 Tissue Distribution, 22, 110 Tolerance, 7, 8, 45, 50, 51, 89, 91, 110 Tonic, 91, 110 Topical, 98, 111 Toxic, iv, 46, 88, 96, 98, 103, 108, 111 Toxicity, 44, 95, 111 Toxicology, 5, 6, 19, 20, 21, 22, 23, 24, 28, 40, 45, 70, 111 Toxins, 87, 90, 99, 111 Trace element, 96, 111 Tramadol, 5, 15, 18, 45, 111

Transcutaneous, 39, 111 Transdermal, 22, 111 Transfection, 89, 111 Transmitter, 94, 104, 111 Transplantation, 28, 90, 111 Trauma, 93, 97, 103, 111 Tremor, 29, 111 Tubal ligation, 24, 34, 111 Tyrosine, 94, 111 U Ultrafiltration, 17, 98, 111 Unconscious, 98, 111 Urethra, 111, 112 Urinary, 50, 51, 112 Urinary Retention, 50, 51, 112 Urinate, 112 Urine, 7, 14, 19, 89, 94, 111, 112 Uterus, 96, 101, 104, 111, 112 V Vaccine, 85, 112 Vasodilation, 105, 112 Vasodilator, 94, 105, 112 Vein, 100, 108, 112 Venules, 90, 112 Vertebrae, 100, 109, 112 Veterinary Medicine, 69, 112 Virulence, 88, 111, 112 Virus, 95, 112 Vitro, 55, 112 Vivo, 112 W Wakefulness, 93, 112 White blood cell, 87, 100, 101, 106, 112 Withdrawal, 6, 13, 93, 101, 112

Index 119

120 Oxycodone

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Foot and Mouth Disease - A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References

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