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

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

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NORVASC 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., 1960Norvasc: 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: 0-597-84131-4 1. Norvasc-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 Norvasc. 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 NORVASC .................................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Norvasc ......................................................................................... 4 The National Library of Medicine: PubMed .................................................................................. 6 CHAPTER 2. NUTRITION AND NORVASC ........................................................................................ 23 Overview...................................................................................................................................... 23 Finding Nutrition Studies on Norvasc ........................................................................................ 23 Federal Resources on Nutrition ................................................................................................... 24 Additional Web Resources ........................................................................................................... 24 CHAPTER 3. ALTERNATIVE MEDICINE AND NORVASC .................................................................. 27 Overview...................................................................................................................................... 27 National Center for Complementary and Alternative Medicine.................................................. 27 Additional Web Resources ........................................................................................................... 29 General References ....................................................................................................................... 31 CHAPTER 4. CLINICAL TRIALS AND NORVASC .............................................................................. 33 Overview...................................................................................................................................... 33 Recent Trials on Norvasc............................................................................................................. 33 Keeping Current on Clinical Trials ............................................................................................. 34 CHAPTER 5. PATENTS ON NORVASC............................................................................................... 37 Overview...................................................................................................................................... 37 Patents on Norvasc ...................................................................................................................... 37 Patent Applications on Norvasc .................................................................................................. 44 Keeping Current .......................................................................................................................... 54 CHAPTER 6. BOOKS ON NORVASC .................................................................................................. 55 Overview...................................................................................................................................... 55 The National Library of Medicine Book Index ............................................................................. 55 Chapters on Norvasc .................................................................................................................... 56 CHAPTER 7. PERIODICALS AND NEWS ON NORVASC .................................................................... 57 Overview...................................................................................................................................... 57 News Services and Press Releases................................................................................................ 57 Academic Periodicals covering Norvasc ...................................................................................... 59 CHAPTER 8. RESEARCHING MEDICATIONS .................................................................................... 61 Overview...................................................................................................................................... 61 U.S. Pharmacopeia....................................................................................................................... 61 Commercial Databases ................................................................................................................. 62 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 65 Overview...................................................................................................................................... 65 NIH Guidelines............................................................................................................................ 65 NIH Databases............................................................................................................................. 67 Other Commercial Databases....................................................................................................... 69 APPENDIX B. PATIENT RESOURCES ................................................................................................. 71 Overview...................................................................................................................................... 71 Patient Guideline Sources............................................................................................................ 71 Finding Associations.................................................................................................................... 72 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 75 Overview...................................................................................................................................... 75 Preparation................................................................................................................................... 75 Finding a Local Medical Library.................................................................................................. 75 Medical Libraries in the U.S. and Canada ................................................................................... 75

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ONLINE GLOSSARIES.................................................................................................................. 81 Online Dictionary Directories ..................................................................................................... 81 NORVASC DICTIONARY ............................................................................................................ 83 INDEX .............................................................................................................................................. 115

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

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

Amlodipine-Induced Gingival Overgrowth: Periodontal Responses to Stopping and Restarting the Drug Source: SCD. Special Care in Dentistry. 21(2): 60-62. March-April 2001. Contact: Available from Special Care Dentistry. 211 East Chicago Avenue, Chicago, IL 60611. (312) 440-2660. Summary: This article presents a case history of a woman with gingival (gum) overgrowth (GO) induced by amlodipine (Norvasc, an antihypertensive agent). A 49 year old Japanese woman, who was taking amlodipine, had GO and swelling on examination. No specific periodontal treatment was provided to the patient for the GO; however, the amlodipine was replaced with an ACE inhibitor after consultation with her medical practitioner. Within two months, the suspension of amlodipine resulted in a

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significant improvement in her periodontal condition. Failure to control her hypertension (high blood pressure) with the ACE inhibitor caused the physician to re prescribe amlodipine. After three months, the gingival overgrowth returned; however, its severity was less when compared with the original periodontal condition, due to reduction in drug dose and periodontal therapy. The authors note that this experience suggests that temporary suspension of a drug which can induce GO can improve the periodontal condition without the aid of surgical treatment. 4 figures. 1 table. 23 references.

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

Project Title: AMLODIPINE TREATMENT FOR COCAINE DEPENDENCE Principal Investigator & Institution: Malcolm, Robert J.; Professor; Psychiatry and Behavioral Scis; Medical University of South Carolina 171 Ashley Ave Charleston, Sc 29425 Timing: Fiscal Year 2001; Project Start 05-JAN-1998; Project End 31-DEC-2002 Summary: Pharmacotherapies have not proven to be clinically useful in the treatment of cocaine dependence. Two lines of research indicate that calcium channel antagonists are promising in the treatment of cocaine dependence. 1) Clinical studies of chronic cocaine use have demonstrated multiple neurovascular changes on PET, SPECT and MRI scans of the brain. These studies demonstrate functional abnormalities in energy utilization and reductions in regional cerebral blood flow. Some improvement in these deficits have been noted with lengthening abstinence from cocaine; however, recent work indicates that some regional blood flow changes are persistent over many months. It is possible that these neurovascular abnormalities decrease cognitive abilities and thus reduce the benefits of rehabilitative treatment for cocaine dependence such as cognitive-behavioral therapy (CBT). Calcium channel antagonists antagonize cerebral vasoconstriction, enhance regional cerebral blood flow and possibly could lead to cognitive improvement. 2) Preclinical studies indicate that dihydropyridine type channel antagonists have specific binding sites in rat brains and play a role in modulating dopaminergic

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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reinforcement. Calcium channel antagonists reduce cocaine- related behaviors. One human trial demonstrated that a calcium channel antagonist decreased the subjective rush of cocaine and reduced euphoric properties of cocaine. Thus, there is animal and human evidence that calcium channel antagonists may improve cerebral circulation, enhancing cognitive functioning, and alter the subjective rewarding experience of cocaine. This protocol proposes to evaluate amlodipine, a marketed dihydropyridine calcium channel antagonist which has a well-established safety profile and has known effects of enhancing regional cerebral blood flow. In conjunction with CBT, amlodipine versus placebo will be tested for efficacy in 160 males and females, Caucasians and African-Americans. After screening and informed consent, cocaine dependent individuals will enter a two week placebo period followed by randomization to 12 weeks of amlodipine plus CBT or placebo plus CBT. Follow-up will occur three months after treatment ends. Treatment outcome will be measured with twice weekly quantitative urine drug screens for cocaine and cocaine metabolites, retention in treatment,subjective cocaine craving, and psychometric testing of cognitive functions. Evaluation of this agent for effectiveness and safety provides the opportunity to examine the rationale that improvements in regional cerebral blood flow or modulation of dopamine mechanisms through calcium channel antagonism will enhance recovery from cocaine dependence. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: ANTIPROTEINURIC AMLODIPINE IN TYPE II DIABETES

EFFECTS

OF

OMAPATRILAT

AND

Principal Investigator & Institution: Mcgill, Janet; Washington University Lindell and Skinker Blvd St. Louis, Mo 63130 Timing: Fiscal Year 2001 Summary: There is no text on file for this abstract. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF AMLODIPINE ON SURVIVAL IN PATIENTS WITH CONGESTIVE HEART FAILURE Principal Investigator & Institution: Starling, Mark R.; University of Michigan at Ann Arbor 3003 South State, Room 1040 Ann Arbor, Mi 481091274 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: METHAMPHETAMINE AND AMLODIPINE INTERACTIONS Principal Investigator & Institution: Batki, Steven; University of California San Francisco 500 Parnassus Ave San Francisco, Ca 94122 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: PRAISE 2--EFFECT OF AMLODIPINE ON SURVIVAL IN PATIENTS WITH CHF Principal Investigator & Institution: Adams, Kirkwood F.; University of North Carolina Chapel Hill Office of Sponsored Research Chapel Hill, Nc 27599 Timing: Fiscal Year 2001 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.3 The advantage of PubMed over previously mentioned sources is that it covers a greater number of domestic and foreign references. It is also free to use. If the publisher has a Web site that offers full text of its journals, PubMed will provide links to that site, as well as to sites offering other related data. User registration, a subscription fee, or some other type of fee may be required to access the full text of articles in some journals. To generate your own bibliography of studies dealing with Norvasc, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “Norvasc” (or synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for Norvasc (hyperlinks lead to article summaries): •

A comparative analysis of amlodipine and felodipine in a military outpatient population: efficacy, outcomes, and cost considerations. Author(s): Blivin SJ, Pippins J, Annis LG, Lyons F. Source: Military Medicine. 2003 July; 168(7): 530-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12901461&dopt=Abstract

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A comparative assessment of the duration of action of amlodipine and nifedipine GITS in normotensive subjects. Author(s): Ueda S, Meredith PA, Howie CA, Elliott HL. Source: British Journal of Clinical Pharmacology. 1993 December; 36(6): 561-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959273&dopt=Abstract

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A comparative crossover evaluation of amlodipine and nifedipine GITS before and after a missed dose: 48-h blood pressure profiles. Author(s): Nussinovitch N, Rosenberg G, Peleg E, Rosenthal T. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 June; 15(6): 580-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074363&dopt=Abstract

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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 cost-effectiveness evaluation of amlodipine usage in patients with coronary artery disease in Sweden. Author(s): Doyle JJ, McGuire A, Arocho R, Arikian S, Casciano J, Svangren P, Casciano R, Kim R, Kugel H. Source: Int J Clin Pract. 2002 March; 56(2): 76-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11926709&dopt=Abstract

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A double-blind, parallel-group study of amlodipine versus long-acting nitrate in the management of elderly patients with stable angina. Author(s): Hall R, Chong C. Source: Cardiology. 2001; 96(2): 72-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11740135&dopt=Abstract

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A granuloma annulare-like eruption associated with the use of amlodipine. Author(s): Lim AC, Hart K, Murrell D. Source: The Australasian Journal of Dermatology. 2002 February; 43(1): 24-7. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11869204&dopt=Abstract

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A multicenter, randomized double-blind study of valsartan/hydrochlorothiazide combination versus amlodipine in patients with mild to moderate hypertension. Author(s): Palatini P, Malacco E, Fogari R, Carretta R, Bonaduce D, Bertocchi F, Mann J, Condorelli M; Italian Collaborative Study Group. Source: Journal of Hypertension. 2001 September; 19(9): 1691-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11564991&dopt=Abstract

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A pharmacoeconomic evaluation of results from the Coronary Angioplasty Amlodipine Restenosis Study (CAPARES) in Norway and Canada. Author(s): Thaulow E, Jorgensen B, Doyle JJ, Casciano R, Casciano J, Kopp Z, Arikian S, Kim R. Source: International Journal of Cardiology. 2002 July; 84(1): 23-30; Discussion 30-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12104059&dopt=Abstract

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A randomized, double-blind comparison of the efficacy and tolerability of once-daily modified-release diltiazem capsules with once-daily amlodipine tablets in patients with stable angina. Author(s): Chugh SK, Digpal K, Hutchinson T, McDonald CJ, Miller AJ, Lahiri A. Source: Journal of Cardiovascular Pharmacology. 2001 September; 38(3): 356-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486240&dopt=Abstract

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A retrospective electronic chart review of blood pressure changes in elderly patients treated with amlodipine or an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker. Author(s): Dollar A, Brown C, Putnam D, McLaughlin T, Okamoto L, Arocho R. Source: Clinical Therapeutics. 2002 June; 24(6): 930-41. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12117083&dopt=Abstract

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Amlodipine and grapefruit juice. Author(s): Josefsson M, Ahlner J. Source: British Journal of Clinical Pharmacology. 2002 April; 53(4): 405; Author Reply 406. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966676&dopt=Abstract

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Amlodipine bioequivalence study: quantification by liquid chromatography coupled to tandem mass spectrometry. Author(s): Carvalho M, Oliveira CH, Mendes GD, Sucupira M, Moraes ME, De Nucci G. Source: Biopharmaceutics & Drug Disposition. 2001 December; 22(9): 383-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11870677&dopt=Abstract

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Amlodipine or lisinopril was not better than chlorthalidone in lowering CHD risk in hypertension. Author(s): Heckman GA, Psaty BM. Source: Acp Journal Club. 2003 November-December; 139(3): A15; Author Reply A15. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14594435&dopt=Abstract

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Amlodipine PREVENTS angina, not atherosclerosis. Author(s): Williams C. Source: Pharmacotherapy. 2002 March; 22(3): 400-1; Discussion 401-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11898898&dopt=Abstract

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Amlodipine reduces blood pressure and headache frequency in cocaine-dependent outpatients. Author(s): Malcolm R, Liao J, Michel M, Cochran K, Pye W, Yeager D, Halushka PV. Source: J Psychoactive Drugs. 2002 October-December; 34(4): 415-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12562110&dopt=Abstract

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Amlodipine therapy in pediatric patients with hypertension. Author(s): Parker ML, Robinson RF, Nahata MC. Source: Journal of the American Pharmaceutical Association (Washington,D.C. : 1996). 2002 January-February; 42(1): 114-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11833502&dopt=Abstract

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Amlodipine versus Angiotensin-receptor blockers for nonhypertension indications. Author(s): Kalus JS, White CM. Source: The Annals of Pharmacotherapy. 2002 November; 36(11): 1759-66. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12398574&dopt=Abstract

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Amlodipine versus chlorthalidone versus placebo in the treatment of stage I isolated systolic hypertension. Author(s): Grimm RH Jr, Black H, Rowen R, Lewin A, Shi H, Ghadanfar M; Amlodipine Study Group. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 January; 15(1 Pt 1): 31-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11824857&dopt=Abstract

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Amlodipine, but not MDR1 polymorphisms, alters the pharmacokinetics of cyclosporine A in Japanese kidney transplant recipients. Author(s): Kuzuya T, Kobayashi T, Moriyama N, Nagasaka T, Yokoyama I, Uchida K, Nakao A, Nabeshima T. Source: Transplantation. 2003 September 15; 76(5): 865-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14501869&dopt=Abstract

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Amlodipine, but not verapamil or nifedipine, dilates rabbit femoral artery largely through a nitric oxide- and kinin-dependent mechanism. Author(s): Xu B, Xiao-hong L, Lin G, Queen L, Ferro A. Source: British Journal of Pharmacology. 2002 June; 136(3): 375-82. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12023940&dopt=Abstract

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Amlodipine: effective for treatment of mild to moderate essential hypertension and left ventricular hypertrophy. Author(s): Islim IF, Watson RD, Ihenacho HN, Ebanks M, Singh SP. Source: Cardiology. 2001; 96 Suppl 1: 10-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11574741&dopt=Abstract

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Amlodipine-induced gynecomastia in two patients on long-term hemodialysis therapy. Author(s): Komine N, Takeda Y, Nakamata T. Source: Clinical and Experimental Nephrology. 2003 March; 7(1): 85-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=14586751&dopt=Abstract

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Analysis of amlodipine in human plasma by liquid chromatography-mass spectrometry. Author(s): Feng Y, Zhang L, Shen Z, Pan F, Zhang Z. Source: Journal of Chromatographic Science. 2002 January; 40(1): 49-53. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11866387&dopt=Abstract

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Anemia predicts mortality in severe heart failure: the prospective randomized amlodipine survival evaluation (PRAISE). Author(s): Mozaffarian D, Nye R, Levy WC. Source: Journal of the American College of Cardiology. 2003 June 4; 41(11): 1933-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12798560&dopt=Abstract

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Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension. Author(s): Chrysant SG, Marbury TC, Robinson TD. Source: Journal of Human Hypertension. 2003 June; 17(6): 425-32. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12764406&dopt=Abstract

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Atheroprotection with amlodipine: cells to lesions and the PREVENT trial. Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial. Author(s): Tulenko TN, Brown J, Laury-Kleintop L, Khan M, Walter MF, Mason RP. Source: Journal of Cardiovascular Pharmacology. 1999; 33 Suppl 2: S17-22. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10071259&dopt=Abstract

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Azelnidipine and amlodipine: a comparison of their pharmacokinetics and effects on ambulatory blood pressure. Author(s): Kuramoto K, Ichikawa S, Hirai A, Kanada S, Nakachi T, Ogihara T. Source: Hypertens Res. 2003 March; 26(3): 201-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12675275&dopt=Abstract

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Blood pressure reduction and tolerability of amlodipine versus nifedipine retard in Chinese patients with type 2 diabetes mellitus and hypertension: a randomized 1-year clinical trial. Author(s): Ko GT, Chan HC, Chan CH. Source: Int J Clin Pharmacol Ther. 2001 August; 39(8): 331-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11515707&dopt=Abstract

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Case report: treatment of amlodipine associated gingival overgrowth in periodontitis patients. Author(s): Obiechina NS, Fine JB. Source: Dent Today. 2000 September; 19(9): 76-8, 80-3. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12524730&dopt=Abstract

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Cilnidipine more highly attenuates cold pressor stress-induced platelet activation in hypertension than does amlodipine. Author(s): Tomiyama H, Kimura Y, Kuwabara Y, Maruyama C, Yoshida Y, Kuwata S, Kinouchi T, Yoshida H, Doba N. Source: Hypertens Res. 2001 November; 24(6): 679-84. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11768727&dopt=Abstract

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Clinical trials report. The effect of Ramipril versus Amlodipine on renal outcomes in hypertension nephrosclerosis. Author(s): Vidt DG. Source: Current Hypertension Reports. 2001 October; 3(5): 379-80. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11551370&dopt=Abstract

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Combination therapy of amlodipine/benazepril versus monotherapy of amlodipine in a practice-based setting. Author(s): Messerli FH, Weir MR, Neutel JM. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 June; 15(6): 550-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12074358&dopt=Abstract

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Comparative effects of atenolol-based and amlodipine-based antihypertensive therapy on QT dispersion in hypertensive subjects. Author(s): Oikarinen L, Viitasalo M, Toivonen L, Nieminen MS; Anglo-Scandinavian Cardiac Outcomes Trial. Source: Journal of Human Hypertension. 2001 August; 15 Suppl 1: S43-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685909&dopt=Abstract

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Comparative pharmacokinetics and pharmacodynamics of amlodipine in hypertensive patients with and without type II diabetes mellitus. Author(s): Preston RA, Chung M, Gaffney M, Alonso A, Baltodano NM, Epstein M. Source: Journal of Clinical Pharmacology. 2001 November; 41(11): 1215-24. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11697754&dopt=Abstract

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Comparison of 24-hour blood pressure profiles in patients with hypertension who were switched from amlodipine to nisoldipine. Author(s): Lenz TL, Wurdeman RL, Hilleman DE. Source: Pharmacotherapy. 2001 August; 21(8): 898-903. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11718496&dopt=Abstract

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Comparison of benazepril-amlodipine and captopril-thiazide combinations in the management of mild-to-moderate hypertension. Author(s): Malacco E, Piazza S, Carretta R, Di Somma S, Mugellini A, Bertocchi F, Palatini P; Italian Blood Pressure Study Group. Source: Int J Clin Pharmacol Ther. 2002 June; 40(6): 263-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12078940&dopt=Abstract

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Comparison of effects of nisoldipine-extended release and amlodipine in patients with systemic hypertension and chronic stable angina pectoris. Author(s): Pepine CJ, Cooper-DeHoff RM, Weiss RJ, Koren M, Bittar N, Thadani U, Minkwitz MC, Michelson EL, Hutchinson HG; Comparative Efficacy and Safety of Nisoldipine and Amlodipine (CESNA-II) Study Investigators. Source: The American Journal of Cardiology. 2003 February 1; 91(3): 274-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12565082&dopt=Abstract

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Comparison of the blood pressure-lowering effects and tolerability of Losartan- and Amlodipine-based regimens in patients with isolated systolic hypertension. Author(s): Volpe M, Junren Z, Maxwell T, Rodriguez A, Gamboa R, Gomez-Fernandez P, Ortega-Gonzalez G, Matadamas N, Rodriguez F, Dass B, Kyle C, Clarysse L, Bryce A, Moreno-Heredia E, Germano G, Gilles L, Smith RD, Sanderson JE; CDSP-944 Study Group. Source: Clinical Therapeutics. 2003 May; 25(5): 1469-89. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12867222&dopt=Abstract

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Comparison of the effects of amlodipine and losartan on 24-hour ambulatory blood pressure in hypertensive patients. Author(s): Ishimitsu T, Minami J, Yoshii M, Suzuki T, Inada H, Ohta S, Futoh Y, Ono H, Matsuoka H. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2002 JanuaryFebruary; 24(1-2): 41-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11848168&dopt=Abstract

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Contrasting effects of verapamil and amlodipine on cardiovascular stress responses in hypertension. Author(s): Lefrandt JD, Heitmann J, Sevre K, Castellano M, Hausberg M, Fallon M, Urbigkeit A, Rostrup M, Agabiti-Rosei E, Rahn KH, Murphy M, Zannad F, de Kam PJ, Smit AJ. Source: British Journal of Clinical Pharmacology. 2001 December; 52(6): 687-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11736880&dopt=Abstract

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Coronary angiographic changes in patients with cardiac events in the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT). Author(s): Mancini GB, Pitt B. Source: The American Journal of Cardiology. 2002 October 1; 90(7): 776-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12356398&dopt=Abstract

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Determination of amlodipine in human plasma by high-performance liquid chromatography with fluorescence detection. Author(s): Tatar S, Atmaca S. Source: J Chromatogr B Biomed Sci Appl. 2001 July 15; 758(2): 305-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11486841&dopt=Abstract

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Differential effects of a long-acting angiotensin converting enzyme inhibitor (temocapril) and a long-acting calcium antagonist (amlodipine) on ventricular ectopic beats in older hypertensive patients. Author(s): Eguchi K, Kario K, Shimada K. Source: Hypertens Res. 2002 May; 25(3): 329-33. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12135309&dopt=Abstract

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Differential response to amlodipine and atenolol mono-therapy for hypertension by ethnic group. Author(s): Kirby PL, Caulfield MC, Collier DJ, Eldridge S, Griffiths CG, Hemingway H, Poulter NR, Feder GS; Anglo-Scandinavian Cardiac Outcomes Trial. Source: Journal of Human Hypertension. 2001 August; 15 Suppl 1: S61-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11685913&dopt=Abstract

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Doxazosin, but not amlodipine decreases insulin resistance in patients with chronic renal failure: a prospective, randomized-controlled study. Author(s): Yildiz A, Hursit M, Celik AV, Kayacan SM, Yazici H, Akkaya V, Gurol AO, Karsidag K. Source: Clinical Nephrology. 2002 December; 58(6): 405-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508961&dopt=Abstract

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Dual mechanism of action of amlodipine in human vascular smooth muscle cells. Author(s): Stepien O, Zhang Y, Zhu D, Marche P. Source: Journal of Hypertension. 2002 January; 20(1): 95-102. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11791031&dopt=Abstract

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Economic benefits of amlodipine treatment in patients with coronary artery disease. Author(s): Casciano R, Doyle JJ, Chen J, Arikian S, Casciano J, Kugel H, Arocho R. Source: Pharmacoeconomics. 2002; 20(8): 553-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12109920&dopt=Abstract

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Effect of amlodipine and hormone replacement therapy on blood pressure and bone markers in menopause. Author(s): Zacharieva S, Shigarminova R, Nachev E, Kamenov Z, Atanassova I, Orbetzova M, Stoynev A, Doncheva N, Borissova AM. Source: Methods Find Exp Clin Pharmacol. 2003 April; 25(3): 209-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12743626&dopt=Abstract

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Effect of amlodipine compared to atenolol on small arteries of previously untreated essential hypertensive patients. Author(s): Schiffrin EL, Pu Q, Park JB. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 February; 15(2 Pt 1): 105-10. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11863244&dopt=Abstract

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Effect of amlodipine on systolic blood pressure. Author(s): Levine CB, Fahrbach KR, Frame D, Connelly JE, Estok RP, Stone LR, Ludensky V. Source: Clinical Therapeutics. 2003 January; 25(1): 35-57. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12637111&dopt=Abstract

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Effect of benazepril addition to amlodipine on ankle oedema and subcutaneous tissue pressure in hypertensive patients. Author(s): Fogari R, Malamani GD, Zoppi A, Mugellini A, Rinaldi A, Vanasia A, Preti P. Source: Journal of Human Hypertension. 2003 March; 17(3): 207-12. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12624612&dopt=Abstract

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Effect of indomethacin on blood pressure in elderly people with essential hypertension well controlled on amlodipine or enalapril. Author(s): Spence JD. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2001 August; 14(8 Pt 1): 835. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11497204&dopt=Abstract

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Effect of losartan and amlodipine on proteinuria and transforming growth factorbeta1 in patients with IgA nephropathy. Author(s): Park HC, Xu ZG, Choi S, Goo YS, Kang SW, Choi KH, Ha SK, Lee HY, Han DS. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 June; 18(6): 1115-21. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12748343&dopt=Abstract

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Effect of ramipril versus amlodipine on renal outcomes in hypertensive nephrosclerosis. Author(s): Flack JM. Source: Current Hypertension Reports. 2002 June; 4(3): 183-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12003698&dopt=Abstract

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Effects of amlodipine fosinopril combination on microalbuminuria in hypertensive type 2 diabetic patients. Author(s): Fogari R, Preti P, Zoppi A, Rinaldi A, Corradi L, Pasotti C, Poletti L, Marasi G, Derosa G, Mugellini A, Voglini C, Lazzari P. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 December; 15(12): 1042-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12460699&dopt=Abstract

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Effects of amlodipine on ischemia after percutaneous transluminal coronary angioplasty: secondary results of the Coronary Angioplasty Amlodipine Restenosis (CAPARES) Study. Author(s): Jorgensen B, Thaulow E; Coronary Angioplasty Amlodipine Restenosis Study. Source: American Heart Journal. 2003 June; 145(6): 1030-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12796759&dopt=Abstract

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Effects of amlodipine, atorvastatin and combination of both on advanced atherosclerotic plaque in APOE*3-Leiden transgenic mice. Author(s): van de Poll SW, Delsing DJ, Wouter Jukema J, Princen HM, Havekes LM, Puppels GJ, van der Laarse A. Source: Journal of Molecular and Cellular Cardiology. 2003 January; 35(1): 109-18. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12623305&dopt=Abstract

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Effects of blood pressure lowering with amlodipine or lisinopril on vascular structure of the common carotid artery. Author(s): Stanton AV, Chapman JN, Mayet J, Sever PS, Poulter NR, Hughes AD, Thom SA. Source: Clinical Science (London, England : 1979). 2001 November; 101(5): 455-64. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11672450&dopt=Abstract

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Effects of candesartan and amlodipine on renal function and electrolytes in renal allograft recipients. Author(s): Kisters K, Tokmak F, Kosch M, Barenbrock M, Hausberg M. Source: Clinical Nephrology. 2002 December; 58(6): 461-2. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12508971&dopt=Abstract

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Effects of intravenous amlodipine on coronary hemodynamics in subjects with angiographically normal coronary arteries. Author(s): Neglia D, Gallopin M, Marraccini P, Simonetti I, Micalizzi M, Macerata A, Marzilli M, L'Abbate A. Source: Journal of Cardiovascular Pharmacology. 2002 June; 39(6): 884-91. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12021583&dopt=Abstract

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Effects of long-acting ACE inhibitor (temocapril) and long-acting Ca channel blocker (amlodipine) on 24-h ambulatory BP in elderly hypertensive patients. Author(s): Eguchi K, Kario K, Shimada K. Source: Journal of Human Hypertension. 2001 September; 15(9): 643-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11550111&dopt=Abstract

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Effects of long-acting calcium channel antagonists on neurohumoral factors: comparison of nifedipine coat-core with amlodipine. Author(s): Tsutamoto T, Tsutsui T, Maeda K, Hayashi M, Wada A, Ohnishi M, Fujii M, Ishii C. Source: Journal of Cardiovascular Pharmacology. 2003 January; 41 Suppl 1: S77-81. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12688402&dopt=Abstract

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Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension. Author(s): White WB, Duprez D, St Hillaire R, Krause S, Roniker B, Kuse-Hamilton J, Weber MA. Source: Hypertension. 2003 May; 41(5): 1021-6. Epub 2003 April 07. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682082&dopt=Abstract

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Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension. Author(s): Caro JJ, Lee K. Source: Current Hypertension Reports. 2002 December; 4(6): 417-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419166&dopt=Abstract

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Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension. Author(s): Hilleman DE, Reyes AP, Wurdeman RL, Faulkner M. Source: Journal of Human Hypertension. 2001 August; 15(8): 559-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494095&dopt=Abstract

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Efficacy, tolerability and influence on “quality of life” of nifedipine GITS versus amlodipine in elderly patients with mild-moderate hypertension. Author(s): Pessina AC, Boari L, De Dominicis E, Giusti C, Marchesi M, Marelli G, Mattarei M, Mos L, Novo S, Pirrelli A, Santini M, Santonastaso M, Semeraro S, Uslenghi E, Kilama MO. Source: Blood Pressure. 2001; 10(3): 176-83. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11688766&dopt=Abstract

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Efficacy, tolerability, and impact on quality of life of long-term treatment with manidipine or amlodipine in patients with essential hypertension. Author(s): Zanchetti A, Omboni S, La Commare P, De Cesaris R, Palatini P. Source: Journal of Cardiovascular Pharmacology. 2001 October; 38(4): 642-50. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11588535&dopt=Abstract

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Enantiomeric determination of amlodipine in human plasma by liquid chromatography coupled to tandem mass spectrometry. Author(s): Streel B, Laine C, Zimmer C, Sibenaler R, Ceccato A. Source: Journal of Biochemical and Biophysical Methods. 2002 December 31; 54(1-3): 357-68. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12543511&dopt=Abstract

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Exponential-exponential cosine fitting of blood pressure decay induced by a longacting calcium blocker, amlodipine, using home blood pressure measurement. Author(s): Mashima K, Nakatsu T, Murakami T, Kusachi S, Tominaga Y, Yamane S, Uesugi T, Mayumi E, Mitsuda T, Tsuji T. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 2003 April; 25(3): 145-54. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12716077&dopt=Abstract

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Fosinopril versus amlodipine comparative treatments study: a randomized trial to assess effects on plasminogen activator inhibitor-1. Author(s): Pahor M, Franse LV, Deitcher SR, Cushman WC, Johnson KC, Shorr RI, Kottke-Marchant K, Tracy RP, Somes GW, Applegate WB. Source: Circulation. 2002 January 29; 105(4): 457-61. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11815428&dopt=Abstract

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Haemodynamic comparison of amlodipine and atenolol in essential hypertension using the quantascope. Author(s): Tham TC, Herity N, Guy S, Silke B. Source: British Journal of Clinical Pharmacology. 1993 December; 36(6): 555-60. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12959272&dopt=Abstract

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Improvement of endothelial function by amlodipine and vitamin C in essential hypertension. Author(s): On YK, Kim CH, Sohn DW, Oh BH, Lee MM, Park YB, Choi YS. Source: Korean J Intern Med. 2002 June; 17(2): 131-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12164090&dopt=Abstract

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Inhibition of oxidized LDL aggregation with the calcium channel blocker amlodipine: role of electrostatic interactions. Author(s): Phillips JE, Preston Mason R. Source: Atherosclerosis. 2003 June; 168(2): 239-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12801606&dopt=Abstract

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Mechanisms of atherosclerotic plaque stabilization for a lipophilic calcium antagonist amlodipine. Author(s): Mason RP. Source: The American Journal of Cardiology. 2001 November 21; 88(10A): 2M-6M. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11705416&dopt=Abstract

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Mechanisms of plaque stabilization for the dihydropyridine calcium channel blocker amlodipine: review of the evidence. Author(s): Mason RP. Source: Atherosclerosis. 2002 December; 165(2): 191-9. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12417269&dopt=Abstract

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Mix-ups with Norvasc and Navane. Author(s): Cohen MR, Davis NM. Source: Am Pharm. 1993 August; Ns33(8): 26. No Abstract Available. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8213467&dopt=Abstract

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Nebivolol vs amlodipine as first-line treatment of essential arterial hypertension in the elderly. Author(s): Mazza A, Gil-Extremera B, Maldonato A, Toutouzas T, Pessina AC. Source: Blood Pressure. 2002; 11(3): 182-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12126265&dopt=Abstract

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Neurohormones and oxidative stress in nonischemic cardiomyopathy: relationship to survival and the effect of treatment with amlodipine. Author(s): Wijeysundera HC, Hansen MS, Stanton E, Cropp AS, Hall C, Dhalla NS, Ghali J, Rouleau JL; PRAISE II Investigators. Source: American Heart Journal. 2003 August; 146(2): 291-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12891198&dopt=Abstract

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Nitrendipine and amlodipine mimic the acute effects of enalapril on renal haemodynamics and reduce glomerular hyperfiltration in patients with chronic kidney disease. Author(s): Morrone LF, Ramunni A, Fassianos E, Saracino A, Coratelli P, Passavanti G. Source: Journal of Human Hypertension. 2003 July; 17(7): 487-93. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12821956&dopt=Abstract

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Overview of the prospective randomized evaluation of the vascular effects of Norvasc (amlodipine) trial: PREVENT. Author(s): Mancini GB. Source: The Canadian Journal of Cardiology. 2000 July; 16 Suppl D: 5D-7D. Review. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10932029&dopt=Abstract

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Parkinsonian syndrome induced by amlodipine: case report. Author(s): Teive HA, Germiniani FM, Werneck LC. Source: Movement Disorders : Official Journal of the Movement Disorder Society. 2002 July; 17(4): 833-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12210888&dopt=Abstract

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Persistence of antihypertensive efficacy after missed doses: comparison of amlodipine and nifedipine gastrointestinal therapeutic system. Author(s): Elliott HL, Elawad M, Wilkinson R, Singh SP. Source: Journal of Hypertension. 2002 February; 20(2): 333-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11821720&dopt=Abstract

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Persistence of the antihypertensive efficacy of amlodipine and nifedipine GITS after two 'missed doses': a randomised, double-blind comparative trial in Asian patients. Author(s): Ongtengco I, Morales D, Sanderson J, Lu ZR, Beilin LJ, Burke V, Puddey IB, Tanomsup S, Dayi H, Rahardjo P, Zambahari DR, Chen CY, Soenarta AA, Buranakitjaroen P, Tan C, Soon TK, Wu DJ. Source: Journal of Human Hypertension. 2002 November; 16(11): 805-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12444542&dopt=Abstract

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Post hoc analysis of coronary findings from the prospective randomized evaluation of the vascular effects of the Norvasc trial (PREVENT). Author(s): Mancini GB, Miller ME, Evans GW, Byington R, Furberg CD, Pitt B; PREVENT Study Group. Prospective randomized evaluation of the vascular effects of norvasc. Source: The American Journal of Cardiology. 2002 June 15; 89(12): 1414-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12062738&dopt=Abstract

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Randomized, comparative, double-blind study of amlodipine vs. nicardipine as a treatment of isolated systolic hypertension in the elderly. Author(s): Mounier-Vehier C, Jaboureck O, Emeriau JP, Bernaud C, Clerson P, Carre A. Source: Fundamental & Clinical Pharmacology. 2002 December; 16(6): 537-44. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12685513&dopt=Abstract

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Rationale, design, and baseline characteristics of the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT). Author(s): Byington RP, Miller ME, Herrington D, Riley W, Pitt B, Furberg CD, Hunninghake DB, Mancini GB. Source: The American Journal of Cardiology. 1997 October 15; 80(8): 1087-90. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9352986&dopt=Abstract

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Restoration of nocturnal dip in blood pressure is associated with improvement in left ventricular ejection fraction. A 1-year clinical study comparing the effects of amlodipine and nifedipine retard on ambulatory blood pressure and left ventricular systolic function in Chinese hypertensive type 2 diabetic patients. Author(s): Ko GT, Chan HC. Source: International Journal of Cardiology. 2003 June; 89(2-3): 159-66. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12767538&dopt=Abstract

•

Results of a pilot pharmacotherapy quality improvement program using fixed-dose, combination amlodipine/benazepril antihypertensive therapy in a long-term care setting. Author(s): Sapienza S, Sacco P, Floyd K, DiCesare J, Doan QD. Source: Clinical Therapeutics. 2003 June; 25(6): 1872-87. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12860503&dopt=Abstract

•

Sex bias and underutilization of lipid-lowering therapy in patients with coronary artery disease at academic medical centers in the United States and Canada. Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) Investigators. Author(s): Miller M, Byington R, Hunninghake D, Pitt B, Furberg CD. Source: Archives of Internal Medicine. 2000 February 14; 160(3): 343-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10668836&dopt=Abstract

•

Stereoselective pharmacokinetics of amlodipine in elderly hypertensive patients. Author(s): Ohmori M, Arakawa M, Harada K, Takasaki H, Hifumi S, Miyamori I, Fujimura A. Source: American Journal of Therapeutics. 2003 January-February; 10(1): 29-31. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12522517&dopt=Abstract

•

Syncope following oral chloroquine administration in a hypertensive patient controlled on amlodipine. Author(s): Ajayi AA, Adigun AQ. Source: British Journal of Clinical Pharmacology. 2002 April; 53(4): 404-5. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11966675&dopt=Abstract

Studies

21

•

Telangiectasia and gingival hyperplasia as side-effects of amlodipine (Norvasc) in a 3-year-old girl. Author(s): van der Vleuten CJ, Trijbels-Smeulders MA, van de Kerkhof PC. Source: Acta Dermato-Venereologica. 1999 July; 79(4): 323-4. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10429995&dopt=Abstract

•

The economic efficiency of amlodipine in the treatment of coronary atherosclerosis-an analysis based on the PREVENT study. Author(s): Cathomas G, Erne P, Schwenkglenks M, Szucs TD. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 2002 January; 16(1): 61-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12085980&dopt=Abstract

•

The effect of amlodipine on exercise-induced pulmonary hypertension and right heart function in patients with chronic obstructive pulmonary disease. Author(s): Franz IW, Van Der Meyden J, Schaupp S, Tonnesmann U. Source: Zeitschrift Fur Kardiologie. 2002 October; 91(10): 833-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12395224&dopt=Abstract

•

The effects of amlodipine compared to losartan in patients with mild to moderately severe hypertension. Author(s): Phillips RA, Kloner RA, Grimm RH Jr, Weinberger M. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 January-February; 5(1): 17-23. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12556649&dopt=Abstract

•

The effects of amlodipine on cerebral circulatory values in patients with essential hypertension. Author(s): Alizade IG, Karayeva NT. Source: Anadolu Kardiyoloji Dergisi : Akd = the Anatolian Journal of Cardiology. 2001 March; 1(1): 14-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12122965&dopt=Abstract

•

The hyperlipemic hamster - a model for testing the anti-atherogenic effect of amlodipine. Author(s): Sima A, Stancu C, Constantinescu E, Ologeanu L, Simionescu M. Source: Journal of Cellular and Molecular Medicine. 2001 April-June; 5(2): 153-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12067498&dopt=Abstract

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Tolerability of long-term treatment with lercanidipine versus amlodipine and lacidipine in elderly hypertensives. Author(s): Leonetti G, Magnani B, Pessina AC, Rappelli A, Trimarco B, Zanchetti A; COHORT Study Group. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 November; 15(11): 932-40. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12441211&dopt=Abstract

•

Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine. Author(s): Kes S, Caglar N, Canberk A, Deger N, Demirtas M, Dortlemez H, Kiliccioglu B, Kozan O, Ovunc K, Turkoglu C. Source: Current Medical Research and Opinion. 2003; 19(3): 226-37. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12803737&dopt=Abstract

•

Trough:peak ratio and smoothness index in the evaluation of 24-h blood pressure control in hypertension: a comparative study between valsartan/hydrochlorothiazide combination and amlodipine. Author(s): Palatini P, Malacco E, Di SS, Carretta R, Dorigatti F, Bertocchi F, Mann J. Source: European Journal of Clinical Pharmacology. 2002 January; 57(11): 765-70. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11868797&dopt=Abstract

23

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

Finding Nutrition Studies on Norvasc The National Institutes of Health’s Office of Dietary Supplements (ODS) offers a searchable bibliographic database called the IBIDS (International Bibliographic Information on Dietary Supplements; National Institutes of Health, Building 31, Room 1B29, 31 Center Drive, MSC 2086, Bethesda, Maryland 20892-2086, Tel: 301-435-2920, Fax: 301-480-1845, E-mail: [email protected]). The IBIDS contains over 460,000 scientific citations and summaries about dietary supplements and nutrition as well as references to published international, scientific literature on dietary supplements such as vitamins, minerals, and botanicals.4 The IBIDS includes references and citations to both human and animal research studies. As a service of the ODS, access to the IBIDS database is available free of charge at the following Web address: http://ods.od.nih.gov/databases/ibids.html. After entering the search area, you have three choices: (1) IBIDS Consumer Database, (2) Full IBIDS Database, or (3) Peer Reviewed Citations Only. Now that you have selected a database, click on the “Advanced” tab. An advanced search allows you to retrieve up to 100 fully explained references in a comprehensive format. Type “Norvasc” (or synonyms) into the search box, and click “Go.” To narrow the search, you can also select the “Title” field.

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

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The following is a typical result when searching for recently indexed consumer information on Norvasc: •

Coronary angiographic changes in patients with cardiac events in the Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT). Author(s): University of British Columbia, Vancouver, British Columbia, Canada. [email protected] Source: Mancini, G B Pitt, B Am-J-Cardiol. 2002 October 1; 90(7): 776-8 0002-9149

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

•

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/

•

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/

•

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/

•

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

•

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

•

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

•

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

•

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

•

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

Nutrition

•

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

•

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

25

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

Minerals Calcium-Channel Blockers Source: Healthnotes, Inc.; www.healthnotes.com

•

Food and Diet Hypertension Source: Healthnotes, Inc.; www.healthnotes.com

27

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

Amlodipine and benazeprilat differently affect the responses to endothelin-1 and bradykinin in porcine ciliary arteries: effects of a low and high dose combination. Author(s): Lang MG, Zhu P, Meyer P, Noll G, Haefliger IO, Flammer J, Luscher TF. Source: Current Eye Research. 1997 March; 16(3): 208-13. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9088736&dopt=Abstract

•

Amlodipine lowers blood pressure without affecting cerebral blood flow as measured by single photon emission computed tomography in elderly hypertensive subjects. Author(s): Pandita-Gunawardena ND, Clarke SE. Source: Age and Ageing. 1999 September; 28(5): 451-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10529039&dopt=Abstract

•

Circadian heart rate response to chronotherapy versus conventional therapy in patients with hypertension and myocardial ischemia. Author(s): Glasser SP, Frishman W, White WB, Stone P, Johnson MF.

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Source: Clin Cardiol. 2000 July; 23(7): 524-9. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10894441&dopt=Abstract •

Comparison of efficacy and side effects of combination therapy of angiotensinconverting enzyme inhibitor (benazepril) with calcium antagonist (either nifedipine or amlodipine) versus high-dose calcium antagonist monotherapy for systemic hypertension. Author(s): Messerli FH, Oparil S, Feng Z. Source: The American Journal of Cardiology. 2000 December 1; 86(11): 1182-7. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11090788&dopt=Abstract

•

Deleterious effects of nifedipine on smooth muscle cells implies alterations of intracellular calcium signaling. Author(s): Raicu M, Florea S. Source: Fundamental & Clinical Pharmacology. 2001 December; 15(6): 387-92. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11860526&dopt=Abstract

•

Divergent effects of calcium channel and angiotensin converting enzyme blockade on glomerulotubular function in cyclosporine-treated renal allograft recipients. Author(s): Sennesael JJ, Lamote JG, Violet I, Tasse S, Verbeelen DL. Source: American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation. 1996 May; 27(5): 701-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8629631&dopt=Abstract

•

Effects of cilazapril and amlodipine on kidney function in hypertensive NIDDM patients. Author(s): Velussi M, Brocco E, Frigato F, Zolli M, Muollo B, Maioli M, Carraro A, Tonolo G, Fresu P, Cernigoi AM, Fioretto P, Nosadini R. Source: Diabetes. 1996 February; 45(2): 216-22. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=8549868&dopt=Abstract

•

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension. Author(s): Caro JJ, Lee K. Source: Current Hypertension Reports. 2002 December; 4(6): 417-8. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12419166&dopt=Abstract

•

Efficacy and safety of a therapeutic interchange from high-dose calcium channel blockers to a fixed-dose combination of amlodipine/benazepril in patients with moderate-to-severe hypertension. Author(s): Hilleman DE, Reyes AP, Wurdeman RL, Faulkner M.

Alternative Medicine 29

Source: Journal of Human Hypertension. 2001 August; 15(8): 559-65. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11494095&dopt=Abstract •

Lack of effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of amlodipine. Author(s): Vincent J, Harris SI, Foulds G, Dogolo LC, Willavize S, Friedman HL. Source: British Journal of Clinical Pharmacology. 2000 November; 50(5): 455-63. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11069440&dopt=Abstract

•

Mechanism of action of angiotensin II in human isolated subcutaneous resistance arteries. Author(s): Garcha RS, Sever PS, Hughes AD. Source: British Journal of Pharmacology. 2001 September; 134(1): 188-96. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=11522611&dopt=Abstract

•

Randomized, double-blind crossover study to investigate the effects of amlodipine and isosorbide mononitrate on the time course and severity of exercise-induced myocardial stunning. Author(s): Rinaldi CA, Linka AZ, Masani ND, Avery PG, Jones E, Saunders H, Hall RJ. Source: Circulation. 1998 August 25; 98(8): 749-56. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=9727544&dopt=Abstract

•

The effect of high dose losartan on erythropoietin resistance in patients undergoing haemodialysis. Author(s): Odabas AR, Cetinkaya R, Selcuk Y, Keles S, Bilen H. Source: Panminerva Medica. 2003 March; 45(1): 59-62. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=12682621&dopt=Abstract

•

The inhibitory mechanisms of amlodipine in human vascular smooth muscle cell proliferation. Author(s): Zhang YZ, Gao PJ, Wang XY, Stepien O, Marche P, Zhang ZL, Zhu DL. Source: Hypertens Res. 2000 July; 23(4): 403-6. http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_ uids=10912781&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/

•

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

•

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/

•

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

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

•

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

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

•

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

•

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

•

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

The following is a specific Web list relating to Norvasc; 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 High Blood Pressure Source: Integrative Medicine Communications; www.drkoop.com Hypertension Source: Integrative Medicine Communications; www.drkoop.com

•

Herbs and Supplements Amlodipine Source: Healthnotes, Inc.; www.healthnotes.com Dehydroepiandrosterone Source: Healthnotes, Inc.; www.healthnotes.com Flavonoids Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,782,00.html Hawthorn Source: WholeHealthMD.com, LLC.; www.wholehealthmd.com Hyperlink: http://www.wholehealthmd.com/refshelf/substances_view/0,1525,10035,00.html Lotrel Source: Healthnotes, Inc.; www.healthnotes.com

Alternative Medicine 31

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.

33

CHAPTER 4. CLINICAL TRIALS AND NORVASC Overview In this chapter, we will show you how to keep informed of the latest clinical trials concerning Norvasc.

Recent Trials on Norvasc The following is a list of recent trials dedicated to Norvasc.5 Further information on a trial is available at the Web site indicated. •

Amlodipine Plus Botulinum Toxin for Focal Dystonia Condition(s): Focal Dystonia Study Status: This study is currently recruiting patients. Sponsor(s): National Institute of Neurological Disorders and Stroke (NINDS) Purpose - Excerpt: This study will examine whether amlodipine (Norvasc) can improve the effect of botulinum toxin injections for dystonia a movement disorder causing abnormal postures and disrupted movements. Amlodipine, a drug commonly used to treat high blood pressure and heart disease, prevents calcium from entering cells under certain conditions. Botulinum toxin works by weakening muscles that are overactive in dystonia. It prevents the release of a chemical called acetylcholine from nerve terminals that signal the muscle to contract. The release of acetylcholine also requires that small amounts of calcium enter the cell. This calcium can be blocked by amlodipine. Therefore, the use of the two drugs together may produce more weakness and possibly more benefit than botulinum toxin injection alone. Patients enrolled in NINDS's protocol 85-N-0195 (Efficacy and Pathophysiology of Botulinum Toxin for Treatment of Involuntary Movement Disorders) who are being treated with botulinum toxin for focal hand dystonia or cervical dystonia may be eligible for this study. Candidates will be screened with blood tests and electrocardiogram (EKG). Participants will have three injections of botulinum toxin, during which the following will occur: First injection Patients' dystonia will be rated and their hand strength tested. They will be randomly assigned to receive either amlodipine or placebo (a look-alike pill with no active

5

These are listed at www.ClinicalTrials.gov.

34

Norvasc

ingredient) for 6 months or until the effects of the botulinum toxin injection have worn off and the second injection is required. Second injection - No amlodipine or placebo will be given with the second injection in order to allow any effects of amlodipine to wear off. Third injection - Will be given when the effects of the second injection have worn off. At this time, patients who received amlodipine at the time of the first injection will now be given placebo, and vice versa. Patients will be seen at monthly intervals after the first and third injections to evaluate their response to treatment. At each visit, patients will report any side effects of treatment, their dystonia will be videotaped and rated and their hand strength will be tested. In addition, 2 weeks after the first and third injections, patients will have electromyography (EMG) testing to evaluate how the study medication affects the nerves and release of acetylcholine from the nerve. This test involves inserting a needle into an arm muscle. For part of the study, patients will tense the muscle slightly and maintain tension while the EMG signal is collected. This test may take 1 to 2 hours. Phase(s): Phase II Study Type: Interventional Contact(s): see Web site below Web Site: http://clinicaltrials.gov/ct/show/NCT00015457

Keeping Current on Clinical Trials The U.S. National Institutes of Health, through the National Library of Medicine, has developed ClinicalTrials.gov to provide current information about clinical research across the broadest number of diseases and conditions. The site was launched in February 2000 and currently contains approximately 5,700 clinical studies in over 59,000 locations worldwide, with most studies being conducted in the United States. ClinicalTrials.gov receives about 2 million hits per month and hosts approximately 5,400 visitors daily. To access this database, simply go to the Web site at http://www.clinicaltrials.gov/ and search by “Norvasc” (or synonyms). While ClinicalTrials.gov is the most comprehensive listing of NIH-supported clinical trials available, not all trials are in the database. The database is updated regularly, so clinical trials are continually being added. The following is a list of specialty databases affiliated with the National Institutes of Health that offer additional information on trials: •

For clinical studies at the Warren Grant Magnuson Clinical Center located in Bethesda, Maryland, visit their Web site: http://clinicalstudies.info.nih.gov/

•

For clinical studies conducted at the Bayview Campus in Baltimore, Maryland, visit their Web site: http://www.jhbmc.jhu.edu/studies/index.html

•

For cancer trials, visit the National Cancer Institute: http://cancertrials.nci.nih.gov/

•

For eye-related trials, visit and search the Web page of the National Eye Institute: http://www.nei.nih.gov/neitrials/index.htm

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For heart, lung and blood trials, visit the Web page of the National Heart, Lung and Blood Institute: http://www.nhlbi.nih.gov/studies/index.htm

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For trials on aging, visit and search the Web site of the National Institute on Aging: http://www.grc.nia.nih.gov/studies/index.htm

Clinical Trials 35

•

For rare diseases, visit and search the Web site sponsored by the Office of Rare Diseases: http://ord.aspensys.com/asp/resources/rsch_trials.asp

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For alcoholism, visit the National Institute on Alcohol Abuse and Alcoholism: http://www.niaaa.nih.gov/intramural/Web_dicbr_hp/particip.htm

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For trials on infectious, immune, and allergic diseases, visit the site of the National Institute of Allergy and Infectious Diseases: http://www.niaid.nih.gov/clintrials/

•

For trials on arthritis, musculoskeletal and skin diseases, visit newly revised site of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health: http://www.niams.nih.gov/hi/studies/index.htm

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For hearing-related trials, visit the National Institute on Deafness and Other Communication Disorders: http://www.nidcd.nih.gov/health/clinical/index.htm

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For trials on diseases of the digestive system and kidneys, and diabetes, visit the National Institute of Diabetes and Digestive and Kidney Diseases: http://www.niddk.nih.gov/patient/patient.htm

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For drug abuse trials, visit and search the Web site sponsored by the National Institute on Drug Abuse: http://www.nida.nih.gov/CTN/Index.htm

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For trials on mental disorders, visit and search the Web site of the National Institute of Mental Health: http://www.nimh.nih.gov/studies/index.cfm

•

For trials on neurological disorders and stroke, visit and search the Web site sponsored by the National Institute of Neurological Disorders and Stroke of the NIH: http://www.ninds.nih.gov/funding/funding_opportunities.htm#Clinical_Trials

37

CHAPTER 5. PATENTS ON NORVASC 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.6 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 “Norvasc” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on Norvasc, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Norvasc By performing a patent search focusing on Norvasc, 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

6Adapted from the United States Patent and Trademark Office: http://www.uspto.gov/web/offices/pac/doc/general/whatis.htm.

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

Amlodipine hemimaleate Inventor(s): Ettema; Gerrit J. B. (Nijmegen, NL) Assignee(s): Synthon BV (Nijmegen, NL) Patent Number: 6,538,012 Date filed: August 27, 2001 Abstract: Amlodipine hemimaleate is useful as a calcium channel blocker and can be used to treat or prevent angina or hypertension. Excerpt(s): The present invention relates to a novel compound, to processes for preparing it and to its use in treating medical disorders. In particular the present invention relates to a novel acid addition salt of amlodipine. This compound is used for the preparation of a medicament having calcium channel blocking activity, useful in the management of the hypertension and angina pectoris. Particularly useful forms of amlodipine for use in human medicine are maleate and benzenesulfonate salts thereof. Examples 9, 11, 12 and 22 of U.S. Pat. No. 4,572,909 as well as J. Med. Chem. 29,1698(1986) disclose the preparation of amlodipine maleate (in 1:1 molar ratio) by dissolving a reaction mixture containing in situ prepared raw amlodipine base in ethylacetate or in ethanol and adding solid maleic acid while the maleate salt of amlodipine precipitates. The salt is then isolated by filtration and recrystallized from ethyl acetate or from acetone/ethyl acetate 1:1. The prior art disclosure of amlodipine maleate has thus been of a compound having a 1:1 molar ratio between amlodipine and maleic acid. This compound should be more precisely called amlodipine hydrogenmaleate. Another aspect of the present invention relates to a process that comprises contacting amlodipine free base or a salt thereof with maleic acid or its ammonium salt in the presence of a solvent to form amlodipine hemimaleate. Web site: http://www.delphion.com/details?pn=US06538012__

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Composition containing amlodipine or a pharmaceutically acceptable salt thereof, and an ACE inhibitor Inventor(s): Cropp; Anne B. (Madison, CT), Kraska; Allen R. (Old Lyme, CT) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,245,787 Date filed: February 26, 1998 Abstract: Methods of treating congestive heart failure in a mammal, especially a human, by co-administration of (1) amlodipine, a pharmaceutically acceptable salt of amlodipine; (2) an ACE inhibitor; and optionally (3) a diuretic and/or (4) digoxin. Excerpt(s): This invention relates to compositions comprising (1) amlodipine, a pharmaceutically acceptable amlodipine acid addition salt, or felodipine and (2) an angiotensin converting enzyme (ACE) inhibitor. The invention further relates to methods for reducing mortality and/or morbidity in patients with congestive heart failure, comprising co-administering a congestive heart failure treating amount of a combination comprising amlodipine, a pharmaceutically acceptable amlodipine salt, or

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felodipine and an ACE inhibitor. Congestive heart failure, regardless of its etiology, is characterized by a weakness of the myocardial tissue of the left and/or right ventricle of the heart to pump and circulate blood into systemic and/or pulmonary circulations. It is accompanied by circulatory and neurohumoral changes which result in failure to deliver sufficient blood and oxygen supply to peripheral tissues and vital organs. If left untreated, the health of a patient with congestive heart failure could progress to the point where the disease would be fatal. Amlodipine, 3-ethyl-5-methyl-2-(2aminoethoxymethyl)4-(2-chlorophenyl)-1,4-dihydro-6-m ethylpyridine-3,5dicarboxylate, and its pharmaceutically acceptable acid addition salts are calcium channel blockers known for their effectiveness in the treatment, inter alia, of congestive heart failure, see U.S. Pat. No. 5,155,120 to Lazar et al. Amlodipine is currently marketed as the besylate salt. Web site: http://www.delphion.com/details?pn=US06245787__ •

Inhibition of smooth muscle cell migration by (R)-amlodipine Inventor(s): Chahwala; Suresh Bababhai (Sandwich, GB), Winslow; Derek Paul (Sandwich, GB) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,080,761 Date filed: February 21, 1996 Abstract: The R(+) isomer of amlodipine is a potent inhibitor of smooth muscle cell migration despite its lack of calcium channel-blocking activity. It is useful for treating atherosclerosis, re-stenosis after angioplasty and endometriosis. Excerpt(s): This invention relates to treatment of medical conditions involving smooth muscle cell migration using the R(+) isomer of 3-ethyl-5-methyl-2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-1,4-dihydro-6 -methylpyridine-3,5-dicarboxylate, a compound having the approved non-proprietary name "amlodipine". Amlodipine is a known calcium channel-blocking agent having vasodilatory activity and is currently used, generally in the form of a pharmaceutically acceptable salt such as its maleate or besylate, in treatment of hypertension and angina. The compound and its preparation are described in European patent 0089167 B1. Amlodipine is a racemic compound due to its symmetry at position 4 of the dihydropyridine ring and the R- and S-enantiomers may be prepared by methods described in J. Med. Chem. 1986 29 1696 (Arrowsmith et al.) and European Patent Application 0331315 A. It was formerly believed that the two resolved enantiomers consisted of the R-(-) and S-(+) isomers but it has subsequently been found that these are in fact the S(-) and the R(+) isomer, respectively (see J. Med. Chem., 35, 3341-3344 (1992), Goldmann et al.). It is known that the calcium channel blocking activity of amlodipine is substantially confined to the S(-) form and the racemic mixture of R(+) and S(-) forms; the R(+) isomer has little or no calcium channel blocking activity and so is not likely to have significant cardiovascular effects when administered to a patient. It is known that calcium channel blockers in general tend to inhibit smooth muscle cell migration. Thus they have been found to impede lesion development in various animal models of atherosclerosis (see Arteriosclerosis 5; 250 (1985), Willis et al., Arteriosclerosis 6; 237 (1986), Sugano et al.); also smooth muscle cell proliferative lesions following endothelial cell damage by balloon angioplasty are reduced by Isradipine, a calcium channel blocker (see Am. J. Pathol 124, 88-93 (1986) Handley et al.). During restenosis following balloon angioplasty and atherogenesis, vascular smooth muscle cells migrate from the media to the intima where they

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proliferate. It is believed that the efficacy of calcium channel blockers in animal models of re-stenosis post-balloon angioplasty and atherosclerosis is due to inhibition of vascular smooth muscle cell migration and subsequent reduction in smooth muscle cell proliferation and neointimal formation. Web site: http://www.delphion.com/details?pn=US06080761__ •

Methods for treating hypertension, and angina using optically pure (-) amlodipine Inventor(s): Young; James W. (Palo Alto, CA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 6,057,344 Date filed: November 4, 1994 Abstract: Methods are disclosed utilizing the optically pure (-) isomer of amlodipine. This compound is a potent drug for the treatment of hypertension while avoiding the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. The (-) isomer of amlodipine is also useful for the treatment of angina without the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. Excerpt(s): This invention relates to novel compositions of matter containing optically pure (-) amlodipine. These compositions possess potent activity in treating both systolic and diastolic hypertension while avoiding adverse effects including but not limited to edema of the extremities, headache and dizziness, which are associated with administration of the racemic mixture of amlodipine. Additionally, these novel compositions of matter containing optically pure (-) amlodipine are useful in treating angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist including but not limited to cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure--while avoiding the adverse effects associated with administration of the racemic mixture of amlodipine. Also disclosed are methods for treating the above-described conditions in a human while avoiding the adverse effects that are associated with the racemic mixture of amlodipine, by administering the (-) isomer of amlodipine to said human. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of planepolarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 12 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://www.delphion.com/details?pn=US06057344__

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Methods of pharmacological treatment using S(-) amlodipine Inventor(s): Foster; Robert T. (Edmonton, CA) Assignee(s): Isotechnika, INC (Edmonton, CA) Patent Number: 6,333,342 Date filed: November 4, 1999 Abstract: Methods and compositions are disclosed utilizing the optically pure S(-) isomer of amlodipine. This compound is a potent drug for the treatment of hypertension while avoiding the concomitant liability of adverse effects associated with the administration of the racemic mixture of amlodipine. The S(-) isomer of amlodipine is also useful for the treatment of angina and such other conditions as may be related to the activity of S(-) amlodipine as a calcium channel antagonist without the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. Excerpt(s): Pharmacological therapy utilizing pure formulations of S(-) amlodipine results in effective theraputic results while avoiding toxicities and adverse effects of racemic amlodipine. The methods and compositions described include the enriched deuterated forms of amlodipine as well as the nonenriched form. Amlodipine and deuteroamlodipine have a chiral center at C4 in the dihydropyridine ring, and thus can exist as optical isomers. The isomers may be separated by various methods, for example selective crystallization and column chromatography. See for example T. Shibanuma, et al., Chem. Pharm. Bull., 28, 2809-2812 (1980). Alternatively, S(-) amlodipine may be prepared using optically active reactants, or by a combination of separation and chiral synthesis. Optical isomers of compounds are specified (+) or (-), indicating the direction the chiral center rotates a plane of polarized light. Optically active amlodipine, amlodipine derivatives and salts and deuterated amlodipine or deuterated amlodipine derivatives and salts are designated herein using the IUPAC R-S convention, sometimes called the "sequence rule." A description of the R-S convention may be found, for example, in "Introduction to Organic Chemistry" by A. Streitwieser, Jr. and C. Heathcock, (Macmillan Pub. Co., New York, 1976), pages 110-114. Optical purity is important since certain isomers may actually be deleterious rather than simply inert. For example, it has been suggested that the D-enantiomer of thalidomide was a safe and effective sedative when prescribed for the control of morning sickness during pregnancy, while the corresponding L-enantiomer has been thought to be a potent teratogen. Web site: http://www.delphion.com/details?pn=US06333342__

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Mutual prodrugs of amlodipine and atorvastatin Inventor(s): Chang; George (Ivoryton, CT), Hamanaka; Ernest S. (Gales Ferry, CT), LaMattina; John L. (Ledyard, CT) Assignee(s): Pfizer Inc (New York, NY) Patent Number: 6,486,182 Date filed: May 24, 2000 Abstract: This invention relates to mutual prodrugs of amlodipine and atorvastatin and to pharmaceutical compositions thereof. This invention also relates to methods of treating angina pectoris, atherosclerosis, and hypertension and hyperlipidemia in a mammal using those prodrugs and compositions. This invention also relates to methods

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of managing cardiac risk in a mammal, including humans, presenting with symptoms of cardiac risk by administering those prodrugs and compositions. Excerpt(s): This invention relates to mutual prodrugs of amlodipine and atorvastatin, pharmaceutically acceptable acid addition salts thereof, pharmaceutical compositions thereof and methods of using such prodrugs and compositions to treat subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and to treat subjects presenting with symptoms of cardiac risk, including humans. The conversion of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) to mevalonate is an early and rate-limiting step in the cholesterol biosynthetic pathway. This step is catalyzed by the enzyme HMG-CoA reductase. Statins inhibit HMG-CoA reductase from catalyzing this conversion. As such, statins are collectively potent lipid lowering agents. and is disclosed in U.S. Pat. No. 4,681,893, which is incorporated herein by reference. Web site: http://www.delphion.com/details?pn=US06486182__ •

Process for making S(-) Amlodipine salts Inventor(s): Gurjar; Mukund Keshav (Pune, IN), Joshi; Ramesh Anna (Pune, IN), Joshi; Rohini Ramesh (Pune, IN) Assignee(s): Council of Scientific & Industrial Research (New Delhi, IN) Patent Number: 6,608,206 Date filed: October 30, 2002 Abstract: A process for the preparation of S(-) Amlodipine salts which comprises reaction of S(-)Amlodipine base with a solution of pharmaceutically acceptable acid such as benzene sulfonic acid, oxalic acid, maleic acid, succinic acid and p-toluene sulfonic acid. The reaction is carried out in the presence of an organic solvent at room temperature. The organic solvents include alcohols like ethanol methanol 2 propanol hydrocarbons like toluene and polar solvent like dimethyl sulfoxide. The salt is obtained by addition of water and isolation of the salt formed by filtration. The unique feature of the invention is production of S(-) Amlodipine besylate in good chemical yield, high enantiomeric purity and with the quality required for preparation of pharmaceutical composition i.e. tablet formulation. Excerpt(s): Wherein R=Benzene sulfonic acid, succinic acid, maleic acid, oxalic acid and p-toluene sulfonic acid. Salts of S(-) Amlodipine are prepared as per the procedure of the present invention from S (-) Amlodipine, the procedure for the preparation of the S() Amlodipine has been fully described and claimed in co-pending Indian patent application No. NF 383/2001. Of all the salts of S (-) Amlodipine mentioned above, the compound S (-) Amlodipine besylate; (4-S)-2-{[(2-aminoethyl)oxy]methyl}-4-(2chlorophenyl)-6-methyl-1,4-dihydr opyridine-3,5-dicarboxylate benzene sulfonate has commercial importance and is a potent and long acting calcium channel blocker. Web site: http://www.delphion.com/details?pn=US06608206__

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Separation of the enantiomers of amlodipine via their diastereomeric tartrates Inventor(s): Spargo; Peter Lionel (Sandwich, GB) Assignee(s): Pfizer Inc. (New York, NY) Patent Number: 6,046,338 Date filed: May 5, 1998 Abstract: A method for the separation of R-(+)- and S-(-)-isomers of amlodipine (I) from mixtures thereof, which comprises the reaction of the mixture of isomers with either Lor D-tartaric acid in an organic solvent containing sufficient dimethyl sulphoxide (DMSO) for the precipitation of, respectively, a DMSO, solvate of an L-tartate salt of R(+)-amlodipine, or a DMSO solvate of a D-tartrate salt of S-(-)-amlodipine. Excerpt(s): The invention described herein provides an efficient method for the separation of the optical isomers of amlodipine via salt formation with tartaric acid in the presence of dimethyl sulphoxide. Amlodipine 1a, and its salts are long-acting calcium channel blockers, and are thus useful for the treatment of cardiovascular disorders, such as angina, hypertension and congestive heart failure. The two enantiomers of amlodipine, and their salts, have different pharmacological profiles. The S-(-)-isomer is the more potent calcium channel blocker, and the R-(+)-isomer also exhibits activity in the treatment or prevention of atherosclerosis. None of the disclosed methods for resolution of amlodipine intermediates or derivatives offer an efficient and economic method susceptible of industrial application. Other methods of providing enantiomerically enriched amlodipine isomers are thus needed. Web site: http://www.delphion.com/details?pn=US06046338__

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Synergistic combination therapy using benazepril and amlodipine for the treatment of cardiovascular disorders and compositions therefor Inventor(s): Henis; Marc M. J. (9 Glen Rd., Randolph, NJ 07869), Papa; Joseph (Muhlebachweg 19, Allschwil, CH) Assignee(s): none reported Patent Number: 6,162,802 Date filed: March 10, 1992 Abstract: A method for the treatment of a variety of cardiovascular disorders and related conditions in a mammal having at least one such disorder or condition is disclosed comprising treating the mammal with cotherapy comprising benazepril and amlodipine or pharmaceutically acceptable salts of either or both. Combination formulations of benazepril and amlodipine for use in the method are also disclosed. Excerpt(s): The present invention relates to cardiovascular disease states, whether the underlying problem is cardiovascular in nature or secondary to some other condition, and their treatment. It further relates to the treatment of underlying cardiovascular problems which lead to, or present as, non-cardiovascular disease states as well. In addition, the invention relates to angiotensin coverting enzyme inhibitors (ACEI) and the conditions for which treatment therewith is known to be useful. Still further, the invention relates to calcium channel blockers (CCB) and the conditions for which treatment therewith is known to be useful. More specifically, the invention is concerned with the field of combination therapy of an ACEI and a CCB. Cardiovascular disease treatment has evolved rapidly over the last few decades from the early diuretics and

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natural products such as rauwolfia serpentina to the newest agents such as angiotensin converting enzyme inhibitors (ACEI) of the last few years and the even more recent calcium channel blockers (CCB). In efforts to achieve improved therapy (primarily for the treatment of hypertension, its sequelae, reversible conditions secondary to hypertension, and hypertension secondary to other conditions), a number of agents in each of these classes have been tested both alone as well as in combination with other agents. Some of the conditions for which at least one of these agents has been used or is believed useful include, without limitation, hypertension, angina, myocardial infarction, atherosclerosis, diabetic nephropathy, diabetic cardiac myopathy, renal insufficiency, peripheral vascular disease, left ventricular hypertrophy, cognitive dysfunction, stroke, and headache. Others will be apparent to those of ordinary skill in the art based on a knowledge of the underlying mechanisms involved as well as on general clinical and pre-clinical experience. Benazepril, benazeprilat, and their pharmaceutically acceptable salts are disclosed in U.S. Pat. No. 4,410,520, along with pharmaceutically acceptable dosage forms thereof, dosage ranges and suitable routes of administration therewith, and uses therefor, all of which are incorporated herein by reference. Amlodipine and its pharmaceutically acceptable salts are set forth in U.S. Pat. No. 4,572,909, incorporated herein by reference. Phamaceutically acceptable dosage forms, dosage ranges, suitable routes of administration, and uses of amlodipine and its salts are set out there. U.S. Pat. No. 4,879,303 is directed to the besylate salt of amlodipine, and it too is incorporated herein by reference. More specific dosages, routes of administration, formulations, and uses for amlodipine besylate can be found there. An excellant review of amlodipine is Burges et al, Cardiovas Drug Dev. 8(1) 25-44, 1990. Web site: http://www.delphion.com/details?pn=US06162802__

Patent Applications on Norvasc As of December 2000, U.S. patent applications are open to public viewing.7 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 Norvasc: •

Amlodipine free base Inventor(s): Benneker, Franciscus B.G.; (Rheden, NL), Keltjens, Rolf; (Nijmegen, NL), Lemmens, Jacobus M.; (Mook, NL), Peters, Theodorus H.A.; (Arnhem, NL) Correspondence: Synthon Pharmaceuticals, LTD.; Patent DEPT.; P.O. Box 161; Catharpin; VA; 20143; US Patent Application Number: 20030022922 Date filed: December 21, 2001 Abstract: Amlodipine free base can be formulated into a convenient oral dosage form, especially a tablet, without excessive stickiness or tablet punch residue. The amlodipine free base can be crystalline Form I or a novel Form II. Methods of making and using the amlodipine free base are set forth. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn.119(e) from provisional patent application Serial No. 60/258,613, filed Dec. 29, 2000. The present

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

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invention relates to amlodipine free base, compositions comprising amlodipine free base and to use of amlodipine free base in therapy. While amlodipine as a free base and as a pharmaceutically acceptable acid addition salt are generally taught, the amlodipine examples all make amlodipine maleate; e.g. examples 9, 11, 12, and 22 of EP 089 167. The maleate salt is identified as the most preferred acid addition salt. Surprisingly, amlodipine free base is not characterized. The examples appear to describe the formation of the free base but only as a solution/slurry (example 11) or as a residue remaining after evaporation of the solvent (examples 12 and 22). Only the amlodipine maleate salt is described as precipitating from a solution (examples 12 and 22). Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Amlodipine fumarate Inventor(s): Benneker, Franciscus B.G.; (Rheden, NL), Lemmens, Jacobus M.; (Mook, NL), Peters, Theodorus H.A.; (Arnhem, NL), Picha, Frantisek; (Brno, CZ) Correspondence: Synthon Pharmaceuticals, LTD.; Patent DEPT.; P.O. Box 161; Catharpin; VA; 20143; US Patent Application Number: 20020123519 Date filed: August 27, 2001 Abstract: Amlodipine fumarate salt compounds are useful as calcium channel blockers and in treating or preventing angina or hypertension. The fumarate salts avoid the formation of certain potential impurities that have been found to be associated with amlodipine maleate. Excerpt(s): This application is a continuing application under 35 U.S.C.sctn.120 of prior co-pending U.S. application Ser. No. 09/809,350, filed Mar. 16, 2001, the entire contents of which are incorporated herein by reference. Further this application claims the benefit of priority under 35 U.S.C.sctn.119(e) from provisional patent application Ser. No. 60/258,604, filed Dec. 29, 2000, the entire contents of which are incorporated herein by reference. The present invention relates to a novel compound, to processes for preparing it and to its use in treating medical disorders. In particular the present invention relates to novel acid addition salts of amlodipine. The present invention relates to fumarate salts of amlodipine. In particular, one aspect of the invention relates to an acid addition salt of amlodipine with fumaric acid. Another aspect of the invention relates to amlodipine fumarate in a crystalline state. A preferred form of amlodipine fumarate is amlodipine hemifumarate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Amlodipine maleate formulations Inventor(s): Chakole, Dinesh Dayaramji; (Hyderabad, IN), Dhanorkar, Vipin Tatyasaheb; (Hyderabad, IN), Mohan, Mailatur Sivaraman; (Hyderabad, IN), Reddy, Billa Praveen; (Hyderabad, IN), Reddy, Pallempalli Venkata Siva; (Hyderabad, IN) Correspondence: Ladas & Parry; 26 West 61 Street; New York; NY; 10023; US Patent Application Number: 20030180354 Date filed: September 13, 2002

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Abstract: The present invention relates to the stable solid orally administrable pharmaceutical formulation of Amlodipine Maleate. The invention also describes the process of producing such stable formulations and more specifically a direct compression method of producing tablet formulations. The tablet formulation of Amlodipine Maleate thus prepared is bioequivalent to the tablets containing Amlodipine Besylate salt commercially available with the brand name of Norvasc. The formulation also avoids the common problem of sticking observed during manufacturing. Excerpt(s): Stable formulations comprising Amlodipine Maleate are disclosed. Amlodipine belongs to dihydropyridine group of compounds having chemical name (.+-.)-2-[(2-Aminoethoxy) methyl]-4-(2-chlorophenyl)-3-ethoxycarbonyl-5methoxycarbonyl-6-methyl-1,4-dihydropyridine and molecular formula C.sub.20H.sub.25-Cl-N.sub.2-O.sub.5. It exists in various salt forms amongst which is Amlodipine Besylate. Amlodipine Besylate is commercially available as Norvasc in the form of oral tablets by Pfizer in 2.5 mg, 5 mg and 10 mg base preparations. Therapeutically Amlodipine belongs to the class of antianginals and antihypertensives. The main mechanism of action of Amlodipine is the inhibition of calcium channels. It is also available in combination with diuretics and angiotensin converting enzyme inhibitors. Amlodipine is well absorbed through gut. Oral bioavailability of Amlodipine in man was found to be 64%. Plasma protein binding for Amlodipine is high in man corresponding to 97%. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Amlodipine salt forms and processes for preparing them Inventor(s): Ettema, Gerrit J. B.; (Nijmegen, NL), Hoorn, Hans; (Nijmegen, NL), Lemmens, Jacobus M.; (Nijmegen, NL) Correspondence: Fleshner & Kim, Llp; P.O. Box 221200; Chantilly; VA; 20153; US Patent Application Number: 20030139455 Date filed: November 20, 2002 Abstract: Amlodipine besylate forms are described, including amlodipine besylate hydrates and novel amlodipine besylate anhydrates. A method of making various amlodipine besylate forms from an aqueous medium as well as the use of the same as a calcium channel blocker are described. Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn.119(e) from prior U.S. provisional application No. 60/331,742, filed Nov. 21, 2001, the entire contents of which are incorporated herein by reference. The present invention relates to amlodipine salt forms, including hydrate and anhydrate forms, and to processes for making amlodipine salt forms. This compound is used for the preparation of a medicament having calcium channel blocking activity that is useful, inter alia, in the management of hypertension, congestive heart failure and angina pectoris. The commercial product of amlodipine (NORVASCO.RTM. by Pfizer, Inc.) contains amlodipine besylate, which is described in U.S. Pat. No. 4,879,303 and corresponding EP 244 944. This patent discloses a single form of amlodipine besylate, namely a crystalline anhydrous besylate salt of amlodipine. This salt form is described as being non-hygroscopic; e.g., it does not form a hydrate. It is formed in the examples by combining either benzene sulphonic acid or ammonium benzenesulphonate with a slurry of amlodipine free base in industrial methylated spirits.

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

Aspartate derivative of amlodipine Inventor(s): Benneker, Franciscus B.G.; (Rheden, NL), Lemmens, Jacobus M.; (Mook, NL), Peters, Theodorus H. A.; (Arnhem, NL) Correspondence: Synthon Pharmaceuticals, LTD.; Patent DEPT.; P.O. Box 161; Catharpin; VA; 20143; US Patent Application Number: 20020128296 Date filed: August 27, 2001 Abstract: An amlodipine derivative having the following formula is useful, either alone or in combination with amlodipine, as a pharmaceutical in treating angina and hypertension. 1 Excerpt(s): This application claims the benefit of priority under 35 U.S.C.sctn. 120 from prior co-pending U.S. patent application Ser. No. 09/809,349, filed Mar. 16, 2001, the entire contents of which are incorporated herein by reference. Further, this application claims the benefit of priority under 35 U.S.C.sctn.119(e) from provisional patent application Serial No. 60/258,602, filed Dec. 29, 2000, the entire contents of which are incorporated herein by reference. The present invention relates to a novel compound, to processes for preparing it and to its use in treating medical disorders. In particular the present invention relates to a novel derivative of Amlodipine. or a pharmaceutically acceptable salt thereof. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Intermediate for the synthesis of amlodipine, a process for the preparation there and corresponding use Inventor(s): Campon Pardo, Julio; (Barcelona, ES), Coppi, Laura; (Barcelona, ES), Gasanz Guillen, Yolanda; (Barcelona, ES) Correspondence: Sughrue Mion, Pllc; 2100 Pennsylvania Avenue; Washington; DC; 20037-3213; US Patent Application Number: 20020068831 Date filed: January 10, 2002 Abstract: An intermediate for the synthesis of amlodipine, a process for the preparation thereof and the corresponding use are disclosed. The intermediate is ethyl 3-amino-4-(2(phthalimido)ethoxy)crotonate and is of formula III 1The process for the preparation thereof comprises reacting the acetoacetate of formula 2with ammonium acetate; and the use thereof is for the preparation of the compound of formula 3the process being conducted by reacting ethyl 3-amino-4-[2-(phthalimido)et- hoxy]crotonate with a benzylidene derivative. Excerpt(s): The present invention relates to an intermediate for the synthesis of amlodipine, to a process for the preparation thereof and to a use of the intermediate. The invention belongs to the field of heterocyclic chemistry and, as indicated, it relates to a chemical intermediate, ethyl 3-amino-4-(2-(phthalimido)ethoxy)crotonate, to the process for the preparation thereof, and to the use thereof for the synthesis of 2-((2aminoethoxy)methyl)-4-(2-chlorophenyl)-3-ethoxycarbonyl-5-methoxycarbonyl-6-

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methyl-1,4-dihydropyridine, generically known as amlodipine, a product having a therapeutical activity used as an antiischaemic and antihypertensive agent. Patent EP 0 060 674 discloses two processes for the preparation of 1,4-dihydropyridines containing in the 2 position a substituent having an amino group and having antiischaemic and antihypertensive utility. In both cases, the yields indicated are very low (.about.15%) and the products have to be purified by chromatography, making the industrial application thereof difficult. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Method for preparing amlodipine Inventor(s): Kim, Nam-Du; (Osan-si, KR), Lee, Kwan-Sun; (Seoul, KR), Lee, Kyung-Ik; (Incheon, KR), Moon, Young-Ho; (Suwon-si, KR) Correspondence: David A. Einhorn, ESQ.; Anderson Kill & Olick, P.C.; 1251 Avenue OF The America; New York; NY; 10020; US Patent Application Number: 20020132834 Date filed: March 11, 2002 Abstract: Amlodipine is prepared in a high yield by subjecting a pyrrole derivative, methyl aminocrotonate and 2-chlorobenzaldehyde to a Hantzsch reaction, and converting the pyrrole residue of the resulting 1,4-dihydropyridine derivative to an amine group by the action of hydroxylamine hydrochloride. Excerpt(s): The present invention relates to a synthetic method of preparing amlodipine in a high yield. There have been reported a number of methods for amlodipine synthesis but these methods generally suffer from the problem of low productivity caused by low yields observed at the critical Hantzsch reaction step, as further explained below. However, this method gives a yield of only 19% and is not suitable for a large scale production due to the explosion hazard of the azide compound. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Optically pure (-) amlodipine compositions Inventor(s): Young, James W.; (Palo Alto, CA) Correspondence: Pennie & Edmonds Llp; 1155 Avenue OF The Americas; New York; NY; 10036-2711; US Patent Application Number: 20020010200 Date filed: July 27, 2001 Abstract: Methods and compositions are disclosed utilizing the optically pure (-) isomer of amlodipine. This compound is a potent drug for the treatment of hypertension while avoiding the concomitant liability of adverse effects associated with the racemic mixture of amlodipine. The (-) isomer of amlodipine is also useful for the treatment of angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist such as cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure, without the concomitant liability of adverse effects associated with the racemic mixture of amlodipine.

Patents 49

Excerpt(s): This invention relates to novel compositions of matter containing optically pure (-) amlodipine. These compositions possess potent activity in treating both systolic and diastolic hypertension while avoiding adverse effects including but not limited to edema of the extremities, headache and dizziness, which are associated with administration of the racemic mixture of amlodipine. Additionally, these novel compositions of matter containing optically pure (-) amlodipine are useful in treating angina and such other conditions as may be related to the activity of (-) amlodipine as a calcium channel antagonist including but not limited to cerebral ischemia, cerebral disorders, arrhythmias, cardiac hypertrophy, coronary vasospasm, myocardial infarction, renal impairment and acute renal failure--while avoiding the adverse effects associated with administration of the racemic mixture of amlodipine. Also disclosed are methods for treating the above-described conditions in a human while avoiding the adverse effects that are associated with the racemic mixture of amlodipine, by administering the (-) isomer of amlodipine to said human. Many organic compounds exist in optically active forms, i.e., they have the ability to rotate the plane of planepolarized light. In describing an optically active compound, the prefixes D and L or R and S are used to denote the absolute configuration of the molecule about its chiral center(s). The prefixes d and l or (+) and (-) are employed to designate the sign of rotation of plane-polarized light by the compound, with (-) or 1 meaning that the compound is levorotatory. A compound prefixed with (+) or d is dextrorotatory. For a given chemical structure, these compounds, called stereoisomers, are identical except that they are mirror images of one another. A specific stereoisomer may also be referred to as an enantiomer, and a mixture of such isomers is often called an enantiomeric or racemic mixture. Stereochemical purity is of importance in the field of pharmaceuticals, where 12 of the 20 most prescribed drugs exhibit chirality. A case in point is provided by the L-form of the.beta.-adrenergic blocking agent, propranolol, which is known to be 100 times more potent than the D-enantiomer. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical compositions comprising amlodipine maleate Inventor(s): Lemmens, Jacobus M.; (Mook, NL), van Dalen, Frans; (Nijmegen, NL), Vanderheijden, Arlette; (Nijmegen, NL) Correspondence: Synthon Pharmaceuticals, LTD.; Patent DEPT.; P.O. Box 161; Catharpin; VA; 20143; US Patent Application Number: 20020176889 Date filed: August 27, 2001 Abstract: An amlodipine maleate pharmaceutical composition is provided with good stability when formulated with a pH within the range of 5.5 to 7, when measured as a 20 wt % aqueous slurry. The stability can also be aided by making the pharmaceutical composition from amlodipine maleate particles having an average particle size of greater than 20 microns, preferably greater than 100 microns. Excerpt(s): This application is a continuing application under 35 U.S.C.sctn.120 of prior co-pending U.S. patent application Ser. No. 09/809,346, filed Mar. 16, 2001, the entire contents of which are incorporated herein by reference. Further, this application claims the benefit of priority under 35 U.S.C.sctn.119(e) from U.S. provisional application No. 60/258,562, filed Dec. 29, 2000, the entire contents of which are incorporated herein by reference. The present invention relates to pharmaceutical compositions comprising amlodipine maleate and to processes for making the same. Examples 8, 11, 12, and 22 of

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EP 089 167 show the synthesis of amlodipine in the maleate salt form. While a variety of acid addition salts are taught to be suitable, the maleate salt is identified as the most preferred acid addition salt. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Pharmaceutical compositions of amlodipine and atorvastatin Inventor(s): Alani, Laman; (Ann Arbor, MI), Khan, Sadath U.; (Randolph, NJ), MacNeil, Thomas; (Ann Arbor, MI), Muhammad, Nouman A.; (Long Valley, NJ) Correspondence: Francis J. Tinney; Warner-lambert Company; 2800 Plymouth Road; Ann Arbor; MI; 48105; US Patent Application Number: 20030114497 Date filed: July 25, 2002 Abstract: A pharmaceutical composition comprising two components:(a) one component comprising a granulation of atorvastatin or pharmaceutically acceptable salts thereof and a carrier including an alkalizing agent that forms a pH greater than 5; and(b) a second component comprising amlodipine or pharmaceutically acceptable salts thereof and a carrier excluding an alkalizing agent that forms a pH greater than 5, wherein the two components are combined to form a final composition for a solid dosage form is described as well as methods to prepare the compositions, kits for containing such compositions, and a method of treating angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and/or hypercholesterolemia, and symptoms of cardiac risk using a therapeutically effective amount of the pharmaceutical composition. Excerpt(s): This invention relates to pharmaceutical compositions comprising amlodipine and pharmaceutically acceptable salts thereof, and atorvastatin and pharmaceutically acceptable salts thereof, and a process for the preparation of the same, kits containing such compositions, as well as methods of using such compositions to treat subjects suffering from angina pectoris, atherosclerosis, combined hypertension and hyperlipidemia and/or hypercholesterolemia and to treat subjects presenting with symptoms of cardiac risk, including human subjects. The conversion of 3-hydroxy-3methylglutaryl-coenzyme A (HMG-CoA) to mevalonate is an early and rate-limiting step in the cholesterol biosynthetic pathway. This step is catalyzed by the enzyme HMG-CoA reductase. Statins inhibit HMG-CoA reductase from catalyzing this conversion. As such, statins are collectively potent lipid lowering agents. Atorvastatin and pharmaceutically acceptable salts thereof are selective, competitive inhibitors of HMG-CoA reductase. As such, atorvastatin calcium is a potent lipid lowering compound and is thus useful as a hypolipidemic and/or hypocholesterolemic agent. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

Patents 51

•

Process for making amlodipine maleate Inventor(s): Benneker, Franciscus B.G.; (Rheden, NL), Picha, Frantisek; (Brno, CZ), Slanina, Pavel; (Lelekovice, CA) Correspondence: Synthon Pharmaceuticals, LTD.; Patent DEPT.; P.O. Box 161; Catharpin; VA; 20143; US Patent Application Number: 20020086888 Date filed: August 27, 2001 Abstract: A process for making amlodipine maleate comprises reacting amlodipine or an acid addition salt thereof with maleic acid under an acidic environment to form an amlodipine maleate product. The process allows for the formation of amlodipine maleate substantially free from amlodipine aspartate. Excerpt(s): This application is a continuing application under 35 U.S.C.sctn. 120 of prior co-pending U.S. patent application Ser. No. 09/809,343, filed Mar. 16, 2001, the entire contents of which are incorporated herein by reference. Further, this application claims the benefit of priority under 35 U.S.C.sctn. 119(e) from U.S. provisional application No. 60/258,612, filed Dec. 29, 2001, the entire contents of which are incorporated herein by reference. The present invention relates to a process for making amlodipine maleate with good purity. Amlodipine exhibits good bioavailability and has a long half-life in the body. While a variety of acid addition salts are taught in these patents to be suitable, the maleate salt is identified as the most preferred acid addition salt. Examples 9,11,12 and 22 of EP 89167 as well as J. Med. Chem. 29, 1698 (1986) disclose the preparation of amlodipine maleate (with 1:1 molar ratio of both components) by dissolving a reaction mixture containing an in situ prepared raw amlodipine base into ethyl acetate or into ethanol and adding thereto solid maleic acid whereby the maleate salt of amlodipine precipitates. The salt is then isolated by filtration and recrystallized from ethyl acetate or from acetone/ethyl acetate 1:1 mixture. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Process for making amlodipine, derivatives therof, and precursors therefor Inventor(s): Bartl, Jiri; (Strelice, CZ), Benneker, Franciscus B. G.; (Rheden, NL), Peters, Theodorus H. A.; (Arnhem, NL), Slanina, Pavel; (Lelekovice, CZ) Correspondence: Synthon Pharmaceuticals, LTD.; Patent DEPT.; P.O. Box 161; Catharpin; VA; 20143; US Patent Application Number: 20020143046 Date filed: August 27, 2001 Abstract: Amlodipine and related analogues thereof are prepared by the following general reaction scheme: 1R.sub.1 and R.sub.2 each independently represent a C.sub.1C.sub.4 alkyl group. The process provides for the formation of compounds of formula (1) in good yield and purity. Further, the compounds of formula (1) can be used as calcium channel blockers or as reference standards or reference markers for checking the purity of amlodipine. Excerpt(s): This application is a continuing application under 35 U.S.C.sctn. 120 of prior U.S. application Ser. No. 09/809,351, filed Mar. 16, 2001, the entire contents of which are incorporated herein by reference. Further, this application claims the benefit of priority under 35 U.S.C.sctn. 119(e) from provisional patent application Serial No. 60/258,613,

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filed Dec. 29, 2000. The present invention relates to novel intermediates useful in the synthesis of amlodipine and related compounds as well as to processes of making and using the same. This compound, in the form of its besylate salt as described in EP 244 944 and in corresponding U.S. Pat. No. 4,879,303, is the active ingredient in the prescription pharmaceutical composition NORVASC sold by Pfizer Pharmaceuticals for management of hypertension and angina pectoris. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Reference standards for determining the purity or stability of amlodipine maleate and processes therefor Inventor(s): Bakker, Peter F.A.; (Veghel, NL), Lemmens, Jacobus M.; (Mook, NL), Peters, Theodorus H.A.; (Arnhem, NL), Picha, Frantisek; (Brno, CZ) Correspondence: Synthon Pharmaceuticals, LTD.; Patent DEPT.; P.O. Box 161; Catharpin; VA; 20143; US Patent Application Number: 20020137223 Date filed: August 27, 2001 Abstract: Amlodipine aspartate and amlodipine maleamide are used as reference standards or markers in determining the purity of amlodipine maleate substances and products. Excerpt(s): This application is a continuing application under 35 U.S.C.sctn.120 from prior co-pending U.S. patent application Ser. No. 09/809,347, filed Mar. 16, 2001, the entire contents of which are incorporated herein by reference. Further, this application claims the benefit of priority under 35 U.S.C.sctn.119(e) from provisional application Serial No. 60/258,601, filed Dec. 29, 2001, the entire contents of which are incorporated herein by reference. The present invention relates to the use of two novel compounds as reference standards for determining the purity or stability of amlodipine maleate substances and pharmaceutical compositions. Pharmaceutical products are regulated in most countries by a government agency. For example, the U.S. Food & Drug Administration (FDA) generally requires an applicant to show safety and efficacy of the pharmaceutical product during the approval/review phase and continues to monitor the safety of the drug post-approval. Similar requirements exist in many European countries and elsewhere in the world. In order to satisfy safety concerns, the regulatory agencies generally require a manufacturing specification that sets the maximum amount of each identified impurity as well as the maximum amount for all remaining unidentified impurities. Once approved, each batch or lot of the pharmaceutical product is tested to insure that the specification is met. Further, stability testing is performed on the pharmaceutical product in order to show that the composition does not substantially or materially change over time; i.e. over its indicated shelf-life. It is important that before its administration to a patient that the pharmaceutical product does not deviate from its approved specification in a way that might detract from its safety or efficacy. Good practice warrants keeping a sample from every commercial batch released to the public so that the stability can be monitored and any defect uncovered and corrected. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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•

Resolution of the enantiomers of amlodipine Inventor(s): Xitian, Zhang; (JiLin, CN) Correspondence: Jacobson Holman Pllc; 400 Seventh Street N.W.; Suite 600; Washington; DC; 20004; US Patent Application Number: 20030028031 Date filed: August 16, 2002 Abstract: The invitation provides an efficient method for the resolution of (R)-(+)(formula (I)) and (S)-(-)(formula (II))-enantiomers of amlodipine, where the chiral reagent for resolution is tartaric acid and the chiral auxiliary reagent for resolution is deuterated dimethyl sulphoxide (DMSO-d6). Excerpt(s): The invention provides a feasible method for the separation of both (S)-(-)enantiomer and (R)-(+)-enantiomer of racemic amlodipine. The chiral reagent for separation is tartaric acid and the chiral auxiliary reagent is hexadeuterium dimethyl sulphoxide (DMSO-d.sub.6). Pfizer invented a feasible method for the separation of the enantiomers of amlodipine (W095/25722), in very good optical purity and yield. The use of both dimethyl sulphoxide (DMSO) and chiral reagent tartaric acid are essential to this method. The invention indicates that hexadeuterium dimethyl sulphoxide (DMSOd.sub.6), in optical purity of up to 100% e.e. and very good yield, is a chiral auxiliary reagent better than DMSO. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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Synergistic effects of amlodipine and atorvastatin metabolite as a basis for combination therapy Inventor(s): Mason, R. Preston; (Manchester, MA) Correspondence: Perkins, Smith & Cohen Llp; One Beacon Street; 30th Floor; Boston; MA; 02108; US Patent Application Number: 20020086889 Date filed: October 19, 2001 Abstract: The combination of amlodipine with atorvastatin metabolite shows a synergistic antioxidant effect on lipid peroxidation in human low-density lipoproteins and membrane vesicles enriched with polyunsaturated fatty acids. Inhibition of oxyradical damage by this drug combination was observed at therapeutic levels in a manner that could not be reproduced by the combination of amlodipine with other statins or the natural antioxidant, vitamin E. The basis for this potent activity is attributed to the chemical structures of these compounds and their molecular interactions with phospholipid molecules, as determined by x-ray diffraction analyses. This combination therapy can be used to treat cardiovascular disorders, especially coronary artery disease, by increasing the resistance of low-density lipoproteins and vascular cell membranes against oxidative modification. Excerpt(s): This application claims priority from the following four provisional patent applications: U.S. application No. 60/130,665, filed on Apr. 23, 1999; U.S. application No. 60/145,305, filed on Jul. 23, 1999; U.S. application No. 60/151,121, filed on Aug. 27, 1999; and U.S. application No. 60/166,592, filed on Nov. 19, 1999, and is a continuationin-part application of our U.S. application Ser. No. 09/556,930 filed Apr. 21, 2000. The present invention relates to pharmaceutical compositions and combinations to treat

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arterial and related heart disease and related ailments. Coronary artery disease (CAD) is the leading cause of mortality in the developed world, and is associated with substantial morbidity as well. Typically, the patient with CAD has several concomitant conditions, including hypertension, diabetes, and dyslipidemia, increasing overall risk for poor outcomes and complicating treatment. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

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

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CHAPTER 6. BOOKS ON NORVASC Overview This chapter provides bibliographic book references relating to Norvasc. In addition to online booksellers such as www.amazon.com and www.bn.com, excellent sources for book titles on Norvasc include the Combined Health Information Database and the National Library of Medicine. Your local medical library also may have these titles available for loan.

The National Library of Medicine Book Index The National Library of Medicine at the National Institutes of Health has a massive database of books published on healthcare and biomedicine. Go to the following Internet site, http://locatorplus.gov/, and then select “Search LOCATORplus.” Once you are in the search area, simply type “Norvasc” (or synonyms) into the search box, and select “books only.” From there, results can be sorted by publication date, author, or relevance. The following was recently catalogued by the National Library of Medicine:8 •

Amlodipine Author: Nayler, Winifred G.; Year: 1995; Berlin: New York: SpringerVerlag, c1993; ISBN: 3540566988 http://www.amazon.com/exec/obidos/ASIN/3540566988/icongroupinterna

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Amlodipine: continuous control and protection in hypertension and myocardial ischemia: March 10, 1991: IX Scientific Meeting of the Inter-American Society of Hypertension, Rio de Janeiro. Author: Interamerican Society of Hypertension. Scientific Meeting; Year: 1996; [United States?]: Academy Professional Information Services, c1991

•

Amlodipine. Author: Winifred G. Nayler; Year: 1993

8

In addition to LOCATORPlus, in collaboration with authors and publishers, the National Center for Biotechnology Information (NCBI) is currently adapting biomedical books for the Web. The books may be accessed in two ways: (1) by searching directly using any search term or phrase (in the same way as the bibliographic database PubMed), or (2) by following the links to PubMed abstracts. Each PubMed abstract has a "Books" button that displays a facsimile of the abstract in which some phrases are hypertext links. These phrases are also found in the books available at NCBI. Click on hyperlinked results in the list of books in which the phrase is found. Currently, the majority of the links are between the books and PubMed. In the future, more links will be created between the books and other types of information, such as gene and protein sequences and macromolecular structures. See http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=Books.

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Management of angina and hypertension in patients with left ventricular dysfunction: focus on amlodipine Author: McMurray, John,; Year: 1998; London; New York, NY: Royal Society of Medicine Press, c1998; ISBN: 1853153346

Chapters on Norvasc In order to find chapters that specifically relate to Norvasc, an excellent source of abstracts is the Combined Health Information Database. You will need to limit your search to book chapters and Norvasc using the “Detailed Search” option. Go to the following hyperlink: http://chid.nih.gov/detail/detail.html. To find book chapters, use the drop boxes at the bottom of the search page where “You may refine your search by.” Select the dates and language you prefer, and the format option “Book Chapter.” Type “Norvasc” (or synonyms) into the “For these words:” box.

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CHAPTER 7. PERIODICALS AND NEWS ON NORVASC Overview In this chapter, we suggest a number of news sources and present various periodicals that cover Norvasc.

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

Dr Reddy gets US approval for version of Norvasc Source: Reuters Industry Breifing Date: November 03, 2003

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Pfizer raises UK price of amlodipine Source: Reuters Industry Breifing Date: July 07, 2003

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India's Reddy wins US right to sell modified Norvasc Source: Reuters Industry Breifing Date: December 18, 2002

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Reddy moves closer to FDA OK for amlodipine, shares rise Source: Reuters Industry Breifing Date: October 22, 2002

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Dr. Reddy says sued by Pfizer over generic Norvasc Source: Reuters Industry Breifing Date: June 20, 2002 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 “Norvasc” (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 “Norvasc” (or synonyms). If you know the name of a company that is relevant to Norvasc, 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/.

Periodicals and News

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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 “Norvasc” (or synonyms).

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

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CHAPTER 8. RESEARCHING MEDICATIONS Overview While a number of hard copy or CD-ROM resources are available for researching medications, a more flexible method is to use Internet-based databases. Broadly speaking, there are two sources of information on approved medications: public sources and private sources. We will emphasize free-to-use public sources.

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

Systemic - U.S. Brands: Norvasc http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202670.html

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

Mosby’s Drug Consult Mosby’s Drug Consult database (also available on CD-ROM and book format) covers 45,000 drug products including generics and international brands. It provides prescribing information, drug interactions, and patient information. Subscription information is available at the following hyperlink: http://www.mosbysdrugconsult.com/. PDRhealth The PDRhealth database is a free-to-use, drug information search engine that has been written for the public in layman’s terms. It contains FDA-approved drug information adapted from the Physicians’ Desk Reference (PDR) database. PDRhealth can be searched by brand name, generic name, or indication. It features multiple drug interactions reports. Search PDRhealth at http://www.pdrhealth.com/drug_info/index.html. Other Web Sites Drugs.com (www.drugs.com) reproduces the information in the Pharmacopeia as well as commercial information. You may also want to consider the Web site of the Medical Letter, Inc. (http://www.medletter.com/) which allows users to download articles on various drugs and therapeutics for a nominal fee. If you have any questions about a medical treatment, the FDA may have an office near you. Look for their number in the blue pages of the phone book. You can also contact the FDA through its toll-free number, 1-888-INFO-FDA (1-888-463-6332), or on the World Wide Web at www.fda.gov.

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APPENDICES

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APPENDIX A. PHYSICIAN RESOURCES Overview In this chapter, we focus on databases and Internet-based guidelines and information resources created or written for a professional audience.

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute9: •

Office of the Director (OD); guidelines consolidated across agencies available at http://www.nih.gov/health/consumer/conkey.htm

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National Institute of General Medical Sciences (NIGMS); fact sheets available at http://www.nigms.nih.gov/news/facts/

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National Library of Medicine (NLM); extensive encyclopedia (A.D.A.M., Inc.) with guidelines: http://www.nlm.nih.gov/medlineplus/healthtopics.html

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National Cancer Institute (NCI); guidelines available at http://www.cancer.gov/cancerinfo/list.aspx?viewid=5f35036e-5497-4d86-8c2c714a9f7c8d25

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National Eye Institute (NEI); guidelines available at http://www.nei.nih.gov/order/index.htm

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National Heart, Lung, and Blood Institute (NHLBI); guidelines available at http://www.nhlbi.nih.gov/guidelines/index.htm

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National Human Genome Research Institute (NHGRI); research available at http://www.genome.gov/page.cfm?pageID=10000375

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National Institute on Aging (NIA); guidelines available at http://www.nia.nih.gov/health/

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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.10 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:11 •

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

10 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). 11 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 Gateway12 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.13 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “Norvasc” (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 1231 6 916 2 0 2155

HSTAT14 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.15 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.16 Simply search by “Norvasc” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

12

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

13

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

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 Biologists17 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.18 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.19 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/.

17 Adapted 18

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. 19 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 Norvasc 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 Norvasc. 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 Norvasc. 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 “Norvasc”:

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Other guides Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Movement Disorders http://www.nlm.nih.gov/medlineplus/movementdisorders.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 Norvasc. The drawbacks of this approach are that the information is not organized by theme and that the references are often a mix of information for professionals and patients. Nevertheless, a large number of the listed Web sites provide useful background information. We can only recommend this route, therefore, for relatively rare or specific disorders, or when using highly targeted searches. To use the NIH search utility, visit the following Web page: http://search.nih.gov/index.html. Additional Web Sources A number of Web sites are available to the public that often link to government sites. These can also point you in the direction of essential information. The following is a representative sample: •

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to Norvasc. By consulting all of associations listed in

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this chapter, you will have nearly exhausted all sources for patient associations concerned with Norvasc. 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 Norvasc. 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 “Norvasc” (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 “Norvasc”. 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 “Norvasc” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months. The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “Norvasc” (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.20

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

20

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)21: •

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/

21

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

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

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

•

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

•

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

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

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

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NORVASC DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Academic Medical Centers: Medical complexes consisting of medical school, hospitals, clinics, libraries, administrative facilities, etc. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Acetylcholine: A neurotransmitter. Acetylcholine in vertebrates is the major transmitter at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. It is generally not used as an administered drug because it is broken down very rapidly by cholinesterases, but it is useful in some ophthalmological applications. [NIH] Acute renal: A condition in which the kidneys suddenly stop working. In most cases, kidneys can recover from almost complete loss of function. [NIH] Adaptation: 1. The adjustment of an organism to its environment, or the process by which it enhances such fitness. 2. The normal ability of the eye to adjust itself to variations in the intensity of light; the adjustment to such variations. 3. The decline in the frequency of firing of a neuron, particularly of a receptor, under conditions of constant stimulation. 4. In dentistry, (a) the proper fitting of a denture, (b) the degree of proximity and interlocking of restorative material to a tooth preparation, (c) the exact adjustment of bands to teeth. 5. In microbiology, the adjustment of bacterial physiology to a new environment. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] 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] Agar: A complex sulfated polymer of galactose units, extracted from Gelidium cartilagineum, Gracilaria confervoides, and related red algae. It is used as a gel in the preparation of solid culture media for microorganisms, as a bulk laxative, in making emulsions, and as a supporting medium for immunodiffusion and immunoelectrophoresis. [NIH]

Age of Onset: The age or period of life at which a disease or the initial symptoms or

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manifestations of a disease appear in an individual. [NIH] Agonist: In anatomy, a prime mover. In pharmacology, a drug that has affinity for and stimulates physiologic activity at cell receptors normally stimulated by naturally occurring substances. [EU] Aldosterone: (11 beta)-11,21-Dihydroxy-3,20-dioxopregn-4-en-18-al. A hormone secreted by the adrenal cortex that functions in the regulation of electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. [NIH] Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task. [NIH] Alkaline: Having the reactions of an alkali. [EU] Alkaloid: A member of a large group of chemicals that are made by plants and have nitrogen in them. Some alkaloids have been shown to work against cancer. [NIH] Allograft: An organ or tissue transplant between two humans. [NIH] Allylamine: Possesses an unusual and selective cytotoxicity for vascular smooth muscle cells in dogs and rats. Useful for experiments dealing with arterial injury, myocardial fibrosis or cardiac decompensation. [NIH] Alternative medicine: Practices not generally recognized by the medical community as standard or conventional medical approaches and used instead of standard treatments. 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] Aminoethyl: A protease inhibitor. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. [NIH] Amphetamines: Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopression, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. [NIH] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are

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procedures performed by catheterization. When reconstruction of an artery is performed surgically, it is called endarterectomy. [NIH] Angiotensin converting enzyme inhibitor: A drug used to decrease pressure inside blood vessels. [NIH] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Antineoplastic: Inhibiting or preventing the development of neoplasms, checking the maturation and proliferation of malignant cells. [EU] Antineoplastic Agents: Substances that inhibit or prevent the proliferation of neoplasms. [NIH]

Antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. [NIH] Antiseptic: A substance that inhibits the growth and development of microorganisms without necessarily killing them. [EU] Anxiety: Persistent feeling of dread, apprehension, and impending disaster. [NIH] Aorta: The main trunk of the systemic arteries. [NIH] Aqueous: Having to do with water. [NIH] Arginine: An essential amino acid that is physiologically active in the L-form. [NIH] Arrhythmia: Any variation from the normal rhythm or rate of the heart beat. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is

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considered an antioxidant. [NIH] Aspartate: A synthetic amino acid. [NIH] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atherogenic: Causing the formation of plaque in the lining of the arteries. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] 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] Autonomic: Self-controlling; functionally independent. [EU] Bactericidal: Substance lethal to bacteria; substance capable of killing bacteria. [NIH] Bacteriophage: A virus whose host is a bacterial cell; A virus that exclusively infects bacteria. It generally has a protein coat surrounding the genome (DNA or RNA). One of the coliphages most extensively studied is the lambda phage, which is also one of the most important. [NIH] Barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy. [NIH] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Benzene: Toxic, volatile, flammable liquid hydrocarbon biproduct of coal distillation. It is used as an industrial solvent in paints, varnishes, lacquer thinners, gasoline, etc. Benzene causes central nervous system damage acutely and bone marrow damage chronically and is carcinogenic. It was formerly used as parasiticide. [NIH] Binding Sites: The reactive parts of a macromolecule that directly participate in its specific combination with another molecule. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU] Bioequivalent: Having the same strength and similar bioavailability in the same dosage form as another specimen of a given drug substance. [EU] Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH]

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Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] 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] Bone scan: A technique to create images of bones on a computer screen or on film. A small amount of radioactive material is injected into a blood vessel and travels through the bloodstream; it collects in the bones and is detected by a scanner. [NIH] Bowel: The long tube-shaped organ in the abdomen that completes the process of digestion. There is both a small and a large bowel. Also called the intestine. [NIH] Bowel Movement: Body wastes passed through the rectum and anus. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Bronchitis: Inflammation (swelling and reddening) of the bronchi. [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 blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx

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through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calcium Channels: Voltage-dependent cell membrane glycoproteins selectively permeable to calcium ions. They are categorized as L-, T-, N-, P-, Q-, and R-types based on the activation and inactivation kinetics, ion specificity, and sensitivity to drugs and toxins. The L- and T-types are present throughout the cardiovascular and central nervous systems and the N-, P-, Q-, & R-types are located in neuronal tissue. [NIH] Calcium Signaling: Signal transduction mechanisms whereby calcium mobilization (from outside the cell or from intracellular storage pools) to the cytoplasm is triggered by external stimuli. Calcium signals are often seen to propagate as waves, oscillations, spikes or puffs. The calcium acts as an intracellular messenger by activating calcium-responsive proteins. [NIH]

Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] Captopril: A potent and specific inhibitor of peptidyl-dipeptidase A. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. [NIH] Carbohydrates: The largest class of organic compounds, including starches, glycogens, cellulose, gums, and simple sugars. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n. [NIH] Carcinogenic: Producing carcinoma. [EU] Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] 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)

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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] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] 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 membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] Cell proliferation: An increase in the number of cells as a result of cell growth and cell division. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Central Nervous System Infections: Pathogenic infections of the brain, spinal cord, and meninges. DNA virus infections; RNA virus infections; bacterial infections; mycoplasma infections; Spirochaetales infections; fungal infections; protozoan infections; helminthiasis; and prion diseases may involve the central nervous system as a primary or secondary process. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebrovascular: Pertaining to the blood vessels of the cerebrum, or brain. [EU] Cerebrum: The largest part of the brain. It is divided into two hemispheres, or halves, called the cerebral hemispheres. The cerebrum controls muscle functions of the body and also controls speech, emotions, reading, writing, and learning. [NIH] Cervical: Relating to the neck, or to the neck of any organ or structure. Cervical lymph nodes are located in the neck; cervical cancer refers to cancer of the uterine cervix, which is the lower, narrow end (the "neck") of the uterus. [NIH] Cervix: The lower, narrow end of the uterus that forms a canal between the uterus and vagina. [NIH] Character: In current usage, approximately equivalent to personality. The sum of the relatively fixed personality traits and habitual modes of response of an individual. [NIH] Chemotherapy: Treatment with anticancer drugs. [NIH] Cholesterol: The principal sterol of all higher animals, distributed in body tissues, especially the brain and spinal cord, and in animal fats and oils. [NIH] Chronic: A disease or condition that persists or progresses over a long period of time. [NIH] Chronic Obstructive Pulmonary Disease: Collective term for chronic bronchitis and emphysema. [NIH] 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]

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Chronotherapy: The adaptation of the administration of drugs to circadian rhythms. The concept is based on the response of biological functions to time-related events, such as the low point in epinephrine levels between 10 p.m. and 4 a.m. or the elevated histamine levels between midnight and 4 a.m. The treatment is aimed at supporting normal rhythms or modifying therapy based on known variations in body rhythms. While chronotherapy is commonly used in cancer chemotherapy, it is not restricted to cancer therapy or to chemotherapy. [NIH] Cilazapril: An angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. Preliminary results also indicate its potential in the treatment of congestive heart failure. It is a prodrug that is hydrolyzed after absorption to its main metabolite cilazaprilat. [NIH] Ciliary: Inflammation or infection of the glands of the margins of the eyelids. [NIH] Ciliary Arteries: Three groups of arteries found in the eye which supply the iris, pupil, sclera, conjunctiva, and the muscles of the iris. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Circadian Rhythm: The regular recurrence, in cycles of about 24 hours, of biological processes or activities, such as sensitivity to drugs and stimuli, hormone secretion, sleeping, feeding, etc. This rhythm seems to be set by a 'biological clock' which seems to be set by recurring daylight and darkness. [NIH] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] 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] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] Cofactor: A substance, microorganism or environmental factor that activates or enhances the action of another entity such as a disease-causing agent. [NIH] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is

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differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] 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 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] Computed tomography: CT scan. A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized tomography and computerized axial tomography (CAT) scan. [NIH] Computerized axial tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called CAT scan, computed tomography (CT scan), or computerized

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tomography. [NIH] Computerized tomography: A series of detailed pictures of areas inside the body, taken from different angles; the pictures are created by a computer linked to an x-ray machine. Also called computerized axial tomography (CAT) scan and computed tomography (CT scan). [NIH] Concomitant: Accompanying; accessory; joined with another. [EU] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjunctiva: The mucous membrane that lines the inner surface of the eyelids and the anterior part of the sclera. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Consultation: A deliberation between two or more physicians concerning the diagnosis and the proper method of treatment in a case. [NIH] Contractility: Capacity for becoming short in response to a suitable stimulus. [EU] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [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 Arteriosclerosis: Thickening and loss of elasticity of the coronary arteries. [NIH] Coronary Circulation: The circulation of blood through the coronary vessels of the heart. [NIH]

Coronary heart disease: A type of heart disease caused by narrowing of the coronary arteries that feed the heart, which needs a constant supply of oxygen and nutrients carried by the blood in the coronary arteries. When the coronary arteries become narrowed or clogged by fat and cholesterol deposits and cannot supply enough blood to the heart, CHD results. [NIH] Coronary Thrombosis: Presence of a thrombus in a coronary artery, often causing a myocardial infarction. [NIH] Coronary Vasospasm: Spasm of the large- or medium-sized coronary arteries. [NIH] Cranial: Pertaining to the cranium, or to the anterior (in animals) or superior (in humans) end of the body. [EU] Craniocerebral Trauma: Traumatic injuries involving the cranium and intracranial structures (i.e., brain; cranial nerves; meninges; and other structures). Injuries may be classified by whether or not the skull is penetrated (i.e., penetrating vs. nonpenetrating) or whether there is an associated hemorrhage. [NIH] Crystallization: The formation of crystals; conversion to a crystalline form. [EU]

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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] Cytokine: Small but highly potent protein that modulates the activity of many cell types, including T and B cells. [NIH] Cytoplasm: The protoplasm of a cell exclusive of that of the nucleus; it consists of a continuous aqueous solution (cytosol) and the organelles and inclusions suspended in it (phaneroplasm), and is the site of most of the chemical activities of the cell. [EU] 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] Density: The logarithm to the base 10 of the opacity of an exposed and processed film. [NIH] Dextrorotatory: Turning towards the right hand. [NIH] Diabetes Insipidus: A metabolic disorder due to disorders in the production or release of vasopressin. It is characterized by the chronic excretion of large amounts of low specific gravity urine and great thirst. [NIH] Diabetes Mellitus: A heterogeneous group of disorders that share glucose intolerance in common. [NIH] Diagnostic procedure: A method used to identify a disease. [NIH] Dialyzer: A part of the hemodialysis machine. (See hemodialysis under dialysis.) The dialyzer has two sections separated by a membrane. One section holds dialysate. The other holds the patient's blood. [NIH] Diastole: Period of relaxation of the heart, especially the ventricles. [NIH] Diastolic: Of or pertaining to the diastole. [EU] 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] Digestive system: The organs that take in food and turn it into products that the body can use to stay healthy. Waste products the body cannot use leave the body through bowel movements. The digestive system includes the salivary glands, mouth, esophagus, stomach, liver, pancreas, gallbladder, small and large intestines, and rectum. [NIH] Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dihydrotestosterone: Anabolic agent. [NIH] Dilatation: The act of dilating. [NIH] Dilation: A process by which the pupil is temporarily enlarged with special eye drops (mydriatic); allows the eye care specialist to better view the inside of the eye. [NIH] Diltiazem: A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of the calcium ion in membrane functions. It is also teratogenic. [NIH] Dimethyl: A volatile metabolite of the amino acid methionine. [NIH]

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Direct: 1. Straight; in a straight line. 2. Performed immediately and without the intervention of subsidiary means. [EU] Disinfectant: An agent that disinfects; applied particularly to agents used on inanimate objects. [EU] Diuretic: A drug that increases the production of urine. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] 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] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Dyslipidemia: Disorders in the lipoprotein metabolism; classified as hypercholesterolemia, hypertriglyceridemia, combined hyperlipidemia, and low levels of high-density lipoprotein (HDL) cholesterol. All of the dyslipidemias can be primary or secondary. Both elevated levels of low-density lipoprotein (LDL) cholesterol and low levels of HDL cholesterol predispose to premature atherosclerosis. [NIH] Dystonia: Disordered tonicity of muscle. [EU] Ectopic: Pertaining to or characterized by ectopia. [EU] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH] Effector: It is often an enzyme that converts an inactive precursor molecule into an active second messenger. [NIH] Efficacy: The extent to which a specific intervention, procedure, regimen, or service produces a beneficial result under ideal conditions. Ideally, the determination of efficacy is based on the results of a randomized control trial. [NIH] Ejection fraction: A measure of ventricular contractility, equal to normally 65 8 per cent; lower values indicate ventricular dysfunction. [EU] Electrocardiogram: Measurement of electrical activity during heartbeats. [NIH] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electromyography: Recording of the changes in electric potential of muscle by means of surface or needle electrodes. [NIH] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the

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chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emphysema: A pathological accumulation of air in tissues or organs. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] Endometrial: Having to do with the endometrium (the layer of tissue that lines the uterus). [NIH]

Endometriosis: A condition in which tissue more or less perfectly resembling the uterine mucous membrane (the endometrium) and containing typical endometrial granular and stromal elements occurs aberrantly in various locations in the pelvic cavity. [NIH] Endometrium: The layer of tissue that lines the uterus. [NIH] Endothelial cell: The main type of cell found in the inside lining of blood vessels, lymph vessels, and the heart. [NIH] Endothelium: A layer of epithelium that lines the heart, blood vessels (endothelium, vascular), lymph vessels (endothelium, lymphatic), and the serous cavities of the body. [NIH] Endothelium-derived: Small molecule that diffuses to the adjacent muscle layer and relaxes it. [NIH] 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] Environmental Health: The science of controlling or modifying those conditions, influences, or forces surrounding man which relate to promoting, establishing, and maintaining health. [NIH]

Enzymatic: Phase where enzyme cuts the precursor protein. [NIH] Enzyme: A protein that speeds up chemical reactions in the body. [NIH] Enzyme Inhibitors: Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. [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] Erythropoietin: Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU]

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Extrapyramidal: Outside of the pyramidal tracts. [EU] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. [NIH] Femoral: Pertaining to the femur, or to the thigh. [EU] Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Femur: The longest and largest bone of the skeleton, it is situated between the hip and the knee. [NIH] Fetus: The developing offspring from 7 to 8 weeks after conception until birth. [NIH] Fibrinogen: Plasma glycoprotein clotted by thrombin, composed of a dimer of three nonidentical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides A and B, the proteolytic action of other enzymes yields different fibrinogen degradation products. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Fluorescence: The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat. [NIH] Gallbladder: The pear-shaped organ that sits below the liver. Bile is concentrated and stored in the gallbladder. [NIH] Ganglia: Clusters of multipolar neurons surrounded by a capsule of loosely organized connective tissue located outside the central nervous system. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gasoline: Volative flammable fuel (liquid hydrocarbons) derived from crude petroleum by processes such as distillation reforming, polymerization, etc. [NIH] Gastric: Having to do with the stomach. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

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.

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[NIH]

Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Granuloma: A relatively small nodular inflammatory lesion containing grouped mononuclear phagocytes, caused by infectious and noninfectious agents. [NIH] Granuloma Annulare: Benign granulomatous disease of unknown etiology characterized by a ring of localized or disseminated papules or nodules on the skin and palisading histiocytes surrounding necrobiotic tissue resulting from altered collagen structures. [NIH] Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Guanylate Cyclase: An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC 4.6.1.2. [NIH] Haemodialysis: The removal of certain elements from the blood by virtue of the difference in the rates of their diffusion through a semipermeable membrane, e.g., by means of a haemodialyzer. [EU] Half-Life: The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. [NIH] Hand Strength: Force exerted when gripping or grasping. [NIH] Headache: Pain in the cranial region that may occur as an isolated and benign symptom or as a manifestation of a wide variety of conditions including subarachnoid hemorrhage; craniocerebral trauma; central nervous system infections; intracranial hypertension; and other disorders. In general, recurrent headaches that are not associated with a primary disease process are referred to as headache disorders (e.g., migraine). [NIH] Headache Disorders: Common conditions characterized by persistent or recurrent headaches. Headache syndrome classification systems may be based on etiology (e.g., vascular headache, post-traumatic headaches, etc.), temporal pattern (e.g., cluster headache, paroxysmal hemicrania, etc.), and precipitating factors (e.g., cough headache). [NIH] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] 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] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [EU] Histamine: 1H-Imidazole-4-ethanamine. A depressor amine derived by enzymatic decarboxylation of histidine. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. [NIH] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hormone Replacement Therapy: Therapeutic use of hormones to alleviate the effects of hormone deficiency. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which may be associated with dilation of cerebral ventricles, intracranial hypertension; headache; lethargy; urinary incontinence; and ataxia (and in infants macrocephaly). This condition may be caused by obstruction of cerebrospinal fluid pathways due to neurologic abnormalities, intracranial hemorrhages; central nervous system infections; brain neoplasms; craniocerebral trauma; and other conditions. Impaired resorption of cerebrospinal fluid from the arachnoid villi results in a communicating form of hydrocephalus. Hydrocephalus ex-vacuo refers to ventricular dilation that occurs as a result of brain substance loss from cerebral infarction and other conditions. [NIH] Hydrochlorothiazide: A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [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] Hydroxylamine: A colorless inorganic compound (HONH2) used in organic synthesis and as a reducing agent, due to its ability to donate nitric oxide. [NIH] Hypercholesterolemia: Abnormally high levels of cholesterol in the blood. [NIH] Hyperlipidemia: An excess of lipids in the blood. [NIH] Hypertension: Persistently high arterial blood pressure. Currently accepted threshold levels are 140 mm Hg systolic and 90 mm Hg diastolic pressure. [NIH] Hyperthyroidism: Excessive functional activity of the thyroid gland. [NIH] Hypertriglyceridemia: Condition of elevated triglyceride concentration in the blood; an inherited form occurs in familial hyperlipoproteinemia IIb and hyperlipoproteinemia type IV. It has been linked to higher risk of heart disease and arteriosclerosis. [NIH]

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Hypertrophy: General increase in bulk of a part or organ, not due to tumor formation, nor to an increase in the number of cells. [NIH] Hypnotic: A drug that acts to induce sleep. [EU] Hypolipidemic: A drug that lowers abnormally high plasma concentrations of cholesterol or triglycerides or both. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Iliac Artery: Either of two large arteries originating from the abdominal aorta; they supply blood to the pelvis, abdominal wall and legs. [NIH] Impairment: In the context of health experience, an impairment is any loss or abnormality of psychological, physiological, or anatomical structure or function. [NIH] In situ: In the natural or normal place; confined to the site of origin without invasion of neighbouring tissues. [EU] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] 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] 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]

Informed Consent: Voluntary authorization, given to the physician by the patient, with full comprehension of the risks involved, for diagnostic or investigative procedures and medical and surgical treatment. [NIH] Inorganic: Pertaining to substances not of organic origin. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role in the regulation of glucose metabolism, generally promoting the cellular utilization of glucose. It is also an important regulator of protein and lipid metabolism. Insulin is used as a drug to control insulin-dependent diabetes mellitus. [NIH] Insulin-dependent diabetes mellitus: A disease characterized by high levels of blood glucose resulting from defects in insulin secretion, insulin action, or both. Autoimmune, genetic, and environmental factors are involved in the development of type I diabetes. [NIH] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intestines: The section of the alimentary canal from the stomach to the anus. It includes the large intestine and small intestine. [NIH] Intracellular: Inside a cell. [NIH]

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Intravenous: IV. Into a vein. [NIH] Ions: An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as cations; those with a negative charge are anions. [NIH] Iris: The most anterior portion of the uveal layer, separating the anterior chamber from the posterior. It consists of two layers - the stroma and the pigmented epithelium. Color of the iris depends on the amount of melanin in the stroma on reflection from the pigmented epithelium. [NIH] Ischemia: Deficiency of blood in a part, due to functional constriction or actual obstruction of a blood vessel. [EU] Isosorbide: 1,4:3,6-Dianhydro D-glucitol. Chemically inert osmotic diuretic used mainly to treat hydrocephalus; also used in glaucoma. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] Ketone Bodies: Chemicals that the body makes when there is not enough insulin in the blood and it must break down fat for its energy. Ketone bodies can poison and even kill body cells. When the body does not have the help of insulin, the ketones build up in the blood and then "spill" over into the urine so that the body can get rid of them. The body can also rid itself of one type of ketone, called acetone, through the lungs. This gives the breath a fruity odor. Ketones that build up in the body for a long time lead to serious illness and coma. [NIH] Kidney Disease: Any one of several chronic conditions that are caused by damage to the cells of the kidney. People who have had diabetes for a long time may have kidney damage. Also called nephropathy. [NIH] Kinetic: Pertaining to or producing motion. [EU] 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] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Lipid: Fat. [NIH] Lipid Peroxidation: Peroxidase catalyzed oxidation of lipids using hydrogen peroxide as an electron acceptor. [NIH] Lipophilic: Having an affinity for fat; pertaining to or characterized by lipophilia. [EU] Lipoprotein: Any of the lipid-protein complexes in which lipids are transported in the blood; lipoprotein particles consist of a spherical hydrophobic core of triglycerides or cholesterol esters surrounded by an amphipathic monolayer of phospholipids, cholesterol,

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and apolipoproteins; the four principal classes are high-density, low-density, and very-lowdensity lipoproteins and chylomicrons. [EU] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Liver scan: An image of the liver created on a computer screen or on film. A radioactive substance is injected into a blood vessel and travels through the bloodstream. It collects in the liver, especially in abnormal areas, and can be detected by the scanner. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Long-Term Care: Care over an extended period, usually for a chronic condition or disability, requiring periodic, intermittent, or continuous care. [NIH] Low-density lipoprotein: Lipoprotein that contains most of the cholesterol in the blood. LDL carries cholesterol to the tissues of the body, including the arteries. A high level of LDL increases the risk of heart disease. LDL typically contains 60 to 70 percent of the total serum cholesterol and both are directly correlated with CHD risk. [NIH] Lymph: The almost colorless fluid that travels through the lymphatic system and carries cells that help fight infection and disease. [NIH] Lymph node: A rounded mass of lymphatic tissue that is surrounded by a capsule of connective tissue. Also known as a lymph gland. Lymph nodes are spread out along lymphatic vessels and contain many lymphocytes, which filter the lymphatic fluid (lymph). [NIH]

Lymphatic: The tissues and organs, including the bone marrow, spleen, thymus, and lymph nodes, that produce and store cells that fight infection and disease. [NIH] Magnetic Resonance Imaging: Non-invasive method of demonstrating internal anatomy based on the principle that atomic nuclei in a strong magnetic field absorb pulses of radiofrequency energy and emit them as radiowaves which can be reconstructed into computerized images. The concept includes proton spin tomographic techniques. [NIH] Mediate: Indirect; accomplished by the aid of an intervening medium. [EU] Medicament: A medicinal substance or agent. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Menstruation: The normal physiologic discharge through the vagina of blood and mucosal tissues from the nonpregnant uterus. [NIH] Mental Disorders: Psychiatric illness or diseases manifested by breakdowns in the adaptational process expressed primarily as abnormalities of thought, feeling, and behavior producing either distress or impairment of function. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methanol: A colorless, flammable liquid used in the manufacture of formaldehyde and acetic acid, in chemical synthesis, antifreeze, and as a solvent. Ingestion of methanol is toxic and may cause blindness. [NIH] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH]

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MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Migration: The systematic movement of genes between populations of the same species, geographic race, or variety. [NIH] Mobilization: The process of making a fixed part or stored substance mobile, as by separating a part from surrounding structures to make it accessible for an operative procedure or by causing release into the circulation for body use of a substance stored in the body. [EU] Modification: A change in an organism, or in a process in an organism, that is acquired from its own activity or environment. [NIH] Molecular: Of, pertaining to, or composed of molecules : a very small mass of matter. [EU] Molecule: A chemical made up of two or more atoms. The atoms in a molecule can be the same (an oxygen molecule has two oxygen atoms) or different (a water molecule has two hydrogen atoms and one oxygen atom). Biological molecules, such as proteins and DNA, can be made up of many thousands of atoms. [NIH] Monitor: An apparatus which automatically records such physiological signs as respiration, pulse, and blood pressure in an anesthetized patient or one undergoing surgical or other procedures. [NIH] Monocytes: Large, phagocytic mononuclear leukocytes produced in the vertebrate bone marrow and released into the blood; contain a large, oval or somewhat indented nucleus surrounded by voluminous cytoplasm and numerous organelles. [NIH] Mononuclear: A cell with one nucleus. [NIH] Monotherapy: A therapy which uses only one drug. [EU] Motility: The ability to move spontaneously. [EU] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myopathy: Any disease of a muscle. [EU] Nausea: An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. [NIH] NCI: National Cancer Institute. NCI, part of the National Institutes of Health of the United States Department of Health and Human Services, is the federal government's principal agency for cancer research. NCI conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the NCI Web site at http://cancer.gov. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes

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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] Nephropathy: Disease of the kidneys. [EU] Nerve: A cordlike structure of nervous tissue that connects parts of the nervous system with other tissues of the body and conveys nervous impulses to, or away from, these tissues. [NIH] Nervous System: The entire nerve apparatus composed of the brain, spinal cord, nerves and ganglia. [NIH] Neuromuscular: Pertaining to muscles and nerves. [EU] Neuromuscular Junction: The synapse between a neuron and a muscle. [NIH] Neuronal: Pertaining to a neuron or neurons (= conducting cells of the nervous system). [EU] Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. [NIH] Nicardipine: 1,4-Dihydro-2,6-dimethyl-4-(3-nitrophenyl) methyl 2(methyl(phenylmethyl)amino)-3,5-pyridinecarboxylic acid ethyl ester. A potent calcium channel blockader with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardiodepressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. [NIH] Nifedipine: A potent vasodilator agent with calcium antagonistic action. It is a useful antianginal agent that also lowers blood pressure. The use of nifedipine as a tocolytic is being investigated. [NIH] Nisoldipine: 1,4-Dihydro-2,6-dimethyl-4 (2-nitrophenyl)-3,5-pyridinedicarboxylic acid methyl 2-methylpropyl ester. Nisoldipine is a dihydropyridine calcium channel antagonist that acts as a potent arterial vasodilator and antihypertensive agent. It is also effective in patients with cardiac failure and angina. [NIH] Nitric Oxide: A free radical gas produced endogenously by a variety of mammalian cells. It is synthesized from arginine by a complex reaction, catalyzed by nitric oxide synthase. Nitric oxide is endothelium-derived relaxing factor. It is released by the vascular endothelium and mediates the relaxation induced by some vasodilators such as acetylcholine and bradykinin. It also inhibits platelet aggregation, induces disaggregation of aggregated platelets, and inhibits platelet adhesion to the vascular endothelium. Nitric oxide activates cytosolic guanylate cyclase and thus elevates intracellular levels of cyclic GMP. [NIH]

Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight 14. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells. [NIH] Norepinephrine: Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers and of the diffuse projection system in the brain arising from the locus ceruleus. It is also found in plants and is used pharmacologically as a sympathomimetic. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue

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spaces of the body; usually applied to demonstrable accumulation of excessive fluid in the subcutaneous tissues. Edema may be localized, due to venous or lymphatic obstruction or to increased vascular permeability, or it may be systemic due to heart failure or renal disease. Collections of edema fluid are designated according to the site, e.g. ascites (peritoneal cavity), hydrothorax (pleural cavity), and hydropericardium (pericardial sac). Massive generalized edema is called anasarca. [EU] Ointments: Semisolid preparations used topically for protective emollient effects or as a vehicle for local administration of medications. Ointment bases are various mixtures of fats, waxes, animal and plant oils and solid and liquid hydrocarbons. [NIH] Opacity: Degree of density (area most dense taken for reading). [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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] Oxalic Acid: A strong dicarboxylic acid occurring in many plants and vegetables. It is produced in the body by metabolism of glyoxylic acid or ascorbic acid. It is not metabolized but excreted in the urine. It is used as an analytical reagent and general reducing agent. [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]

Oxidative Stress: A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products (Sies, Oxidative Stress, 1991, pxv-xvi). [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] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Pelvic: Pertaining to the pelvis. [EU] Penicillin: An antibiotic drug used to treat infection. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] Periodontitis: Inflammation of the periodontal membrane; also called periodontitis simplex. [NIH]

Peripheral Vascular Disease: Disease in the large blood vessels of the arms, legs, and feet. People who have had diabetes for a long time may get this because major blood vessels in

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their arms, legs, and feet are blocked and these limbs do not receive enough blood. The signs of PVD are aching pains in the arms, legs, and feet (especially when walking) and foot sores that heal slowly. Although people with diabetes cannot always avoid PVD, doctors say they have a better chance of avoiding it if they take good care of their feet, do not smoke, and keep both their blood pressure and diabetes under good control. [NIH] Peritoneal: Having to do with the peritoneum (the tissue that lines the abdominal wall and covers most of the organs in the abdomen). [NIH] Peritoneal Cavity: The space enclosed by the peritoneum. It is divided into two portions, the greater sac and the lesser sac or omental bursa, which lies behind the stomach. The two sacs are connected by the foramen of Winslow, or epiploic foramen. [NIH] PH: The symbol relating the hydrogen ion (H+) concentration or activity of a solution to that of a given standard solution. Numerically the pH is approximately equal to the negative logarithm of H+ concentration expressed in molarity. pH 7 is neutral; above it alkalinity increases and below it acidity increases. [EU] 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] Pharmacodynamics: The study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure; also, such effects on the actions of a particular drug or drugs. [EU] 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] Pharmacotherapy: A regimen of using appetite suppressant medications to manage obesity by decreasing appetite or increasing the feeling of satiety. These medications decrease appetite by increasing serotonin or catecholamine—two brain chemicals that affect mood and appetite. [NIH] 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] Phosphorylated: Attached to a phosphate group. [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] Plaque: A clear zone in a bacterial culture grown on an agar plate caused by localized destruction of bacterial cells by a bacteriophage. The concentration of infective virus in a fluid can be estimated by applying the fluid to a culture and counting the number of. [NIH] Plasma: The clear, yellowish, fluid part of the blood that carries the blood cells. The proteins that form blood clots are in plasma. [NIH] Plasmin: A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (B) and heavy (A), with a molecular weight

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of 75,000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. EC 3.4.21.7. [NIH] Plasminogen: Precursor of fibrinolysin (plasmin). It is a single-chain beta-globulin of molecular weight 80-90,000 found mostly in association with fibrinogen in plasma; plasminogen activators change it to fibrinolysin. It is used in wound debriding and has been investigated as a thrombolytic agent. [NIH] Plasminogen Activators: A heterogeneous group of proteolytic enzymes that convert plasminogen to plasmin. They are concentrated in the lysosomes of most cells and in the vascular endothelium, particularly in the vessels of the microcirculation. EC 3.4.21.-. [NIH] Platelet Activation: A series of progressive, overlapping events triggered by exposure of the platelets to subendothelial tissue. These events include shape change, adhesiveness, aggregation, and release reactions. When carried through to completion, these events lead to the formation of a stable hemostatic plug. [NIH] Platelet Aggregation: The attachment of platelets to one another. This clumping together can be induced by a number of agents (e.g., thrombin, collagen) and is part of the mechanism leading to the formation of a thrombus. [NIH] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Pleural: A circumscribed area of hyaline whorled fibrous tissue which appears on the surface of the parietal pleura, on the fibrous part of the diaphragm or on the pleura in the interlobar fissures. [NIH] Pleural cavity: A space enclosed by the pleura (thin tissue covering the lungs and lining the interior wall of the chest cavity). It is bound by thin membranes. [NIH] Polyunsaturated fat: An unsaturated fat found in greatest amounts in foods derived from plants, including safflower, sunflower, corn, and soybean oils. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Practice Guidelines: Directions or principles presenting current or future rules of policy for the health care practitioner to assist him in patient care decisions regarding diagnosis, therapy, or related clinical circumstances. The guidelines may be developed by government agencies at any level, institutions, professional societies, governing boards, or by the convening of expert panels. The guidelines form a basis for the evaluation of all aspects of health care and delivery. [NIH] Precipitation: The act or process of precipitating. [EU] Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] Prodrug: A substance that gives rise to a pharmacologically active metabolite, although not itself active (i. e. an inactive precursor). [NIH] Progression: Increase in the size of a tumor or spread of cancer in the body. [NIH] Progressive: Advancing; going forward; going from bad to worse; increasing in scope or severity. [EU] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial

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infarction, arrhythmias, angina pectoris, hypertension, hypertensive emergencies, hyperthyroidism, migraine, pheochromocytoma, menopause, and anxiety. [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] Protease: Proteinase (= any enzyme that catalyses the splitting of interior peptide bonds in a protein). [EU] Protective Agents: Synthetic or natural substances which are given to prevent a disease or disorder or are used in the process of treating a disease or injury due to a poisonous agent. [NIH]

Protein 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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Protocol: The detailed plan for a clinical trial that states the trial's rationale, purpose, drug or vaccine dosages, length of study, routes of administration, who may participate, and other aspects of trial design. [NIH] Psychometric testing: Psychological and mental testing and quantitative analysis of an individual's psychological traits or attitudes or mental processes. [NIH] Public Policy: A course or method of action selected, usually by a government, from among alternatives to guide and determine present and future decisions. [NIH] Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Circulation: The circulation of blood through the lungs. [NIH] Pulmonary hypertension: Abnormally high blood pressure in the arteries of the lungs. [NIH] Pulse: The rhythmical expansion and contraction of an artery produced by waves of pressure caused by the ejection of blood from the left ventricle of the heart as it contracts. [NIH]

Pupil: The aperture in the iris through which light passes. [NIH] 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] Race: A population within a species which exhibits general similarities within itself, but is both discontinuous and distinct from other populations of that species, though not sufficiently so as to achieve the status of a taxon. [NIH]

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Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] Random Allocation: A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. [NIH] Randomization: Also called random allocation. Is allocation of individuals to groups, e.g., for experimental and control regimens, by chance. Within the limits of chance variation, random allocation should make the control and experimental groups similar at the start of an investigation and ensure that personal judgment and prejudices of the investigator do not influence allocation. [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] Rauwolfia: A genus of the Apocynaceae or dogbane family of tropical trees and shrubs containing alkaloids. These alkaloids have been used as tranquilizers and antihypertensive agents. Reserpine is derived from R. serpentina. [NIH] Reabsorption: 1. The act or process of absorbing again, as the selective absorption by the kidneys of substances (glucose, proteins, sodium, etc.) already secreted into the renal tubules, and their return to the circulating blood. 2. Resorption. [EU] Reagent: A substance employed to produce a chemical reaction so as to detect, measure, produce, etc., other substances. [EU] Receptor: A molecule inside or on the surface of a cell that binds to a specific substance and causes a specific physiologic effect in the cell. [NIH] Rectum: The last 8 to 10 inches of the large intestine. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reference Standards: A basis of value established for the measure of quantity, weight, extent or quality, e.g. weight standards, standard solutions, methods, techniques, and procedures used in diagnosis and therapy. [NIH] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Rehabilitative: Instruction of incapacitated individuals or of those affected with some mental disorder, so that some or all of their lost ability may be regained. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an

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alpha-2 globulin produced by the liver, forming angiotensin I. The converting enzyme contained in the lung acts on angiotensin I in the plasma converting it to angiotensin II, the most powerful directly pressor substance known. It causes contraction of the arteriolar smooth muscle and has other indirect actions mediated through the adrenal cortex. [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] Retrospective: Looking back at events that have already taken place. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Scans: Pictures of structures inside the body. Scans often used in diagnosing, staging, and monitoring disease include liver scans, bone scans, and computed tomography (CT) or computerized axial tomography (CAT) scans and magnetic resonance imaging (MRI) scans. In liver scanning and bone scanning, radioactive substances that are injected into the bloodstream collect in these organs. A scanner that detects the radiation is used to create pictures. In CT scanning, an x-ray machine linked to a computer is used to produce detailed pictures of organs inside the body. MRI scans use a large magnet connected to a computer to create pictures of areas inside the body. [NIH] Sclera: The tough white outer coat of the eyeball, covering approximately the posterior fivesixths of its surface, and continuous anteriorly with the cornea and posteriorly with the external sheath of the optic nerve. [EU] Screening: Checking for disease when there are no symptoms. [NIH] Sedative: 1. Allaying activity and excitement. 2. An agent that allays excitement. [EU] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] 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] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation,

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maintenance of fluid volume, and electrolyte balance. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Soybean Oil: Oil from soybean or soybean plant. [NIH] 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] Stabilization: The creation of a stable state. [EU] Staging: Performing exams and tests to learn the extent of the cancer within the body, especially whether the disease has spread from the original site to other parts of the body. [NIH]

Stem Cells: Relatively undifferentiated cells of the same lineage (family type) that retain the ability to divide and cycle throughout postnatal life to provide cells that can become specialized and take the place of those that die or are lost. [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] Stroke: Sudden loss of function of part of the brain because of loss of blood flow. Stroke may be caused by a clot (thrombosis) or rupture (hemorrhage) of a blood vessel to the brain. [NIH] Stromal: Large, veil-like cell in the bone marrow. [NIH] Subarachnoid: Situated or occurring between the arachnoid and the pia mater. [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]

Substrate: A substance upon which an enzyme acts. [EU] Suction: The removal of secretions, gas or fluid from hollow or tubular organs or cavities by means of a tube and a device that acts on negative pressure. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Synergistic: Acting together; enhancing the effect of another force or agent. [EU]

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Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Systolic blood pressure: The maximum pressure in the artery produced as the heart contracts and blood begins to flow. [NIH] Teratogen: A substance which, through immediate, prolonged or repeated contact with the skin may involve a risk of subsequent non-hereditable birth defects in offspring. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Testosterone: A hormone that promotes the development and maintenance of male sex characteristics. [NIH] Thalidomide: A pharmaceutical agent originally introduced as a non-barbiturate hypnotic, but withdrawn from the market because of its known tetratogenic effects. It has been reintroduced and used for a number of immunological and inflammatory disorders. Thalidomide displays immunosuppresive and anti-angiogenic activity. It inhibits release of tumor necrosis factor alpha from monocytes, and modulates other cytokine action. [NIH] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thigh: A leg; in anatomy, any elongated process or part of a structure more or less comparable to a leg. [NIH] Threshold: For a specified sensory modality (e. g. light, sound, vibration), the lowest level (absolute threshold) or smallest difference (difference threshold, difference limen) or intensity of the stimulus discernible in prescribed conditions of stimulation. [NIH] Thrombolytic: 1. Dissolving or splitting up a thrombus. 2. A thrombolytic agent. [EU] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tomography: Imaging methods that result in sharp images of objects located on a chosen plane and blurred images located above or below the plane. [NIH] Tonicity: The normal state of muscular tension. [NIH] 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] Toxicokinetics: Study of the absorption, distribution, metabolism, and excretion of test substances. [NIH] 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

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biological properties, including immunogenicity, produced by microbes, higher plants, or animals. [NIH] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] 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] Trees: Woody, usually tall, perennial higher plants (Angiosperms, Gymnosperms, and some Pterophyta) having usually a main stem and numerous branches. [NIH] Tumor Necrosis Factor: Serum glycoprotein produced by activated macrophages and other mammalian mononuclear leukocytes which has necrotizing activity against tumor cell lines and increases ability to reject tumor transplants. It mimics the action of endotoxin but differs from it. It has a molecular weight of less than 70,000 kDa. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Tyrosine: A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine, thyroid hormones, and melanin. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

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] Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Ventricle: One of the two pumping chambers of the heart. The right ventricle receives oxygen-poor blood from the right atrium and pumps it to the lungs through the pulmonary artery. The left ventricle receives oxygen-rich blood from the left atrium and pumps it to the body through the aorta. [NIH]

Dictionary 113

Ventricular: Pertaining to a ventricle. [EU] Ventricular Dysfunction: A condition in which the ventricles of the heart exhibit a decreased functionality. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [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] Xenograft: The cells of one species transplanted to another species. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

115

INDEX A Academic Medical Centers, 20, 83 Acetone, 38, 51, 83, 100 Acetylcholine, 33, 83, 103 Acute renal, 40, 48, 49, 83 Adaptation, 83, 90 Adrenal Cortex, 83, 84, 109 Adrenergic, 40, 49, 83, 85, 86, 94, 95, 106, 110 Adverse Effect, 40, 41, 48, 49, 83, 109 Affinity, 83, 84, 100, 109 Agar, 83, 105 Age of Onset, 83, 112 Agonist, 84, 94 Aldosterone, 16, 84 Algorithms, 84, 86 Alkaline, 84, 87 Alkaloid, 84, 90 Allograft, 15, 28, 84 Allylamine, 84 Alternative medicine, 58, 84 Amine, 48, 84, 98 Aminoethyl, 42, 84 Ammonia, 84 Amphetamines, 84, 90 Anatomical, 84, 86, 92, 99 Angina, 7, 8, 12, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 52, 56, 84, 103, 107 Angina Pectoris, 12, 38, 41, 42, 46, 50, 52, 84, 107 Anginal, 84, 103 Angioplasty, 7, 15, 39, 84 Angiotensin converting enzyme inhibitor, 13, 44, 46, 85 Animal model, 39, 85 Ankle, 14, 85 Antagonism, 5, 85, 93 Antibiotic, 85, 104 Antihypertensive, 3, 10, 11, 19, 20, 48, 85, 103, 108 Antihypertensive Agents, 85, 108 Anti-inflammatory, 85, 99 Antineoplastic, 85, 103 Antineoplastic Agents, 85, 103 Antioxidant, 53, 85, 86, 104 Antiseptic, 83, 85 Anxiety, 85, 107 Aorta, 85, 99, 112

Aqueous, 46, 49, 85, 86, 93, 98 Arginine, 85, 103 Arrhythmia, 72, 85, 113 Arterial, 18, 54, 84, 85, 88, 98, 103, 107, 111 Arteries, 14, 15, 29, 85, 86, 87, 90, 92, 99, 101, 102, 107 Arteriolar, 85, 87, 96, 109 Arterioles, 85, 87, 88, 102 Ascites, 85, 104 Ascorbic Acid, 85, 104 Aspartate, 47, 51, 52, 86 Atenolol, 11, 13, 14, 17, 86 Atherogenic, 21, 86 Atrium, 86, 112 Autacoids, 86, 99 Autonomic, 83, 86, 103 B Bactericidal, 86, 95 Bacteriophage, 86, 105, 112 Barbiturate, 86, 111 Base, 38, 42, 44, 45, 46, 51, 86, 93, 100 Benign, 86, 97 Benzene, 42, 46, 86 Binding Sites, 4, 86 Bioavailability, 46, 51, 86 Biochemical, 17, 86, 105, 109 Bioequivalent, 46, 86 Biopsy, 86, 104 Biotechnology, 6, 55, 58, 67, 86 Biotransformation, 87 Bladder, 87, 112 Blood Coagulation, 87 Blood vessel, 85, 87, 88, 89, 95, 97, 100, 101, 104, 109, 110, 111, 112 Body Fluids, 87, 109 Bone Marrow, 86, 87, 93, 95, 101, 102, 110 Bone scan, 87, 109 Bowel, 87, 93 Bowel Movement, 87, 93 Bradykinin, 27, 87, 100, 103 Branch, 79, 87, 104, 110, 111 Bronchitis, 87, 89 C Calcium blocker, 17, 87 Calcium channel blocker, 16, 18, 22, 28, 38, 39, 42, 43, 45, 46, 51, 84, 85, 87, 113 Calcium Channel Blockers, 16, 22, 28, 39, 43, 45, 51, 85, 87

116 Norvasc

Calcium Channels, 46, 88 Calcium Signaling, 28, 88 Capillary, 87, 88 Capillary Permeability, 87, 88 Capsules, 7, 88, 94 Captopril, 11, 88 Carbohydrates, 88, 89 Carcinogenic, 86, 88 Cardiac, 11, 12, 13, 24, 40, 42, 44, 48, 49, 50, 84, 88, 95, 102, 103 Cardiomyopathy, 18, 88 Cardioselective, 86, 88, 106 Cardiovascular, 7, 10, 12, 15, 16, 17, 21, 39, 43, 53, 88, 109 Cardiovascular disease, 43, 88 Case report, 10, 19, 88, 90 Case series, 88, 90 Catecholamine, 89, 94, 105 Catheterization, 85, 89 Cell, 29, 33, 39, 53, 84, 86, 88, 89, 91, 93, 95, 99, 102, 103, 105, 106, 108, 109, 110, 112 Cell Division, 89, 105 Cell membrane, 53, 88, 89 Cell proliferation, 29, 40, 89 Central Nervous System, 83, 84, 86, 88, 89, 90, 96, 97, 98, 109 Central Nervous System Infections, 89, 97, 98 Cerebral, 4, 21, 27, 40, 48, 49, 89, 95, 98 Cerebrovascular, 88, 89 Cerebrum, 89 Cervical, 33, 89 Cervix, 89 Character, 84, 89 Chemotherapy, 89, 90 Cholesterol, 42, 50, 89, 92, 94, 98, 99, 100, 101 Chronic, 4, 12, 13, 18, 21, 85, 89, 93, 95, 99, 100, 101 Chronic Obstructive Pulmonary Disease, 21, 89 Chronic renal, 13, 89 Chronotherapy, 27, 90 Cilazapril, 28, 90 Ciliary, 27, 90 Ciliary Arteries, 27, 90 Circadian, 27, 90 Circadian Rhythm, 90 Clinical study, 20, 90 Clinical trial, 4, 10, 11, 33, 34, 67, 90, 92, 93, 107, 108 Cloning, 86, 90

Coal, 86, 90 Coca, 90 Cocaine, 4, 8, 90 Coenzyme, 42, 50, 85, 90 Cofactor, 90, 107 Collagen, 90, 97, 106 Combination Therapy, 28, 43, 53, 91 Complement, 91 Complementary and alternative medicine, 27, 31, 91 Complementary medicine, 27, 91 Computational Biology, 67, 91 Computed tomography, 27, 91, 92, 109 Computerized axial tomography, 91, 92, 109 Computerized tomography, 91, 92 Concomitant, 40, 41, 48, 54, 92 Congestive heart failure, 38, 43, 46, 90, 92, 101 Conjunctiva, 90, 92 Constriction, 92, 100, 112 Constriction, Pathologic, 92, 112 Consultation, 3, 92 Contractility, 92, 94 Contraindications, ii, 92 Controlled study, 13, 92 Conventional therapy, 27, 92 Conventional treatment, 92 Coronary, 7, 12, 13, 15, 19, 20, 21, 24, 40, 48, 49, 53, 54, 84, 88, 92, 102, 103 Coronary Arteriosclerosis, 92, 102 Coronary Circulation, 84, 92 Coronary heart disease, 88, 92 Coronary Thrombosis, 92, 102 Coronary Vasospasm, 40, 48, 49, 92 Cranial, 92, 97 Craniocerebral Trauma, 92, 97, 98 Crystallization, 41, 92 Curative, 93, 111 Cyclic, 93, 97, 103 Cyclosporine, 9, 28, 93 Cytokine, 93, 111 Cytoplasm, 88, 89, 93, 102 D Databases, Bibliographic, 67, 93 Density, 53, 93, 94, 101, 104 Dextrorotatory, 40, 49, 93 Diabetes Insipidus, 93, 98 Diabetes Mellitus, 11, 93, 97 Diagnostic procedure, 37, 58, 93 Dialyzer, 93, 97 Diastole, 93

Index 117

Diastolic, 40, 49, 93, 98 Diffusion, 88, 93, 97 Digestive system, 35, 93 Dihydropyridines, 48, 93 Dihydrotestosterone, 93, 108 Dilatation, 84, 93 Dilation, 87, 93, 98 Diltiazem, 7, 93 Dimethyl, 42, 43, 53, 93, 103 Direct, iii, 46, 61, 94, 108 Disinfectant, 94, 95 Diuretic, 38, 94, 98, 100 Dizziness, 40, 49, 94 Dopamine, 5, 90, 94 Dosage Forms, 44, 94 Drug Interactions, 62, 94 Dyslipidemia, 54, 94 Dystonia, 33, 94 E Ectopic, 13, 94 Edema, 40, 49, 94, 98, 104 Effector, 83, 91, 94 Efficacy, 5, 6, 7, 10, 12, 16, 17, 19, 28, 33, 40, 52, 94 Ejection fraction, 20, 94 Electrocardiogram, 33, 94 Electrolyte, 84, 94, 106, 110 Electromyography, 34, 94 Electrons, 85, 86, 94, 100, 104, 108 Emphysema, 89, 95 Enalapril, 14, 18, 95 Endarterectomy, 85, 95 Endometrial, 95 Endometriosis, 39, 95 Endometrium, 95 Endothelial cell, 39, 95 Endothelium, 95, 103, 106 Endothelium-derived, 95, 103 End-stage renal, 89, 95 Environmental Health, 66, 68, 95 Enzymatic, 87, 91, 95, 98 Enzyme, 8, 28, 38, 42, 43, 50, 85, 90, 94, 95, 96, 97, 99, 101, 106, 107, 108, 110 Enzyme Inhibitors, 43, 85, 95 Epinephrine, 83, 90, 94, 95, 103, 112 Erythropoietin, 29, 95 Esophagus, 93, 95, 110 Ethanol, 38, 42, 51, 95 Exhaustion, 85, 95 Exogenous, 87, 88, 95, 107, 112 Extrapyramidal, 94, 96

F Family Planning, 67, 96 Fat, 87, 92, 96, 100, 106 Fatigue, 96, 97 Felodipine, 6, 38, 96 Femoral, 9, 96 Femoral Artery, 9, 96 Femur, 96 Fetus, 95, 96, 112 Fibrinogen, 96, 106 Filtration, 38, 42, 51, 96 Fluorescence, 12, 96 Forearm, 87, 96 Fosinopril, 15, 17, 96 G Gallbladder, 93, 96 Ganglia, 83, 96, 103 Gas, 84, 93, 96, 98, 103, 110 Gasoline, 86, 96 Gastric, 94, 96, 98 Gastrin, 96, 98 Gastrointestinal, 19, 87, 95, 96, 109, 110 Gastrointestinal tract, 95, 96, 109 Gene, 55, 86, 96 Gingival Hyperplasia, 21, 97 Glomerular, 18, 97, 108 Glomerulus, 97 Glucose, 85, 93, 97, 99, 108 Glucose Intolerance, 93, 97 Governing Board, 97, 106 Granuloma, 7, 97 Granuloma Annulare, 7, 97 Growth, 14, 85, 89, 97, 105 Guanylate Cyclase, 97, 103 H Haemodialysis, 29, 97 Half-Life, 51, 97 Hand Strength, 33, 97 Headache, 8, 40, 44, 49, 97, 98 Headache Disorders, 97 Heart attack, 88, 97 Heart failure, 10, 38, 97, 104 Hemodialysis, 9, 93, 97 Hemodynamics, 15, 98 Hemorrhage, 92, 97, 98, 110 Heredity, 96, 98 Histamine, 90, 98 Hormone, 13, 84, 90, 95, 96, 98, 99, 111 Hormone Replacement Therapy, 13, 98 Hydrocephalus, 98, 100 Hydrochlorothiazide, 7, 22, 98

118 Norvasc

Hydrogen, 84, 86, 88, 93, 98, 100, 102, 104, 105 Hydrogen Peroxide, 98, 100 Hydroxylamine, 48, 98 Hypercholesterolemia, 50, 94, 98 Hyperlipidemia, 41, 42, 50, 94, 98 Hyperthyroidism, 98, 107 Hypertriglyceridemia, 94, 98 Hypertrophy, 9, 40, 44, 48, 49, 99 Hypnotic, 86, 99, 111 Hypolipidemic, 50, 99 I Id, 24, 29, 72, 78, 80, 99 Iliac Artery, 96, 99 Impairment, 40, 48, 49, 99, 101 In situ, 38, 51, 99 Indicative, 99, 104, 112 Indomethacin, 14, 99 Infarction, 98, 99 Infection, 90, 99, 101, 104 Informed Consent, 5, 99 Inorganic, 98, 99 Inotropic, 86, 94, 96, 99 Insulin, 13, 99, 100, 112 Insulin-dependent diabetes mellitus, 99 Intermittent, 99, 101 Interstitial, 99, 108 Intestines, 96, 99 Intracellular, 28, 88, 99, 103, 106 Intravenous, 15, 100 Ions, 86, 88, 94, 98, 100 Iris, 90, 100, 107 Ischemia, 15, 40, 48, 49, 100 Isosorbide, 29, 100 K Kallidin, 87, 100 Kb, 66, 100 Ketone Bodies, 83, 100 Kidney Disease, 18, 28, 35, 66, 100 Kinetic, 100 L Large Intestine, 93, 99, 100, 108, 109 Lesion, 39, 97, 100 Leukocytes, 87, 99, 100, 102, 112 Library Services, 78, 100 Ligaments, 92, 100 Lipid, 20, 42, 50, 53, 88, 99, 100, 104 Lipid Peroxidation, 53, 100, 104 Lipophilic, 18, 100 Lipoprotein, 94, 100, 101 Lisinopril, 8, 15, 101 Liver, 93, 95, 96, 101, 108, 109

Liver scan, 101, 109 Localized, 97, 99, 101, 104, 105 Long-Term Care, 20, 101 Low-density lipoprotein, 53, 94, 101 Lymph, 89, 95, 101 Lymph node, 89, 101 Lymphatic, 95, 99, 101, 104 M Magnetic Resonance Imaging, 101, 109 Mediate, 94, 101 Medicament, 38, 46, 101 MEDLINE, 67, 101 Membrane, 53, 89, 91, 92, 93, 95, 97, 101, 104 Menopause, 13, 101, 107 Menstruation, 101 Mental Disorders, 35, 101 Metabolite, 53, 87, 90, 93, 96, 101, 106, 108 Methanol, 42, 101 Methionine, 93, 101 MI, 50, 81, 102 Migration, 39, 102 Mobilization, 88, 102 Modification, 53, 102, 107 Molecular, 15, 21, 46, 53, 67, 69, 86, 91, 96, 100, 102, 105, 106, 112 Molecule, 40, 49, 86, 88, 90, 91, 94, 95, 102, 104, 108 Monitor, 52, 102 Monocytes, 100, 102, 111 Mononuclear, 97, 102, 112 Monotherapy, 11, 28, 102 Motility, 99, 102, 109 Myocardial infarction, 40, 44, 48, 49, 92, 102, 107 Myocardial Ischemia, 27, 55, 84, 102 Myocardium, 84, 102 Myopathy, 44, 102 N Nausea, 94, 102, 112 NCI, 1, 34, 65, 102 Necrosis, 99, 102 Need, 3, 56, 73, 89, 103 Nephropathy, 14, 44, 100, 103 Nerve, 33, 83, 103, 109, 112 Nervous System, 89, 103, 110 Neuromuscular, 83, 103 Neuromuscular Junction, 83, 103 Neuronal, 88, 103 Neurons, 90, 96, 103 Nicardipine, 19, 103 Nifedipine, 6, 9, 10, 16, 19, 20, 22, 28, 103

Index 119

Nisoldipine, 11, 12, 103 Nitric Oxide, 9, 98, 103 Nitrogen, 84, 103 Norepinephrine, 83, 94, 103 Normotensive, 6, 103 O Oedema, 14, 103 Ointments, 94, 104 Opacity, 93, 104 Osmotic, 100, 104 Outpatient, 6, 104 Oxalic Acid, 42, 104 Oxidation, 85, 87, 100, 104 Oxidative Stress, 18, 104 P Palliative, 104, 111 Pancreas, 93, 99, 104 Paroxysmal, 84, 97, 104 Particle, 49, 104, 112 Pathologic, 86, 92, 104 Pelvic, 95, 104 Penicillin, 85, 104 Percutaneous, 15, 104 Periodontitis, 10, 104 Peripheral Vascular Disease, 44, 104 Peritoneal, 85, 104, 105 Peritoneal Cavity, 85, 104, 105 PH, 27, 105 Pharmaceutical Solutions, 94, 105 Pharmacodynamics, 11, 29, 105 Pharmacokinetic, 105 Pharmacologic, 86, 97, 105, 111 Pharmacotherapy, 8, 9, 11, 20, 21, 105 Phosphorus, 87, 105 Phosphorylated, 90, 105 Physiologic, 84, 97, 101, 105, 108 Plants, 84, 90, 97, 103, 104, 105, 106, 112 Plaque, 15, 18, 84, 86, 105 Plasma, 9, 12, 17, 46, 89, 96, 97, 99, 105, 106, 108, 109 Plasmin, 105, 106 Plasminogen, 17, 105, 106 Plasminogen Activators, 105, 106 Platelet Activation, 10, 106 Platelet Aggregation, 103, 106 Platelets, 103, 106, 109, 111 Pleural, 104, 106 Pleural cavity, 104, 106 Polyunsaturated fat, 53, 106 Potassium, 84, 98, 106 Practice Guidelines, 68, 106 Precipitation, 43, 106

Precursor, 94, 95, 103, 106, 112 Prodrug, 90, 96, 106, 108 Progression, 85, 106 Progressive, 89, 97, 102, 106, 108 Propranolol, 40, 49, 86, 106 Prostaglandins, 99, 107 Prostaglandins A, 99, 107 Protease, 84, 91, 107 Protective Agents, 88, 107 Protein Binding, 46, 107 Protein S, 55, 86, 107 Proteins, 88, 89, 91, 102, 103, 105, 107, 108, 109, 111 Proteinuria, 14, 107 Protocol, 5, 33, 107 Psychometric testing, 5, 107 Public Policy, 67, 107 Pulmonary, 21, 39, 87, 107, 112 Pulmonary Artery, 87, 107, 112 Pulmonary Circulation, 39, 107 Pulmonary hypertension, 21, 107 Pulse, 102, 107 Pupil, 90, 93, 107 Q Quality of Life, 16, 17, 107 R Race, 39, 40, 41, 48, 49, 53, 102, 107 Radiation, 84, 96, 108, 109, 113 Radioactive, 87, 97, 98, 101, 108, 109 Radiological, 104, 108 Ramipril, 11, 14, 108 Random Allocation, 108 Randomization, 5, 108 Randomized, 7, 10, 12, 13, 17, 19, 20, 24, 29, 94, 108 Rauwolfia, 44, 108 Reabsorption, 98, 108 Reagent, 53, 104, 108 Receptor, 8, 9, 83, 94, 108, 109 Rectum, 87, 93, 96, 100, 108 Reductase, 42, 50, 108 Refer, 1, 91, 94, 108 Reference Standards, 51, 52, 108 Regimen, 94, 105, 108 Rehabilitative, 4, 108 Renal failure, 108 Renin, 88, 108 Renin-Angiotensin System, 88, 108 Respiration, 102, 109 Retrospective, 8, 109 S Salivary, 93, 109

120 Norvasc

Salivary glands, 93, 109 Scans, 4, 109 Sclera, 90, 92, 109 Screening, 5, 90, 109 Sedative, 41, 86, 109 Serotonin, 105, 109 Serum, 91, 101, 109, 112 Side effect, 28, 34, 61, 83, 109, 111 Small intestine, 98, 99, 109 Smooth muscle, 13, 28, 29, 39, 84, 86, 88, 96, 98, 109, 110 Social Environment, 107, 109 Sodium, 84, 98, 108, 109 Solvent, 38, 42, 43, 45, 83, 86, 95, 101, 104, 105, 110 Soybean Oil, 106, 110 Spatial disorientation, 94, 110 Specialist, 73, 93, 110 Species, 95, 102, 107, 110, 112, 113 Specificity, 83, 88, 110 Spinal cord, 89, 103, 110 Stabilization, 18, 110 Staging, 109, 110 Stem Cells, 95, 110 Stomach, 93, 95, 96, 98, 99, 102, 105, 109, 110 Stress, 10, 12, 89, 102, 104, 110 Stroke, 33, 35, 44, 66, 88, 110 Stromal, 95, 110 Subarachnoid, 97, 110 Subcutaneous, 14, 29, 94, 104, 110 Substance P, 101, 110 Substrate, 95, 110 Suction, 96, 110 Sympathomimetic, 94, 95, 103, 110 Synergistic, 43, 53, 110 Systemic, 12, 28, 39, 62, 85, 87, 95, 98, 99, 104, 111 Systolic, 9, 12, 14, 16, 19, 20, 40, 49, 98, 111 Systolic blood pressure, 14, 111 T Teratogen, 41, 111 Teratogenic, 93, 111 Testosterone, 108, 111 Thalidomide, 41, 111 Therapeutics, 8, 12, 14, 20, 62, 111

Thigh, 96, 111 Threshold, 98, 111 Thrombolytic, 106, 111 Thrombosis, 107, 110, 111 Thrombus, 92, 99, 102, 106, 111 Tomography, 111 Tonicity, 94, 111 Topical, 95, 98, 111 Toxic, iv, 86, 101, 111 Toxicity, 94, 111 Toxicokinetics, 111 Toxicology, 68, 111 Toxins, 88, 99, 111 Transduction, 88, 112 Transfection, 86, 112 Transmitter, 83, 94, 103, 112 Transplantation, 9, 14, 89, 112 Trees, 108, 112 Tumor Necrosis Factor, 111, 112 Type 2 diabetes, 10, 112 Tyrosine, 94, 112 U Unconscious, 99, 112 Uremia, 108, 112 Urethra, 112 Urine, 5, 87, 93, 94, 100, 104, 107, 112 Uterus, 89, 95, 101, 112 V Vaccine, 107, 112 Vascular, 10, 12, 13, 15, 19, 20, 24, 29, 39, 53, 84, 88, 95, 96, 97, 99, 103, 104, 106, 111, 112 Vasoconstriction, 4, 95, 112 Vasodilator, 85, 87, 94, 98, 103, 112 Vein, 100, 112 Venous, 104, 107, 112 Ventricle, 39, 107, 111, 112, 113 Ventricular, 9, 13, 20, 44, 56, 94, 98, 113 Ventricular Dysfunction, 56, 94, 113 Verapamil, 9, 12, 113 Veterinary Medicine, 67, 113 Virus, 86, 89, 105, 112, 113 X Xenograft, 85, 113 X-ray, 53, 91, 92, 96, 109, 113

Index 121

122 Norvasc

Index 123

124 Norvasc

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