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

FELODIPINE A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET R EFERENC...

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FELODIPINE A 3-IN-1 MEDICAL REFERENCE Medical Dictionary Bibliography & Annotated Research Guide TO I NTERNET

R EFERENCES

FELODIPINE 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., 1960Felodipine: 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: 0-497-00462-3 1. Felodipine-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 felodipine. 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 FELODIPINE ............................................................................................... 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Felodipine ...................................................................................... 4 The National Library of Medicine: PubMed .................................................................................. 5 CHAPTER 2. NUTRITION AND FELODIPINE ..................................................................................... 51 Overview...................................................................................................................................... 51 Finding Nutrition Studies on Felodipine..................................................................................... 51 Federal Resources on Nutrition ................................................................................................... 55 Additional Web Resources ........................................................................................................... 55 CHAPTER 3. ALTERNATIVE MEDICINE AND FELODIPINE ............................................................... 57 Overview...................................................................................................................................... 57 National Center for Complementary and Alternative Medicine.................................................. 57 Additional Web Resources ........................................................................................................... 63 General References ....................................................................................................................... 64 CHAPTER 4. PATENTS ON FELODIPINE ........................................................................................... 65 Overview...................................................................................................................................... 65 Patents on Felodipine................................................................................................................... 65 Patent Applications on Felodipine ............................................................................................... 72 Keeping Current .......................................................................................................................... 75 CHAPTER 5. PERIODICALS AND NEWS ON FELODIPINE ................................................................. 77 Overview...................................................................................................................................... 77 News Services and Press Releases................................................................................................ 77 Academic Periodicals covering Felodipine ................................................................................... 79 CHAPTER 6. RESEARCHING MEDICATIONS .................................................................................... 81 Overview...................................................................................................................................... 81 U.S. Pharmacopeia....................................................................................................................... 81 Commercial Databases ................................................................................................................. 82 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 85 Overview...................................................................................................................................... 85 NIH Guidelines............................................................................................................................ 85 NIH Databases............................................................................................................................. 87 Other Commercial Databases....................................................................................................... 89 APPENDIX B. PATIENT RESOURCES ................................................................................................. 91 Overview...................................................................................................................................... 91 Patient Guideline Sources............................................................................................................ 91 Finding Associations.................................................................................................................... 93 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 95 Overview...................................................................................................................................... 95 Preparation................................................................................................................................... 95 Finding a Local Medical Library.................................................................................................. 95 Medical Libraries in the U.S. and Canada ................................................................................... 95 ONLINE GLOSSARIES................................................................................................................ 101 Online Dictionary Directories ................................................................................................... 101 FELODIPINE DICTIONARY ...................................................................................................... 103 INDEX .............................................................................................................................................. 137

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

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

Calcium Channel Blockers: A Unique Group of Antihypertensives Source: For Patients Only. 6(4): 16-17. July/August 1993. Summary: This article discusses calcium channel blockers, agents that are used to treat hypertension, to relieve the chest pain of angina, or to treat certain heart irregularities. Nine drugs are discussed: amlodipine (Norvasc), bepridil (Vascor), diltiazem (Cardizem), felodipine (Plendil), isradipine (Dynacirc), nicardipine (Cardene), nifedipine (Procardia), nimodipine (Nimotop), and verapamil (Calan, Isoptin, Verelan). Topics include sustained-release dosage; side effects of calcium channel blockers; and drug interactions.

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Drugs Used to Manage Cardiovascular Disease: Part V-Calcium Channel Blockers Source: Access. 15(7): 38-40. August 2001. Contact: Available from American Dental Hygienists' Association. 444 North Michigan Avenue, Chicago, IL 60611. Summary: This article in one in a series that familiarizes dental hygienists with the drugs that may be use to manage cardiovascular disease; this fifth entry in the ongoing series focuses on calcium channel blockers. The series addresses the classes of medications used to manage a variety of cardiac conditions, including hypertension (HTN), angina, myocardial infarction, arrhythmias, heart murmurs, and stroke. Drug interactions, oral side effects, and general side effects of these cardiac medications are discussed, along with recommendations for client management and risk assessment strategies. In this article, the author focuses on calcium channel blockers (CCBs), which are divided into three main chemical classes: benzothiazepines, including diltiazem (Cardizem, Dilacor); diphenylalkylamines, notably verapamil (Calan); and dihydropyridines, including nifedipine (Procardia, Adalat), amlodipine (Norvasc), felodipine (Plendil), isradipine (DynaCirc), nicardipine (Cardene), and nisoldipine (Sular). Two additional drugs are discussed: bepridil (Vascor) and nimodipine (Nimotop). Gingival hyperplasia (gum overgrowth) occurs with some of these CCBs, including nifedipine, diltiazem, verapamil, and amlodipine. Good oral hygiene may help to limit the degree of severity of overgrowth; however, plaque control will not prevent overgrowth from occurring. One chart summarizes drug interactions with calcium channel blockers. 2 tables. 16 references.

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

Project Title: DRUG-DIETARY INTERACTION

FLAVONOID

INTESTINAL

ABSORPTION

Principal Investigator & Institution: Rodriguez, Rosita J.; None; Oregon State University Corvallis, or 973391086 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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Timing: Fiscal Year 2002; Project Start 17-SEP-2001; Project End 31-AUG-2004 Summary: (provided by applicant): The opportunity for drug-dietary interaction is an everyday occurrence whether the interaction is with food, juice, or dietary supplements. Moreover, the consumption of flavonoids is being urged because of their multiple health benefits; thus, understanding the possible biological effects of the flavonoids on intestinal drug absorption is essential. Flavonoids may be a particularly important class of modulators due to their ubiquitous occurrence in foods and drinks of plant origin and their known interactions with P-glycoprotein (Pgp) and cytochrome P450 (CYP). These dietary constituents may modulate transport in the intestinal tract and significantly alter the absorption of important therapeutic agents. The increased systemic bioavailability of some drugs, nifedipine and felodipine, associated with ingestion of grapefruit juice represents a couple of widely publicized drug-dietary-interactions. An increase or decrease in drug absorption may be due to (i) alterations in Pgp mediated or non Pgp mediated transport and/or (ii) presystemic intestinal metabolism by CYP and/or the flavin-containing monooxygenases. Furthermore, patents have been filed which incorporate flavonoids as excipients in pharmaceutical formations with the intent to alter drug absorption. Thus, the specific hypothesis of this study is that dietary flavonoids can alter the Pgp-dependent or Pgp-independent transport of certain therapeutic drugs. Studies will be conducted using flavonoids belonging to different subclasses such as isoflavone, flavanone, flavonol, and flavanol (e.g., genistein, naringenin, quercetin, and epigallocatechin gallate, respectively) to gain an insight into structure-activity relationships in the alteration of transport of Pgp-dependent substrates and Pgp-independent substrates by these phytochemicals. The flavonoids will be evaluated using Caco-2 cells, a human intestinal cell line. These cells have been well characterized to express Pgp transporters and non Pgp transporters such as Na+/K+, Na+/H+, amino acids, peptides, bile acid, and vitamin B12. This project will provide new knowledge on how flavonoids affect the dynamic transport mechanisms located in the intestinal mucosa. Thus, the results of this study will increase our understanding of the role of flavonoids found in tea, vegetables, soy, and dietary supplements in the intestinal absorption of therapeutic drugs. 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 felodipine, simply go to the PubMed Web site at http://www.ncbi.nlm.nih.gov/pubmed. Type “felodipine” (or

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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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synonyms) into the search box, and click “Go.” The following is the type of output you can expect from PubMed for felodipine (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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12901461

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A comparison of candesartan, felodipine, and their combination in the treatment of elderly patients with systolic hypertension. Author(s): Morgan T, Anderson A. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 June; 15(6): 544-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12074357

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A comparison of isradipine and felodipine in Australian patients with hypertension: focus on ankle oedema. The Physician's Study Group. Author(s): Hammond JJ, Cutler SA. Source: Blood Pressure. 1993 September; 2(3): 205-11. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8205314

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A comparison of nisoldipine coat-core and felodipine in the treatment of mild-tomoderate hypertension. Author(s): Hoglund C, Hutchinson HG. Source: Int J Clin Pract. 1998 June; 52(4): 221-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9744143

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A comparison of the antihypertensive efficacy and safety of felodipine IV and nifedipine IV in patients with hypertensive crisis or emergency not responding to oral nifedipine. Author(s): Risler T, Bohm R, Wetzchewald D, Nast HP, Koch HH, Stein G, Erley CM. Source: European Journal of Clinical Pharmacology. 1998 June; 54(4): 295-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9696952

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A crossover comparison of extended release felodipine with prolonged action nifedipine in hypertension. Author(s): Moncica I, Oh PI, ul Qamar I, Scolnik D, Arbus GS, Hebert D, Balfe JW, Koren G. Source: Archives of Disease in Childhood. 1995 August; 73(2): 154-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7574861

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A felodipine-metoprolol extended-release tablet: its properties and clinical development. Author(s): Dahlof B, Andersson OK. Source: Journal of Human Hypertension. 1995 July; 9 Suppl 2: S43-7. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7562899

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A parallel group randomised comparative study of felodipine and nifedipine in hypertension. Author(s): Sharma SM, Sethi KK, Kaul UA, Arora R, Khalilullah M. Source: Indian Heart J. 1991 May-June; 43(3): 171-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1800302

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A population study of the pharmacokinetics of felodipine. Author(s): Blychert E, Edgar B, Elmfeldt D, Hedner T. Source: British Journal of Clinical Pharmacology. 1991 January; 31(1): 15-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2015166

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A randomised trial to compare the efficacy and safety of Felodipine (Plendil) and Nifedipine (Adalat) retard in patients with mild-to-moderate hypertension. Author(s): Onwubere BJ, Obodo JO, Oke DA, Okeahialam BN, Danbauchi SS, Mbakwem AC. Source: West Afr J Med. 2001 October-December; 20(4): 196-202. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11885871

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A study of the acute pharmacodynamic interaction of ramipril and felodipine in normotensive subjects. Author(s): Bainbridge AD, MacFadyen RJ, Lees KR, Reid JL. Source: British Journal of Clinical Pharmacology. 1991 February; 31(2): 148-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1646621

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A study of the efficacy of felodipine given once or twice daily in the management of elderly hypertensive patients. Author(s): Morgan T, Morgan O, Anderson A. Source: Journal of Human Hypertension. 1996 March; 10(3): 193-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8733039

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Absorption, gastrointestinal transit, and tablet erosion of felodipine extended-release (ER) tablets. Author(s): Abrahamsson B, Alpsten M, Hugosson M, Jonsson UE, Sundgren M, Svenheden A, Tolli J. Source: Pharmaceutical Research. 1993 May; 10(5): 709-14. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8321836

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Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance. Author(s): Edgar B, Bailey D, Bergstrand R, Johnsson G, Regardh CG. Source: European Journal of Clinical Pharmacology. 1992; 42(3): 313-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1577050

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Acute effects on exercise tolerance of felodipine and diltiazem, alone and in combination, in stable effort angina. Author(s): Pucci PD, Pollavini G, Zerauscheck M, Fazzini P. Source: European Heart Journal. 1991 January; 12(1): 55-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2009894

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Acute renal tubular and hemodynamic effects of the calcium antagonist felodipine in healthy volunteers. Author(s): Katzman PL, DiBona GF, Hokfelt B, Hulthen UL. Source: Journal of the American Society of Nephrology : Jasn. 1991 November; 2(5): 1000-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1760535

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Addition of felodipine to metoprolol vs replacement of metoprolol by felodipine in patients with angina pectoris despite adequate beta-blockade. Results of the Felodipine ER and Metoprolol CR in Angina (FEMINA) Study. Working Group on Cardiovascular Research, The Netherlands (WCN). Author(s): Dunselman P, Liem AH, Verdel G, Kragten H, Bosma A, Bernink P. Source: European Heart Journal. 1997 November; 18(11): 1755-64. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9402450

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Adverse event monitoring in clinical trials of felodipine and omeprazole. Author(s): Wallander MA, Lundborg P, Svardsudd K. Source: European Journal of Clinical Pharmacology. 1992; 42(5): 517-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1606998

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Alternative solvent-free preparation methods for felodipine surface solid dispersions. Author(s): Kerc J, Srcic S, Kofler B. Source: Drug Development and Industrial Pharmacy. 1998 April; 24(4): 359-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9876596

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Ambulatory 24-h blood pressure assessment of the felodipine-metoprolol combination versus amlodipine in mild to moderate hypertension. Lorraine General Physician Investigators Group. Author(s): Zannad F, Boivin JM. Source: Journal of Hypertension. 1999 July; 17(7): 1023-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10419077

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Amlodipine, felodipine, and isradipine in the treatment of Chinese patients with mild-to-moderate hypertension. Author(s): Cheung BM, Lau CP, Wu BZ. Source: Clinical Therapeutics. 1998 November-December; 20(6): 1159-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9916609

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Antianginal efficacy of the combination of felodipine-metoprolol 10/100 mg compared with each drug alone in patients with stable effort-induced angina pectoris: a multicenter parallel group study. The TRAFFIC Study Group. Author(s): Emanuelsson H, Egstrup K, Nikus K, Ellstrom J, Glud T, Pater C, Scheibel M, Tisell A, Totterman KJ, Forsby M. Source: American Heart Journal. 1999 May; 137(5): 854-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10220634

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Antihypertensive and anti-albuminuric effects of losartan potassium and felodipine in Chinese elderly hypertensive patients with or without non-insulin-dependent diabetes mellitus. Author(s): Chan JC, Critchley JA, Tomlinson B, Chan TY, Cockram CS. Source: American Journal of Nephrology. 1997; 17(1): 72-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9057957

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Antihypertensive drugs and glucose metabolism: a comparison between a diuretic and felodipine, a new calcium antagonist, when added to a beta-blocker in nondiabetic hypertensive women. Author(s): Bengtsson C, Lapidus L. Source: Scott Med J. 1994 June; 39(3): 71-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8720766

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Antihypertensive effect and tolerability of felodipine extended release (ER) tablets in comparison with felodipine plain tablets (PT) and placebo in hypertensives on a diuretic. Canadian Study Group. Author(s): Carruthers SG, Vint-Reed C. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 1993 October; 16(5): 386-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8261692

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Antihypertensive effect of felodipine associated with persistent sympathetic activation and minimal regression of left ventricular hypertrophy. Author(s): Leenen FH, Holliwell DL. Source: The American Journal of Cardiology. 1992 March 1; 69(6): 639-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1531566

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Felodipine

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Antihypertensive profiles with ascending dose combinations of ramipril and felodipine ER. Author(s): Scholze J, Bauer B, Massaro J. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 1999 November; 21(8): 1447-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10574423

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Antihypertensive treatment with felodipine but not with a diuretic reduces episodes of myocardial ischaemia in elderly patients with hypertension. Author(s): Trenkwalder P, Dobrindt R, Aulehner R, Lydtin H. Source: European Heart Journal. 1994 December; 15(12): 1673-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7698138

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Aspects of quality of life on treatment with felodipine. Author(s): Dimenas E, Wallander MA, Svardsudd K, Wiklund I. Source: European Journal of Clinical Pharmacology. 1991; 40(2): 141-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2065695

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Baroreceptor activity in man during administration of the calcium channel blocker felodipine. Author(s): Weisser B, Lieder P, Gobel B, Vetter H, Dusing R. Source: Int J Clin Pharmacol Res. 1990; 10(6): 325-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1965983

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Beta-adrenergic receptors and reflex tachycardia after single and repeated felodipine administration in essential hypertension. Author(s): Savonitto S, Bevilacqua M, Chebat E, Vago T, Bertora P, Baldi G, Renesto E, Peruzzi E, Sardina M, Norbiato G. Source: Journal of Cardiovascular Pharmacology. 1991 June; 17(6): 970-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1714023

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Bioequivalence, pharmacokinetic and pharmacodynamic response to combined extended release formulations of felodipine and metoprolol in healthy volunteers. Author(s): Aberg J, Abrahamsson B, Grind M, Nyberg G, Olofsson B. Source: European Journal of Clinical Pharmacology. 1997; 52(6): 471-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9342583

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Biotransformation of felodipine in liver microsomes from rat, dog, and man. Author(s): Baarnhielm C, Backman A, Hoffmann KJ, Weidolf L. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1986 September-October; 14(5): 613-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2876870

Studies

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Blood pressure reduction and tolerability of felodipine ER in older and younger hypertensive patients. The Felodipine ER in the Elderly versus Young Working Group. Author(s): Fagan TC. Source: Journal of the American Geriatrics Society. 1997 June; 45(6): 712-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9180665

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Calcium antagonists, a useful additional therapy in treatment resistant hypertension: comparison of felodipine ER and nifedipine Retard by 24-h ambulatory blood pressure monitoring. Author(s): Dees A, Kremer Hovinga T, Breed JG, Verstappen VM, Puister SM, Meems L. Source: The Netherlands Journal of Medicine. 1997 January; 50(1): 2-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9038037

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Calcium channel blockade with felodipine does not affect metabolic coronary vasodilation in patients with coronary artery disease. Author(s): Kal JE, Spaan JA, van Wezel HB. Source: Journal of Cardiovascular Pharmacology. 2002 February; 39(2): 225-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11791008

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Catecholamines and the renin-angiotensin-aldosterone system during treatment with felodipine ER or hydrochlorothiazide in essential hypertension. Author(s): Koenig W, Binner L, Gabrielsen F, Sund M, Rosenthal J, Hombach V. Source: Journal of Cardiovascular Pharmacology. 1991 September; 18(3): 349-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1720834

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Central and peripheral haemodynamic responses to felodipine in congestive heart failure. Author(s): Capewell S, Wathen CG, Muir AL. Source: European Journal of Clinical Pharmacology. 1991; 41(2): 95-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1743253

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Characteristics of serum protein binding of felodipine. Author(s): Valle M, Esteban M, Rodriguez-Sasiain JM, Calvo R, Aguirre C. Source: Res Commun Mol Pathol Pharmacol. 1996 October; 94(1): 73-88. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8948016

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Clinical equivalence of two tablet formulations of felodipine. A placebo-controlled study of 24-hour blood pressure control and tolerability. Author(s): McGrath BP, Watts RW, Elmfeldt DB. Source: European Journal of Clinical Pharmacology. 1995; 49(3): 169-72. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8665991

12

Felodipine

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Clinical trial of extended-release felodipine in pediatric essential hypertension. Author(s): Trachtman H, Frank R, Mahan JD, Portman R, Restaino I, Matoo TK, Tou C, Klibaner M. Source: Pediatric Nephrology (Berlin, Germany). 2003 June; 18(6): 548-53. Epub 2003 April 17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12700955

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Combination therapy with felodipine and metoprolol compared with captopril and hydrochlorothiazide. German MC Study Group. Author(s): Klein G. Source: Blood Pressure. 1998 November; 7(5-6): 308-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10321444

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Combined enalapril and felodipine extended release (ER) for systemic hypertension. Enalapril-Felodipine ER Factorial Study Group. Author(s): Gradman AH, Cutler NR, Davis PJ, Robbins JA, Weiss RJ, Wood BC. Source: The American Journal of Cardiology. 1997 February 15; 79(4): 431-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9052345

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Comment on "Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine". Author(s): Yeleswaram K. Source: European Journal of Clinical Pharmacology. 1997; 52(2): 159, 161. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9174687

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Comparative effect of lercanidipine, felodipine, and nifedipine GITS on blood pressure and heart rate in patients with mild to moderate arterial hypertension: the Lercanidipine in Adults (LEAD) Study. Author(s): Romito R, Pansini MI, Perticone F, Antonelli G, Pitzalis M, Rizzon P. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2003 July-August; 5(4): 249-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12939564

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Comparative effects of amlodipine and felodipine ER on office and ambulatory blood pressure in patients with mild to moderate hypertension. Danish Multicentre Group. Author(s): Hoegholm A, Wiinberg N, Rasmussen E, Nielsen PE. Source: Journal of Human Hypertension. 1995 March; 9 Suppl 1: S25-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7783110

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Comparative effects of felodipine ER, amlodipine and nifedipine GITS on 24 h blood pressure control and trough to peak ratios in mild to moderate ambulatory hypertension: a forced titration study. Author(s): Lefebvre J, Poirier L, Archambault F, Jewell D, Reed CV, Lacourciere Y. Source: The Canadian Journal of Cardiology. 1998 May; 14(5): 682-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9627524

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Comparison between felodipine and isosorbide mononitrate as adjunct to beta blockade in patients > 65 years of age with angina pectoris. Author(s): de Vries RJ, Dunselman PH, van Veldhuisen DJ, van den Heuvel AF, Wielenga RP, Lie KI. Source: The American Journal of Cardiology. 1994 December 15; 74(12): 1201-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7977090

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Comparison of antihypertensive efficacy and tolerability of losartan and extendedrelease felodipine in patients with mild to moderate hypertension. Author(s): Hung MJ, Lin FC, Cherng WJ, Wang CH, Hung KC, Hsieh IC, Wen MS, Wu D. Source: J Formos Med Assoc. 1999 June; 98(6): 403-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10443063

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Comparison of clinical efficacy and adverse effects between extended-release felodipine and atenolol in patients with mild and moderate essential hypertension. Author(s): Chern MS, Lin FC, Wu D. Source: Changgeng Yi Xue Za Zhi. 1997 June; 20(2): 86-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9260367

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Comparison of clinical efficacy and adverse effects between extended-release felodipine and slow-release diltiazem in patients with isolated systolic hypertension. Author(s): Chern MS, Lin FC, Wu D. Source: Changgeng Yi Xue Za Zhi. 1999 March; 22(1): 44-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10418209

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Comparison of effects of felodipine versus hydrochlorothiazide on arterial diameter and pulse-wave velocity in essential hypertension. Author(s): Asmar RG, Benetos A, Chaouche-Teyara K, Raveau-Landon CM, Safar ME. Source: The American Journal of Cardiology. 1993 October 1; 72(11): 794-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8213511

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Felodipine

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Comparison of effects on peak oxygen consumption, quality of life, and neurohormones of felodipine and enalapril in patients with congestive heart failure. Author(s): de Vries RJ, Quere M, Lok DJ, Sijbring P, Bucx JJ, van Veldhuisen DJ, Dunselman PH. Source: The American Journal of Cardiology. 1995 December 15; 76(17): 1253-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7503006

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Comparison of irbesartan vs felodipine in the regression after 1 year of left ventricular hypertrophy in hypertensive patients (the SILVER trial). Study of Irbesartan in Left VEntricular hypertrophy Regression. Author(s): Cohen A, Bregman B, Agabiti Rosei E, Williams B, Dubourg O, Clairefond P, Brudi P, Gosse P, Gueret P. Source: Journal of Human Hypertension. 1998 July; 12(7): 479-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9702935

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Comparison of once daily felodipine 10 mg ER and hydrochlorothiazide 25 mg in the treatment of mild to moderate hypertension. Author(s): Koenig W, Sund M, Binner L, Hehr R, Rosenthal J, Hombach V. Source: European Journal of Clinical Pharmacology. 1991; 41(3): 197-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1748135

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Comparison of the effects of felodipine and cilazapril on exercise performance in patients with mild to moderate hypertension. A crossover study. Author(s): Paterna S, Di Pasquale P, Parrinello G, Tuttolomondo A, Follone G, Cardinale A, Ortoleva A, Giambanco F, Abruzzese G, Colomba D, Bologna P, Fernandez P, Giubilato A, Valdes L, Albano V, Licata G. Source: Drugs Exp Clin Res. 2000; 26(4): 125-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11109512

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Comparison of the time courses and potencies of the vasodilator effects of nifedipine and felodipine in the human forearm. Author(s): van der Lee R, Pfaffendorf M, Koopmans RP, van Lieshout JJ, van Montfrans GA, van Zwieten PA. Source: Blood Pressure. 2001; 10(4): 217-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11800060

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Comparison of two strategies for intensifying antihypertensive treatment: low-dose combination (enalapril + felodipine ER) versus increased dose of monotherapy (enalapril). LEVEL (Lexxel vs Enalapril) Study Group. Author(s): Elliott WJ, Montoro R, Smith D, Leibowitz M, Hwang C, Gradman AH, Schleman M, Klibaner M. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1999 July; 12(7): 691-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10411366

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Comparison of verapamil versus felodipine on heart rate variability after acute myocardial infarction. Author(s): Bonaduce D, Petretta M, Ianniciello A, Apicella C, Cavallaro V, Marciano F. Source: The American Journal of Cardiology. 1997 March 1; 79(5): 564-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9068509

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Comparison of verapamil versus felodipine on heart rate variability in hypertensive patients. Author(s): Petretta M, Canonico V, Madrid A, Mickiewicz M, Spinelli L, Marciano F, Vetrano A, Signorini A, Bonaduce D. Source: Journal of Hypertension. 1999 May; 17(5): 707-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10403616

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Cost-effectiveness of felodipine-metoprolol (Logimax) and enalapril in the treatment of hypertension. Author(s): Andersson F, Kartman B, Andersson OK. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 1998 November; 20(8): 833-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9817605

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Costs and outcomes of switching from amlodipine to felodipine. Author(s): Williams CD. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2000 December 15; 57(24): 2287-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11146977

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Cross-over comparison of nifedipine Oros and felodipine extended release with blind 24 h ambulatory blood pressure assessments. Author(s): Taverner D, Marley J, Tonkin AL. Source: Clinical and Experimental Pharmacology & Physiology. 1999 November; 26(11): 909-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10561813

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Crossover comparison of the pharmacokinetics of amlodipine and felodipine ER in hypertensive patients. Author(s): Videbaek LM, Jacobsen IA. Source: Int J Clin Pharmacol Ther. 1997 November; 35(11): 514-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9401833

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Felodipine

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Design and pharmacokinetics of Logimax, a new extended-release combination tablet of felodipine and metoprolol. Author(s): Abrahamsson B, Edgar B, Lidman K, Wingstrand K. Source: Blood Pressure. Supplement. 1993; 1: 10-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8173686

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Determination of felodipine and its metabolites in plasma using capillary gas chromatography with electron-capture detection and their identification by gas chromatography-mass spectrometry. Author(s): Nishioka R, Umeda I, Oi N, Tabata S, Uno K. Source: Journal of Chromatography. 1991 April 19; 565(1-2): 237-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1874870

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Determination of felodipine enantiomers using chiral stationary phase liquid chromatography and gas chromatography/mass spectrometry, and the study of their pharmacokinetic profiles in human and dog. Author(s): Sakamoto T, Ohtake Y, Itoh M, Tabata S, Kuriki T, Uno K. Source: Biomedical Chromatography : Bmc. 1993 March-April; 7(2): 99-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8485383

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Determination of felodipine, its enantiomers, and a pyridine metabolite in human plasma by capillary gas chromatography with mass spectrometric detection. Author(s): Dru JD, Hsieh JY, Matuszewski BK, Dobrinska MR. Source: Journal of Chromatography. B, Biomedical Applications. 1995 April 21; 666(2): 259-67. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7633602

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Determination of four carboxylic acid metabolites of felodipine in plasma by highperformance liquid chromatography. Author(s): Gabrielsson M, Hoffmann KJ, Regardh CG. Source: Journal of Chromatography. 1992 January 17; 573(2): 265-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1601959

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Different results in cardiopulmonary exercise tests after long-term treatment with felodipine and enalapril in patients with congestive heart failure due to ischaemic heart disease. Author(s): Dunselman PH, van der Mark TW, Kuntze CE, van Bruggen A, Hamer JP, Scaf AH, Wesseling H, Lie KI. Source: European Heart Journal. 1990 March; 11(3): 200-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2318222

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Differential effects of felodipine and nifedipine on 24-h blood pressure and left ventricular mass. Author(s): Myers MG, Leenen FH, Tanner J. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1995 July; 8(7): 712-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7546497

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Differential effects of once-daily antihypertensive drugs on blood pressure, left ventricular mass and sympathetic activity: Nifedipine-GITS versus felodipine-ER versus enalapril. Author(s): Leenen FH, Myers MG, Joyner CD, Toal CB. Source: The Canadian Journal of Cardiology. 2002 December; 18(12): 1285-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12518180

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Digoxin-felodipine interaction in patients with congestive heart failure. Author(s): Dunselman PH, Scaf AH, Kuntze CE, Lie KI, Wesseling H. Source: European Journal of Clinical Pharmacology. 1988; 35(5): 461-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3069476

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Does felodipine have a positive inotropic effect in the human? Author(s): Drake-Holland AJ, Pugh S, Mills C, Noble MI. Source: Journal of Cardiovascular Pharmacology. 1987; 10 Suppl 1: S119-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2442503

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Dose-dependent effects of felodipine on diuresis and natriuresis in healthy subjects. Author(s): Bengtsson-Hasselgren B, Edgar B, Ronn O. Source: Journal of Cardiovascular Pharmacology. 1988 August; 12(2): 134-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2459543

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Dose-plasma concentration--effect relationship of felodipine in essential hypertension: a review. Author(s): Reid JL. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S50-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693728

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Drugs recently released in Belgium. Felodipine--olsalazine. Author(s): Harvengt C. Source: Acta Clin Belg. 1989; 44(2): 137-9. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2800886

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Felodipine

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Early renal graft function in recipients treated with the calcium channel blocker felodipine. Author(s): Nyberg G, Haljamae U, Herlitz H, Norden G, Blohme I. Source: Scandinavian Journal of Urology and Nephrology. 1994 March; 28(1): 17-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8009187

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Effect of amlodipine and felodipine on sympathetic activity and baroreflex function in normal humans. Author(s): Goldsmith SR. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1995 September; 8(9): 902-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8541005

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Effect of amlodipine versus felodipine extended release on 24-hour ambulatory blood pressure in hypertension. Author(s): Ostergren J, Isaksson H, Brodin U, Schwan A, Ohman KP. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1998 June; 11(6 Pt 1): 690-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9657628

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Effect of felodipine on arterial blood flow and venous function at rest in patients with mild essential hypertension. Author(s): Bicchi M, Vedovini G, Cappelli R, Arrigucci S, Righi GA, Forconi S. Source: Angiology. 1998 May; 49(5): 373-80. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9591529

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Effect of felodipine on regional blood supply and collateral vascular resistance in patients with peripheral arterial occlusive disease. Author(s): Liu Y, Opitz-Gress A, Rott A, Liewald F, Sunder-Plassmann L, Lehmann M, Stauch M, Steinacker JM. Source: Vascular Medicine (London, England). 1997; 2(1): 13-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9546944

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Effect of felodipine on renal function and vasoactive hormones in infrarenal aortic surgery. Author(s): de Lasson L, Hansen HE, Juhl B, Paaske WP, Pedersen EB. Source: British Journal of Anaesthesia. 1997 December; 79(6): 719-25. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9496202

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Effect of felodipine on renal haemodynamics and tubular sodium handling after single-dose cyclosporin infusion in renal transplant recipients treated with azathioprine and prednisolone. Author(s): Madsen JK, Kornerup HJ, Pedersen EB. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1995 November; 55(7): 625-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8633187

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Effect of felodipine on tacrolimus pharmacokinetics in a renal transplant recipient. Author(s): Butani L, Berg G, Makker SP. Source: Transplantation. 2002 January 15; 73(1): 159-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11793001

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Effect of felodipine-ER on blood pressure, platelet function, and rheological properties in hypertension. Author(s): Chou TZ, Lee KW, Ding YA. Source: The Canadian Journal of Cardiology. 1993 June; 9(5): 423-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8394193

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Effect of oral felodipine on ocular circulation. Author(s): Schocket LS, Grunwald JE, Dupont J. Source: International Ophthalmology. 1999; 23(2): 79-84. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11196124

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Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. VasodilatorHeart Failure Trial (V-HeFT) Study Group. Author(s): Cohn JN, Ziesche S, Smith R, Anand I, Dunkman WB, Loeb H, Cintron G, Boden W, Baruch L, Rochin P, Loss L. Source: Circulation. 1997 August 5; 96(3): 856-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9264493

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Effects of felodipine ER, a dihydropyridine calcium antagonist, on blood pressure and serum lipids. Author(s): Reuter MK, Lorenz H, Verho P, Smith N, Degen A, Verho M. Source: Current Medical Research and Opinion. 1998; 14(2): 97-103. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9704199

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Effects of felodipine versus nifedipine on exercise tolerance in stable angina pectoris. Author(s): Ekelund LG, Ulvenstam G, Walldius G, Aberg A. Source: The American Journal of Cardiology. 1994 April 1; 73(9): 658-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8166061

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Felodipine

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Effects of felodipine, metoprolol and their combination on blood pressure at rest and during exercise and on volume regulatory hormones in hypertensive patients. Author(s): Gordon RD, Klemm SA, Tunny TJ, Wicks JR, Elmfeldt DB. Source: Blood Pressure. 1995 September; 4(5): 300-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8535552

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Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Author(s): Lundahl J, Regardh CG, Edgar B, Johnsson G. Source: European Journal of Clinical Pharmacology. 1997; 52(2): 139-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9174684

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Effects of intensified blood-pressure reduction on renal function and albumin excretion in primary hypertension. Addition of felodipine or ramipril to long-term treatment with beta-blockade. Author(s): Siewert-Delle A, Ljungman S, Hartford M, Wikstrand J. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1995 February; 8(2): 113-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7755939

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Effects of intracoronary felodipine versus nifedipine on left ventricular contractility and coronary sinus blood flow in stable angina pectoris. Author(s): Koolen JJ, Van Wezel HB, Piek J, van Liebergen R, Swaan A, Visser CA. Source: The American Journal of Cardiology. 1994 October 1; 74(7): 730-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7942536

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Effects of nimodipine, felodipine, and verapamil on isolated human arteries. Author(s): Yao MH, Dai ZX, Xu DZ, Yang ZC. Source: Zhongguo Yao Li Xue Bao. 1995 January; 16(1): 36-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7771193

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Effects of the calcium antagonist felodipine on renal haemodynamics, tubular sodium handling, and blood pressure in cyclosporin-treated dermatological patients. Author(s): Madsen JK, Zachariae H, Pedersen EB. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1997 March; 12(3): 480-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9075128

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Efficacy and safety of barnidipine compared with felodipine in the treatment of hypertension in Chinese patients. Author(s): Liau CS, Chien KL, Chao CL, Lee TM. Source: J Int Med Res. 2002 May-June; 30(3): 330-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12166353

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Efficacy and tolerability of extended-release felodipine and extended-release nifedipine in patients with mild-to-moderate essential hypertension. Author(s): Fagan TC, Haggert BE, Liss C. Source: Clinical Therapeutics. 1994 July-August; 16(4): 634-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7982251

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Efficacy and tolerability of felodipine ER and diltiazem SR as monotherapy in primary hypertension: a double-blind randomized study. Author(s): Thulin T, Almkvist H, Berglund L, Bjornsson T, Fagher B, Henningsen N, Honkavaara M, Naukkarinen V, Nordenstrom P, Sillanpaa J, et al. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1994 December; 8(6): 845-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7742263

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Efficacy of low felodipine dose monotherapy in mild-to-moderate hypertension: a comparison between office and ambulatory blood pressure monitoring. Author(s): Podjarny E, Korzets Z, Bernheim J. Source: Journal of Human Hypertension. 1996 September; 10 Suppl 3: S153-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8872849

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Efficacy of once-daily felodipine monotherapy in systemic hypertension. Author(s): Hwang YS, Yen HW, Wong EC. Source: The American Journal of Cardiology. 1992 January 15; 69(3): 271-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1731473

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Enantioselective determination of felodipine in human plasma by chiral normalphase liquid chromatography and electrospray ionisation mass spectrometry. Author(s): Lindmark B, Ahnoff M, Persson BA. Source: Journal of Pharmaceutical and Biomedical Analysis. 2002 January 15; 27(3-4): 489-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11755750

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Erythromycin-felodipine interaction: magnitude, mechanism, and comparison with grapefruit juice. Author(s): Bailey DG, Bend JR, Arnold JM, Tran LT, Spence JD. Source: Clinical Pharmacology and Therapeutics. 1996 July; 60(1): 25-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8689808

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Felodipine

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Evaluation of a therapeutic conversion from amlodipine to felodipine. Author(s): Manzo BA, Matalka MS, Ravnan SL. Source: Pharmacotherapy. 2003 November; 23(11): 1508-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14620396

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Evaluation of solubilizers in the drug release testing of hydrophilic matrix extendedrelease tablets of felodipine. Author(s): Abrahamsson B, Johansson D, Torstensson A, Wingstrand K. Source: Pharmaceutical Research. 1994 August; 11(8): 1093-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7971707

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Exogenous aldosterone antagonizes distal tubular effects of calcium entry blocker felodipine. Author(s): Van Hamersvelt HW, Wetzels JF, Kloke HJ, Koene RA, Huysmans FT. Source: The American Journal of Physiology. 1994 June; 266(6 Pt 2): F843-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8023964

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Extended-release felodipine in patients with mild to moderate hypertension. Felodipine ER Dose-Response Study Group. Author(s): Weber MA, Goldberg AI, Faison EP, Lipschutz K, Shapiro DA, Nelson EB, Irvin JD. Source: Clinical Pharmacology and Therapeutics. 1994 March; 55(3): 346-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8143399

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Felodipine (once daily) versus nifedipine (four times daily) for Prinzmetal's angina pectoris. Author(s): Ardissino D, Savonitto S, Mussini A, Zanini P, Rolla A, Barberis P, Sardina M, Specchia G. Source: The American Journal of Cardiology. 1991 December 15; 68(17): 1587-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1746458

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Felodipine and amlodipine in stable angina pectoris: results of a randomized doubleblind crossover trial. Author(s): Koenig W, Hoher M. Source: Journal of Cardiovascular Pharmacology. 1997 April; 29(4): 520-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9156363

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Felodipine as an alternative to more expensive calcium antagonists in mild to moderate hypertension. Author(s): Landry FJ, Horwhat JD, Tomich D, Pinski L. Source: Southern Medical Journal. 1996 June; 89(6): 573-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8638195

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Felodipine as monotherapy and associated with enalapril for essential hypertension. Author(s): Navarro JF, Garcia-Perez J, Rodriguez-Perez JC. Source: The American Journal of Cardiology. 1997 September 1; 80(5): 683-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9295013

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Felodipine clinical pharmacokinetics. Author(s): Dunselman PH, Edgar B. Source: Clinical Pharmacokinetics. 1991 December; 21(6): 418-30. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1782737

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Felodipine does not increase the reflux episodes in patients with gastroesophageal reflux disease. Author(s): Wu JH, Chang CS, Chen GH, Poon SK, Ko CW. Source: Hepatogastroenterology. 2000 September-October; 47(35): 1328-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11100344

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Felodipine extended release in mild to moderate hypertension. Author(s): Wester A, Lorimer AR, Westberg B. Source: Current Medical Research and Opinion. 1991; 12(5): 275-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2004539

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Felodipine extended release versus conventional diuretic therapy for the treatment of systolic hypertension in elderly patients. The National Trial Group. Author(s): McClennen W, Wilson T. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 1998 June; 21(3): 142-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9627768

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Felodipine improves left ventricular emptying in patients with chronic heart failure: V-HeFT III echocardiographic substudy of multicenter reproducibility and detecting functional change. Author(s): Wong M, Germanson T, Taylor WR, Cohen IS, Perry G, Baruch L, Deedwania P, Lopez B, Cohn JN. Source: Journal of Cardiac Failure. 2000 March; 6(1): 19-28. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10746815

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Felodipine improves pulmonary hemodynamics in chronic obstructive pulmonary disease. Author(s): Sajkov D, McEvoy RD, Cowie RJ, Bradley JA, Antic R, Morris RG, Frith PA. Source: Chest. 1993 May; 103(5): 1354-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8486010

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Felodipine

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Felodipine in addition to beta-adrenergic blockade for angina pectoris. a multicentre, randomized, placebo-controlled trial. Author(s): Ronnevik PK, Silke B, Ostergaard O. Source: European Heart Journal. 1995 November; 16(11): 1535-41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8881845

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Felodipine in hypertensive heart transplant recipients. Author(s): Ambrosi P, Bertucci B, Bertault-Peres P, Metras D. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1996 May; 15(5): 540-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8771512

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Felodipine in the treatment of hypertensive type II diabetics: effect on glucose homeostasis. Author(s): Kjellstrom T, Blychert E, Lindgarde F. Source: Journal of Internal Medicine. 1991 March; 229(3): 233-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2007841

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Felodipine in the treatment of severe refractory hypertension. Author(s): Nussinovitch N, Carroll J, Shamiss A, Grossman E, Katz A, Rachima C, Rosenthal T. Source: Journal of Human Hypertension. 1996 September; 10 Suppl 3: S165-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8872852

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Felodipine inhibits free-radical production by cytokines and glucose in human smooth muscle cells. Author(s): Hishikawa K, Luscher TF. Source: Hypertension. 1998 December; 32(6): 1011-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9856965

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Felodipine inhibits nuclear translocation of p42/44 mitogen-activated protein kinase and human smooth muscle cell growth. Author(s): Yang Z, Madinova A, Kozai T, Joch H, Aebi U, Luscher TF. Source: Cardiovascular Research. 2002 January; 53(1): 227-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11744032

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Felodipine once daily in elderly hypertensives. Binational MC Study Group (United Kingdom and Netherlands). Author(s): Hosie J, Mulder AW, Westberg B. Source: Journal of Human Hypertension. 1991 February; 5(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2041036

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Felodipine or hydrochlorothiazide/triamterene for treatment of hypertension in the elderly: effects on blood pressure, hypertensive heart disease, metabolic and hormonal parameters. Author(s): Trenkwalder P, Plaschke M, Aulehner R, Lydtin H. Source: Blood Pressure. 1996 May; 5(3): 154-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8790926

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Felodipine pharmacokinetics and plasma concentration vs effect relationships. Author(s): Blychert E. Source: Blood Pressure. Supplement. 1992; 2: 1-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1343111

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Felodipine population dose-response and concentration-response relationships in patients with essential hypertension. Author(s): Wade JR, Sambol NC. Source: Clinical Pharmacology and Therapeutics. 1995 May; 57(5): 569-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7768080

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Felodipine protects human atrial muscle from hypoxia-reoxygenation dysfunction: a force-frequency relationship study in an in vitro model of stunning. Author(s): Iwashiro K, Criniti A, Sinatra R, Dawodu AA, d'Amati G, Monti F, Pannarale L, Bernucci P, Brancaccio GL, Vetuschi A, Gaudio E, Gallo P, Puddu PE. Source: International Journal of Cardiology. 1997 November 20; 62(2): 107-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9431863

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Felodipine therapy may not alter glucose and lipid metabolism in hypertensives. Felodipine Multicenter Prospective Study Group in Japan. Author(s): Shionoiri H, Takizawa T, Ohyama Y, Ishii J, Katayama S, Nagasawa T, Kitamoto K, Nagasawa K, Hariya Y, Sato R, et al. Source: Hypertension. 1994 January; 23(1 Suppl): I215-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8282362

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Felodipine use in pregnancy. Report of three cases. Author(s): Casele HL, Windley KC, Prieto JA, Gratton R, Laifer SA. Source: J Reprod Med. 1997 June; 42(6): 378-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9219129

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Felodipine versus placebo in stable effort-induced angina pectoris in patients inadequately controlled with metoprolol--a dose-finding study. Author(s): Emanuelsson H, Ahlstrom P, Kujacic V, Lundkvist L, Rosenqvist U, Tisell A, Angman K. Source: Journal of Cardiovascular Pharmacology. 1994 August; 24(2): 303-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7526065

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Felodipine, metoprolol and their combination compared with placebo in isolated systolic hypertension in the elderly. Author(s): Wing LM, Russell AE, Tonkin AL, Bune AJ, West MJ, Chalmers JP. Source: Blood Pressure. 1994 March; 3(1-2): 82-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8199723

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Felodipine/metoprolol: a review of the fixed dose controlled release formulation in the management of essential hypertension. Author(s): Haria M, Plosker GL, Markham A. Source: Drugs. 2000 January; 59(1): 141-57. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10718104

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Felodipine: a new dihydropyridine calcium-channel antagonist. Author(s): Yedinak KC, Lopez LM. Source: Dicp. 1991 November; 25(11): 1193-206. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1763537

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Felodipine-induced gingival hyperplasia. Author(s): Young PC, Turiansky GW, Sau P, Liebman MD, Benson PM. Source: Cutis; Cutaneous Medicine for the Practitioner. 1998 July; 62(1): 41-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9675532

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Felodipine-induced gingival hyperplasia: a clinical and histologic study. Author(s): Lombardi T, Fiore-Donno G, Belser U, Di Felice R. Source: Journal of Oral Pathology & Medicine : Official Publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology. 1991 February; 20(2): 89-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2016700

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Felodipine-metoprolol combination tablet: a valuable option to initiate antihypertensive therapy? Author(s): Waeber B, Detry JM, Dahlof B, Puig JG, Gundersen T, Hosie J, Januszewicz W, Lindstrom CJ, Magometschnigg D, Safar M, Tanser P, Toutouzas P. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1999 September; 12(9 Pt 1): 915-20. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10509550

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Glucoregulatory hormone response to insulin-induced hypoglycaemia following long-term calcium antagonism with felodipine in patients with essential hypertension. Author(s): Katzman PL, Hulthen UL, Hokfelt B. Source: Acta Endocrinol (Copenh). 1987 December; 116(4): 473-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3321819

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Glucose tolerance and secretion and clearance of insulin during long term felodipine treatment. Author(s): Katzman PL, Hulthen UL, Hokfelt B. Source: Drugs. 1987; 34 Suppl 3: 93-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3327685

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Glucose tolerance in hypertensive patients during treatment with the calcium antagonist, felodipine. Author(s): Hedner T, Elmfeldt D, Von Schenck H, Sjogren E, Smith U. Source: British Journal of Clinical Pharmacology. 1987 August; 24(2): 145-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3304386

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Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. Author(s): Lown KS, Bailey DG, Fontana RJ, Janardan SK, Adair CH, Fortlage LA, Brown MB, Guo W, Watkins PB. Source: The Journal of Clinical Investigation. 1997 May 15; 99(10): 2545-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9153299

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Grapefruit juice--felodipine interaction in the elderly. Author(s): Dresser GK, Bailey DG, Carruthers SG. Source: Clinical Pharmacology and Therapeutics. 2000 July; 68(1): 28-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10945313

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Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. Author(s): Bailey DG, Arnold JM, Munoz C, Spence JD. Source: Clinical Pharmacology and Therapeutics. 1993 June; 53(6): 637-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8513655

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Haemodynamic and renal effects of felodipine in young and elderly subjects. Author(s): Lernfelt B, Landahl S, Johansson P, Seligman L, Aberg J. Source: European Journal of Clinical Pharmacology. 1998 October; 54(8): 595-601. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9860145

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Haemodynamic effects and pharmacokinetics of felodipine at rest and during exercise in hypertensive patients treated with metoprolol or atenolol. Author(s): Bengtsson-Hasselgren B, Elmfeldt D, Moberg L, Ronn O. Source: European Journal of Clinical Pharmacology. 1989; 37(5): 459-65. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2598984

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Haemodynamic effects of a new vasodilator drug, felodipine, in healthy subjects. Author(s): Johnsson G, Murray G, Tweddel A, Hutton I. Source: European Journal of Clinical Pharmacology. 1983; 24(1): 49-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6832201

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Haemodynamic effects of felodipine during supine resting and exercising states and orthostatic tilt in patients with chronic congestive heart failure. Author(s): Kassis E, Waldorff S, Amtorp O. Source: Drugs. 1987; 34 Suppl 3: 69-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3443067

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Haemodynamic effects of felodipine in congestive heart failure. Author(s): Held P, Swedberg K. Source: Drugs. 1987; 34 Suppl 3: 81-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3443068

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Haemodynamic effects of intravenous felodipine in normotensive and hypertensive subjects. Author(s): Sluiter HE, Huysmans FT, Thien TA, Koene RA. Source: Drugs. 1985; 29 Suppl 2: 144-53. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3987541

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Haemodynamic effects of single-dose felodipine in normal man. Author(s): Agner E, Rehling M, Trap-Jensen J. Source: Drugs. 1985; 29 Suppl 2: 36-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3987549

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Haemodynamic, hormonal, and diuretic effects of felodipine in healthy normotensive volunteers. Author(s): Sluiter HE, Huysmans FT, Thien TA, van Lier HJ, Koene RA. Source: Drugs. 1985; 29 Suppl 2: 26-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2985351

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Hemodynamic and long-term renal effects of felodipine in severely hypertensive patients. Author(s): Andersson OK, Granerus G, Volkmann R, Wysocki M. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S41. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693725

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Hemodynamic comparisons of enalapril and felodipine and their combination. Author(s): Morgan TO, Anderson A. Source: Kidney International. Supplement. 1992 May; 36: S78-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1614072

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Hemodynamic effects of felodipine at rest and during exercise in exertional angina pectoris. Author(s): Detry JM, De Coster PM, Renkin J. Source: The American Journal of Cardiology. 1983 September 1; 52(5): 453-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6613867

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Hemodynamic effects of felodipine in congestive heart failure. Author(s): Binetti G, Pancaldi S, Giovanelli N, Negroni S, Ferretti RM, Branzi A, Specchia S, Magnani B. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1987 August; 1(2): 161-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3154319

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Hemodynamic effects of felodipine in hypertension: a review. Author(s): Lund-Johansen P. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S34-9. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693723

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Hemodynamic effects of the vascular selective calcium antagonist felodipine in patients with impaired left ventricular function. Author(s): Gradman AH. Source: American Heart Journal. 1992 January; 123(1): 273-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1729848

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Higher AUCs on oral administration of omeprazole and felodipine in Indian volunteers--are they clinically important? Author(s): Joseph T, Gowrishankar R. Source: Indian J Physiol Pharmacol. 1996 July; 40(3): 253-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8950143

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Hormonal and blood pressure responses to tilting in beta-blocked essential hypertension treated with felodipine or prazosin. Author(s): Jackson B, McGrath BP, Johnston CI. Source: Drugs. 1987; 34 Suppl 3: 87-92. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2894979

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Hormonal and hemodynamic changes following single-dose felodipine treatment during mental stress. Author(s): Haedersdal C, Petersen CL, Lund JO, Trap-Jensen J. Source: Angiology. 1993 December; 44(12): 965-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8285374

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Hypertension in the elderly. Its diagnosis in general practice and treatment with felodipine and metoprolol. Author(s): Davis RH, Burton RH, Freeling P, Graham-Evans JN, Goves JR, Orne-Smith EA, Osborne CJ, Ward DE. Source: Drugs. 1987; 34 Suppl 3: 149-50. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3327675

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Improved antihypertensive efficacy of the felodipine-metoprolol extended-release tablet compared with each drug alone. Author(s): Dahlof B, Jonsson L, Borgholst O, Ekblad G, Engstrand C, Grundestam I, Lindh A. Source: Blood Pressure. Supplement. 1993; 1: 37-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8173689

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Improved efficacy with maintained tolerability in the treatment of primary hypertension. Comparison between the felodipine-metoprolol combination tablet and monotherapy with enalapril. Swedish Multicentre Group. Author(s): Andersson OK. Source: Journal of Human Hypertension. 1999 January; 13(1): 55-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9928753

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Improved tolerability of felodipine compared with amlodipine in elderly hypertensives: a randomised, double-blind study in 535 patients, focusing on vasodilatory adverse events. The International Study Group. Author(s): Schaefer RM, Aldons PM, Burgess ED, Tilvis R, Girerd X, Singh GP, Rehn L, Morgan TO. Source: Int J Clin Pract. 1998 September; 52(6): 381-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9894374

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Improvement in renal function by felodipine during cyclosporine treatment in acute and short-term studies. Author(s): Pedersen EB, Madsen JK, Sorensen SS, Zachariae H. Source: Kidney International. Supplement. 1996 June; 55: S94-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8743522

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Improving the therapeutic balance between efficacy and tolerability in antihypertensive drugs--the rationale and benefits of combining felodipine and metoprolol. Author(s): Trenkwalder P, Elmfeldt D. Source: Journal of Human Hypertension. 1995 July; 9 Suppl 2: S37-42. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7562898

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In vitro-in vivo correlation of pharmacodynamics of felodipine in essential hypertensive patients based on an ion-channel binding model. Author(s): Nakajima Y, Yamamoto K, Shimada S, Kotaki H, Sawada Y, Iga T. Source: Biological & Pharmaceutical Bulletin. 1996 August; 19(8): 1097-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8874826

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In vivo pharmacokinetics of felodipine predicted from in vitro studies in rat, dog and man. Author(s): Baarnhielm C, Dahlback H, Skanberg I. Source: Acta Pharmacol Toxicol (Copenh). 1986 August; 59(2): 113-22. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3776550

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Increased exercise tolerance and reduced electrocardiographic ischaemia 3 and 12 hours after oral felodipine in effort angina. Author(s): Verdecchia P, Gatteschi C, Benemio G, Guerrieri M, Boldrini F, Pollavini G, Porcellati C. Source: European Heart Journal. 1989 January; 10(1): 70-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2702968

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Influence of felodipine on left ventricular hypertrophy and systolic function in orthotopic heart transplant recipients: possible interaction with cyclosporine medication. Author(s): Schwitter J, De Marco T, Globits S, Sakuma H, Klinski C, Chatterjee K, Parmley WW, Higgins CB. Source: The Journal of Heart and Lung Transplantation : the Official Publication of the International Society for Heart Transplantation. 1999 October; 18(10): 1003-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10561111

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Felodipine

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Influence of oral felodipine on serum cyclosporine concentrations. Author(s): Cohen DJ, Teng SN, Appel GB. Source: Clinical Transplantation. 1994 December; 8(6): 541-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7865916

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Influence of single and repeated doses of oxcarbazepine on the pharmacokinetic profile of felodipine. Author(s): Zaccara G, Gangemi PF, Bendoni L, Menge GP, Schwabe S, Monza GC. Source: Therapeutic Drug Monitoring. 1993 February; 15(1): 39-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8451779

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Interaction between cyclosporine A and verapamil, felodipine, and isradipine. Author(s): Yildiz A, Sever MS, Turkmen A, Ecder T, Turk S, Akkaya V, Ark E. Source: Nephron. 1999 January; 81(1): 117-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9884436

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Interaction between cyclosporine and felodipine in renal transplant recipients. Author(s): Pedersen EB, Sorensen SS, Eiskjaer H, Skovbon H, Thomsen K. Source: Kidney International. Supplement. 1992 May; 36: S82-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1614074

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Interaction of citrus juices with felodipine and nifedipine. Author(s): Chayen R, Rosenthal T. Source: Lancet. 1991 April 6; 337(8745): 854. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1672944

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Interaction of indomethacin with felodipine and enalapril. Author(s): Morgan T, Anderson A. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1993 December; 11 Suppl 5: S338-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8158412

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Is natriuresis on felodipine due to reversal of the renal effects of angiotensin II? Author(s): van Hamersvelt HW, Sluiter HE, Wetzels JF, Koene RA, Huysmans FT. Source: Kidney International. Supplement. 1992 May; 36: S73-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1535400

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Is the renal dopaminergic system involved in the natriuretic effect of felodipine? Author(s): van Hamersvelt HW, Wetzels JF, Kloke HJ, Koene RA, Huysmans FT. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1993 December; 11 Suppl 5: S352-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8158419

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Itraconazole greatly increases plasma concentrations and effects of felodipine. Author(s): Jalava KM, Olkkola KT, Neuvonen PJ. Source: Clinical Pharmacology and Therapeutics. 1997 April; 61(4): 410-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9129558

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Itraconazole interacts with felodipine. Author(s): Neuvonen PJ, Suhonen R. Source: Journal of the American Academy of Dermatology. 1995 July; 33(1): 134-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7601933

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Long term experience of felodipine in combination with beta-blockade and diuretics in refractory hypertension. Author(s): Collste P, Danielsson M, Elmfeldt D, Feleke E, Gelin A, Hedner T, Ryden L. Source: Drugs. 1985; 29 Suppl 2: 124-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2859184

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Long-term clinical, hemodynamic, angiographic, and neurohumoral responses to vasodilation with felodipine in patients with chronic congestive heart failure. Author(s): Kassis E, Amtorp O. Source: Journal of Cardiovascular Pharmacology. 1990 March; 15(3): 347-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1691355

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Long-term efficacy, tolerability, and safety of the combination of enalapril and felodipine ER in the treatment of hypertension. Enalapril-Felodipine ER Factorial Study Group. Author(s): Gradman AH, Cutler NR, Davis PJ, Robbins JA, Weiss RJ, Wood BC, Michelson EL. Source: Clinical Therapeutics. 1998 May-June; 20(3): 527-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9663368

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Long-term hemodynamic effects at rest and during exercise of newer antihypertensive agents and salt restriction in essential hypertension: review of epanolol, doxazosin, amlodipine, felodipine, diltiazem, lisinopril, dilevalol, carvedilol, and ketanserin. Author(s): Omvik P, Lund-Johansen P. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1993 April; 7(2): 193-206. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8395198

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Felodipine

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Long-term treatment of hypertension with felodipine. Author(s): Flygt G. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S103-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693711

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Long-term treatment with a new calcium antagonist, felodipine, in chronic obstructive lung disease. Author(s): Bratel T, Hedenstierna G, Nyquist O, Ripe E. Source: Eur J Respir Dis. 1986 May; 68(5): 351-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3732430

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Low dosages of felodipine ER once daily as monotherapy in elderly hypertensive patients: effect on ambulatory blood pressure and quality of life. Author(s): van Ree JW, van der Pol GA. Source: Journal of Human Hypertension. 1996 September; 10(9): 613-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8953207

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Metoclopramide stimulates kaliuresis during felodipine without affecting its natriuresis. Author(s): van Hamersvelt HW, Wetzels JF, Koene RA, Huysmans FT. Source: Hypertension. 1994 November; 24(5): 633-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7960025

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Microvascular effects and oedema formation of felodipine in man. Author(s): Gustafsson D, Lanne T, Bjerkhoel P, Johansson P, Lundvall J. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1989 September; 7(4): S161-7; Discussion S168. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2681592

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Mono- and combination therapy with felodipine or enalapril in elderly patients with systolic hypertension. Author(s): Wing LM, Russell AE, Tonkin AL, Watts RW, Bune AJ, West MJ, Chalmers JP. Source: Blood Pressure. 1994 March; 3(1-2): 90-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8199724

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Monotherapy with felodipine, a new calcium antagonist, in mild and moderate hypertension. Author(s): Hamilton DV, Barnes PC, Bowles RM, Rajaratnam DV, Comerford MB, Ginks WR, Ginks SE, Goves JR, Grabau WJ, Malcolm JP, et al. Source: Journal of Cardiovascular Pharmacology. 1987; 10 Suppl 10: S111-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2455107

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Natriuretic and diuretic effects of felodipine and hydrochlorothiazide after single and repeated doses. Author(s): Hasselgren B, Johansson P. Source: European Journal of Clinical Pharmacology. 1995; 47(5): 395-400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7720759

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Nelfinavir and felodipine: a cytochrome P450 3A4-mediated drug interaction. Author(s): Izzedine H, Launay-Vacher V, Deray G, Hulot JS. Source: Clinical Pharmacology and Therapeutics. 2004 April; 75(4): 362-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=15060514

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No adverse effects from high doses of felodipine to patients with coronary heart disease. Author(s): Emanuelsson H, Holmberg S. Source: Clin Cardiol. 1985 June; 8(6): 329-36. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=4006342

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Noninvasive tracking of coronary atherosclerosis by electron beam computed tomography: rationale and design of the Felodipine Atherosclerosis Prevention Study (FAPS). Author(s): Wong ND, Teng W, Abrahamson D, Willner R, Henein N, Franklin SS, Kashyap ML, Rosenzweig B, Kukes G, Detrano RC. Source: The American Journal of Cardiology. 1995 December 15; 76(17): 1239-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7503003

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Office and ambulatory blood pressure: a comparison between amlodipine and felodipine ER. Danish Multicentre Group. Author(s): Hoegholm A, Wiinberg N, Rasmussen E, Nielsen PE. Source: Journal of Human Hypertension. 1995 August; 9(8): 611-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8523374

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Once daily felodipine in patients with primary Raynaud's phenomenon. Author(s): Kallenberg CG, Wouda AA, Meems L, Wesseling H. Source: European Journal of Clinical Pharmacology. 1991; 40(3): 313-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2060571

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Once daily felodipine in preventing ergonovine-induced myocardial ischaemia in Prinzmetal's variant angina. Author(s): Chimienti M, Negroni MS, Pusineri E, Regazzi MB, Inglese L, Klersy C, De Ambroggi L. Source: European Heart Journal. 1994 March; 15(3): 389-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8013514

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Felodipine

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Once daily felodipine monotherapy in mild to moderate hypertension. Author(s): Kon SP, Tan HW, Chua CT, Ong ML, Kamsiah J, Maheendran KK, Ponniah CA, Tariq AR, Mahendran T. Source: Med J Malaysia. 1992 December; 47(4): 290-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1303482

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One-year study of felodipine or placebo for stage 1 isolated systolic hypertension. Author(s): Black HR, Elliott WJ, Weber MA, Frishman WH, Strom JA, Liebson PR, Hwang CT, Ruff DA, Montoro R, DeQuattro V, Zhang D, Schleman MM, Klibaner MI. Source: Hypertension. 2001 November; 38(5): 1118-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11711508

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Optimal felodipine dose when combined with metoprolol in arterial hypertension: a Swedish multicenter study within primary health care. Swedish General Practitioner Felodipine Study Group. Author(s): Brun J, Froberg L, Kronmann P, Olsson LB, Skoog P, Tygesen G, Bengtsson C, Schersten B, Tibblin G. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S60-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693732

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Oral pharmacokinetics of felodipine in patients with congestive heart failure: variable prediction using intravenous data. Author(s): Dunselman PH, Scaf AH, Wesseling H. Source: Journal of Clinical Pharmacology. 1989 June; 29(6): 518-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2754021

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Outcomes of an amlodipine-to-felodipine therapeutic interchange program. Author(s): Clay DR, Bourg MP, Lawrence DB. Source: American Journal of Health-System Pharmacy : Ajhp : Official Journal of the American Society of Health-System Pharmacists. 2000 September 1; 57(17): 1604-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10984813

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Overview of the safety of felodipine based on clinical trials in patients with hypertension. Author(s): Welin L, Elvelin L, Niklasson A, Olsson G, Elmfeldt D. Source: The American Journal of Cardiology. 1997 April 1; 79(7): 996-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9104926

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Patterns of amlodipine and felodipine use in an elderly Quebec population. Author(s): Sheehy O, LeLorier J. Source: The Canadian Journal of Cardiology. 2000 September; 16(9): 1109-17. English, French. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11021955

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Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model. Author(s): Takanaga H, Ohnishi A, Matsuo H, Murakami H, Sata H, Kuroda K, Urae A, Higuchi S, Sawada Y. Source: British Journal of Clinical Pharmacology. 2000 January; 49(1): 49-58. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10606837

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Pharmacokinetic and pharmacodynamic studies of felodipine in healthy subjects after various single, oral and intravenous doses. Author(s): Edgar B, Regardh CG, Lundborg P, Romare S, Nyberg G, Ronn O. Source: Biopharmaceutics & Drug Disposition. 1987 May-June; 8(3): 235-48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3593901

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Pharmacokinetic interaction between cyclosporine and the dihydropyridine calcium antagonist felodipine. Author(s): Madsen JK, Jensen JD, Jensen LW, Pedersen EB. Source: European Journal of Clinical Pharmacology. 1996; 50(3): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8737760

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Pharmacokinetic interactions between felodipine and metoprolol. Author(s): Smith SR, Wilkins MR, Jack DB, Kendall MJ, Laugher S. Source: European Journal of Clinical Pharmacology. 1987; 31(5): 575-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3830242

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Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects. Author(s): Landahl S, Edgar B, Gabrielsson M, Larsson M, Lernfelt B, Lundborg P, Regardh CG. Source: Clinical Pharmacokinetics. 1988 June; 14(6): 374-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3396260

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Pharmacokinetics and haemodynamic effects of felodipine as monotherapy in hypertensive patients. Author(s): Edgar B, Collste P, Haglund K, Regardh CG. Source: Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 1987 September; 10(5): 388-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3677507

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Pharmacokinetics and haemodynamics of felodipine as monotherapy in hypertensive patients. Author(s): Edgar B, Collste P, Haglund K, Regardh CG. Source: Drugs. 1987; 34 Suppl 3: 28-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3443061

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Pharmacokinetics and hemodynamic and diuretic/natriuretic effects of felodipine administered as an extended-release tablet. Author(s): Hasselgren B, Ronn O, Edgar B, Johansson P, Wall B. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1990 December; 4(6): 1495-500. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2081141

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Pharmacokinetics of felodipine after intravenous and chronic oral administration in patients with congestive heart failure. Author(s): Dunselman PH, Edgar B, Scaf AH, Kuntze CE, Wesseling H. Source: British Journal of Clinical Pharmacology. 1989 July; 28(1): 45-52. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2673315

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Pharmacokinetics of felodipine and effect on digoxin plasma levels in patients with heart failure. Author(s): Rehnqvist N, Billing E, Moberg L, Lundman T, Olsson G. Source: Drugs. 1987; 34 Suppl 3: 33-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3443063

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Pharmacokinetics of felodipine in chronic hemodialysis patients. Author(s): Buur T, Larsson R, Regardh CG, Aberg J. Source: Journal of Clinical Pharmacology. 1991 August; 31(8): 709-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1880229

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Pharmacokinetics of felodipine in patients with impaired renal function. Author(s): Edgar B, Regardh CG, Attman PO, Aurell M, Herlitz H, Johnsson G. Source: British Journal of Clinical Pharmacology. 1989 January; 27(1): 67-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2706189

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Pharmacokinetics of felodipine in patients with liver disease. Author(s): Regardh CG, Edgar B, Olsson R, Kendall M, Collste P, Shansky C. Source: European Journal of Clinical Pharmacology. 1989; 36(5): 473-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2753065

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Photodistributed felodipine-induced facial telangiectasia. Author(s): Silvestre JF, Albares MP, Carnero L, Botella R. Source: Journal of the American Academy of Dermatology. 2001 August; 45(2): 323-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11464208

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Placebo controlled trial of felodipine in patients with mild to moderate heart failure. UK Study Group. Author(s): Littler WA, Sheridan DJ. Source: British Heart Journal. 1995 May; 73(5): 428-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7786657

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Plasma concentration profiles and antihypertensive effect of conventional and extended-release felodipine tablets. Author(s): Blychert E, Wingstrand K, Edgar B, Lidman K. Source: British Journal of Clinical Pharmacology. 1990 January; 29(1): 39-45. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2404502

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Plasma concentration vs. effect relationship for felodipine. Author(s): Blychert E, Edgar B, Elmfeldt D, Shapiro D. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S57. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693729

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Plasma concentration-effect relationship of felodipine intravenously in patients with congestive heart failure. Author(s): Dunselman PH, Edgar B, Scaf AH, Kuntze CE, van Bruggen A, Lie KI, Wesseling H. Source: Journal of Cardiovascular Pharmacology. 1989 September; 14(3): 438-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2476624

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Plasma concentration-effect relationships of intravenous and extended-release oral felodipine in hypertensive patients. Author(s): Blychert E, Hedner T, Dahlof C, Elmfeldt D. Source: Journal of Cardiovascular Pharmacology. 1990 March; 15(3): 428-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1691367

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Plasma norepinephrine and atrial natriuretic peptide in heart failure: influence of felodipine in the third Vasodilator Heart Failure Trial. V-HeFT III investigators. Author(s): Smith RF, Germanson T, Judd D, Wong M, Ziesche S, Anand IS, Taylor WR, Cohn JN. Source: Journal of Cardiac Failure. 2000 June; 6(2): 97-107. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10908083

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Prevention of left ventricular hypertrophy by ACE-inhibitor, ramipril in comparison with calcium-channel antagonist, felodipine. Author(s): Cacciapuoti F, Capasso A, Mirra G, De Nicola A, Minicucci F, Gentile S. Source: International Journal of Cardiology. 1998 January 31; 63(2): 175-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9510492

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Problem of measuring the positive inotropic property of a vasodilating drug: an illustration using felodipine. Author(s): Drake-Holland AJ, Pugh S, Noble MI, Mills C. Source: Cardiovascular Research. 1987 September; 21(9): 631-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3446366

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Quinidine interaction with nifedipine and felodipine: pharmacokinetic and pharmacodynamic evaluation. Author(s): Bailey DG, Freeman DJ, Melendez LJ, Kreeft JH, Edgar B, Carruthers SG. Source: Clinical Pharmacology and Therapeutics. 1993 March; 53(3): 354-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8453855

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Ramipril and felodipine: a comparison of the efficacy and safety of monotherapy versus combination therapy. Author(s): Poisson P, Bauer B, Schueler E, Rangoonwala B. Source: Current Medical Research and Opinion. 1996; 13(8): 445-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9010611

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Randomised, double-blind, parallel study of the anti-hypertensive efficacy and safety of losartan potassium compared with felodipine ER in elderly patients with mild to moderate hypertension. Author(s): Chan JC, Critchley JA, Lappe JT, Raskin SJ, Snavely D, Goldberg AI, Sweet CS. Source: Journal of Human Hypertension. 1995 September; 9(9): 765-71. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8551492

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Rationale and design of the third vasodilator-heart failure trial (V-HeFT III): felodipine as adjunctive therapy to enalapril and loop diuretics with or without digoxin in chronic congestive heart failure. V-HeFT III investigators. Author(s): Boden WE, Ziesche S, Carson PE, Conrad CH, Syat D, Cohn JN. Source: The American Journal of Cardiology. 1996 May 15; 77(12): 1078-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8644661

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Reduced felodipine bioavailability in patients taking anticonvulsants. Author(s): Capewell S, Freestone S, Critchley JA, Pottage A, Prescott LF. Source: Lancet. 1988 August 27; 2(8609): 480-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2900404

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Regression of left ventricular hypertrophy by felodipine or a combination of felodipine and metoprolol. Author(s): Wetzchewald D, Klaus D, Garanin G, Hoffmann J, Lohr E. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S48. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693727

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Regression of left ventricular hypertrophy during long-term antihypertensive treatment--a comparison between felodipine and the combination of felodipine and metoprolol. Author(s): Wetzchewald D, Klaus D, Garanin G, Lohr E, Hoffmann J. Source: Journal of Internal Medicine. 1992 March; 231(3): 303-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1532616

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Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Author(s): Lundahl J, Regardh CG, Edgar B, Johnsson G. Source: European Journal of Clinical Pharmacology. 1995; 49(1-2): 61-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8751023

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Relationship of changes in felodipine pharmacokinetics to haemodynamics during chronic oral treatment of congestive heart failure patients. Author(s): Scaf AH, Dunselman PH, Wesseling H. Source: European Journal of Clinical Pharmacology. 1995; 49(3): 203-10. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8665996

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Renal and antihypertensive effects of felodipine in hypertensive patients. Author(s): Leonetti G, Gradnik R, Terzoli L, Fruscio M, Rupoli L, Cuspidi C, Sampieri L, Zanchetti A. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1985 December; 3 Suppl 3: S161-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2856695

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Renal effects of a nonhypotensive i.v. dose of felodipine. Author(s): Larochelle P, Cusson JR, du Souich P, Thibault G, Edgar B. Source: Journal of Clinical Pharmacology. 1993 August; 33(8): 732-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8408734

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Renal effects of acute and long-term treatment with felodipine in essential hypertension. Author(s): Hulthen UL, Katzman PL. Source: Journal of Hypertension. 1988 March; 6(3): 231-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3361121

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Renal effects of felodipine in hypertension. Author(s): Leonetti G, Terzoli L, Rupoli L, Gradnik R, Zanchetti A. Source: Drugs. 1987; 34 Suppl 3: 59-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3443065

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Renal effects of felodipine: a review of experimental evidence and clinical data. Author(s): DiBona GF. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S29-32. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693722

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Renal hypoxanthine balance in cardiac surgery: effects of felodipine. Author(s): Jeppsson A, Andersson LG, Ekroth R, Joachimsson PO. Source: Journal of Cardiothoracic and Vascular Anesthesia. 1999 December; 13(6): 715-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10622655

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Response of patients to enalapril, felodipine and their combination. Author(s): Anderson A, Morgan TO. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1991 December; 9(6): S380-1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1819001

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Rest and effort hemodynamic responses during prolonged treatment with felodipine, 24-h blood pressure monitoring, and echocardiographic changes. Author(s): Zimlichman R, Schwartz J, Tobar R. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1997 August; 10(8): 905-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9270086

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Reversal of cardiac hypertrophy and left ventricular function with the calcium antagonist felodipine in hypertensive patients. Author(s): Cerasola G, Cottone S, Nardi E, Fulantelli MA, Carone MB, D'Ignoto G. Source: Journal of Human Hypertension. 1990 December; 4(6): 703-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2151392

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Reversal of left ventricular hypertrophy following once daily administration of felodipine for two years to elderly subjects with isolated systolic hypertension. Author(s): De Rosa ML, Giordano A, Della Guardia D, Maddaluno G, Lionetti F, Marsicani N, Vigorito C. Source: Cardiology. 1999; 92(1): 39-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10640795

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Safety and efficacy of therapeutically equivalent doses of sustained-release formulations of isradipine and felodipine. Author(s): Ganz MB, Saska BA. Source: Congestive Heart Failure (Greenwich, Conn.). 2003 November-December; Suppl 2: 1-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14688501

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Safety and tolerability of losartan potassium, an angiotensin II receptor antagonist, compared with hydrochlorothiazide, atenolol, felodipine ER, and angiotensinconverting enzyme inhibitors for the treatment of systemic hypertension. Author(s): Goldberg AI, Dunlay MC, Sweet CS. Source: The American Journal of Cardiology. 1995 April 15; 75(12): 793-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7717281

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Scintigraphic evaluation of the short- and long-term renal effects of oral felodipine using technetium-99m-mercaptoacetyl triglycine. Author(s): Ozdemir O, Erbas B, Ugur O, Varoglu E, Erbengi G, Bekdik C, Oram E. Source: American Journal of Nephrology. 1993; 13(4): 249-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8267021

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Seville orange juice-felodipine interaction: comparison with dilute grapefruit juice and involvement of furocoumarins. Author(s): Malhotra S, Bailey DG, Paine MF, Watkins PB. Source: Clinical Pharmacology and Therapeutics. 2001 January; 69(1): 14-23. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11180034

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Short and long term treatment of essential hypertension with felodipine as monotherapy. Author(s): Harrington K, Fitzgerald P, O'Donnell P, Hill KW, O'Brien E, O'Malley K. Source: Drugs. 1987; 34 Suppl 3: 178-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3327679

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Short- and long-term controlled studies of felodipine in patients with congestive heart failure. Author(s): Kassis E, Amtorp O. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693721

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Short- and long-term effects of felodipine on circulating endothelin and atrial natriuretic peptide levels in essential hypertension. Author(s): Erbas B, Ozdemir O, Pasaoglu I, Ugur O, Varoglu E, Koray Z, Yorgancioglu C, Hazan E, Oram E, Bekdik CF. Source: Nephron. 1993; 63(3): 363-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8446283

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Short-term effects of felodipine in hypertensive type II diabetic males on sulfonylurea treatment. Author(s): Kjellstrom T, Blychert E, Lindgarde F. Source: Journal of Internal Medicine. 1994 July; 236(1): 51-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8021573

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Short-term effects of felodipine, a new dihydropyridine, in hypertension. Author(s): Andersson O, Bengtsson C, Elmfeldt D, Haglund K, Hedner T, Seideman P, Sjoberg KH, Stromgren E, Aberg H, Ostman J. Source: British Journal of Clinical Pharmacology. 1984 March; 17(3): 257-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6712859

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Significance of blood pressure levels achieved with felodipine anti-hypertensive treatment on cardiovascular structure and function changes. Author(s): Vyssoulis GP, Trikas AG, Paleologos AA, Toutouza MG, Toutouzas PK. Source: Journal of Human Hypertension. 1998 July; 12(7): 427-32. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9702927

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Smooth blood pressure control obtained with extended-release felodipine in elderly patients with hypertension: evaluation by 24-hour ambulatory blood pressure monitoring. Author(s): Antonicelli R, Omboni S, Giovanni DC, Ansuini R, Mori A, Gesuita R, Parati G, Paciaroni E. Source: Drugs & Aging. 2002; 19(7): 541-51. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12182690

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Stereoselective metabolism of felodipine in liver microsomes from rat, dog, and human. Author(s): Eriksson UG, Lundahl J, Baarnhielm C, Regardh CG. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1991 September-October; 19(5): 889-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1686232

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Stereoselective pharmacokinetics of oral felodipine and nitrendipine in healthy subjects: correlation with nifedipine pharmacokinetics. Author(s): Soons PA, Mulders TM, Uchida E, Schoemaker HC, Cohen AF, Breimer DD. Source: European Journal of Clinical Pharmacology. 1993; 44(2): 163-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8453961

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Structural changes in hypertension, the potential for their prevention, arrest and reversal: a focus on felodipine. Author(s): Purcell H, Coats A. Source: Br J Clin Pract. 1994 November-December; 48(6): 311-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7848795

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Studies with felodipine in congestive heart failure. Author(s): Timmis AD, Jewitt DE. Source: Drugs. 1985; 29 Suppl 2: 66-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3987553

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Sustained haemodynamic effects of felodipine in patients with chronic cardiac failure. Author(s): Tweddel AC, Martin W, McGhie AI, Hutton I. Source: British Journal of Clinical Pharmacology. 1988 June; 25(6): 689-94. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3203040

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Synthesis and preparative liquid chromatographic purification of reference compounds of three metabolites of the vasodilating drug felodipine. Author(s): Weidolf L, Hoffmann KJ, Carlsson S, Borg KO. Source: Acta Pharm Suec. 1984; 21(4): 209-22. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6516867

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The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension. Author(s): Bainbridge AD, Macfadyen RJ, Stark S, Lees KR, Reid JL. Source: British Journal of Clinical Pharmacology. 1993 October; 36(4): 323-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12959310

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The effect of felodipine on endothelin-1 levels, peripheral vasoconstriction and flap survival during microvascular breast reconstruction. Author(s): Tuominen HP, Svartling NE, Tikkanen IT, Asko-Seljavaara S. Source: British Journal of Plastic Surgery. 1997 December; 50(8): 624-31. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9613405

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The effect of felodipine on renal function and blood pressure in cyclosporin-treated renal transplant recipients during the first three months after transplantation. Author(s): Madsen JK, Sorensen SS, Hansen HE, Pedersen EB. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1998 September; 13(9): 2327-34. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9761517

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The effects of felodipine in angina pectoris. Author(s): Lorimer AR, MacFarlane P, Pringle S, Barbour MP, Fox Y, Lawrie TD. Source: European Journal of Clinical Pharmacology. 1990; 38(5): 415-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2116311

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The effects of felodipine on the pharmacokinetics of diazepam. Author(s): Meyer BH, Muller FO, Hundt HK, Luus HG, de la Rey N, Rothig HJ. Source: Int J Clin Pharmacol Ther Toxicol. 1992 April; 30(4): 117-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1572756

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The efficacy and tolerability of long-term felodipine treatment in hypertension. The Scandinavian Multicenter Group. Author(s): Ibsen H, Westberg B. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1990 June; 4(3): 641-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1981681

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The efficacy of felodipine ER on regression of left ventricular hypertrophy in patients with primary hypertension. Author(s): Nalbantgil I, Onder R, Killiccioglu B, Boydak B, Terzioglu E, Yilmaz H. Source: Blood Pressure. 1996 September; 5(5): 285-91. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8879601

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The evolving role of calcium channel blockers in the treatment of angina pectoris: focus on felodipine. Author(s): Gradman AH. Source: The Canadian Journal of Cardiology. 1995 April; 11 Suppl B: 14B-21B. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7728649

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The haemodynamic effects of long term felodipine therapy in previously untreated essential hypertension. Author(s): Capewell S, Wathen CG, Hannan WJ, Muir AL. Source: European Journal of Clinical Pharmacology. 1990; 39(6): 539-43. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2095339

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The influence of infusion rate on the hemodynamic effects of felodipine. Author(s): Cohen AF, van Hall MA, van Harten J, Schoemaker RC, Johansson P, Breimer DD, Visser R, Edgar B. Source: Clinical Pharmacology and Therapeutics. 1990 September; 48(3): 309-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2401128

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The pharmacodynamic and pharmacokinetic profiles of controlled-release formulations of felodipine and metoprolol in free and fixed combinations in elderly hypertensive patients. Author(s): McLay JS, MacDonald TM, Hosie J, Elliott HL; Logimax Group. Source: European Journal of Clinical Pharmacology. 2000 November; 56(8): 529-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11151741

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The pharmacokinetics of extended release felodipine in children. Author(s): Blowey DI, Moncica I, Scolnik D, Arbus GS, Hebert D, Balfe JW, Koren G. Source: European Journal of Clinical Pharmacology. 1996; 50(1-2): 147-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8739826

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Truncal telangiectases coinciding with felodipine. Author(s): Karonen T, Stubb S, Keski-Oja J. Source: Dermatology (Basel, Switzerland). 1998; 196(2): 272-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9568427

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Twenty-four hour blood pressure profiles in hypertensive patients following various formulations and dosage regimens of felodipine. Author(s): Blychert E, Frisen M, Karlsson O, Ryden L. Source: European Journal of Clinical Pharmacology. 1992; 42(1): 25-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1541312

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Twenty-four hour profile of the hypotensive action of felodipine in essential hypertension. Author(s): Crozier IG, Ikram H, Nicholls MG, Low CJ. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1990 April; 4(2): 439-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2285628

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Twenty-four-hour activity of felodipine extended release in chronic stable angina pectoris. Author(s): Santoro G, Savonitto S, Di Bello V, Alberti D, Giusti C. Source: The American Journal of Cardiology. 1991 August 15; 68(5): 457-62. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1872271

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Twenty-four-hour antihypertensive efficacy of felodipine 10 mg extended-release: the Italian inter-university study. Author(s): Pannarale G, Puddu PE, Monti F, Irace L, Bentivoglio M, Collauto F, Barsotti A, Corea L, Trevi G, Campa PP, Jacono A. Source: Journal of Cardiovascular Pharmacology. 1996 February; 27(2): 255-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8720425

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Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine in elderly patients with mild to moderate hypertension: a randomized, double-blind, cross-over study. Author(s): Bonaduce D, Canonico V, Petretta M, Forgione L, Ianniciello A, Cavallaro V, Bertocchi F, Rengo F. Source: European Journal of Clinical Pharmacology. 1997; 53(2): 95-100. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9403278

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Twenty-four-hour blood pressure monitoring during treatment with extended-release felodipine versus slow-release nifedipine: cross-over study. Author(s): Carroll J, Shamiss A, Zevin D, Levi J, Rosenthal T. Source: Journal of Cardiovascular Pharmacology. 1995 December; 26(6): 974-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8606536

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Unchanged insulin secretion and glucose tolerance but increased insulin clearance during long-term calcium antagonism with felodipine in essential hypertension. Author(s): Katzman PL, Hulthen UL, Hokfelt B. Source: Hormone and Metabolic Research. Hormon- Und Stoffwechselforschung. Hormones Et Metabolisme. 1987 September; 19(9): 426-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3319861

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Urinary metabolites of felodipine, a new vasodilator drug, in man, dog, rat and mouse. Author(s): Weidolf L, Borg KO, Hoffmann KJ. Source: Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 1984 August; 14(8): 657-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=6495759

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Vascular selective calcium entry blockers in the treatment of cardiovascular disorders: focus on felodipine. Author(s): Little WC, Cheng CP, Elvelin L, Nordlander M. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1995 October; 9(5): 657-63. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8573548

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Vascular selectivity of felodipine: clinical experience. Author(s): Thomas P, Sheridan DJ. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S17-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693718

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Vascular selectivity of felodipine: experimental pharmacology. Author(s): Ljung B. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S11-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693715

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Vasodilatation with felodipine in chronic asymptomatic aortic regurgitation. Author(s): Sondergaard L, Aldershvile J, Hildebrandt P, Kelbaek H, Stahlberg F, Thomsen C. Source: American Heart Journal. 2000 April; 139(4): 667-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10740150

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

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

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

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

A trial of the calcium antagonist felodipine in hypertensive type 2 diabetic patients. Author(s): Department of Medicine, Edinburgh Royal Infirmary, UK. Source: Capewell, S Collier, A Matthews, D Hajducka, C Collier, R Clarke, B F Muir, A L Diabet-Med. 1989 December; 6(9): 809-12 0742-3071

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Acute renal tubular and hemodynamic effects of the calcium antagonist felodipine in healthy volunteers. Author(s): Department of Endocrinology, Lund University Clinics, General Hospital, Malmo, Sweden. Source: Katzman, P L DiBona, G F Hokfelt, B Hulthen, U L J-Am-Soc-Nephrol. 1991 November; 2(5): 1000-6 1046-6673

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Antagonist capacity of felodipine on cyclosporin A nephrotoxicity in the rat. Author(s): Laboratory of Nephropathology, Odense University Hospital, Denmark. Source: Dieperink, H Hansen, H V Kemp, M Leyssac, P P Starklint, H Kemp, E NephrolDial-Transplant. 1992; 7(11): 1124-9 0931-0509

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Cardiovascular and renal effects of the combination of felodipine and metoprolol during a high-salt and a moderate-salt diet in spontaneously hypertensive rats. Author(s): Department of Pharmacology and Toxicology, University of Helsinki, Finland. Source: Mervaala, E M Teravainen, T L Malmberg, L Laakso, J Porsti, I Vapaatalo, H Karppanen, H Jpn-Circ-J. 1997 May; 61(5): 421-31 0047-1828

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Combination therapy with felodipine and metoprolol compared with captopril and hydrochlorothiazide. German MC Study Group. Author(s): Klinik Hohenried fur Herz- und Kreislauferkrankungen, Germany. Source: Klein, G Blood-Press. 1998 November; 7(5-6): 308-12 0803-7051

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Comparison of verapamil and felodipine treatment on lipid and glucose metabolism in obese female SHHF/Mcc-fa(cp) rats. Source: Park, S.C. Radin, M.J. Hoepf, T. McCune, S.A. Proc-Soc-Exp-Biol-Med. Malden, Ma. : Blackwell Science, Inc. July 1999. volume 221 (3) page 224-233. 0037-9727

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Determination of felodipine enantiomers using chiral stationary phase liquid chromatography and gas chromatography/mass spectrometry, and the study of their pharmacokinetic profiles in human and dog. Author(s): Pharma Research Laboratories, Hoechst Japan Ltd., Saitama. Source: Sakamoto, T Ohtake, Y Itoh, M Tabata, S Kuriki, T Uno, K Biomed-Chromatogr. 1993 Mar-April; 7(2): 99-103 0269-3879

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Effect of felodipine on blood pressure, body sodium, plasma renin activity and plasma aldosterone in hypertensive and normotensive rats. Author(s): Department of Pharmacology and Wellcome Medical Research Institute, University of Otago Medical School, Dunedin, New Zealand. Source: Ledingham, J M Hamada, M Simpson, F O Clin-Exp-Pharmacol-Physiol-Suppl. 1995; 1S323-5 0143-9294

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Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Author(s): Department of Clinical Research, Ferring AB, MalmoSweden. Source: Lundahl, J Regardh, C G Edgar, B Johnsson, G Eur-J-Clin-Pharmacol. 1997; 52(2): 139-45 0031-6970

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Glucoregulatory hormone response to insulin-induced hypoglycaemia following long-term calcium antagonism with felodipine in patients with essential hypertension. Author(s): Department of Endocrinology, University of Lund, Malmo General Hospital, Sweden. Source: Katzman, P L Hulthen, U L Hokfelt, B Acta-Endocrinol-(Copenh). 1987 December; 116(4): 473-8 0001-5598

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Grapefruit juice increases felodipine oral availability in humans by decreasing intestinal CYP3A protein expression. Author(s): Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA. Source: Lown, K S Bailey, D G Fontana, R J Janardan, S K Adair, C H Fortlage, L A Brown, M B Guo, W Watkins, P B J-Clin-Invest. 1997 May 15; 99(10): 2545-53 0021-9738

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Influence of dietary salts on the cardiovascular effects of low-dose combination of ramipril and felodipine in spontaneously hypertensive rats. Author(s): Institute of Biomedicine, Department of Pharmacology and Toxicology, University of Helsinki, Finland. Source: Mervaala, E M Malmberg, L Teravainen, T L Laakso, J Vapaatalo, H Karppanen, H Br-J-Pharmacol. 1998 January; 123(2): 195-204 0007-1188

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Influence of hydrodynamics and particle size on the absorption of felodipine in labradors. Author(s): Institut fur Pharmazeutische Technologie, Johann Wolfgang GoetheUniversitat, Frankfurt am Main, Germany. Source: Scholz, Annette Abrahamsson, Bertil Diebold, Steffen M Kostewicz, Edmund Polentarutti, Britta I Ungell, Anna Lena Dressman, Jennifer B Pharm-Res. 2002 January; 19(1): 42-6 0724-8741

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Interaction between cyclosporine and felodipine in renal transplant recipients. Author(s): Department of Medicine and Nephrology C, Skejby Hospital, Aarhus, Denmark. Source: Pedersen, E B Sorensen, S S Eiskjaer, H Skovbon, H Thomsen, K Kidney-IntSuppl. 1992 May; 36S82-6 0098-6577

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Low-dose felodipine treatment attenuates endothelial dysfunction in rabbits fed an atherogenic diet. Author(s): SBU Cardiovascular Agents, Hoechst AG, Frankfurt/Main, Germany. Source: Becker, R H Linz, W Wiemer, G Nordlander, M J-Cardiovasc-Pharmacol. 1991; 18 Suppl 10S36-41 0160-2446

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Once daily felodipine in preventing ergonovine-induced myocardial ischaemia in Prinzmetal's variant angina. Author(s): E. Malan University Cardiovascular Centre, S. Donato Hospital, S. Donato Milanese, Italy. Source: Chimienti, M Negroni, M S Pusineri, E Regazzi, M B Inglese, L Klersy, C De Ambroggi, L Eur-Heart-J. 1994 March; 15(3): 389-93 0195-668X

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Oral pharmacokinetics of felodipine in patients with congestive heart failure: variable prediction using intravenous data. Author(s): Department of Cardiology, Groningen University, The Netherlands. Source: Dunselman, P H Scaf, A H Wesseling, H J-Clin-Pharmacol. 1989 June; 29(6): 51823 0091-2700

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Pharmacokinetic and pharmacodynamic studies of felodipine in healthy subjects after various single, oral and intravenous doses. Source: Edgar, B Regardh, C G Lundborg, P Romare, S Nyberg, G Ronn, O BiopharmDrug-Dispos. 1987 May-June; 8(3): 235-48 0142-2782

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Pharmacokinetics and blood pressure effects of felodipine in elderly hypertensive patients. A comparison with young healthy subjects. Author(s): Department of Long Term Care, Vasa Hospital, Goteborg. Source: Landahl, S Edgar, B Gabrielsson, M Larsson, M Lernfelt, B Lundborg, P Regardh, C G Clin-Pharmacokinet. 1988 June; 14(6): 374-83 0312-5963

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Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats. Author(s): Pharmacology Department, Faculty of Pharmacy, King Saud University, Riyadh, 11495, Saudi Arabia. Source: Zuhair, H A Abd El Fattah, A A El Sayed, M I Pharmacol-Res. 2000 May; 41(5): 555-63 1043-6618

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Reduced felodipine bioavailability in patients taking anticonvulsants. Author(s): Department of Clinical Pharmacology, Royal Infirmary, Edinburgh. Source: Capewell, S Freestone, S Critchley, J A Pottage, A Prescott, L F Lancet. 1988 August 27; 2(8609): 480-2 0140-6736

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Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Author(s): Department Clinical Research, Malmo, Sweden. Source: Lundahl, J Regardh, C G Edgar, B Johnsson, G Eur-J-Clin-Pharmacol. 1995; 49(12): 61-7 0031-6970

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Renoprotective effects of felodipine and/or enalapril in spontaneously hypertensive rats with and without L-NAME. Author(s): Alton Ochsner Medical Foundation, New Orleans, La 70121, USA. Source: Francischetti, A Ono, H Frohlich, E D Hypertension. 1998 March; 31(3): 795-801 0194-911X

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Silver-induced frog skeletal muscle contraction and its modulation by calcium antagonists nifedipine and felodipine and calcium agonist Bay K 8644. Author(s): Department of Veterinary Anatomy and Cellular Biology, Ohio State University, Columbus 43210. Source: Lu, A Oba, T Yamano, S Sako, T Yamaguchi, M Gen-Pharmacol. 1992 July; 23(4): 747-52 0306-3623

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Smooth blood pressure control obtained with extended-release felodipine in elderly patients with hypertension: evaluation by 24-hour ambulatory blood pressure monitoring. Author(s): Centro di Ipertensione, Dipartimento de Cardiologia, INRCA, Via S. Margherita 5, 60121 Ancona, Italy. [email protected] Source: Antonicelli, R Omboni, S Giovanni, D C Ansuini, R Mori, A Gesuita, R Parati, G Paciaroni, E Drugs-Aging. 2002; 19(7): 541-51 1170-229X

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The acute renal haemodynamic and endocrine response to felodipine in normal man. Author(s): Department of Medicine, University of Edinburgh, Royal Infirmary, U.K. Source: Jenkins, D A Craig, K Cumming, A D Watson, M L Eur-J-Clin-Pharmacol. 1988; 33(6): 581-5 0031-6970

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The effects of felodipine and bepridil on calcium-stimulated calmodulin binding and calcium pumping ATPase of cardiac sarcolemma before and after removal of endogenous calmodulin. Author(s): Department of Biochemistry I, Erasmus University Rotterdam, The Netherlands. Source: Lamers, J M Verdouw, P D Mas Oliva, J Mol-Cell-Biochem. 1987 December; 78(2): 169-76 0300-8177

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to felodipine; 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 Source: Healthnotes, Inc.; www.healthnotes.com Calcium-Channel Blockers Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Healthnotes, Inc.; www.healthnotes.com Magnesium Source: Integrative Medicine Communications; www.drkoop.com Potassium Source: Healthnotes, Inc.; www.healthnotes.com Quercetin Source: Healthnotes, Inc.; www.healthnotes.com

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

A comparison of the effect of ramipril, felodipine and placebo on glomerular filtration rate, albuminuria, blood pressure and vasoactive hormones in chronic glomerulonephritis. A randomized, prospective, double-blind, placebo-controlled study over two years. Author(s): Pedersen EB, Bech JN, Nielsen CB, Kornerup HJ, Hansen HE, Spencer ES, Solling J, Jensen KT. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1997 December; 57(8): 673-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9458489

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Benazepril versus felodipine as supplement to bendroflumethiazide: evaluation by office and ambulatory blood pressure. Author(s): Kristensen KS, Wiinberg N, Hoegholm A, Kornerup HJ, Svendsen TL, Molby L, Pindborg T, Nielsen PE. Source: Blood Pressure Monitoring. 1998 April; 3(2): 115-120. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10212340

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Blood pressure-lowering effect of adding grapefruit juice to nifedipine and terazosin in a patient with severe renovascular hypertension. Author(s): Pisarik P. Source: Archives of Family Medicine. 1996 July-August; 5(7): 413-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8665000

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Clinical evaluation of felodipine in patients with refractory hypertension. Author(s): Herlitz H, Bjorck S, Nyberg G, Granerus G, Aurell M. Source: Drugs. 1987; 34 Suppl 3: 151-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3443059

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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11860526

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Dietary effects on drug metabolism and transport. Author(s): Harris RZ, Jang GR, Tsunoda S. Source: Clinical Pharmacokinetics. 2003; 42(13): 1071-88. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14531721

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Diltiazem stimulates parathyroid hormone secretion in vivo whereas felodipine does not. Author(s): Villiger L, Casez JP, Takkinen R, Jaeger P. Source: The Journal of Clinical Endocrinology and Metabolism. 1993 April; 76(4): 890-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8473401

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Does prophylactic treatment with felodipine, a calcium antagonist, prevent lowosmolar contrast-induced renal dysfunction in hydrated diabetic and nondiabetic patients with normal or moderately reduced renal function? Author(s): Spangberg-Viklund B, Berglund J, Nikonoff T, Nyberg P, Skau T, Larsson R. Source: Scandinavian Journal of Urology and Nephrology. 1996 February; 30(1): 63-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8727868

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Drug interactions with grapefruit juice. Extent, probable mechanism and clinical relevance. Author(s): Fuhr U. Source: Drug Safety : an International Journal of Medical Toxicology and Drug Experience. 1998 April; 18(4): 251-72. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9565737

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Effect of calcium-channel blockers on calcium-phosphate metabolism in patients with end-stage renal disease. Author(s): Lippuner K, Zehnder HJ, Casez JP, Takkinen R, Descoeudres C, Jaeger P. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 1996 January; 11(1): 70-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8649655

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Effects of Felodipine on the dog kidney: a lithium clearance study. Author(s): Abildgaard U, Daugaard G, Leyssac PP, Amtorp O. Source: Scandinavian Journal of Clinical and Laboratory Investigation. 1991 April; 51(2): 175-83. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1645885

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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/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11494095

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Evaluation of peppermint oil and ascorbyl palmitate as inhibitors of cytochrome P4503A4 activity in vitro and in vivo. Author(s): Dresser GK, Wacher V, Wong S, Wong HT, Bailey DG. Source: Clinical Pharmacology and Therapeutics. 2002 September; 72(3): 247-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12235445

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Felodipine in the treatment of patients with severe hypertension and impaired renal function. Author(s): Larsson R, Lindsjo MK, Danielsson B, Bengtsson U, Hardlund JH, Sjostrom PA, Elmfeldt D, Moberg L. Source: Cardiovascular Drugs and Therapy / Sponsored by the International Society of Cardiovascular Pharmacotherapy. 1990 February; 4(1): 253-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2285618

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Felodipine. A calcium-inhibiting vasodilator in refractory hypertension. Author(s): Andersson OK, Granerus G, Hedner T. Source: Drugs. 1985; 29 Suppl 2: 102-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3886356

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Functional and stereologic estimations of myocardial capillary exchange capacity in treated and untreated spontaneously hypertensive rats. Author(s): Wahlander H, Nordborg C, Nordlander M, Friberg P. Source: Acta Physiologica Scandinavica. 1992 October; 146(2): 165-75. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1442132

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Grapefruit juice activates P-glycoprotein-mediated drug transport. Author(s): Soldner A, Christians U, Susanto M, Wacher VJ, Silverman JA, Benet LZ. Source: Pharmaceutical Research. 1999 April; 16(4): 478-85. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10227700

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Grapefruit juice-drug interactions. Author(s): Bailey DG, Malcolm J, Arnold O, Spence JD. Source: British Journal of Clinical Pharmacology. 1998 August; 46(2): 101-10. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9723817

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Grapefruit juice-felodipine interaction: effect of naringin and 6',7'dihydroxybergamottin in humans. Author(s): Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Source: Clinical Pharmacology and Therapeutics. 1998 September; 64(3): 248-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9757148

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Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. Author(s): Bailey DG, Arnold JM, Bend JR, Tran LT, Spence JD. Source: British Journal of Clinical Pharmacology. 1995 August; 40(2): 135-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8562295

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Grapefruit-felodipine interaction: effect of unprocessed fruit and probable active ingredients. Author(s): Bailey DG, Dresser GK, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Source: Clinical Pharmacology and Therapeutics. 2000 November; 68(5): 468-77. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11103749

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In vitro inhibition of dihydropyridine oxidation and aflatoxin B1 activation in human liver microsomes by naringenin and other flavonoids. Author(s): Guengerich FP, Kim DH.

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Source: Carcinogenesis. 1990 December; 11(12): 2275-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2265479 •

In vivo reversal of multidrug resistance by two new dihydropyridine derivatives, S16317 and S16324. Author(s): Kraus-Berthier L, Guilbaud N, Peglion JL, Leonce S, Lombet A, Pierre A, Atassi G. Source: Acta Oncologica (Stockholm, Sweden). 1994; 33(6): 631-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7946440

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Influence of d-limonene on the transdermal penetration of felodipine. Author(s): Diez I, Peraire C, Obach R, Domenech J. Source: Eur J Drug Metab Pharmacokinet. 1998 January-March; 23(1): 7-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9625266

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Interaction of citrus juices with felodipine and nifedipine. Author(s): Bailey DG, Spence JD, Munoz C, Arnold JM. Source: Lancet. 1991 February 2; 337(8736): 268-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1671113

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Long-term effects of felodipine in patients with reduced renal function. Author(s): Herlitz H. Source: Kidney International. Supplement. 1992 May; 36: S110-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1614060

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Long-term effects of felodipine on blood pressure and renal hemodynamics in severe hypertension. Author(s): Herlitz H, Granerus G, Aurell M. Source: Journal of Cardiovascular Pharmacology. 1990; 15 Suppl 4: S100-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1693710

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Low Dose Combination Therapy vs. High Dose Monotherapy in the Management of Hypertension. Author(s): Neutel JM, Smith DH, Weber MA. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 1999 November; 1(3): 7986. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11416610

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Manganese can inhibit or potentiate contractile responses in mesenteric portal vein. Author(s): Sutter MC, May PB, Lim SL.

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Source: Canadian Journal of Physiology and Pharmacology. 1988 June; 66(6): 737-44. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3167689 •

Metabolism of taxol by human hepatic microsomes and liver slices: participation of cytochrome P450 3A4 and an unknown P450 enzyme. Author(s): Harris JW, Rahman A, Kim BR, Guengerich FP, Collins JM. Source: Cancer Research. 1994 August 1; 54(15): 4026-35. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7913410

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Pumpkin-seed oil modulates the effect of felodipine and captopril in spontaneously hypertensive rats. Author(s): Zuhair HA, Abd El-Fattah AA, El-Sayed MI. Source: Pharmacological Research : the Official Journal of the Italian Pharmacological Society. 2000 May; 41(5): 555-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10753555

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Raynaud's phenomenon. Author(s): Coffman JD. Source: Current Treatment Options in Cardiovascular Medicine. 2000 June; 2(3): 219-226. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11096527

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Renal effects of felodipine in hypertensive patients with reduced renal function. Author(s): Herlitz H, Aurell M, Bjorck S, Granerus G. Source: Drugs. 1985; 29 Suppl 2: 192-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=3987548

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Renal function during cardiopulmonary bypass: influence of the calcium entry blocker felodipine. Author(s): Andersson LG, Jeppsson A, Bratteby LE, Ekroth R, Joachimsson PO, van der Linden J, Wesslen O. Source: Anesthesia and Analgesia. 1996 July; 83(1): 34-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8659761

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Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Author(s): Rahman A, Korzekwa KR, Grogan J, Gonzalez FJ, Harris JW. Source: Cancer Research. 1994 November 1; 54(21): 5543-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7923194

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Stereoisomers of calcium antagonists which differ markedly in their potencies as calcium blockers are equally effective in modulating drug transport by Pglycoprotein. Author(s): Hollt V, Kouba M, Dietel M, Vogt G.

Alternative Medicine 63

Source: Biochemical Pharmacology. 1992 June 23; 43(12): 2601-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1352973 •

Systemic and renal hemodynamic effects of single oral doses of felodipine in patients with refractory hypertension receiving chronic therapy with beta-blockers and diuretics. Author(s): Andersson OK, Granerus G, Hedner T, Wysocki M. Source: Journal of Cardiovascular Pharmacology. 1985 May-June; 7(3): 544-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2410688

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The effect of felodipine on bile flow in pentobarbital anaesthetized rats and conscious rats receiving bile salt supplementation. Author(s): Wang SX, Sutfin TA, Regardh CG. Source: Eur J Drug Metab Pharmacokinet. 1992 October-December; 17(4): 263-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=1301355

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The interaction effect of grapefruit juice is maximal after the first glass. Author(s): Lundahl JU, Regardh CG, Edgar B, Johnsson G. Source: European Journal of Clinical Pharmacology. 1998 March; 54(1): 75-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9591935

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The use of a vasodilator, felodipine, as an adjuvant to long-term oxygen treatment in COLD patients. Author(s): Bratel T, Hedenstierna G, Nyquist O, Ripe E. Source: The European Respiratory Journal : Official Journal of the European Society for Clinical Respiratory Physiology. 1990 January; 3(1): 46-54. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=2311731

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

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

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

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

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

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

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

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

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

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

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

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

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

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

The following is a specific Web list relating to felodipine; 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 Felodipine Source: Healthnotes, Inc.; www.healthnotes.com

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

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CHAPTER 4. PATENTS ON FELODIPINE Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.5 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “felodipine” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on felodipine, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Felodipine By performing a patent search focusing on felodipine, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 5Adapted

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

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

Manufacturing process for felodipine Inventor(s): Gustavsson; Anders (Nykvarn, SE), Kallstrom;.ANG.ke (Sodertalje, SE), Palmer; Sven (Sodertalje, SE) Assignee(s): Astra Aktiebolag (Sodertalje, SE) Patent Number: 5,942,624 Date filed: February 13, 1997 Abstract: A method for the manufacture of felodipine by reaction dichlorobenzylidene and ethyl 3-aminocrotonate using an alcohol as solvent.

of

Excerpt(s): The present invention relates to an improved method for the manufacture of felodipine (ethyl methyl 4-(2,3-dichlorophenyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylate ) via the route of reacting 2,3-dichlorobenzylideneacetylacetic acidmethylester (in the following dichlorobenzylidene for short) with ethyl 3aminocrotonate. U.S. Pat. No. 5,310,917 discloses a method for the preparation of felodipine using dichlorobenzylidene and ethyl 3-aminocrotonate as starting materials. The solvent used is ethanol. Dichlorobenzylidene is reacted with ethyl 3-aminocrotonate in the presence of pyridine in refluxing alcohol, such as methanol, ethanol or propanol, preferably ethanol. Preferably, the alcohol is then evaporated at reduced pressure and ethyl acetate or methylene chloride is added. The solution can be purified by acidic and neutral aqueous extractions. The solvent can be removed by evaporation. The product can be dissolved in acetone or diisopropyl ether, crystallized by cooling, isolated by filtration and finally washed with acetone, or diisopropyl ether. Web site: http://www.delphion.com/details?pn=US05942624__ •

Method of treating liver disease and like indications with vasodilating agents Inventor(s): McLean; Allan Joseph (South Melbourne, AU) Assignee(s): Pharmacy and Therapeutic Advisory Consultancy Ltd. (London, GB2) Patent Number: 5,854,233 Date filed: June 20, 1996 Abstract: Liver diseases, such as cirrhosis of the liver, toxic and medicamentary liver damage, a liver-parenchymic disorder or hepatitis, are treated by administering to a human or animal subject in need thereof a therapeutically active or prophylactically effective low dose amount of a vasodilating agent which selectively increases the supply of oxygenated blood to the liver by increasing hepatic arterial inflow. Suitable vasodilating agents include calcium blockers, such as a benzothiazepine derivative, nifedipine, felodipine or verapamil. Excerpt(s): The present invention relates to a method for the treatment of liver disease. The invention also relates to compositions suitable for the use in the treatment of liver disease. Diltiazem is the generic name given to the active component of a composition that is primarily used for the treatment of heart disease. Specifically it is known as 3acetoxy-5-(2(dimethylaminoethyl)-2,3-dihydro-2-(4-methoxy phenyl)-1,5benzothiazepine-4)5H-one. This compound is the active ingredient in the heart

Patents 67

treatment drug Cardizem. Cardizem has particular efficacy in the treatment of ischaemic heart disease including angina pectoris and hypertension. Diltiazem is a member of a broad class of benzothiazepine derivatives that are the subject of Australian Patent 426146. The class of compounds are referred to in that specification as having particular utility as anti-depressants, tranquilizers and coronary vasodilators. Web site: http://www.delphion.com/details?pn=US05854233__ •

Methods for treating hypertension using optically pure S(-) felodipine Inventor(s): Young; James W. (Palo Alto, CA) Assignee(s): Sepracor, Inc. (Marlborough, MA) Patent Number: 5,834,496 Date filed: November 21, 1994 Abstract: Methods and compositions are disclosed utilizing the optically pure S(-) isomer of felodipine. 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 felodipine. The S(-) isomer of felodipine is also useful for the treatment of angina and such other conditions as may be related to the activity of S(-) felodipine 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 administration of the racemic mixture of felodipine. Excerpt(s): This invention relates to novel compositions of matter containing optically pure S(-) felodipine. 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 felodipine. Additionally, these novel compositions of matter containing optically pure S(-) felodipine are useful in treating angina and such other conditions as may be related to the activity of S(-) felodipine 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 felodipine. 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 felodipine, by administering the S(-) isomer of felodipine 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 l 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.

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Web site: http://www.delphion.com/details?pn=US05834496__ •

Pharmaceutical composition dihydropyridine compound

containing

the

ace

inhibitor

ramipril

and

a

Inventor(s): Bauer; Brigitte (Darmstadt, DE), Karlsson; Christer (Lindome, SE), Lundberg; Per Johan (Molndal, SE), Nilsson; Berit (Goteborg, SE), Sandberg; Anders (Molndal, SE), Sickmuller; Alfred (Frankfurt/M, DE) Assignee(s): Astra Aktiebolag (Sodertalje, SE) Patent Number: 6,086,919 Date filed: September 12, 1995 Abstract: The invention is directed to a pharmaceutical composition which is a combination of the ACE inhibitor ramipril and a calcium antagonist of one of the dihydropyridine type compounds felodipine, nitrendipine, nifedipine and lacidipine. The pharmaceutical composition is for use in the therapy and treatment of hypertension. Excerpt(s): This Application is a 371 of PCT/SE95/00792 filed Aug. 30, 1995. The present invention being a new pharmaceutical composition is related to a novel pharmaceutical preparation for oral administration and the use of this pharmaceutical preparation in the therapy of hypertension and of diseases in the cardiovascular system and secondary effects thereof in mammals including man. It is also related to compositions and to methods of preparing said pharmaceutical preparations. The pharmaceutical preparation is a fixed unit dosage form of the long-acting angiotensin converting enzyme (ACE) inhibitor, ramipril, in instant release form and a calcium antagonist of the dihydropyridine type i.e. a calcium channel blocking agent (dihydropyridine compound) in an extended release formulation. The present invention also relates to solid preparations which are fixed combinations of the long acting ACE inhibitor ramipril in instant release form and a dihydropyridine compound such as the vascular selective drug felodipine in extended release form having the characteristic of achieving an effect over 24 hours after once daily administration. The pharmaceutical preparations of the present invention retain a good therapeutic effect in the treatment of hypertension even when the active drugs are administered in low doses. The pharmaceutical preparations reduce the dose related adverse events which result from administering higher doses of each of the drugs separately. The pharmaceutical preparations of this invention simplify the regimen and improve patient compliance. Web site: http://www.delphion.com/details?pn=US06086919__ •

Pharmaceutical preparation and a process for its preparation Inventor(s): Ragnarsson; Gert A. (Bro, SE), Silfverstrand; Kajsa M. (Gothenburg, SE), Sjogren; John A. (Molnlycke, SE) Assignee(s): Aktiebolaget Hassle (Molndal, SE) Patent Number: 4,942,040 Date filed: September 29, 1988 Abstract: Preparation giving a controlled and extended release of both a dihydropyridine, e.g. felodipine and a.beta.-adrenoreceptor antagonist, namely metoprolol as well as a method for the manufacture of the new preparation.

Patents 69

Excerpt(s): The present invention is related to pharmaceutical extended-release preparations of two drugs of which one is a poorly water soluble compound, namely a calcium channel blocking agent of the dihydropyridine type, and the other is a salt of the.beta.-adrenoreceptor antagonist metoprolol, and to methods of preparing such preparations. The object of this invention is to obtain a solid preparation with a high extent of bioavailability of the two drugs in combination with an extended absorption from the gastrointestinal tract thus acheiving an even effect over 24 hours after once daily administration. The pharmacological agents calcium antagonists of the dihydropyridine type and.beta.-adrenoreceptor antagonists are widely used in the treatment of cardiovascular disorders. Web site: http://www.delphion.com/details?pn=US04942040__ •

Process for the preparation of 4-substituted-1,4-dihydropydrines Inventor(s): Auerbach; Joseph (Brooklyn, NY) Assignee(s): Merck & Co., Inc. (Rahway, NJ) Patent Number: 5,310,917 Date filed: July 28, 1992 Abstract: 4-Substituted-1,4-dihydropyridines are prepared by a cycloaddition reaction in which the cyclization is driven to completion, after thermal reaction, by addition of an acid. Felodipine, a vasodilator, is prepared by a cycloaddition reaction of ethyl 3aminocrotonate with a suitably substituted dichlorobenzylidine under reaction conditions whereby the product crystallizes out of the reaction solution and may be directly isolated by filtration. Excerpt(s): Other analogous processes for the preparation of felodipine are known in the art (see for example: Span. Appl. Nos. ES-536,229; 537,424; and 549,753). In most of the disclosed syntheses of aryldihydropyridine diesters isolation of the product from the reaction mixture required an extractive workup that typically employed a halogenated solvent. Also because a low-molecular-weight alcohol is typically employed as a solvent in the cycloaddition reaction, such an extractive workup of the crude reaction requires that the solvent first be distilled away. It is an object of the instant invention to provide a process, for the preparation of 4-substituted-1,4-dihydropyridines having shorter thermal reaction times, and, as a consequence, having lower weight percentages of undesirable impurities, than processes previously known in the art. Web site: http://www.delphion.com/details?pn=US05310917__

•

Process to prepare dihydropyridine and derivatives thereof Inventor(s): Aguilar; Daniel Alfonso (Corpus Christi, TX), Aslam; Mohammad (Corpus Christi, TX), Desai; Ranjit (Kendall Park, NJ), Gallegos; Nicholas (Corpus Christi, TX) Assignee(s): Napp Technologies, Inc. (Saddle Brook, NJ) Patent Number: 5,977,369 Date filed: December 28, 1995 Abstract: A novel process is disclosed for the preparation of dihydropyridine compounds and derivatives thereof, and more particularly felodipine. The process to prepare felodipine involves a two step procedure condensing 2,3-dichlorobenzaldehyde

70

Felodipine

with methyl acetoacetate in the presence of a catalyst system. The resultant benzylidine intermediate is sequentially reacted with ethyl aminocrotonate to provide felodipine. The novelty of the present invention resides in part on (1) a new catalyst system not previously disclosed for the preparation of felodipine, (2) the absence of acid(s), (3) the control of reaction conditions to yield lower amounts of unreacted aldehyde compared to known reactions, (4) a simplified purification process, and (5) formation of negligible quantities of symmetrical diester byproducts. Excerpt(s): The invention relates generally to the preparation of dihydropyridines and derivatives thereof, and more particularly to the preparation of felodipine. The preparation of felodipine and related compounds typically involves a multistep synthesis, the last step of which usually involves formation of the dihydropyridine ring. U.S. Pat. No. 5,310,917 describes a synthesis involving heating a mixture of a benzylidine with an amino crotonate ester in the presence of a strong acid to yield the desired dihydropyridine product U.S. Pat. No. 4,600,778 describes a process for the preparation of dihydropyridine compounds by reacting a ketocarboxylic ester with an aldehyde, and a catalytic amount of piperidine acetate in an aliphatic alcohol as solvent. Both patents are herein incorporated by reference in their entirety. Disadvantages with most of the disclosed syntheses for the preparation of dihydropyridine derivatives, and in particular felodipine, include (1) an extractive workup to isolate the desired product; (2) the formation of symmetrical ester byproducts which are difficult to isolate from the desired final compound; (3) use of acids in the reaction which require a neutralization step(s) to remove. The extractive workup and removal of byproducts are labor intensive procedures. From a commercial viewpoint, the use of acids is often costly and environmentally unfriendly. It is preferred to avoid their use and any potential dangers associated with the use of acids. Web site: http://www.delphion.com/details?pn=US05977369__ •

Therapy for herpes neurological viral conditions utilizing 1,4-dihydropyridine calcium channel blockers Inventor(s): Zik; Howard M. (3169 Gomer St., Yorktown Heights, NY 10598) Assignee(s): none reported Patent Number: 6,191,151 Date filed: November 11, 1998 Abstract: A therapy for Bells Palsy in mammals is proposed that rests on a causal hypothesis involving both endothelin and the herpes virus, particularly the herpes simplex virus for Bell's Palsy. Similarly, the same therapy would apply to Ramsay Hunt, but in this case the herpes zoster virus would be involved in the causal hypothesis. Other herpes viral related conditions are also suggested to be amenable such as herpes simplex encephalitis. The therapy uses therapeutically effective doses of calcium channel blockers that are of the 1,4-dihydropyridine derivative class, such as felodipine but also including nifedidine, nimodipine, nisodipine or alenodipine. The treatment is proposed as continuing up to the tenth day of progression, but to be started as early as possible. Acyclovir or other herpes antagonists such as famciclovir may also be administered in therapeutically effective dosages. Excerpt(s): The present invention relates to the treatment of certain herpes viral neurological conditions in mammals, principally Bell's Palsy, a palsy of the facial nerves, and to the use of calcium channel blockers coupled preferably with a herpes virus

Patents 71

antagonist in a treatment therapy. Other herpes conditions include Ramsay Hunt and other herpes caused neurological conditions such as Herpes Simplex Encephalitis. Bell's Palsy (originally described by Charles Bell, 1812) is recognized as a palsy of the facial nerve, generally the seventh cranial nerve. It most commonly affects one side of the face, may be partial or total, and has a progression time of 7 to 10 days. Regarded in the past as idiopathic, there has recently been convincing evidence that it has its cause in the herpes type virus of the simplex type. Some physicians reassure patients that the disease will most likely remit in a period lasting from 3 weeks up to 6 months, (leading some physicians to advocate a no action policy other than facial management, sometimes referred to as "therapeutic nihilism") but the fact remains that about 24% of the victims with current popular therapies are left with some residual paralysis or other aftereffects such as hemi-facial spasm, synkinesis, or loss of tearing or blinking capacity. An understanding as to the likely physiological events (without an identification of their cause) was comprehensively put forward by Hilger (Hilger J, The Nature of Bell's Palsy. Laryngoscope, 54:228-235, 1949) and Blunt (Blunt M, Possible Role of Vascular Changes in the Etiology of Bell's Palsy, J. Laryngol Otol, 70:701-713, 1956)) where they maintained that vasoconstriction of the arterioles within the fallopian aqueduct of the temporal bone was responsible for the facial palsy. This vasoconstriction was believed to lead to primary ischemia (tissue anemia) entailing edema of the nerve sheath and a secondary ischemia due to nerve compression. K. Adour opposed this account and instead put forward a viral theory (Adour K K, Cranial Polyneuritus and Bell's Palsy, Arch Otolarygol, 102:262-4, 1976) based on herpes simplex reactivation and maintained that Bell's Palsy was polycranial which was believed to be inconsistent with an ischemia scenario. However, support of the former ischemia outlook was provided through anatomical electromyographical and histopathological studies summarized by U. Fisch (Fisch U. and Felix, H, On the Parthenogenesis of Bell's Palsy. Acta Otolaryngol, 95:532538, 1983)). Further the ischemia description of events fits well with later causal analysis by M. Ikeda (Ikeda M et al, Plasma Endothelin Level in the Acute Stage of Bell Palsy, Arch Otolyaryngol Head Neck Surg, 122:849-852, August 1996) involving endothelin findings; and work on the immunological role of endothelin has been inferentially linked by the inventor to an ischemia scenario (which requires--a herpes viral role) as will be later explained. Web site: http://www.delphion.com/details?pn=US06191151__ •

Use of felodipine to treat cerebral dysfunction due to solvent exposure Inventor(s): Elmfeldt; Dag (Hov.ang.s, SE), Fagher; Birger (Lund, SE), Jonsson; Lars (Molndal, SE), Lindgren; May (Oskarshamn, SE), Partridge; Stephen (Molndal, SE) Assignee(s): Astra Aktiebolag (Sodertalje, SE) Patent Number: 5,834,497 Date filed: May 30, 1996 Abstract: This invention relates to the use of felodipine or a pharmaceutically acceptable salt thereof for the treatment of cerebral dysfunction due to solvent exposure. Excerpt(s): This application is a 371 PCT/SE96/00601, filed May 8, 1996. The present invention is related to the use of 2,6-dimethyl-4-(2,3-dichlorophenyl-1,4dihydropyridine-3,5-dicarboxylic acid-3-methyl-5-ethyl ester, generic name felodipine, in the form of the racemate or an optical isomer as well as pharmaceutically acceptable salts thereof, for the treatment of cerebral dysfunction due to solvent exposure and in the manufacture of pharmaceutical preparations with effect on cerebral dysfunction due

72

Felodipine

to solvent exposure. Felodipine, which is described in the European patent EP 7293, is a dihydropyridine calcium antagonist which has been shown in hypertensive patients to lower blood pressure through a direct effect on the resistance vessels (small arteries). However, no effect on cerebral dysfunction due to solvent exposure has been reported earlier. Web site: http://www.delphion.com/details?pn=US05834497__

Patent Applications on Felodipine As of December 2000, U.S. patent applications are open to public viewing.6 Applications are patent requests which have yet to be granted. (The process to achieve a patent can take several years.) The following patent applications have been filed since December 2000 relating to felodipine: •

Extended release tablets comprising felodipine Inventor(s): Sherman, Bernard Charles; (Toronto, CA) Correspondence: Nixon & Vanderhye P.C.; 8th Floor; 1100 North Glebe Road; Arlington; VA; 22201-4714; US Patent Application Number: 20030211149 Date filed: May 7, 2002 Abstract: An extended-release tablet comprising felodipine, a non-ionic surfactant, and a release-controlling excipient, wherein the amount of surfactant is more than 0.01 part but less than 1.0 part per part felodipine by weight. Excerpt(s): Felodipine is a substituted dihydropyridine that is effective as a calcium channel blocker, useful for the treatment of hypertension. Extended-release tablets comprising felodipine are sold in the United States and elsewhere under the tradename Plendil.TM. in strengths of 2.5 mg, 5 mg, and 10 mg. Felodipine has very low solubility in water, which makes it difficult to formulate tablets comprising felodipine that will enable maximum absorption upon oral administration. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html

•

Felodipine transdermal device and methods Inventor(s): Alfonso, Mark; (Easton, CT), Marcenyac, Geraldine; (Norwalk, CT), Shevchuk, Ihor; (Yonkers, NY), Tavares, Lino; (Kinnelon, NJ), Valia, Kirti H.; (Plainsboro, NJ) Correspondence: Davidson, Davidson & Kappel, Llc; 485 Seventh Avenue, 14th Floor; New York; NY; 10018; US Patent Application Number: 20030072791 Date filed: October 23, 2001 Abstract: A method of effectively treating hypertension in humans is achieved by administering felodipine via a transdermal formulation. Preferably, the transdermal

6

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

Patents 73

formulation is applied to the skin of the patient and maintained in contact with the skin for at least about 24 hours days, and preferably for about 3 to about 8 days. Excerpt(s): This application claims the benefit of U.S. Provisional Application No. 60/242,514, Filed Oct. 23, 2000, which is hereby incorporated by reference. It is the intent of all sustained-release pharmaceutical preparations to provide a longer period of pharmacologic effect after the administration of a drug than is ordinarily experienced after the administration of immediate release preparations of the same drug. Such longer periods of efficacy can provide many inherent therapeutic benefits that are not achieved with corresponding immediate release preparations. The benefits of prolonged treatment of hypertension (high blood pressure) afforded by sustained release oral preparations have become universally recognized and oral sustained-release preparations are commercially available. Another approach to sustained delivery of a therapeutically active agent is transdermal delivery systems, such as transdermal patches. Generally, transdermal patches contain a therapeutically active agent, a reservoir or matrix containing the active ingredient(s) and an adhesive which allows the transdermal device to adhere to the skin, allowing for the passage of the active agent from the device through the skin of the patient. Once the active agent has penetrated the skin layer, the drug is absorbed into the blood stream where it can exert a desired pharmacotherapeutic effect. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Preparation of micron-size felodipine particles by microfluidization Inventor(s): Hussain, Javed; (Maharashtra, IN), Khorakiwala, Habil F.; (Mumbai, IN), Sharma, Vinay K.; (Long Valley, NJ), Srivastav, Arun K.; (Maharashtra, IN) Correspondence: Schwegman, Lundberg, Woessner & Kluth, P.A.; P.O. Box 2938; Minneapolis; MN; 55402; US Patent Application Number: 20020086061 Date filed: January 18, 2001 Abstract: The present invention provides the components for a stable felodipine composition and a process for preparing the composition. The composition includes felodipine, non-covalently bound to.beta.-cylodextrin, and an optional binder as a moisture carrier component for the migration of hydroxide ions to the non-covalently bound felodipine and.beta.-cylodextrin. The felodipine composition is combined with a carrier comprising cyclodextrin particles, a water-insoluble alkaline component and a swellable polymer. Excerpt(s): This application is a continuation-in-part of U.S. patent application Ser. No. 09/697,670, filed Oct. 26, 2000, which claims priority from U.S. provisional patent application Serial No. 60/______,______, which was filed on Oct. 26, 1999 as U.S. patent application Ser. No. 09/427,231, for which a petition under 37 C.F.R.sctn.1.53(c) to convert the non-provisional application to a provisional application was filed on Aug. 29, 2000, and U.S. provisional patent application Ser. No. 60/______,______, which was filed on filed Jan. 18, 2000 as U.S. patent application Ser. No. 09/484,573, for which a petition under 37 C.F.R.sctn.1.53(c) to convert the non-provisional application to a provisional application was filed on Aug. 29, 2000, all of which are incorporated herein by reference. A commercially available oral dosage form of felodipine, ethyl methyl (RS)-4-(2,3-dichloropentyl)-1,4-dihydro-2,6-dimethypyridine-3,5-dicarboxylate, is Plendil.RTM. ER Tablets. This product is believed to be prepared according to the

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disclosure in U.S. Pat. No. 4,803,081. The drug is dissolved or dispersed in an effective amount of a semi-solid or liquid nonionic solubilizer (active compound and the solubilizer are in a preferred ratio range from 1:2 to 1:6). A preferred solubilizer is polyethoxylated castor oil (e.g., Cremophor.RTM. RH 40 by BASF). Unfortunately, Cremophor.RTM. was implicated in embryo toxicity and allergic reactions. Sharma, A. et. al., Int. J. Cancer 71, 103-107, (1997). It was hypothesized that felodipine undergoes acid-catalyzed, solvolytic oxidation in a solid state due to the degradation of dicalcium phosphate dihydrate to form dehydrogenated felodipine (Impurity A). Other impurities (Impurity B and Impurity C) were not significantly increased during the testing of the current formulation placed at accelerated conditions. Impurity B is the dimethyl ester of felodipine, dimethyl 4-(2,3-dichloropentyl)-1,4-dihydro-2,6-dimethypyridine-3,5dicarboxylate, and Impurity C is the diethyl ester of felodipine, diethyl 4-(2,3dichloropentyl)-1,4-dihydro-2,6-dimethypyridine-3,5-dicarboxylate. Web site: http://appft1.uspto.gov/netahtml/PTO/search-bool.html •

Process for preparing oral sustained-release formulation of felodipine Inventor(s): Changchien, Ya-Ching; (San-Min Dist., TW), Yang, Yea-Sheng; (Hsin-Ying City, TW) Correspondence: Dellett And Walters; 310 S.W. Fourth Avenue; Suite 1101; Portland; OR; 97204; US Patent Application Number: 20030190356 Date filed: April 8, 2002 Abstract: The present invention relates to a process for producing an oral sustainedrelease pharmaceutical composition of felodipine. The process includes mixing together felodipine with at least an ionic surfactant or hydrophilic polymer, and at least a release-controlling excipient. The pharmaceutical composition of felodipine produced by the process of the present invention possesses the enhanced dissolution rate of the insoluble drug of felodipine, whereas the sustained releasing profile and superior bioavailability of the produced pharmaceutical composition of felodipine are retained. Excerpt(s): The present invention relates to a process for preparing an oral formulation of felodipine, and more particularly to a process that manufactures the felodipine formation with sustained releasing efficiency. Felodipine is a calcium blocker that efficiently promotes oxygen and blood supplement to the coronary artery and dilates the periphery of blood vessels. Therefore, felodipine is widely used in clinic for treating patients of coronary stenosis and hypertension. However, conventional felodipine formulations cannot be released over a period of more than a couple of hours so that patients have to take felodipine-containing medicaments frequently. If the patients forget to take felodipine or cannot do so during sleep, no sustained protective effects of felodipine are provided. Consequently, the patients confront a high risk of suffering from a heart attack. There is an existed pharmaceutical preparation of sustained-release medicine, as described in U.S. Pat. No. 4,803,081. U.S. Pat. No. 4,803,081 disclosed an extended release preparation of an active compound, including felodipine, with very low solubility. The conventional preparation contains the active compound dissolved or dispersed in a semi-solid or liquid non-ionic solubilizer as well as a process for the preparation thereof. The process of U.S. Pat. No. 4,803,081 demands the use of the amount by weight of the solubilizer at least equal to the amount by weight of the active compound. It is noted that the solubilizer used according to U.S. Pat. No. 4,803,081 is a non-ionic surfactant, which causes an insufficient dissolubility to the inert-dissolving

Patents 75

felodipine. Therefore, felodipine would not be well mixed with other ingredients contained inside the medicine, unless felodipine has to be dissolved in non-ionic surfactant (preferably polyoxyl 40 stearate) first and then mixed with a carrier material, such as HPMC, xanthan gum, guar gum and calcium phosphate. Inevitably, two steps for admixing are required according to U.S. Pat. No. 4,803,081. 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 felodipine, 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 “felodipine” (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 felodipine. You can also use this procedure to view pending patent applications concerning felodipine. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

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

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

Candesartan plus felodipine effective in elderly with systolic hypertension Source: Reuters Industry Breifing Date: June 27, 2002

•

AstraZeneca files suit against Mutual for infringing on Plendil patent Source: Reuters Industry Breifing Date: September 21, 2000

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•

Grapefruit juice interacts with felodipine in elderly Source: Reuters Industry Breifing Date: August 03, 2000

•

Grapefruit juice enhances felodipine serum concentrations in elderly Source: Reuters Medical News Date: October 05, 1998 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 “felodipine” (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 “felodipine” (or synonyms). If you know the name of a company that is relevant to felodipine, 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/.

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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 “felodipine” (or synonyms).

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

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

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

Systemic - U.S. Brands: Adalat; Adalat CC; Calan; Calan SR; Cardene; Cardizem; Cardizem CD; Cardizem SR; Dilacor-XR; DynaCirc; Isoptin; Isoptin SR; Nimotop; Norvasc; Plendil; Procardia; Procardia XL; Vascor; Verelan http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/202107.html

Enalapril and Felodipine •

Systemic - U.S. Brands: Lexxel http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203638.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

85

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute7: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

7

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

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•

National Institute on Alcohol Abuse and Alcoholism (NIAAA); guidelines available at http://www.niaaa.nih.gov/publications/publications.htm

•

National Institute of Allergy and Infectious Diseases (NIAID); guidelines available at http://www.niaid.nih.gov/publications/

•

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS); fact sheets and guidelines available at http://www.niams.nih.gov/hi/index.htm

•

National Institute of Child Health and Human Development (NICHD); guidelines available at http://www.nichd.nih.gov/publications/pubskey.cfm

•

National Institute on Deafness and Other Communication Disorders (NIDCD); fact sheets and guidelines at http://www.nidcd.nih.gov/health/

•

National Institute of Dental and Craniofacial Research (NIDCR); guidelines available at http://www.nidr.nih.gov/health/

•

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); guidelines available at http://www.niddk.nih.gov/health/health.htm

•

National Institute on Drug Abuse (NIDA); guidelines available at http://www.nida.nih.gov/DrugAbuse.html

•

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

•

National Institute of Mental Health (NIMH); guidelines available at http://www.nimh.nih.gov/practitioners/index.cfm

•

National Institute of Neurological Disorders and Stroke (NINDS); neurological disorder information pages available at http://www.ninds.nih.gov/health_and_medical/disorder_index.htm

•

National Institute of Nursing Research (NINR); publications on selected illnesses at http://www.nih.gov/ninr/news-info/publications.html

•

National Institute of Biomedical Imaging and Bioengineering; general information at http://grants.nih.gov/grants/becon/becon_info.htm

•

Center for Information Technology (CIT); referrals to other agencies based on keyword searches available at http://kb.nih.gov/www_query_main.asp

•

National Center for Complementary and Alternative Medicine (NCCAM); health information available at http://nccam.nih.gov/health/

•

National Center for Research Resources (NCRR); various information directories available at http://www.ncrr.nih.gov/publications.asp

•

Office of Rare Diseases; various fact sheets available at http://rarediseases.info.nih.gov/html/resources/rep_pubs.html

•

Centers for Disease Control and Prevention; various fact sheets on infectious diseases available at http://www.cdc.gov/publications.htm

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NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.8 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:9 •

Bioethics: Access to published literature on the ethical, legal, and public policy issues surrounding healthcare and biomedical research. This information is provided in conjunction with the Kennedy Institute of Ethics located at Georgetown University, Washington, D.C.: http://www.nlm.nih.gov/databases/databases_bioethics.html

•

HIV/AIDS Resources: Describes various links and databases dedicated to HIV/AIDS research: http://www.nlm.nih.gov/pubs/factsheets/aidsinfs.html

•

NLM Online Exhibitions: Describes “Exhibitions in the History of Medicine”: http://www.nlm.nih.gov/exhibition/exhibition.html. Additional resources for historical scholarship in medicine: http://www.nlm.nih.gov/hmd/hmd.html

•

Biotechnology Information: Access to public databases. The National Center for Biotechnology Information conducts research in computational biology, develops software tools for analyzing genome data, and disseminates biomedical information for the better understanding of molecular processes affecting human health and disease: http://www.ncbi.nlm.nih.gov/

•

Population Information: The National Library of Medicine provides access to worldwide coverage of population, family planning, and related health issues, including family planning technology and programs, fertility, and population law and policy: http://www.nlm.nih.gov/databases/databases_population.html

•

Cancer Information: Access to cancer-oriented databases: http://www.nlm.nih.gov/databases/databases_cancer.html

•

Profiles in Science: Offering the archival collections of prominent twentieth-century biomedical scientists to the public through modern digital technology: http://www.profiles.nlm.nih.gov/

•

Chemical Information: Provides links to various chemical databases and references: http://sis.nlm.nih.gov/Chem/ChemMain.html

•

Clinical Alerts: Reports the release of findings from the NIH-funded clinical trials where such release could significantly affect morbidity and mortality: http://www.nlm.nih.gov/databases/alerts/clinical_alerts.html

•

Space Life Sciences: Provides links and information to space-based research (including NASA): http://www.nlm.nih.gov/databases/databases_space.html

•

MEDLINE: Bibliographic database covering the fields of medicine, nursing, dentistry, veterinary medicine, the healthcare system, and the pre-clinical sciences: http://www.nlm.nih.gov/databases/databases_medline.html

8

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 9 See http://www.nlm.nih.gov/databases/databases.html.

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•

Toxicology and Environmental Health Information (TOXNET): Databases covering toxicology and environmental health: http://sis.nlm.nih.gov/Tox/ToxMain.html

•

Visible Human Interface: Anatomically detailed, three-dimensional representations of normal male and female human bodies: http://www.nlm.nih.gov/research/visible/visible_human.html

The NLM Gateway10 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.11 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “felodipine” (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 1347 2 870 0 7 2226

HSTAT12 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.13 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.14 Simply search by “felodipine” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

10

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

11

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 12 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 13 14

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

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

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Coffee Break: Tutorials for Biologists15 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.16 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.17 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

Other Commercial Databases In addition to resources maintained by official agencies, other databases exist that are commercial ventures addressing medical professionals. Here are some examples that may interest you: •

CliniWeb International: Index and table of contents to selected clinical information on the Internet; see http://www.ohsu.edu/cliniweb/.

•

Medical World Search: Searches full text from thousands of selected medical sites on the Internet; see http://www.mwsearch.com/.

15 Adapted 16

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 17 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

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APPENDIX B. PATIENT RESOURCES Overview Official agencies, as well as federally funded institutions supported by national grants, frequently publish a variety of guidelines written with the patient in mind. These are typically called “Fact Sheets” or “Guidelines.” They can take the form of a brochure, information kit, pamphlet, or flyer. Often they are only a few pages in length. Since new guidelines on felodipine 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 felodipine. 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 felodipine. 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 “felodipine”:

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Alzheimer's Disease http://www.nlm.nih.gov/medlineplus/alzheimersdisease.html Arrhythmia http://www.nlm.nih.gov/medlineplus/arrhythmia.html Heart Diseases http://www.nlm.nih.gov/medlineplus/heartdiseases.html Myasthenia Gravis http://www.nlm.nih.gov/medlineplus/myastheniagravis.html Scleroderma http://www.nlm.nih.gov/medlineplus/scleroderma.html Stroke http://www.nlm.nih.gov/medlineplus/stroke.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 felodipine. 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/

Patient Resources

•

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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 felodipine. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with felodipine. 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 felodipine. 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 “felodipine” (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 “felodipine”. 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 “felodipine” (or synonyms) into the “For these words:” box. You should check back periodically with this database since it is updated every three months.

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The National Organization for Rare Disorders, Inc. The National Organization for Rare Disorders, Inc. has prepared a Web site that provides, at no charge, lists of associations organized by health topic. You can access this database at the following Web site: http://www.rarediseases.org/search/orgsearch.html. Type “felodipine” (or a synonym) into the search box, and click “Submit Query.”

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.18

Finding a Local Medical Library The quickest method to locate medical libraries is to use the Internet-based directory published by the National Network of Libraries of Medicine (NN/LM). This network includes 4626 members and affiliates that provide many services to librarians, health professionals, and the public. To find a library in your area, simply visit http://nnlm.gov/members/adv.html or call 1-800-338-7657.

Medical Libraries in the U.S. and Canada In addition to the NN/LM, the National Library of Medicine (NLM) lists a number of libraries with reference facilities that are open to the public. The following is the NLM’s list and includes hyperlinks to each library’s Web site. These Web pages can provide information on hours of operation and other restrictions. The list below is a small sample of

18

Adapted from the NLM: http://www.nlm.nih.gov/psd/cas/interlibrary.html.

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libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)19: •

Alabama: Health InfoNet of Jefferson County (Jefferson County Library Cooperative, Lister Hill Library of the Health Sciences), http://www.uab.edu/infonet/

•

Alabama: Richard M. Scrushy Library (American Sports Medicine Institute)

•

Arizona: Samaritan Regional Medical Center: The Learning Center (Samaritan Health System, Phoenix, Arizona), http://www.samaritan.edu/library/bannerlibs.htm

•

California: Kris Kelly Health Information Center (St. Joseph Health System, Humboldt), http://www.humboldt1.com/~kkhic/index.html

•

California: Community Health Library of Los Gatos, http://www.healthlib.org/orgresources.html

•

California: Consumer Health Program and Services (CHIPS) (County of Los Angeles Public Library, Los Angeles County Harbor-UCLA Medical Center Library) - Carson, CA, http://www.colapublib.org/services/chips.html

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

California: Health Library (Stanford University Medical Center), http://wwwmed.stanford.edu/healthlibrary/

•

California: Patient Education Resource Center - Health Information and Resources (University of California, San Francisco), http://sfghdean.ucsf.edu/barnett/PERC/default.asp

•

California: Redwood Health Library (Petaluma Health Care District), http://www.phcd.org/rdwdlib.html

•

California: Los Gatos PlaneTree Health Library, http://planetreesanjose.org/

•

California: Sutter Resource Library (Sutter Hospitals Foundation, Sacramento), http://suttermedicalcenter.org/library/

•

California: Health Sciences Libraries (University of California, Davis), http://www.lib.ucdavis.edu/healthsci/

•

California: ValleyCare Health Library & Ryan Comer Cancer Resource Center (ValleyCare Health System, Pleasanton), http://gaelnet.stmarysca.edu/other.libs/gbal/east/vchl.html

•

California: Washington Community Health Resource Library (Fremont), http://www.healthlibrary.org/

•

Colorado: William V. Gervasini Memorial Library (Exempla Healthcare), http://www.saintjosephdenver.org/yourhealth/libraries/

•

Connecticut: Hartford Hospital Health Science Libraries (Hartford Hospital), http://www.harthosp.org/library/

•

Connecticut: Healthnet: Connecticut Consumer Health Information Center (University of Connecticut Health Center, Lyman Maynard Stowe Library), http://library.uchc.edu/departm/hnet/

19

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

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•

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

•

Delaware: Consumer Health Library (Christiana Care Health System, Eugene du Pont Preventive Medicine & Rehabilitation Institute, Wilmington), http://www.christianacare.org/health_guide/health_guide_pmri_health_info.cfm

•

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

•

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

•

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

•

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

•

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

•

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

•

Illinois: Medical Library (OSF Saint Francis Medical Center, Peoria), http://www.osfsaintfrancis.org/general/library/

•

Kentucky: Medical Library - Services for Patients, Families, Students & the Public (Central Baptist Hospital, Lexington), http://www.centralbap.com/education/community/library.cfm

•

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

•

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

•

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

•

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

•

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

•

Maine: Hadley Parrot Health Science Library (Eastern Maine Healthcare, Bangor), http://www.emh.org/hll/hpl/guide.htm

•

Maine: Maine Medical Center Library (Maine Medical Center, Portland), http://www.mmc.org/library/

•

Maine: Parkview Hospital (Brunswick), http://www.parkviewhospital.org/

•

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

•

Maine: Stephens Memorial Hospital’s Health Information Library (Western Maine Health, Norway), http://www.wmhcc.org/Library/

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•

Manitoba, Canada: Consumer & Patient Health Information Service (University of Manitoba Libraries), http://www.umanitoba.ca/libraries/units/health/reference/chis.html

•

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

•

Maryland: Health Information Center at the Wheaton Regional Library (Montgomery County, Dept. of Public Libraries, Wheaton Regional Library), http://www.mont.lib.md.us/healthinfo/hic.asp

•

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

•

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

•

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

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FELODIPINE DICTIONARY The definitions below are derived from official public sources, including the National Institutes of Health [NIH] and the European Union [EU]. Acceptor: A substance which, while normally not oxidized by oxygen or reduced by hydrogen, can be oxidized or reduced in presence of a substance which is itself undergoing oxidation or reduction. [NIH] ACE: Angiotensin-coverting enzyme. A drug used to decrease pressure inside blood vessels. [NIH]

ACE Inhibitor: A type of drug used to lower blood pressure. Studies indicate that it may also help prevent or slow the progression of kidney disease in people with diabetes. [NIH] Acetone: A colorless liquid used as a solvent and an antiseptic. It is one of the ketone bodies produced during ketoacidosis. [NIH] Actin: Essential component of the cell skeleton. [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] Adenosine: A nucleoside that is composed of adenine and d-ribose. Adenosine or adenosine derivatives play many important biological roles in addition to being components of DNA and RNA. Adenosine itself is a neurotransmitter. [NIH] Adjunctive Therapy: Another treatment used together with the primary treatment. Its purpose is to assist the primary treatment. [NIH] Adjuvant: A substance which aids another, such as an auxiliary remedy; in immunology, nonspecific stimulator (e.g., BCG vaccine) of the immune response. [EU] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenal Medulla: The inner part of the adrenal gland; it synthesizes, stores and releases catecholamines. [NIH] Adrenaline: A hormone. Also called epinephrine. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] Adrenergic beta-Antagonists: Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic betaantagonists are used for treatment of hypertension, cardiac arrythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. [NIH] Adrenoreceptor: Receptors specifically sensitive to and operated by adrenaline and/or noradrenaline and related sympathomimetic drugs. Adrenoreceptor is an alternative name. [NIH]

Adverse Effect: An unwanted side effect of treatment. [NIH] Aerobic: In biochemistry, reactions that need oxygen to happen or happen when oxygen is present. [NIH] Afferent: Concerned with the transmission of neural impulse toward the central part of the nervous system. [NIH]

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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]

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] Albumin: 1. Any protein that is soluble in water and moderately concentrated salt solutions and is coagulable by heat. 2. Serum albumin; the major plasma protein (approximately 60 per cent of the total), which is responsible for much of the plasma colloidal osmotic pressure and serves as a transport protein carrying large organic anions, such as fatty acids, bilirubin, and many drugs, and also carrying certain hormones, such as cortisol and thyroxine, when their specific binding globulins are saturated. Albumin is synthesized in the liver. Low serum levels occur in protein malnutrition, active inflammation and serious hepatic and renal disease. [EU] Albuminuria: More than normal amounts of a protein called albumin in the urine. Albuminuria may be a sign of kidney disease. [NIH] 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] Alpha-1: A protein with the property of inactivating proteolytic enzymes such as leucocyte collagenase and elastase. [NIH] Alprenolol: 1-((1-Methylethyl)amino)-3-(2-(2-propenyl)phenoxy)-2-propanol. Adrenergic beta-blocker used as an antihypertensive, anti-anginal, and anti-arrhythmic agent. [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] Amino acid: Any organic compound containing an amino (-NH2 and a carboxyl (- COOH) group. The 20 a-amino acids listed in the accompanying table are the amino acids from

Dictionary 105

which proteins are synthesized by formation of peptide bonds during ribosomal translation of messenger RNA; all except glycine, which is not optically active, have the L configuration. Other amino acids occurring in proteins, such as hydroxyproline in collagen, are formed by posttranslational enzymatic modification of amino acids residues in polypeptide chains. There are also several important amino acids, such as the neurotransmitter y-aminobutyric acid, that have no relation to proteins. Abbreviated AA. [EU] 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] Analogous: Resembling or similar in some respects, as in function or appearance, but not in origin or development;. [EU] Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Anemia: A reduction in the number of circulating erythrocytes or in the quantity of hemoglobin. [NIH] Aneurysm: A sac formed by the dilatation of the wall of an artery, a vein, or the heart. [NIH] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Anginal: Pertaining to or characteristic of angina. [EU] Angiotensin-Converting Enzyme Inhibitors: A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. [NIH] Angiotensinogen: An alpha-globulin of which a fragment of 14 amino acids is converted by renin to angiotensin I, the inactive precursor of angiotensin II. It is a member of the serpin superfamily. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Ankle: That part of the lower limb directly above the foot. [NIH] 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]

Antibody: A type of protein made by certain white blood cells in response to a foreign substance (antigen). Each antibody can bind to only a specific antigen. The purpose of this binding is to help destroy the antigen. Antibodies can work in several ways, depending on the nature of the antigen. Some antibodies destroy antigens directly. Others make it easier for white blood cells to destroy the antigen. [NIH] Anticonvulsants: Drugs used to prevent seizures or reduce their severity. [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

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(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]

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] 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] Arterioles: The smallest divisions of the arteries located between the muscular arteries and the capillaries. [NIH] Artery: Vessel-carrying blood from the heart to various parts of the body. [NIH] Ascites: Accumulation or retention of free fluid within the peritoneal cavity. [NIH] Asymptomatic: Having no signs or symptoms of disease. [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] ATP: ATP an abbreviation for adenosine triphosphate, a compound which serves as a carrier of energy for cells. [NIH] Atrial: Pertaining to an atrium. [EU] 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] Auscultation: Act of listening for sounds within the body. [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] Baroreflex: A negative feedback system which buffers short-term changes in blood pressure. Increased pressure stretches blood vessels which activates pressoreceptors (baroreceptors) in the vessel walls. The net response of the central nervous system is a reduction of central sympathetic outflow. This reduces blood pressure both by decreasing peripheral vascular resistance and by lowering cardiac output. Because the baroreceptors are tonically active, the baroreflex can compensate rapidly for both increases and decreases in blood pressure. [NIH]

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Benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body. [NIH]

Bepridil: Beta-((2-Methylpropoxy)methyl)-N-phenyl-N-(phenylmethyl)-1pyrrolidineethanamine. A long-acting calcium-blocking agent with significant anti-anginal activity. The drug produces significant coronary vasodilation and modest peripheral effects. It has antihypertensive and selective anti-arrhythmia activities and acts as a calmodulin antagonist. [NIH] Bile: An emulsifying agent produced in the liver and secreted into the duodenum. Its composition includes bile acids and salts, cholesterol, and electrolytes. It aids digestion of fats in the duodenum. [NIH] Bile Acids: Acids made by the liver that work with bile to break down fats. [NIH] Bile Acids and Salts: Steroid acids and salts. The primary bile acids are derived from cholesterol in the liver and usually conjugated with glycine or taurine. The secondary bile acids are further modified by bacteria in the intestine. They play an important role in the digestion and absorption of fat. They have also been used pharmacologically, especially in the treatment of gallstones. [NIH] Bilirubin: A bile pigment that is a degradation product of heme. [NIH] Bioavailability: The degree to which a drug or other substance becomes available to the target tissue after administration. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Biotransformation: The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alteration may be either nonsynthetic (oxidation-reduction, hydrolysis) or synthetic (glucuronide formation, sulfate conjugation, acetylation, methylation). This also includes metabolic detoxication and clearance. [NIH] Blinking: Brief closing of the eyelids by involuntary normal periodic closing, as a protective measure, or by voluntary action. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood Glucose: Glucose in blood. [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

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of a framework of connective tissue containing branching fibers with the frame being filled with marrow cells. [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] Breast reconstruction: Surgery to rebuild a breast's shape after a mastectomy. [NIH] Bronchitis: Inflammation (swelling and reddening) of the bronchi. [NIH] Buffers: A chemical system that functions to control the levels of specific ions in solution. When the level of hydrogen ion in solution is controlled the system is called a pH buffer. [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 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 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]

Calmodulin: A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capsules: Hard or soft soluble containers used for the oral administration of medicine. [NIH] 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] Carbohydrate: An aldehyde or ketone derivative of a polyhydric alcohol, particularly of the pentahydric and hexahydric alcohols. They are so named because the hydrogen and oxygen are usually in the proportion to form water, (CH2O)n. The most important carbohydrates are the starches, sugars, celluloses, and gums. They are classified into mono-, di-, tri-, polyand heterosaccharides. [EU]

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Cardiac: Having to do with the heart. [NIH] Cardiac Output: The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). [NIH] Cardiopulmonary: Having to do with the heart and lungs. [NIH] Cardiopulmonary Bypass: Diversion of the flow of blood from the entrance of the right atrium directly to the aorta (or femoral artery) via an oxygenator thus bypassing both the heart and lungs. [NIH] 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] Cardiovascular System: The heart and the blood vessels by which blood is pumped and circulated through the body. [NIH] Castor Oil: Oil obtained from seeds of Ricinus communis that is used as a cathartic and as a plasticizer. [NIH] Cations: Postively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. [NIH] Causal: Pertaining to a cause; directed against a cause. [EU] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Cell membrane: Cell membrane = plasma membrane. The structure enveloping a cell, enclosing the cytoplasm, and forming a selective permeability barrier; it consists of lipids, proteins, and some carbohydrates, the lipids thought to form a bilayer in which integral proteins are embedded to varying degrees. [EU] 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] 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] Chest Pain: Pressure, burning, or numbness in the chest. [NIH] Chin: The anatomical frontal portion of the mandible, also known as the mentum, that contains the line of fusion of the two separate halves of the mandible (symphysis menti). This line of fusion divides inferiorly to enclose a triangular area called the mental

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protuberance. On each side, inferior to the second premolar tooth, is the mental foramen for the passage of blood vessels and a nerve. [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] 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] Cirrhosis: A type of chronic, progressive liver disease. [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] Collagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of skin, connective tissue, and the organic substance of bones and teeth. Different forms of collagen are produced in the body but all consist of three alpha-polypeptide chains arranged in a triple helix. Collagen is differentiated from other fibrous proteins, such as elastin, by the content of proline, hydroxyproline, and hydroxylysine; by the absence of tryptophan; and particularly by the high content of polar groups which are responsible for its swelling properties. [NIH] Colloidal: Of the nature of a colloid. [EU] Communis: Common tendon of the rectus group of muscles that surrounds the optic foramen and a portion of the superior orbital fissure, to the anterior margin of which it is attached at the spina recti lateralis. [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

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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 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] Confusion: A mental state characterized by bewilderment, emotional disturbance, lack of clear thinking, and perceptual disorientation. [NIH] Congestive heart failure: Weakness of the heart muscle that leads to a buildup of fluid in body tissues. [NIH] Conjugated: Acting or operating as if joined; simultaneous. [EU] Conjugation: 1. The act of joining together or the state of being conjugated. 2. A sexual process seen in bacteria, ciliate protozoa, and certain fungi in which nuclear material is exchanged during the temporary fusion of two cells (conjugants). In bacterial genetics a form of sexual reproduction in which a donor bacterium (male) contributes some, or all, of its DNA (in the form of a replicated set) to a recipient (female) which then incorporates differing genetic information into its own chromosome by recombination and passes the recombined set on to its progeny by replication. In ciliate protozoa, two conjugants of separate mating types exchange micronuclear material and then separate, each now being a fertilized cell. In certain fungi, the process involves fusion of two gametes, resulting in union of their nuclei and formation of a zygote. 3. In chemistry, the joining together of two compounds to produce another compound, such as the combination of a toxic product with some substance in the body to form a detoxified product, which is then eliminated. [EU]

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Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [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]

Convulsions: A general term referring to sudden and often violent motor activity of cerebral or brainstem origin. Convulsions may also occur in the absence of an electrical cerebral discharge (e.g., in response to hypotension). [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary 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] Corticosteroid: Any of the steroids elaborated by the adrenal cortex (excluding the sex hormones of adrenal origin) in response to the release of corticotrophin (adrenocorticotropic hormone) by the pituitary gland, to any of the synthetic equivalents of these steroids, or to angiotensin II. They are divided, according to their predominant biological activity, into three major groups: glucocorticoids, chiefly influencing carbohydrate, fat, and protein metabolism; mineralocorticoids, affecting the regulation of electrolyte and water balance; and C19 androgens. Some corticosteroids exhibit both types of activity in varying degrees, and others exert only one type of effect. The corticosteroids are used clinically for hormonal replacement therapy, for suppression of ACTH secretion by the anterior pituitary, as antineoplastic, antiallergic, and anti-inflammatory agents, and to suppress the immune response. Called also adrenocortical hormone and corticoid. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] 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] 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

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transplants by the body. It is also used in clinical trials to make cancer cells more sensitive to anticancer drugs. [NIH] Cytochrome: Any electron transfer hemoprotein having a mode of action in which the transfer of a single electron is effected by a reversible valence change of the central iron atom of the heme prosthetic group between the +2 and +3 oxidation states; classified as cytochromes a in which the heme contains a formyl side chain, cytochromes b, which contain protoheme or a closely similar heme that is not covalently bound to the protein, cytochromes c in which protoheme or other heme is covalently bound to the protein, and cytochromes d in which the iron-tetrapyrrole has fewer conjugated double bonds than the hemes have. Well-known cytochromes have been numbered consecutively within groups and are designated by subscripts (beginning with no subscript), e.g. cytochromes c, c1, C2, . New cytochromes are named according to the wavelength in nanometres of the absorption maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Cytokines: Non-antibody proteins secreted by inflammatory leukocytes and some nonleukocytic cells, that act as intercellular mediators. They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialized glands. They generally act locally in a paracrine or autocrine rather than endocrine manner. [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] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Delusion: A false belief, not susceptible to argument or reason, and determined, pathologically, by some form of mental disorder. [NIH] Dental Hygienists: Persons trained in an accredited school or dental college and licensed by the state in which they reside to provide dental prophylaxis under the direction of a licensed dentist. [NIH] Depressive Disorder: An affective disorder manifested by either a dysphoric mood or loss of interest or pleasure in usual activities. The mood disturbance is prominent and relatively persistent. [NIH] Dermis: A layer of vascular connective tissue underneath the epidermis. The surface of the dermis contains sensitive papillae. Embedded in or beneath the dermis are sweat glands, hair follicles, and sebaceous glands. [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] Digestion: The process of breakdown of food for metabolism and use by the body. [NIH]

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Dihydropyridines: Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. [NIH] Dilatation, Pathologic: The condition of an anatomical structure's being dilated beyond normal dimensions. [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] 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] Distal: Remote; farther from any point of reference; opposed to proximal. In dentistry, used to designate a position on the dental arch farther from the median line of the jaw. [EU] Diuresis: Increased excretion of urine. [EU] Diuretic: A drug that increases the production of urine. [NIH] Diuretics, Thiazide: Diuretics characterized as analogs of 1,2,4-benzothiadiazine-1,1dioxide. All have a common mechanism of action and differ primarily in the dose required to produce a given effect. They act directly on the kidney to increase the excretion of sodium chloride and water and also increase excretion of potassium ions. [NIH] Dizziness: An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. [NIH] DNA Topoisomerase: An enzyme catalyzing ATP-independent breakage of single-stranded DNA, followed by passage and rejoining of another single-stranded DNA. This enzyme class brings about the conversion of one topological isomer of DNA into another, e.g., the relaxation of superhelical turns in DNA, the interconversion of simple and knotted rings of single-stranded DNA, and the intertwisting of single-stranded rings of complementary sequences. (From Enzyme Nomenclature, 1992) EC 5.99.1.2. [NIH] Double-blind: Pertaining to a clinical trial or other experiment in which neither the subject nor the person administering treatment knows which treatment any particular subject is receiving. [EU] Doxazosin: A selective alpha-1-adrenergic blocker that lowers serum cholesterol. It is also effective in the treatment of hypertension. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH] Drug Tolerance: Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from drug resistance wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from maximum tolerated dose and no-observed-adverse-effect level. [NIH] Duct: A tube through which body fluids pass. [NIH] Duodenum: The first part of the small intestine. [NIH] Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [NIH]

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Efferent: Nerve fibers which conduct impulses from the central nervous system to muscles and glands. [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] Elastic: Susceptible of resisting and recovering from stretching, compression or distortion applied by a force. [EU] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Electrophysiological: Pertaining to electrophysiology, that is a branch of physiology that is concerned with the electric phenomena associated with living bodies and involved in their functional activity. [EU] Embryo: The prenatal stage of mammalian development characterized by rapid morphological changes and the differentiation of basic structures. [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]

Endogenous: Produced inside an organism or cell. The opposite is external (exogenous) production. [NIH] Endotoxic: Of, relating to, or acting as an endotoxin (= a heat-stable toxin, associated with the outer membranes of certain gram-negative bacteria. Endotoxins are not secreted and are released only when the cells are disrupted). [EU] 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] 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] Ergonovine: An ergot alkaloid with uterine and vascular smooth muscle contractile properties. [NIH] Ergot: Cataract due to ergot poisoning caused by eating of rye cereals contaminated by a fungus. [NIH]

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Erythrocytes: Red blood cells. Mature erythrocytes are non-nucleated, biconcave disks containing hemoglobin whose function is to transport oxygen. [NIH] Esophageal: Having to do with the esophagus, the muscular tube through which food passes from the throat to the stomach. [NIH] Esophagitis: Inflammation, acute or chronic, of the esophagus caused by bacteria, chemicals, or trauma. [NIH] Esophagus: The muscular tube through which food passes from the throat to the stomach. [NIH]

Ethanol: A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. [NIH] Ether: One of a class of organic compounds in which any two organic radicals are attached directly to a single oxygen atom. [NIH] Excipient: Any more or less inert substance added to a prescription in order to confer a suitable consistency or form to the drug; a vehicle. [EU] Excrete: To get rid of waste from the body. [NIH] Exercise Test: Controlled physical activity, more strenuous than at rest, which is performed in order to allow assessment of physiological functions, particularly cardiovascular and pulmonary, but also aerobic capacity. Maximal (most intense) exercise is usually required but submaximal exercise is also used. The intensity of exercise is often graded, using criteria such as rate of work done, oxygen consumption, and heart rate. Physiological data obtained from an exercise test may be used for diagnosis, prognosis, and evaluation of disease severity, and to evaluate therapy. Data may also be used in prescribing exercise by determining a person's exercise capacity. [NIH] Exercise Tolerance: The exercise capacity of an individual as measured by endurance (maximal exercise duration and/or maximal attained work load) during an exercise test. [NIH]

Exhaustion: The feeling of weariness of mind and body. [NIH] Exogenous: Developed or originating outside the organism, as exogenous disease. [EU] Extracellular: Outside a cell or cells. [EU] Facial: Of or pertaining to the face. [EU] Facial Expression: Observable changes of expression in the face in response to emotional stimuli. [NIH] Facial Nerve: The 7th cranial nerve. The facial nerve has two parts, the larger motor root which may be called the facial nerve proper, and the smaller intermediate or sensory root. Together they provide efferent innervation to the muscles of facial expression and to the lacrimal and salivary glands, and convey afferent information for taste from the anterior two-thirds of the tongue and for touch from the external ear. [NIH] Family Planning: Programs or services designed to assist the family in controlling reproduction by either improving or diminishing fertility. [NIH] Fat: Total lipids including phospholipids. [NIH] Fatigue: The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. [NIH]

Femoral: Pertaining to the femur, or to the thigh. [EU]

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Femoral Artery: The main artery of the thigh, a continuation of the external iliac artery. [NIH] Filtration: The passage of a liquid through a filter, accomplished by gravity, pressure, or vacuum (suction). [EU] Flatus: Gas passed through the rectum. [NIH] Fold: A plication or doubling of various parts of the body. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Gallate: Antioxidant present in tea. [NIH] Ganglionic Blockers: Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery. [NIH] Gas: Air that comes from normal breakdown of food. The gases are passed out of the body through the rectum (flatus) or the mouth (burp). [NIH] Gastric: Having to do with the stomach. [NIH] Gastric Acid: Hydrochloric acid present in gastric juice. [NIH] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastroesophageal Reflux: Reflux of gastric juice and/or duodenal contents (bile acids, pancreatic juice) into the distal esophagus, commonly due to incompetence of the lower esophageal sphincter. Gastric regurgitation is an extension of this process with entry of fluid into the pharynx or mouth. [NIH] Gastroesophageal Reflux Disease: Flow of the stomach's contents back up into the esophagus. Happens when the muscle between the esophagus and the stomach (the lower esophageal sphincter) is weak or relaxes when it shouldn't. May cause esophagitis. Also called esophageal reflux or reflux esophagitis. [NIH] Gastrointestinal: Refers to the stomach and intestines. [NIH] Gastrointestinal tract: The stomach and intestines. [NIH] Gastrointestinal Transit: Passage of food (sometimes in the form of a test meal) through the gastrointestinal tract as measured in minutes or hours. The rate of passage through the intestine is an indicator of small bowel function. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Genistein: An isoflavonoid derived from soy products. It inhibits protein-tyrosine kinase and topoisomerase-ii (dna topoisomerase (atp-hydrolysing)) activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 phase arrest in human and murine cell lines. [NIH] Gingival Hyperplasia: A pathological increase in the depth of the gingival crevice surrounding a tooth at the gum margin. [NIH] Gland: An organ that produces and releases one or more substances for use in the body. Some glands produce fluids that affect tissues or organs. Others produce hormones or participate in blood production. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

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Glomerular Filtration Rate: The volume of water filtered out of plasma through glomerular capillary walls into Bowman's capsules per unit of time. It is considered to be equivalent to inulin clearance. [NIH] Glomeruli: Plural of glomerulus. [NIH] Glomerulonephritis: Glomerular disease characterized by an inflammatory reaction, with leukocyte infiltration and cellular proliferation of the glomeruli, or that appears to be the result of immune glomerular injury. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucocorticoid: A compound that belongs to the family of compounds called corticosteroids (steroids). Glucocorticoids affect metabolism and have anti-inflammatory and immunosuppressive effects. They may be naturally produced (hormones) or synthetic (drugs). [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose tolerance: The power of the normal liver to absorb and store large quantities of glucose and the effectiveness of intestinal absorption of glucose. The glucose tolerance test is a metabolic test of carbohydrate tolerance that measures active insulin, a hepatic function based on the ability of the liver to absorb glucose. The test consists of ingesting 100 grams of glucose into a fasting stomach; blood sugar should return to normal in 2 to 21 hours after ingestion. [NIH] Glucose Tolerance Test: Determination of whole blood or plasma sugar in a fasting state before and at prescribed intervals (usually 1/2 hr, 1 hr, 3 hr, 4 hr) after taking a specified amount (usually 100 gm orally) of glucose. [NIH] Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. [NIH] Glycoprotein: A protein that has sugar molecules attached to it. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Graft: Healthy skin, bone, or other tissue taken from one part of the body and used to replace diseased or injured tissue removed from another part of the body. [NIH] 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] Heart Murmurs: Abnormal heart sounds heard during auscultation caused by alterations in the flow of blood into a chamber, through a valve, or by a valve opening or closing

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abnormally. They are classified by the time of occurrence during the cardiac cycle, the duration, and the intensity of the sound on a scale of I to V. [NIH] Heart Sounds: The sounds heard over the cardiac region produced by the functioning of the heart. There are four distinct sounds: the first occurs at the beginning of systole and is heard as a "lubb" sound; the second is produced by the closing of the aortic and pulmonary valves and is heard as a "dupp" sound; the third is produced by vibrations of the ventricular walls when suddenly distended by the rush of blood from the atria; and the fourth is produced by atrial contraction and ventricular filling but is rarely audible in the normal heart. The physiological concept of heart sounds is differentiated from the pathological heart murmurs. [NIH]

Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemoglobin: One of the fractions of glycosylated hemoglobin A1c. Glycosylated hemoglobin is formed when linkages of glucose and related monosaccharides bind to hemoglobin A and its concentration represents the average blood glucose level over the previous several weeks. HbA1c levels are used as a measure of long-term control of plasma glucose (normal, 4 to 6 percent). In controlled diabetes mellitus, the concentration of glycosylated hemoglobin A is within the normal range, but in uncontrolled cases the level may be 3 to 4 times the normal conentration. Generally, complications are substantially lower among patients with Hb levels of 7 percent or less than in patients with HbA1c levels of 9 percent or more. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocytes: The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. [NIH] Herpes: Any inflammatory skin disease caused by a herpesvirus and characterized by the formation of clusters of small vesicles. When used alone, the term may refer to herpes simplex or to herpes zoster. [EU] Herpes Simplex Encephalitis: An inflammatory disease of the skin or mucous membrane characterized by the formation of clusters of small vesicles. [NIH] Herpes virus: A member of the herpes family of viruses. [NIH] Herpes Zoster: Acute vesicular inflammation. [NIH] Homeostasis: The processes whereby the internal environment of an organism tends to remain balanced and stable. [NIH] Hormonal: Pertaining to or of the nature of a hormone. [EU] Hormone: A substance in the body that regulates certain organs. Hormones such as gastrin help in breaking down food. Some hormones come from cells in the stomach and small intestine. [NIH] Hydrocephalus: Excessive accumulation of cerebrospinal fluid within the cranium which

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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] Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [NIH] Hyperplasia: An increase in the number of cells in a tissue or organ, not due to tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. [NIH] 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] 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] Hypoglycaemia: An abnormally diminished concentration of glucose in the blood, which may lead to tremulousness, cold sweat, piloerection, hypothermia, and headache, accompanied by irritability, confusion, hallucinations, bizarre behaviour, and ultimately, convulsions and coma. [EU] Hypotensive: Characterized by or causing diminished tension or pressure, as abnormally low blood pressure. [EU] Hypothermia: Lower than normal body temperature, especially in warm-blooded animals; in man usually accidental or unintentional. [NIH] Hypoxanthine: A purine and a reaction intermediate in the metabolism of adenosine and in the formation of nucleic acids by the salvage pathway. [NIH] Hypoxia: Reduction of oxygen supply to tissue below physiological levels despite adequate perfusion of the tissue by blood. [EU] Idiopathic: Describes a disease of unknown cause. [NIH] Immune response: The activity of the immune system against foreign substances (antigens). [NIH]

Immunogenic: Producing immunity; evoking an immune response. [EU]

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Immunology: The study of the body's immune system. [NIH] Immunosuppressive: Describes the ability to lower immune system responses. [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 vitro: In the laboratory (outside the body). The opposite of in vivo (in the body). [NIH] In vivo: In the body. The opposite of in vitro (outside the body or in the laboratory). [NIH] Incompetence: Physical or mental inadequacy or insufficiency. [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] Infiltration: The diffusion or accumulation in a tissue or cells of substances not normal to it or in amounts of the normal. Also, the material so accumulated. [EU] Inflammation: A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. [NIH] Infusion: A method of putting fluids, including drugs, into the bloodstream. Also called intravenous infusion. [NIH] Ingestion: Taking into the body by mouth [NIH] Inhalation: The drawing of air or other substances into the lungs. [EU] Innervation: 1. The distribution or supply of nerves to a part. 2. The supply of nervous energy or of nerve stimulus sent to a part. [EU] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insight: The capacity to understand one's own motives, to be aware of one's own psychodynamics, to appreciate the meaning of symbolic behavior. [NIH] 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] Intestinal: Having to do with the intestines. [NIH] Intestinal Mucosa: The surface lining of the intestines where the cells absorb nutrients. [NIH] Intestine: A long, tube-shaped organ in the abdomen that completes the process of digestion. There is both a large intestine and a small intestine. Also called the bowel. [NIH] Intracellular: Inside a cell. [NIH] Intravenous: IV. Into a vein. [NIH] Inulin: A starch found in the tubers and roots of many plants. Since it is hydrolyzable to fructose, it is classified as a fructosan. It has been used in physiologic investigation for determination of the rate of glomerular function. [NIH] Involuntary: Reaction occurring without intention or volition. [NIH]

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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] 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] Isradipine: 4-(4-Benzofurazanyl)-1,4-dihydro-2,6-dimethyl-3,5-pyridinedicarboxylic acid methyl 1-methyl ethyl ester. A potent calcium channel antagonist that is highly selective for vascular smooth muscle. It is effective in the treatment of chronic stable angina pectoris, hypertension, and congestive cardiac failure. [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] Ketanserin: A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients. [NIH] Ketoacidosis: Acidosis accompanied by the accumulation of ketone bodies (ketosis) in the body tissues and fluids, as in diabetic acidosis. [EU] 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] Kidney Failure: The inability of a kidney to excrete metabolites at normal plasma levels under conditions of normal loading, or the inability to retain electrolytes under conditions of normal intake. In the acute form (kidney failure, acute), it is marked by uremia and usually by oliguria or anuria, with hyperkalemia and pulmonary edema. The chronic form (kidney failure, chronic) is irreversible and requires hemodialysis. [NIH] Lacrimal: Pertaining to the tears. [EU] Leukocytes: White blood cells. These include granular leukocytes (basophils, eosinophils, and neutrophils) as well as non-granular leukocytes (lymphocytes and monocytes). [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 A: Lipid A is the biologically active component of lipopolysaccharides. It shows strong endotoxic activity and exhibits immunogenic properties. [NIH] Lipopolysaccharides: Substance consisting of polysaccaride and lipid. [NIH] Lisinopril: An orally active angiotensin-converting enzyme inhibitor that has been used in the treatment of hypertension and congestive heart failure. [NIH] Lithium: An element in the alkali metals family. It has the atomic symbol Li, atomic number

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3, and atomic weight 6.94. Salts of lithium are used in treating manic-depressive disorders. [NIH]

Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Localized: Cancer which has not metastasized yet. [NIH] Loop: A wire usually of platinum bent at one end into a small loop (usually 4 mm inside diameter) and used in transferring microorganisms. [NIH] Lower Esophageal Sphincter: The muscle between the esophagus and stomach. When a person swallows, this muscle relaxes to let food pass from the esophagus to the stomach. It stays closed at other times to keep stomach contents from flowing back into the esophagus. [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] Lymphocytes: White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each); those with characteristics of neither major class are called null cells. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Manic: Affected with mania. [EU] Mastectomy: Surgery to remove the breast (or as much of the breast tissue as possible). [NIH] 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] Mental: Pertaining to the mind; psychic. 2. (L. mentum chin) pertaining to the chin. [EU] Mesenteric: Pertaining to the mesentery : a membranous fold attaching various organs to the body wall. [EU] Mesentery: A layer of the peritoneum which attaches the abdominal viscera to the abdominal wall and conveys their blood vessels and nerves. [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] Methylene Chloride: A chlorinated hydrocarbon that has been used as an inhalation anesthetic and acts as a narcotic in high concentrations. Its primary use is as a solvent in manufacturing and food technology. [NIH] Metoprolol: Adrenergic beta-1-blocking agent with no stimulatory action. It is less bound to plasma albumin than alprenolol and may be useful in angina pectoris, hypertension, or cardiac arrhythmias. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary

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arteries, upon which coronary thrombosis is usually superimposed. [NIH] Microbe: An organism which cannot be observed with the naked eye; e. g. unicellular animals, lower algae, lower fungi, bacteria. [NIH] Microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms. [NIH] 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] Monotherapy: A therapy which uses only one drug. [EU] Morphological: Relating to the configuration or the structure of live organs. [NIH] Motility: The ability to move spontaneously. [EU] Multicenter study: A clinical trial that is carried out at more than one medical institution. [NIH]

Multidrug resistance: Adaptation of tumor cells to anticancer drugs in ways that make the drugs less effective. [NIH] Muscle Contraction: A process leading to shortening and/or development of tension in muscle tissue. Muscle contraction occurs by a sliding filament mechanism whereby actin filaments slide inward among the myosin filaments. [NIH] Myocardial infarction: Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Myocardial Ischemia: A disorder of cardiac function caused by insufficient blood flow to the muscle tissue of the heart. The decreased blood flow may be due to narrowing of the coronary arteries (coronary arteriosclerosis), to obstruction by a thrombus (coronary thrombosis), or less commonly, to diffuse narrowing of arterioles and other small vessels within the heart. Severe interruption of the blood supply to the myocardial tissue may result in necrosis of cardiac muscle (myocardial infarction). [NIH] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Myosin: Chief protein in muscle and the main constituent of the thick filaments of muscle fibers. In conjunction with actin, it is responsible for the contraction and relaxation of muscles. [NIH]

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Narcotic: 1. Pertaining to or producing narcosis. 2. An agent that produces insensibility or stupor, applied especially to the opioids, i.e. to any natural or synthetic drug that has morphine-like actions. [EU] Natriuresis: The excretion of abnormal amounts of sodium in the urine. [EU] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] 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] Neurotransmitter: Any of a group of substances that are released on excitation from the axon terminal of a presynaptic neuron of the central or peripheral nervous system and travel across the synaptic cleft to either excite or inhibit the target cell. Among the many substances that have the properties of a neurotransmitter are acetylcholine, norepinephrine, epinephrine, dopamine, glycine, y-aminobutyrate, glutamic acid, substance P, enkephalins, endorphins, and serotonin. [EU] Neutralization: An act or process of neutralizing. [EU] 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] Nihilism: The delusion of non-existence. [NIH] Nimodipine: A calcium channel blockader with preferential cerebrovascular activity. It has marked cerebrovascular dilating effects and lowers blood pressure. [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] Nitrendipine: Ethyl methyl 2,4-dihydro-2,6-dimethyl-4(3-nitrophenyl)-3,5pyridinedicarboxylate. A calcium channel blocker with marked vasodilator action. It is an effective antihypertensive agent and differs from other calcium channel blockers in that it does not reduce glomerular filtration rate and is mildly natriuretic, rather than sodium retentive. [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] Nuclear: A test of the structure, blood flow, and function of the kidneys. The doctor injects a

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mildly radioactive solution into an arm vein and uses x-rays to monitor its progress through the kidneys. [NIH] Nucleic acid: Either of two types of macromolecule (DNA or RNA) formed by polymerization of nucleotides. Nucleic acids are found in all living cells and contain the information (genetic code) for the transfer of genetic information from one generation to the next. [NIH] Ocular: 1. Of, pertaining to, or affecting the eye. 2. Eyepiece. [EU] Oedema: The presence of abnormally large amounts of fluid in the intercellular tissue 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] Omeprazole: A highly effective inhibitor of gastric acid secretion used in the therapy of gastric ulcers and Zollinger-Ellison syndrome. The drug inhibits the H(+)-K(+)-ATPase (H(+)-K(+)-exchanging ATPase) in a pH-dependent manner. This ATPase is considered the proton pump in the secretory membrane of the parietal cell. [NIH] Oral Health: The optimal state of the mouth and normal functioning of the organs of the mouth without evidence of disease. [NIH] Oral Hygiene: The practice of personal hygiene of the mouth. It includes the maintenance of oral cleanliness, tissue tone, and general preservation of oral health. [NIH] Orthostatic: Pertaining to or caused by standing erect. [EU] 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] Oxidation: The act of oxidizing or state of being oxidized. Chemically it consists in the increase of positive charges on an atom or the loss of negative charges. Most biological oxidations are accomplished by the removal of a pair of hydrogen atoms (dehydrogenation) from a molecule. Such oxidations must be accompanied by reduction of an acceptor molecule. Univalent o. indicates loss of one electron; divalent o., the loss of two electrons. [EU]

Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471). [NIH] Oxygen Consumption: The oxygen consumption is determined by calculating the difference between the amount of oxygen inhaled and exhaled. [NIH] Oxygenator: An apparatus by which oxygen is introduced into the blood during circulation outside the body, as during open heart surgery. [NIH] Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Palsy: Disease of the peripheral nervous system occurring usually after many years of increased lead absorption. [NIH]

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Pancreas: A mixed exocrine and endocrine gland situated transversely across the posterior abdominal wall in the epigastric and hypochondriac regions. The endocrine portion is comprised of the Islets of Langerhans, while the exocrine portion is a compound acinar gland that secretes digestive enzymes. [NIH] Pancreatic: Having to do with the pancreas. [NIH] Pancreatic Juice: The fluid containing digestive enzymes secreted by the pancreas in response to food in the duodenum. [NIH] Paralysis: Loss of ability to move all or part of the body. [NIH] Parathyroid: 1. Situated beside the thyroid gland. 2. One of the parathyroid glands. 3. A sterile preparation of the water-soluble principle(s) of the parathyroid glands, ad-ministered parenterally as an antihypocalcaemic, especially in the treatment of acute hypoparathyroidism with tetany. [EU] Parathyroid Glands: Two small paired endocrine glands in the region of the thyroid gland. They secrete parathyroid hormone and are concerned with the metabolism of calcium and phosphorus. [NIH] Parathyroid hormone: A substance made by the parathyroid gland that helps the body store and use calcium. Also called parathormone, parathyrin, or PTH. [NIH] Parietal: 1. Of or pertaining to the walls of a cavity. 2. Pertaining to or located near the parietal bone, as the parietal lobe. [EU] Paroxysmal: Recurring in paroxysms (= spasms or seizures). [EU] Particle: A tiny mass of material. [EU] Patch: A piece of material used to cover or protect a wound, an injured part, etc.: a patch over the eye. [NIH] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] Patient Compliance: Voluntary cooperation of the patient in following a prescribed regimen. [NIH] Penicillin: An antibiotic drug used to treat infection. [NIH] Peptide: Any compound consisting of two or more amino acids, the building blocks of proteins. Peptides are combined to make proteins. [NIH] Perfusion: Bathing an organ or tissue with a fluid. In regional perfusion, a specific area of the body (usually an arm or a leg) receives high doses of anticancer drugs through a blood vessel. Such a procedure is performed to treat cancer that has not spread. [NIH] Peripheral Nervous System: The nervous system outside of the brain and spinal cord. The peripheral nervous system has autonomic and somatic divisions. The autonomic nervous system includes the enteric, parasympathetic, and sympathetic subdivisions. The somatic nervous system includes the cranial and spinal nerves and their ganglia and the peripheral sensory receptors. [NIH] 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] Pharmaceutical Preparations: Drugs intended for human or veterinary use, presented in their finished dosage form. Included here are materials used in the preparation and/or

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formulation of the finished dosage form. [NIH] Pharmacodynamic: Is concerned with the response of living tissues to chemical stimuli, that is, the action of drugs on the living organism in the absence of disease. [NIH] Pharmacokinetic: The mathematical analysis of the time courses of absorption, distribution, and elimination of drugs. [NIH] Pharmacologic: Pertaining to pharmacology or to the properties and reactions of drugs. [EU] Pharynx: The hollow tube about 5 inches long that starts behind the nose and ends at the top of the trachea (windpipe) and esophagus (the tube that goes to the stomach). [NIH] Phenyl: Ingredient used in cold and flu remedies. [NIH] Phosphorus: A non-metallic element that is found in the blood, muscles, nevers, bones, and teeth, and is a component of adenosine triphosphate (ATP; the primary energy source for the body's cells.) [NIH] Physiologic: Having to do with the functions of the body. When used in the phrase "physiologic age," it refers to an age assigned by general health, as opposed to calendar age. [NIH]

Piloerection: Involuntary erection or bristling of hairs. [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] Plasma protein: One of the hundreds of different proteins present in blood plasma, including carrier proteins ( such albumin, transferrin, and haptoglobin), fibrinogen and other coagulation factors, complement components, immunoglobulins, enzyme inhibitors, precursors of substances such as angiotension and bradykinin, and many other types of proteins. [EU] 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] Platinum: Platinum. A heavy, soft, whitish metal, resembling tin, atomic number 78, atomic weight 195.09, symbol Pt. (From Dorland, 28th ed) It is used in manufacturing equipment for laboratory and industrial use. It occurs as a black powder (platinum black) and as a spongy substance (spongy platinum) and may have been known in Pliny's time as "alutiae". [NIH]

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] Pneumonia: Inflammation of the lungs. [NIH] Pollen: The male fertilizing element of flowering plants analogous to sperm in animals. It is

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released from the anthers as yellow dust, to be carried by insect or other vectors, including wind, to the ovary (stigma) of other flowers to produce the embryo enclosed by the seed. The pollens of many plants are allergenic. [NIH] Polypeptide: A peptide which on hydrolysis yields more than two amino acids; called tripeptides, tetrapeptides, etc. according to the number of amino acids contained. [EU] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potentiate: A degree of synergism which causes the exposure of the organism to a harmful substance to worsen a disease already contracted. [NIH] 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] Prazosin: A selective adrenergic alpha-1 antagonist used in the treatment of heart failure, hypertension, pheochromocytoma, Raynaud's syndrome, prostatic hypertrophy, and urinary retention. [NIH] Prednisolone: A glucocorticoid with the general properties of the corticosteroids. It is the drug of choice for all conditions in which routine systemic corticosteroid therapy is indicated, except adrenal deficiency states. [NIH] Prenatal: Existing or occurring before birth, with reference to the fetus. [EU] Pressoreceptors: Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. [NIH] 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] Projection: A defense mechanism, operating unconsciously, whereby that which is emotionally unacceptable in the self is rejected and attributed (projected) to others. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol is used in the treatment or prevention of many disorders including acute myocardial 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]

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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 C: A vitamin-K dependent zymogen present in the blood, which, upon activation by thrombin and thrombomodulin exerts anticoagulant properties by inactivating factors Va and VIIIa at the rate-limiting steps of thrombin formation. [NIH] Protein S: The vitamin K-dependent cofactor of activated protein C. Together with protein C, it inhibits the action of factors VIIIa and Va. A deficiency in protein S can lead to recurrent venous and arterial thrombosis. [NIH] Proteins: Polymers of amino acids linked by peptide bonds. The specific sequence of amino acids determines the shape and function of the protein. [NIH] Protein-Tyrosine Kinase: An enzyme that catalyzes the phosphorylation of tyrosine residues in proteins with ATP or other nucleotides as phosphate donors. EC 2.7.1.112. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] 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] 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]

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] Quercetin: Aglucon of quercetrin, rutin, and other glycosides. It is widely distributed in the plant kingdom, especially in rinds and barks, clover blossoms, and ragweed pollen. [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] Racemic: Optically inactive but resolvable in the way of all racemic compounds. [NIH] Radiation: Emission or propagation of electromagnetic energy (waves/rays), or the waves/rays themselves; a stream of electromagnetic particles (electrons, neutrons, protons, alpha particles) or a mixture of these. The most common source is the sun. [NIH] Radioactive: Giving off radiation. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [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] 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] Reaction Time: The time from the onset of a stimulus until the organism responds. [NIH]

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Reactivation: The restoration of activity to something that has been inactivated. [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] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Reflex: An involuntary movement or exercise of function in a part, excited in response to a stimulus applied to the periphery and transmitted to the brain or spinal cord. [NIH] Reflux: The term used when liquid backs up into the esophagus from the stomach. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Regurgitation: A backward flowing, as the casting up of undigested food, or the backward flowing of blood into the heart, or between the chambers of the heart when a valve is incompetent. [EU] Renal tubular: A defect in the kidneys that hinders their normal excretion of acids. Failure to excrete acids can lead to weak bones, kidney stones, and poor growth in children. [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 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] Renovascular: Of or pertaining to the blood vessels of the kidneys. [EU] Rutin: 3-((6-O-(6-Deoxy-alpha-L-mannopyranosyl)-beta-D-glucopyranosyl)oxy)-2-(3,4dihydroxyphenyl)-5,7-dihydroxy-4H-1-benzopyran-4-one. Found in many plants, including buckwheat, tobacco, forsythia, hydrangea, pansies, etc. It has been used therapeutically to decrease capillary fragility. [NIH] Salivary: The duct that convey saliva to the mouth. [NIH] Salivary glands: Glands in the mouth that produce saliva. [NIH] Sarcolemma: The plasma membrane of a smooth, striated, or cardiac muscle fiber. [NIH] Scleroderma: A chronic disorder marked by hardening and thickening of the skin. Scleroderma can be localized or it can affect the entire body (systemic). [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Secretion: 1. The process of elaborating a specific product as a result of the activity of a gland; this activity may range from separating a specific substance of the blood to the elaboration of a new chemical substance. 2. Any substance produced by secretion. [EU] Secretory: Secreting; relating to or influencing secretion or the secretions. [NIH] Seizures: Clinical or subclinical disturbances of cortical function due to a sudden, abnormal, excessive, and disorganized discharge of brain cells. Clinical manifestations include abnormal motor, sensory and psychic phenomena. Recurrent seizures are usually referred to as epilepsy or "seizure disorder." [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino

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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] Skeletal: Having to do with the skeleton (boney part of the body). [NIH] Skeleton: The framework that supports the soft tissues of vertebrate animals and protects many of their internal organs. The skeletons of vertebrates are made of bone and/or cartilage. [NIH] Skull: The skeleton of the head including the bones of the face and the bones enclosing the brain. [NIH] Small intestine: The part of the digestive tract that is located between the stomach and the large intestine. [NIH] Smooth muscle: Muscle that performs automatic tasks, such as constricting blood vessels. [NIH]

Social Environment: The aggregate of social and cultural institutions, forms, patterns, and processes that influence the life of an individual or community. [NIH] Sodium: An element that is a member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23. With a valence of 1, it has a strong affinity for oxygen and other nonmetallic elements. Sodium provides the chief cation of the extracellular body fluids. Its salts are the most widely used in medicine. (From Dorland, 27th ed) Physiologically the sodium ion plays a major role in blood pressure regulation, maintenance of fluid volume, and electrolyte balance. [NIH] Solvent: 1. Dissolving; effecting a solution. 2. A liquid that dissolves or that is capable of dissolving; the component of a solution that is present in greater amount. [EU] Spasm: An involuntary contraction of a muscle or group of muscles. Spasms may involve skeletal muscle or smooth muscle. [NIH] 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] 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] Stenosis: Narrowing or stricture of a duct or canal. [EU] Sterile: Unable to produce children. [NIH] Stimulus: That which can elicit or evoke action (response) in a muscle, nerve, gland or other excitable issue, or cause an augmenting action upon any function or metabolic process. [NIH]

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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] Stricture: The abnormal narrowing of a body opening. Also called stenosis. [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] Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Other factors contributing to structure-activity relationship include chemical reactivity, electronic effects, resonance, and inductive effects. [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]

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] Supine: Having the front portion of the body upwards. [NIH] Supplementation: Adding nutrients to the diet. [NIH] Surfactant: A fat-containing protein in the respiratory passages which reduces the surface tension of pulmonary fluids and contributes to the elastic properties of pulmonary tissue. [NIH]

Sweat: The fluid excreted by the sweat glands. It consists of water containing sodium chloride, phosphate, urea, ammonia, and other waste products. [NIH] Sympathetic Nervous System: The thoracolumbar division of the autonomic nervous system. Sympathetic preganglionic fibers originate in neurons of the intermediolateral column of the spinal cord and project to the paravertebral and prevertebral ganglia, which in turn project to target organs. The sympathetic nervous system mediates the body's response to stressful situations, i.e., the fight or flight reactions. It often acts reciprocally to the parasympathetic system. [NIH] Sympathomimetic: 1. Mimicking the effects of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. 2. An agent that produces effects similar to those of impulses conveyed by adrenergic postganglionic fibres of the sympathetic nervous system. Called also adrenergic. [EU] Synapse: The region where the processes of two neurons come into close contiguity, and the nervous impulse passes from one to the other; the fibers of the two are intermeshed, but, according to the general view, there is no direct contiguity. [NIH] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Tachycardia: Excessive rapidity in the action of the heart, usually with a heart rate above 100 beats per minute. [NIH]

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Tacrolimus: A macrolide isolated from the culture broth of a strain of Streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. [NIH] Technetium: The first artificially produced element and a radioactive fission product of uranium. The stablest isotope has a mass number 99 and is used diagnostically as a radioactive imaging agent. Technetium has the atomic symbol Tc, atomic number 43, and atomic weight 98.91. [NIH] Telangiectasia: The permanent enlargement of blood vessels, causing redness in the skin or mucous membranes. [NIH] Temporal: One of the two irregular bones forming part of the lateral surfaces and base of the skull, and containing the organs of hearing. [NIH] Teratogenic: Tending to produce anomalies of formation, or teratism (= anomaly of formation or development : condition of a monster). [EU] Tetany: 1. Hyperexcitability of nerves and muscles due to decrease in concentration of extracellular ionized calcium, which may be associated with such conditions as parathyroid hypofunction, vitamin D deficiency, and alkalosis or result from ingestion of alkaline salts; it is characterized by carpopedal spasm, muscular twitching and cramps, laryngospasm with inspiratory stridor, hyperreflexia and choreiform movements. 2. Tetanus. [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Thermal: Pertaining to or characterized by heat. [EU] 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] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thyroid: A gland located near the windpipe (trachea) that produces thyroid hormone, which helps regulate growth and metabolism. [NIH] Thyroid Gland: A highly vascular endocrine gland consisting of two lobes, one on either side of the trachea, joined by a narrow isthmus; it produces the thyroid hormones which are concerned in regulating the metabolic rate of the body. [NIH] Thyroxine: An amino acid of the thyroid gland which exerts a stimulating effect on thyroid metabolism. [NIH] Tissue: A group or layer of cells that are alike in type and work together to perform a specific function. [NIH] Tolerance: 1. The ability to endure unusually large doses of a drug or toxin. 2. Acquired drug tolerance; a decreasing response to repeated constant doses of a drug or the need for increasing doses to maintain a constant response. [EU] 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] Tone: 1. The normal degree of vigour and tension; in muscle, the resistance to passive elongation or stretch; tonus. 2. A particular quality of sound or of voice. 3. To make permanent, or to change, the colour of silver stain by chemical treatment, usually with a heavy metal. [EU] Topical: On the surface of the body. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH]

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Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Toxin: A poison; frequently used to refer specifically to a protein produced by some higher plants, certain animals, and pathogenic bacteria, which is highly toxic for other living organisms. Such substances are differentiated from the simple chemical poisons and the vegetable alkaloids by their high molecular weight and antigenicity. [EU] Transdermal: Entering through the dermis, or skin, as in administration of a drug applied to the skin in ointment or patch form. [EU] Transduction: The transfer of genes from one cell to another by means of a viral (in the case of bacteria, a bacteriophage) vector or a vector which is similar to a virus particle (pseudovirion). [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [NIH] Translation: The process whereby the genetic information present in the linear sequence of ribonucleotides in mRNA is converted into a corresponding sequence of amino acids in a protein. It occurs on the ribosome and is unidirectional. [NIH] Translocation: The movement of material in solution inside the body of the plant. [NIH] Transmitter: A chemical substance which effects the passage of nerve impulses from one cell to the other at the synapse. [NIH] Transplantation: Transference of a tissue or organ, alive or dead, within an individual, between individuals of the same species, or between individuals of different species. [NIH] Triamterene: A pteridine that is used as a mild diuretic. [NIH] Uranium: A radioactive element of the actinide series of metals. It has an atomic symbol U, atomic number 92, and atomic weight 238.03. U-235 is used as the fissionable fuel in nuclear weapons and as fuel in nuclear power reactors. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [NIH] Urinary Retention: Inability to urinate. The etiology of this disorder includes obstructive, neurogenic, pharmacologic, and psychogenic causes. [NIH] 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] Vaccines: Suspensions of killed or attenuated microorganisms (bacteria, viruses, fungi, protozoa, or rickettsiae), antigenic proteins derived from them, or synthetic constructs, administered for the prevention, amelioration, or treatment of infectious and other diseases. [NIH]

Vascular: Pertaining to blood vessels or indicative of a copious blood supply. [EU] Vascular Resistance: An expression of the resistance offered by the systemic arterioles, and to a lesser extent by the capillaries, to the flow of blood. [NIH] Vasoactive: Exerting an effect upon the calibre of blood vessels. [EU] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH] Vasodilation: Physiological dilation of the blood vessels without anatomic change. For

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Felodipine

dilation with anatomic change, dilatation, pathologic or aneurysm (or specific aneurysm) is used. [NIH] Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] 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] Ventricular: Pertaining to a ventricle. [EU] Ventricular Function: The hemodynamic and electrophysiological action of the ventricles. [NIH]

Venules: The minute vessels that collect blood from the capillary plexuses and join together to form veins. [NIH] Verapamil: A calcium channel blocker that is a class IV anti-arrhythmia agent. [NIH] Vesicular: 1. Composed of or relating to small, saclike bodies. 2. Pertaining to or made up of vesicles on the skin. [EU] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Viral: Pertaining to, caused by, or of the nature of virus. [EU] Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. [NIH] Virus: Submicroscopic organism that causes infectious disease. In cancer therapy, some viruses may be made into vaccines that help the body build an immune response to, and kill, tumor cells. [NIH] Vitro: Descriptive of an event or enzyme reaction under experimental investigation occurring outside a living organism. Parts of an organism or microorganism are used together with artificial substrates and/or conditions. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] X-ray: High-energy radiation used in low doses to diagnose diseases and in high doses to treat cancer. [NIH]

137

INDEX A Acceptor, 103, 126 ACE, 40, 68, 103 ACE Inhibitor, 68, 103 Acetone, 66, 103, 122 Actin, 103, 124 Acute renal, 8, 52, 54, 67, 103 Adenosine, 103, 106, 120, 128 Adjunctive Therapy, 40, 103 Adjuvant, 63, 103 Adrenal Cortex, 103, 104, 112, 131 Adrenal Medulla, 103, 115, 125 Adrenaline, 103 Adrenergic, 10, 24, 67, 103, 104, 106, 114, 115, 122, 123, 129, 133 Adrenergic beta-Antagonists, 103, 106 Adrenoreceptor, 68, 69, 103 Adverse Effect, 13, 35, 67, 103, 132 Aerobic, 103, 116 Afferent, 103, 116 Affinity, 104, 132 Agar, 104, 128 Agonist, 54, 104 Albumin, 20, 104, 123, 128 Albuminuria, 57, 104 Aldosterone, 11, 22, 52, 104 Algorithms, 104, 107 Alkaline, 73, 104, 108, 134 Alkaloid, 104, 115 Alpha-1, 104, 114, 129 Alprenolol, 104, 123 Alternative medicine, 78, 104 Amino acid, 5, 104, 105, 114, 118, 123, 127, 129, 130, 132, 133, 134, 135 Amlodipine, 3, 4, 6, 8, 9, 12, 13, 15, 18, 22, 30, 33, 35, 36, 59, 105 Analogous, 69, 105, 128, 135 Anatomical, 71, 105, 106, 109, 112, 114, 121 Anemia, 71, 105 Aneurysm, 105, 117, 136 Angina, 3, 4, 8, 9, 13, 19, 20, 22, 24, 25, 29, 31, 35, 46, 47, 53, 67, 103, 105, 122, 123, 125, 129 Angina Pectoris, 8, 9, 13, 19, 20, 22, 24, 25, 29, 46, 47, 67, 103, 105, 122, 123, 129 Anginal, 104, 105, 107, 125 Angiotensin-Converting Enzyme Inhibitors, 43, 105, 106

Angiotensinogen, 105, 131 Anions, 104, 105, 122 Ankle, 6, 105 Antagonism, 27, 48, 53, 105, 114 Antibiotic, 105, 127 Antibody, 104, 105, 110, 113 Anticonvulsants, 40, 54, 105 Antihypertensive, 6, 9, 10, 13, 14, 17, 26, 30, 31, 33, 39, 41, 45, 48, 104, 105, 107, 125 Antihypertensive Agents, 33, 105 Anti-inflammatory, 106, 112, 118, 121 Antineoplastic, 106, 112, 117, 125 Antineoplastic Agents, 106, 125 Antiseptic, 103, 106 Anxiety, 103, 106, 129 Aorta, 106, 109, 129, 136 Aqueous, 66, 106, 113 Arrhythmia, 92, 106, 107, 136 Arterial, 12, 13, 18, 36, 66, 106, 108, 120, 125, 130, 133 Arteries, 20, 72, 106, 107, 112, 124 Arterioles, 71, 106, 107, 108, 124, 135 Artery, 11, 74, 105, 106, 112, 117, 130 Ascites, 106, 126 Asymptomatic, 49, 106 Atenolol, 13, 28, 43, 106 Atherogenic, 53, 106 ATP, 106, 114, 117, 128, 130 Atrial, 25, 39, 44, 106, 119 Atrium, 106, 109, 136 Auscultation, 106, 118 Autonomic, 106, 117, 125, 127, 133 B Bactericidal, 106, 116 Bacteriophage, 106, 128, 135 Baroreflex, 18, 106 Benign, 107, 118 Bepridil, 3, 4, 55, 107 Bile, 5, 63, 107, 117, 123 Bile Acids, 107, 117 Bile Acids and Salts, 107 Bilirubin, 104, 107 Bioavailability, 5, 40, 54, 69, 74, 107 Biotechnology, 5, 78, 87, 107 Biotransformation, 10, 62, 107 Blinking, 71, 107 Blood Coagulation, 107, 108

138

Felodipine

Blood Glucose, 107, 119, 121 Blood vessel, 74, 103, 106, 107, 108, 109, 110, 118, 122, 123, 127, 131, 132, 133, 134, 135, 136 Body Fluids, 107, 114, 132 Bone Marrow, 107, 112, 123 Bowel, 108, 117, 121 Breast reconstruction, 45, 108 Bronchitis, 108, 110 Buffers, 106, 108 C Calcium blocker, 62, 66, 74, 108 Calcium channel blocker, 3, 4, 10, 18, 46, 59, 70, 72, 105, 106, 108, 125, 136 Calcium Channel Blockers, 3, 4, 46, 59, 70, 106, 108, 125 Calcium Signaling, 58, 108 Calmodulin, 55, 107, 108 Capillary, 16, 60, 108, 118, 131, 136 Capsules, 108, 118 Captopril, 12, 52, 54, 62, 108 Carbohydrate, 108, 112, 118 Cardiac, 4, 23, 39, 42, 45, 55, 67, 103, 106, 109, 115, 119, 122, 123, 124, 125, 131 Cardiac Output, 106, 109 Cardiopulmonary, 16, 62, 109 Cardiopulmonary Bypass, 62, 109 Cardioselective, 106, 109, 129 Cardiovascular disease, 4, 109 Cardiovascular System, 68, 109 Castor Oil, 74, 109 Cations, 109, 122 Causal, 70, 71, 109 Cell membrane, 108, 109 Central Nervous System, 106, 109, 115, 118, 120, 132 Central Nervous System Infections, 109, 118, 120 Cerebral, 67, 71, 109, 112, 115, 120 Cerebrovascular, 108, 109, 125 Cerebrum, 109 Character, 105, 109, 113 Chest Pain, 3, 109 Chin, 109, 123 Cholesterol, 107, 110, 112, 114 Chronic, 19, 23, 28, 33, 34, 38, 40, 41, 45, 47, 49, 57, 63, 105, 110, 113, 115, 116, 122, 131 Chronic Obstructive Pulmonary Disease, 23, 110 Cilazapril, 14, 110 Cirrhosis, 66, 110

Clinical trial, 4, 8, 12, 36, 87, 110, 112, 113, 114, 124, 130 Cloning, 107, 110 Collagen, 105, 110, 128 Colloidal, 104, 110 Communis, 109, 110 Complement, 110, 111, 128 Complementary and alternative medicine, 57, 64, 111 Complementary medicine, 57, 111 Computational Biology, 87, 111 Computed tomography, 35, 111 Computerized axial tomography, 111 Computerized tomography, 111 Concomitant, 67, 111 Confusion, 111, 120 Congestive heart failure, 11, 14, 16, 17, 28, 29, 33, 36, 38, 39, 40, 41, 43, 45, 53, 110, 111, 122 Conjugated, 107, 111, 113 Conjugation, 107, 111 Constriction, 112, 122, 135 Constriction, Pathologic, 112, 135 Contractility, 20, 105, 112 Contraindications, ii, 112 Controlled study, 11, 57, 112 Convulsions, 112, 120 Coronary, 11, 20, 35, 67, 74, 105, 107, 109, 112, 123, 124, 125 Coronary Circulation, 105, 112 Coronary heart disease, 35, 109, 112 Coronary Thrombosis, 112, 124 Coronary Vasospasm, 67, 112 Corticosteroid, 112, 129 Cortisol, 104, 112 Cranial, 71, 112, 116, 118, 127 Craniocerebral Trauma, 112, 118, 120 Curative, 112, 134 Cyclic, 108, 112 Cyclosporine, 12, 31, 32, 37, 53, 112 Cytochrome, 5, 35, 59, 62, 113 Cytokines, 24, 113 Cytoplasm, 108, 109, 113, 123 D Degenerative, 113, 119 Delusion, 113, 125 Dental Hygienists, 4, 113 Depressive Disorder, 113, 123 Dermis, 113, 135 Dextrorotatory, 67, 113 Diabetes Insipidus, 113, 120 Diabetes Mellitus, 113, 119

139

Diagnostic procedure, 65, 78, 113 Dialyzer, 113, 119 Diastole, 113 Diastolic, 67, 113, 120 Digestion, 107, 108, 113, 121, 123, 133 Dihydropyridines, 4, 69, 70, 114 Dilatation, Pathologic, 114, 136 Dilation, 114, 120, 135 Diltiazem, 3, 4, 8, 13, 21, 33, 58, 66, 114 Dimethyl, 66, 71, 74, 114, 122, 125 Direct, iii, 72, 81, 114, 131, 133 Disinfectant, 114, 116 Distal, 22, 114, 117 Diuresis, 17, 114 Diuretic, 9, 10, 23, 28, 35, 38, 114, 120, 122, 135 Diuretics, Thiazide, 106, 114 Dizziness, 67, 114 DNA Topoisomerase, 114, 117 Double-blind, 21, 22, 30, 40, 48, 57, 114 Doxazosin, 33, 114 Drug Interactions, 3, 4, 60, 82, 114 Drug Tolerance, 114, 134 Duct, 114, 131, 132 Duodenum, 107, 114, 127, 133 E Edema, 67, 71, 114, 120, 122, 126 Efferent, 115, 116 Efficacy, 6, 7, 9, 13, 21, 30, 31, 33, 40, 43, 45, 46, 48, 59, 67, 73, 115 Elastic, 115, 133 Elective, 62, 115 Electrolyte, 104, 112, 115, 129, 132 Electrons, 115, 122, 126, 130 Electrophysiological, 115, 136 Embryo, 74, 115, 129 Emphysema, 110, 115 Enalapril, 12, 14, 15, 16, 17, 19, 23, 29, 30, 32, 33, 34, 40, 42, 54, 82, 115 Endogenous, 55, 115, 130 Endotoxic, 115, 122 End-stage renal, 59, 115 Environmental Health, 86, 88, 115 Enzymatic, 105, 108, 110, 115 Enzyme, 37, 62, 68, 103, 110, 114, 115, 121, 122, 128, 130, 131, 136 Epinephrine, 103, 115, 125 Ergonovine, 35, 53, 115 Ergot, 115 Erythrocytes, 105, 107, 116 Esophageal, 116, 117 Esophagitis, 116, 117

Esophagus, 116, 117, 123, 128, 131, 133 Ethanol, 66, 116 Ether, 66, 116 Excipient, 72, 74, 116 Excrete, 116, 122, 131 Exercise Test, 16, 116 Exercise Tolerance, 8, 19, 31, 116 Exhaustion, 105, 116 Exogenous, 22, 107, 108, 115, 116, 130 Extracellular, 116, 132, 134 F Facial, 39, 70, 116 Facial Expression, 116 Facial Nerve, 70, 116 Family Planning, 87, 116 Fat, 107, 112, 116, 122, 133 Fatigue, 116, 118 Femoral, 109, 116, 117 Femoral Artery, 109, 117 Filtration, 66, 69, 117 Flatus, 117 Fold, 117, 123 Forearm, 14, 107, 117 G Gallate, 5, 117 Ganglionic Blockers, 106, 117 Gas, 16, 52, 117, 120, 133 Gastric, 117, 126 Gastric Acid, 117, 126 Gastrin, 117, 119 Gastroesophageal Reflux, 23, 117 Gastroesophageal Reflux Disease, 23, 117 Gastrointestinal, 7, 69, 115, 116, 117, 132, 133 Gastrointestinal tract, 69, 116, 117, 132 Gastrointestinal Transit, 7, 117 Gene, 107, 117 Genistein, 5, 117 Gingival Hyperplasia, 26, 117 Gland, 103, 112, 117, 127, 131, 132, 134 Glomerular, 57, 117, 118, 121, 125 Glomerular Filtration Rate, 57, 118, 125 Glomeruli, 118 Glomerulonephritis, 57, 118 Glomerulus, 117, 118 Glucocorticoid, 118, 129 Glucose, 9, 24, 25, 27, 48, 52, 107, 113, 118, 119, 120, 121, 130 Glucose tolerance, 27, 48, 118 Glucose Tolerance Test, 118 Glycine, 105, 107, 118, 125 Glycoprotein, 5, 60, 62, 118

140

Felodipine

Governing Board, 118, 129 Graft, 18, 118 H Headache, 67, 118, 120 Headache Disorders, 118 Heart attack, 74, 109, 118 Heart failure, 19, 23, 38, 39, 40, 105, 118, 126, 129 Heart Murmurs, 4, 118, 119 Heart Sounds, 118, 119 Heme, 107, 113, 119 Hemodialysis, 38, 113, 119, 122 Hemodynamics, 23, 61, 119 Hemoglobin, 105, 116, 119 Hemorrhage, 112, 118, 119, 133 Hepatic, 62, 66, 104, 118, 119 Hepatitis, 66, 119 Hepatocytes, 119 Herpes, 70, 119 Herpes Simplex Encephalitis, 70, 71, 119 Herpes virus, 70, 119 Herpes Zoster, 70, 119 Homeostasis, 24, 119 Hormonal, 25, 28, 30, 112, 119 Hormone, 27, 48, 53, 103, 104, 112, 115, 117, 119, 121, 134 Hydrocephalus, 119, 122 Hydrochlorothiazide, 11, 12, 13, 14, 25, 35, 43, 52, 120 Hydrogen, 103, 108, 114, 120, 124, 126 Hydrolysis, 107, 120, 129 Hydroxyproline, 105, 110, 120 Hyperplasia, 4, 120 Hyperthyroidism, 120, 129 Hypertrophy, 9, 14, 31, 40, 41, 42, 46, 67, 120, 129 Hypoglycaemia, 27, 53, 120 Hypotensive, 47, 120 Hypothermia, 120 Hypoxanthine, 42, 120 Hypoxia, 25, 120 I Idiopathic, 71, 120 Immune response, 103, 112, 120, 133, 136 Immunogenic, 120, 122 Immunology, 103, 104, 121 Immunosuppressive, 118, 121, 134 Impairment, 67, 121 In vitro, 25, 31, 59, 60, 121, 134 In vivo, 31, 58, 59, 61, 121, 134 Incompetence, 117, 121 Indomethacin, 32, 121

Infarction, 120, 121 Infiltration, 118, 121 Inflammation, 104, 106, 108, 116, 119, 121, 128 Infusion, 19, 47, 121 Ingestion, 5, 20, 52, 118, 121, 123, 134 Inhalation, 121, 123 Innervation, 116, 121 Inotropic, 17, 40, 106, 121 Insight, 5, 121 Insulin, 9, 27, 48, 53, 118, 121, 122 Insulin-dependent diabetes mellitus, 9, 121 Intestinal, 5, 27, 53, 118, 121 Intestinal Mucosa, 5, 121 Intestine, 107, 108, 117, 121, 131, 132 Intracellular, 58, 108, 121, 129 Intravenous, 28, 36, 37, 38, 39, 53, 54, 121 Inulin, 118, 121 Involuntary, 107, 121, 124, 128, 131, 132 Ions, 73, 108, 114, 115, 120, 122 Ischemia, 67, 71, 122 Isosorbide, 13, 122 Isradipine, 3, 4, 6, 9, 32, 43, 122 K Kb, 86, 122 Ketanserin, 33, 122 Ketoacidosis, 103, 122 Ketone Bodies, 103, 122 Kidney Disease, 86, 103, 104, 122 Kidney Failure, 115, 122 L Lacrimal, 116, 122 Leukocytes, 107, 113, 121, 122 Ligaments, 112, 122 Lipid, 25, 52, 121, 122 Lipid A, 52, 122 Lipopolysaccharides, 122 Lisinopril, 33, 122 Lithium, 59, 122 Liver, 10, 38, 44, 60, 62, 66, 104, 107, 110, 118, 119, 123, 130, 131 Localized, 123, 126, 128, 131 Loop, 40, 123 Lower Esophageal Sphincter, 117, 123 Lymphatic, 123, 126 Lymphocytes, 122, 123, 134 M Malnutrition, 104, 123 Manic, 123 Mastectomy, 108, 123 MEDLINE, 87, 123

141

Membrane, 109, 111, 113, 114, 119, 123, 126, 131 Menopause, 123, 129 Mental, iv, 4, 30, 86, 88, 109, 111, 113, 116, 121, 123, 130 Mesenteric, 61, 123 Mesentery, 123 Metabolite, 16, 107, 110, 114, 123, 129, 130 Methanol, 66, 123 Methionine, 114, 123 Methylene Chloride, 66, 123 Metoprolol, 7, 8, 9, 10, 12, 15, 16, 20, 25, 26, 28, 30, 31, 36, 37, 41, 47, 52, 68, 69, 123 MI, 12, 17, 36, 40, 62, 101, 123 Microbe, 124, 135 Microorganism, 124, 136 Migration, 73, 124 Mobilization, 108, 124 Modification, 105, 124, 130 Molecular, 69, 87, 89, 107, 108, 111, 124, 135 Molecule, 67, 110, 120, 124, 126, 131 Monitor, 124, 126 Monotherapy, 14, 21, 23, 30, 34, 36, 37, 38, 40, 43, 61, 124 Morphological, 115, 124 Motility, 121, 124, 132 Multicenter study, 36, 124 Multidrug resistance, 61, 124 Muscle Contraction, 54, 124 Myocardial infarction, 4, 15, 67, 112, 123, 124, 129 Myocardial Ischemia, 105, 124 Myocardium, 105, 123, 124 Myosin, 124 N Narcotic, 123, 125 Natriuresis, 17, 32, 34, 105, 125 Necrosis, 121, 123, 124, 125 Nerve, 71, 103, 110, 115, 116, 121, 125, 132, 135 Nervous System, 103, 109, 125, 127, 133 Neurotransmitter, 103, 105, 118, 125, 133 Neutralization, 70, 125 Nicardipine, 3, 4, 125 Nihilism, 71, 125 Nimodipine, 3, 4, 20, 70, 125 Nisoldipine, 4, 6, 125 Nitrendipine, 45, 68, 125 Norepinephrine, 39, 103, 125 Normotensive, 7, 28, 52, 125

Nuclear, 24, 111, 115, 125, 135 Nucleic acid, 120, 126 O Ocular, 19, 126 Oedema, 6, 34, 126 Omeprazole, 8, 29, 126 Oral Health, 126 Oral Hygiene, 4, 126 Orthostatic, 28, 126 Osmotic, 104, 122, 126 Outpatient, 6, 126 Oxidation, 60, 74, 103, 107, 113, 126 Oxidation-Reduction, 107, 126 Oxygen Consumption, 14, 116, 126 Oxygenator, 109, 126 P Palliative, 126, 134 Palsy, 70, 126 Pancreas, 121, 127 Pancreatic, 117, 127 Pancreatic Juice, 117, 127 Paralysis, 71, 127 Parathyroid, 58, 127, 134 Parathyroid Glands, 127 Parathyroid hormone, 58, 127 Parietal, 126, 127, 128 Paroxysmal, 105, 118, 127 Particle, 53, 127, 135 Patch, 127, 135 Pathologic, 112, 127 Patient Compliance, 68, 127 Penicillin, 105, 127 Peptide, 39, 44, 105, 127, 129, 130 Perfusion, 120, 127 Peripheral Nervous System, 125, 126, 127, 133 Peritoneal, 106, 126, 127 Peritoneal Cavity, 106, 126, 127 Pharmaceutical Preparations, 68, 71, 73, 116, 127 Pharmacodynamic, 7, 10, 37, 40, 47, 54, 128 Pharmacokinetic, 10, 12, 16, 32, 37, 40, 47, 52, 54, 128 Pharmacologic, 73, 128, 135 Pharynx, 117, 128 Phenyl, 66, 107, 128 Phosphorus, 108, 127, 128 Physiologic, 104, 121, 128, 131 Piloerection, 120, 128 Plants, 104, 118, 121, 125, 128, 131, 135 Plaque, 4, 106, 128

142

Felodipine

Plasma, 16, 17, 21, 25, 33, 38, 39, 52, 71, 104, 109, 118, 119, 122, 123, 128, 131 Plasma protein, 104, 128 Platelet Aggregation, 122, 128 Platinum, 123, 128 Pleural, 126, 128 Pleural cavity, 126, 128 Pneumonia, 112, 128 Pollen, 128, 130 Polypeptide, 105, 110, 129 Potassium, 9, 40, 43, 56, 104, 114, 120, 129 Potentiate, 61, 129 Practice Guidelines, 88, 129 Prazosin, 30, 129 Prednisolone, 19, 129 Prenatal, 115, 129 Pressoreceptors, 106, 129 Prodrug, 110, 129, 130 Progression, 70, 71, 103, 129 Progressive, 110, 114, 125, 129 Projection, 125, 129 Prophylaxis, 113, 129 Propranolol, 67, 106, 129 Prostaglandins, 121, 129 Prostaglandins A, 121, 129 Protective Agents, 108, 130 Protein Binding, 11, 130 Protein C, 104, 106, 130 Protein S, 107, 130 Proteins, 105, 108, 109, 110, 113, 124, 127, 128, 130, 132, 135 Protein-Tyrosine Kinase, 117, 130 Psychic, 123, 130, 131 Public Policy, 87, 130 Pulmonary, 23, 107, 116, 119, 122, 130, 133, 136 Pulmonary Artery, 107, 130, 136 Pulse, 13, 124, 130 Q Quality of Life, 10, 14, 34, 130 Quercetin, 5, 56, 130 R Race, 67, 124, 130 Racemic, 67, 130 Radiation, 105, 130, 136 Radioactive, 120, 126, 130, 134, 135 Ramipril, 7, 10, 20, 40, 45, 53, 57, 68, 130 Randomized, 21, 22, 24, 48, 57, 115, 130 Reabsorption, 120, 130 Reaction Time, 69, 130 Reactivation, 71, 131 Receptor, 43, 122, 131, 132

Rectum, 117, 131 Refer, 1, 110, 114, 119, 131, 135 Reflex, 10, 131 Reflux, 23, 117, 131 Refractory, 24, 33, 58, 60, 63, 131 Regimen, 68, 115, 127, 131 Regurgitation, 49, 117, 131 Renal tubular, 131 Renin, 11, 52, 105, 108, 131 Renin-Angiotensin System, 105, 108, 131 Renovascular, 58, 131 Rutin, 130, 131 S Salivary, 116, 131 Salivary glands, 116, 131 Sarcolemma, 55, 131 Scleroderma, 92, 131 Screening, 110, 131 Secretion, 27, 48, 58, 112, 121, 126, 131 Secretory, 126, 131 Seizures, 105, 127, 131 Serotonin, 122, 125, 131 Serum, 11, 19, 32, 78, 104, 110, 114, 132 Side effect, 3, 4, 81, 103, 132, 134 Skeletal, 54, 132 Skeleton, 103, 132 Skull, 112, 132, 134 Small intestine, 114, 119, 121, 132 Smooth muscle, 24, 58, 108, 115, 122, 131, 132, 133 Social Environment, 130, 132 Sodium, 19, 20, 52, 104, 114, 120, 125, 130, 132, 133 Solvent, 8, 66, 69, 70, 71, 103, 116, 123, 126, 132 Spasm, 71, 112, 132, 134 Spatial disorientation, 114, 132 Specialist, 93, 114, 132 Species, 115, 124, 130, 132, 135, 136 Spinal cord, 109, 110, 125, 127, 131, 132, 133 Stenosis, 74, 132, 133 Sterile, 127, 132 Stimulus, 112, 121, 130, 131, 132, 134 Stomach, 116, 117, 118, 119, 123, 127, 128, 131, 132, 133 Stress, 30, 112, 133 Stricture, 132, 133 Stroke, 4, 86, 92, 109, 133 Structure-Activity Relationship, 5, 133 Subarachnoid, 118, 133 Subcutaneous, 114, 126, 133

143

Substance P, 123, 131, 133 Suction, 117, 133 Supine, 28, 133 Supplementation, 63, 133 Surfactant, 72, 74, 133 Sweat, 113, 120, 133 Sympathetic Nervous System, 105, 133 Sympathomimetic, 103, 115, 125, 133 Synapse, 103, 133, 135 Systemic, 5, 12, 21, 43, 63, 82, 106, 107, 115, 119, 126, 129, 131, 133, 135 Systolic, 6, 13, 23, 26, 31, 34, 36, 42, 67, 77, 120, 133 T Tachycardia, 10, 133 Tacrolimus, 19, 134 Technetium, 43, 134 Telangiectasia, 39, 134 Temporal, 71, 118, 134 Teratogenic, 114, 134 Tetany, 127, 134 Therapeutics, 9, 21, 22, 25, 27, 33, 35, 40, 43, 47, 59, 60, 82, 134 Thermal, 69, 134 Threshold, 120, 134 Thrombosis, 130, 133, 134 Thyroid, 120, 127, 134 Thyroid Gland, 120, 127, 134 Thyroxine, 104, 134 Tolerance, 118, 134 Tomography, 134 Tone, 125, 126, 134 Topical, 116, 134 Toxic, iv, 66, 111, 123, 134, 135 Toxicity, 74, 114, 135 Toxicology, 52, 53, 59, 88, 135 Toxin, 115, 134, 135 Transdermal, 61, 72, 73, 135 Transduction, 108, 135

Transfection, 107, 135 Translation, 105, 135 Translocation, 24, 135 Transmitter, 125, 135 Transplantation, 19, 20, 24, 31, 32, 46, 59, 135 Triamterene, 25, 135 U Uranium, 134, 135 Urinary, 48, 120, 129, 135 Urinary Retention, 129, 135 Urine, 104, 113, 114, 122, 125, 135 V Vaccines, 135, 136 Vascular, 18, 29, 42, 48, 49, 68, 71, 106, 108, 113, 115, 118, 121, 122, 126, 129, 134, 135 Vascular Resistance, 18, 106, 135 Vasoactive, 18, 57, 135 Vasoconstriction, 45, 71, 115, 135 Vasodilation, 11, 33, 105, 107, 135 Vasodilator, 14, 19, 28, 39, 40, 48, 60, 63, 69, 106, 125, 136 Vein, 61, 105, 121, 126, 136 Venous, 18, 126, 130, 136 Ventricle, 130, 133, 136 Ventricular, 9, 14, 17, 20, 23, 29, 31, 40, 41, 42, 46, 119, 120, 136 Ventricular Function, 29, 42, 136 Venules, 107, 108, 136 Verapamil, 3, 4, 15, 20, 32, 52, 66, 136 Vesicular, 119, 136 Veterinary Medicine, 87, 136 Viral, 70, 135, 136 Virulence, 135, 136 Virus, 70, 71, 106, 109, 128, 135, 136 Vitro, 136 Vivo, 31, 136 X X-ray, 111, 126, 136

144

Felodipine

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