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

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

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IRBESARTAN 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., 1960Irbesartan: A Medical Dictionary, Bibliography, and Annotated Research Guide to Internet References / James N. Parker and Philip M. Parker, editors p. cm. Includes bibliographical references, glossary, and index. ISBN: 0-597-84469-0 1. Irbesartan-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 irbesartan. 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 IRBESARTAN .............................................................................................. 3 Overview........................................................................................................................................ 3 The Combined Health Information Database................................................................................. 3 Federally Funded Research on Irbesartan ...................................................................................... 4 E-Journals: PubMed Central ......................................................................................................... 9 The National Library of Medicine: PubMed .................................................................................. 9 CHAPTER 2. NUTRITION AND IRBESARTAN .................................................................................... 29 Overview...................................................................................................................................... 29 Finding Nutrition Studies on Irbesartan..................................................................................... 29 Federal Resources on Nutrition ................................................................................................... 30 Additional Web Resources ........................................................................................................... 31 CHAPTER 3. PATENTS ON IRBESARTAN .......................................................................................... 33 Overview...................................................................................................................................... 33 Patents on Irbesartan ................................................................................................................... 33 Patent Applications on Irbesartan ............................................................................................... 35 Keeping Current .......................................................................................................................... 36 CHAPTER 4. PERIODICALS AND NEWS ON IRBESARTAN ................................................................ 37 Overview...................................................................................................................................... 37 News Services and Press Releases................................................................................................ 37 Academic Periodicals covering Irbesartan ................................................................................... 39 CHAPTER 5. RESEARCHING MEDICATIONS .................................................................................... 41 Overview...................................................................................................................................... 41 U.S. Pharmacopeia....................................................................................................................... 41 Commercial Databases ................................................................................................................. 42 APPENDIX A. PHYSICIAN RESOURCES ............................................................................................ 45 Overview...................................................................................................................................... 45 NIH Guidelines............................................................................................................................ 45 NIH Databases............................................................................................................................. 47 Other Commercial Databases....................................................................................................... 49 APPENDIX B. PATIENT RESOURCES ................................................................................................. 51 Overview...................................................................................................................................... 51 Patient Guideline Sources............................................................................................................ 51 Finding Associations.................................................................................................................... 53 APPENDIX C. FINDING MEDICAL LIBRARIES .................................................................................. 55 Overview...................................................................................................................................... 55 Preparation................................................................................................................................... 55 Finding a Local Medical Library.................................................................................................. 55 Medical Libraries in the U.S. and Canada ................................................................................... 55 ONLINE GLOSSARIES.................................................................................................................. 61 Online Dictionary Directories ..................................................................................................... 61 IRBESARTAN DICTIONARY ...................................................................................................... 63 INDEX ................................................................................................................................................ 87

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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 irbesartan 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 irbesartan, 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 irbesartan, 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 irbesartan. 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 irbesartan, 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 irbesartan. The Editors

1

From the NIH, National Cancer Institute (NCI): http://www.cancer.gov/cancerinfo/ten-things-to-know.

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CHAPTER 1. STUDIES ON IRBESARTAN Overview In this chapter, we will show you how to locate peer-reviewed references and studies on irbesartan.

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

Effect of Irbesartan on the Development of Diabetic Nephropathy in Patients with Type 2 Diabetes Source: New England Journal of Medicine. 345(12): 870-877. September 20, 2001. Summary: Microalbuminuria (microscopic protein in the urine) and hypertension (blood pressure) are risk factors for diabetic nephropathy (diabetes associated kidney disease). Blockade of the renin angiotensin system slows the progression to diabetic nephropathy in patients with type 1 diabetes, but similar data are lacking for hypertensive patients with type 2 diabetes. This article reports on a study that evaluated the renoprotective effect of the angiotensin II receptor antagonist irbesartan in hypertensive patients with type 2 diabetes and microalbuminuria. A total of 590 patients were enrolled in the study, at a dose of either 150 milligrams daily or 300 milligrams daily, and were followed for two years. The primary outcome was the time to the onset of diabetic nephropathy,

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defined by persistent albuminuria in overnight specimens, with a urinary albumin excretion rate that was greater than 200 micrograms per minute and at least 30 percent higher than the baseline level. The baseline characteristics in the three groups were similar. Ten of the 194 patients in the 300 milligram group (5.2 percent) and 19 of the 195 patients in the 150 milligram group (9.7 percent) reached the primary end point, as compared with 30 of the 201 patients in the placebo group (14.9 percent). Serious adverse events were less frequent among the patients treated with irbesartan. The authors conclude that iresartan is renoprotective (protects the kidney) independently of its blood pressure lowering effect in patients with type 2 diabetes and microalbuminuria. 3 figures. 2 tables. 33 references. •

Renoprotective Effect of the Angiotensin-Receptor Antagonist Irbesartan in Patients with Nephropathy Due to Type 2 Diabetes Source: New England Journal of Medicine. 345(12): 851-860. September 20, 2001. Summary: This article reports on a study that investigated whether the angiotensin II receptor blocker irbesartan or the calcium channel blocker amlodipine slows the progression of nephropathy (kidney disease) in patients with type 2 diabetes, independently of its capacity to lower the systemic blood pressure. The authors randomly assigned 1,715 patients with hypertension (high blood pressure) and nephropathy due to type 2 diabetes to treatment with irbesartan (300 milligrams daily), amlodipine (10 milligrams daily), or placebo. The target blood pressure was 135 over 85 mm Hg or less in all groups. The mean duration of follow up was 2.6 years. Treatment with irbesartan was associated with a risk of the primary composite end point (a doubling of the baseline serum creatinine concentration, the development of end stage renal disease or ESRD, or death from any cause) that was 20 percent lower than that in the placebo group and 23 percent lower than that in the amlodipine group. The risk of a doubling of the serum creatinine concentration was 33 percent lower in the irbesartan group than in the placebo group and 37 percent lower in the irbesartan group than in the amlodipine group. Treatment with irbesartan was associated with a relative risk of ESRD that was 23 percent lower than that in both other groups. These differences were not explained by differences in the blood pressures that were achieved. There were no significant differences in the rates of death from any cause or in the cardiovascular composite end point. The authors conclude that irbesartan is effective in protecting against the progression of nephropathy due to type 2 diabetes. 2 figures. 3 tables. 26 references.

Federally Funded Research on Irbesartan The U.S. Government supports a variety of research studies relating to irbesartan. 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.

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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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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 irbesartan. 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 irbesartan. The following is typical of the type of information found when searching the CRISP database for irbesartan: •

Project Title: CLINICAL TRIAL TO SLOW THE PROGRESSION OF ADPKD Principal Investigator & Institution: Schrier, Robert W.; Professor; Medicine; University of Colorado Hlth Sciences Ctr P.O. Box 6508, Grants and Contracts Aurora, Co 800450508 Timing: Fiscal Year 2002; Project Start 15-AUG-2002; Project End 31-JAN-2009 Summary: (provided by applicant): Autosomal dominant polycystic kidney disease (ADPKD) affects one in 500-1000 Americans and leads to end-stage renal disease (ESRD) in 50% of patients by age 60 years. Moreover, the life expectancy of ADPKD patients is significantly reduced compared with the general population, despite the availability of dialysis and transplantation, due to premature cardiovascular mortality. Recent advances have lead to greater understanding of the mechanisms of ADPKD, and several agents have been found to slow cyst growth in animal models. However, clinical interventions to ameliorate the course of ADPKD in humans are lacking. Therefore, the National Institute of Diabetes and Digestive and Kidney Diseases has proposed a PKD Clinical Trials Network to design and implement clinical trials to slow the progressive loss of renal function in PKD, including a large trial on blockade of the reninangiotensin-aldosterone system (RAAS). The PKD Research Center at the University of Colorado Health Sciences Center maintains a database of nearly 800 families with ADPKD, and over 1000 family members have participated in previous clinical studies at our Center. Additional patients with ADPKD are available for recruitment from the Polycystic Kidney Research Foundation and from agreements with local health care providers. Thus, we are confident we can identify 500 patients with ADPKD who are eager and eligible to participate in a clinical trial. We propose both a large randomized controlled clinical trial featuring blockade of the RAAS and a pilot study to determine if treatment with an antiangiogenic agent slows the rate of renal growth in patients with ADPKD. Working in collaboration with the PKD Clinical Trials Network, our goal is to identify interventions that not only slow but prevent progression of ADPKD to ESRD, and interventions that ameliorate the cardiovascular complications in ADPKD. A 2 X 2 factorial design is proposed to examine the hypothesis that RAAS inhibition and rigorous blood pressure control will slow progression in advanced ADPKD and prevent progression of renal and cardiovascular disease in early ADPKD. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: EFFECT OF IRBESARTAN IN HYPERTENSIVES WITH TYPE II DIABETES AND NEPHROPATHY Principal Investigator & Institution: Hegeman, Rebecca L.; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002 Summary: The goal of the study is to determine whether irbesartan, an angiotensin II receptor antagonist, will increase the time to doubling of serum creatinine, end-stage

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renal disease or death compared to placebo or amlodipine in hypertensive patients with diabetic nephropathy. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: EFFECT OF IRBESARTAN PLUS ESTRACE COMPARED TO IRBESARTAN ALONE Principal Investigator & Institution: Seely, Ellen W.; Professor; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002; Project Start 01-DEC-2001; Project End 30-NOV-2002 Summary: The purpose of this study is to test the hypothesis that combined irbesarten and estrogen therapy has an additive effect on improving vascular reactivity, renal blood flow, blood pressure lowering, and lipid profile when compared to either agent alone. Irbesarten is an investigational new drug to treat high blood pressure. This is an investigator-initiated, industry sponsored study. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: LOSARTAN IN MILD TO MODERATE ESSENTIAL HYPERTENSION Principal Investigator & Institution: Ziegler, Michael G.; Professor of Medicine; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: MECHANISM CARDIOMYOPATHY

OF

CHRONIC

ALCOHOL

INDUCED

Principal Investigator & Institution: Cheng, Che-Ping; Professor; Internal Medicine; Wake Forest University Health Sciences Winston-Salem, Nc 27157 Timing: Fiscal Year 2002; Project Start 01-MAR-2000; Project End 28-FEB-2005 Summary: This grant will investigate the mechanism of chronic alcoholinduced dilated cardiomyopathy (ADCM), by longitudinally assessing the structural and functional responses of the left ventricle (LV) and isolated cardiomyocytes to chronic alcohol intake. In addition, the role of the renin-angiotensin system (RAS) and the alterations in its intracellular signaling in producing ADCM will be determined. We will test the following specific Hypotheses: [H1] Chronic alcohol intake produces direct depressions in cardiomyocyte contraction, relaxation, [Ca2+]i transient and sarcolemmal Ca2+ channel activity (ICa,L), and thus causes [H2] a progressive impairment of LV systolic, diastolic function, and leads to congestive heart failure, and [H3] the most important factor in promoting the transition to ADCM is the alcohol-induced, sustained activation of circulating and cardiac RAS. This results in alterations in the AT1 receptor-coupled, protein kinase C and/or inhibitory G protein (Gi)-mediated responses of the LV and myocytes to angiotensin II (ANG II). Thus, [H4] blocking the RAS with chronic ACE inhibition or ANG II AT1 receptor blocker will blunt or prevent the chronic alcoholinduced functional and structural changes. The studies will be conducted in three control and four experimental groups studied over eight months: 1) uninstrumented alcohol-fed (22 percent alcohol once per day, providing 33 percent of total daily caloric intake); 2) instrumented alcohol-fed; 3) instrumented alcohol- ramipril (ACE inhibitor, 0.1 mg/kg/day)-fed; 4) instrumented alcohol-irbesartan (ANG II AT1 blocker, 5 mg/kg/day)-fed. The control groups will consist of age-matched dogs under identical

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conditions except dogs in the control groups will not receive alcohol. Serial changes of cardiac systolic and diastolic function and RAS activation will be quantitated in these conscious dogs, chronically instrumented to measure LV pressures and volume. Cell contractile function, [Ca2+]i transient and ICa,L will be serially measured in freshly isolated cardiomyocytes from the LV obtained by biopsy from the same animals. Myocytes will be studied under conditions with superfusion of: 1) calcium, 2) isoproterenol, 3) pimobendan, 4) alcohol, and 5) ANG II. In addition, the studies of myocytes response to ANG II will be repeated after preincubation with an AT1 receptor blocker, a protein kinase C inhibitor, or a Gi protein inhibitor, before, during and after the development of ADCM. These studies will be the first detailed longitudinal studies of cardiac and myocyte structure, function, [Ca2+]i transient, ICa,L during chronic alcohol intake. In addition, these studies will provide unique information on the role of the RAS and the mechanism of ADCM. These studies are necessary to extend our knowledge about the mechanism in the development of ADCM and help target therapy for ADCM. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: RENAL RESPONSES TO ANGIOTENSIN II ANTAGONIST IRBESARTAN IN TYPE II DIABETES Principal Investigator & Institution: Hollenberg, Norman K.; Brigham and Women's Hospital 75 Francis Street Boston, Ma 02115 Timing: Fiscal Year 2002 Summary: The purpose of this study is to investigate a new blood pressure lowering drug. This drug, irbesartan, is a member of a new class of antihypertensive agents which inhibit the renin angiotensin system by blocking the effect of a hormone, angiotensin II. It is hoped that irbesartan, which specifically inhibits the effect of angiotensin will allow blood pressure lowering without contributing to other important side effects, in particular kidney damage to patients with Diabetes Mellitus. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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Project Title: SAFETY AND EFFACY OF IRBESARTAN IN HYPERTENSIVE TYPE II DIABETICS Principal Investigator & Institution: Hunsicker, Lawrence G.; Professor; University of Iowa Iowa City, Ia 52242 Timing: Fiscal Year 2002 Summary: This is a study to ascertain the safety and tolerability of irbesartan, an angiotensin II receptor antagonist in hypertensive subjects with type II diabetes mellitus and proteinuria. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: SERUM TOTAL HOMOCYSTEINE AND C-REACTIVE PROTEIN AS PRED Principal Investigator & Institution: Bostom, Andrew G.; Associate Professor of Medicine; Rhode Island Hospital (Providence, Ri) Providence, Ri 02903 Timing: Fiscal Year 2002; Project Start 01-APR-2001; Project End 30-JUN-2004 Summary: (Applicant's Abstract) Patients with diabetic nephropathy experience markedly increased rates of morbidity and mortality due to arteriosclerotic cardiovascular disease [CVD]. Established arteriosclerotic risk factors such as age, sex,

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cigarette smoking, hypertension, and dysilpidernia do not account adequately for this excess CVD risk. Prospective data from general populations, and much more limited findings from both diabetic cohorts. and cohorts with chronic renal disease, have linked elevated levels of total hornocysteine (tHcy) and C-reactive protein (CRP) to arteriosclerotic CVD morbidity and mortality. Determination of baseline serum tHcy and CRP concentrations in the Irbesartan Type 2 Diabetic Nephropathy Trial (IDNT) cohort affords a truly unique opportunity to evaluate the potential independent relationship between these putative CVD risk factors and subsequent CVD morbidity and mortality, in this patient population. Specific Aim I (Longitudinal analyses): To evaluate the potential "Independent" relationship* between baseline concentrations of serum total hornocysteine (tHcy) and C-reactive protein (CRP) in the full IDNT cohort, and subsequent:pooled CVD morbidity and mortality (primary analysis). total mortality, (*after multivariable -adjustment for the established predictors of CVD morbidity/ mortality, and total mortality). Specific Aim 2 -(Cross- sectional analyses): To assess baseline serum total hornocysteine (tHcy) and C-reactive protein (CRP) concentrations in the full IDNT collort, in relation to potential baseline determinants of these analytes, including: B-vitamin status; age and gender; renal function indices, i.e. both creatinine-based GFR estimates, and proteinuria; indices of glycernia, prevalent cardiovascular disease (CVD), traditional CVD risk factors (i.e., in particular, smoking, blood pressure, and total cholesterol/HDL cholesterol ratio). Using proportional hazards modeling, with complete data available from 1650 total subjects, we will have 83.0% power at a two-tailed alpha of 0.05 to detect a relative risk estimate (hazards ratio) for total CVD Occurrence of 1.4, comparing quartile 4, to quartiles 1-3 of either tHcv or CRP. Our prospective findings will help elucidate whether measurement of these Putative CVD risk factors may provide useful Information for CVD risk assessment in mild to moderate renal insufficiency due to diabetic nephropathy, specifically. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen •

Project Title: THE EFFECT OF IRBESARTAN ON TYPE II DIABETES Principal Investigator & Institution: Ziegler, Micheal G.; University of California San Diego 9500 Gilman Dr, Dept. 0934 La Jolla, Ca 920930934 Timing: Fiscal Year 2002 Summary: This abstract is not available. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

•

Project Title: TREATMENT OF DIABETIC NEPHROPATHY Principal Investigator & Institution: Lewis, Julia B.; Professor of Medicine; Medicine; Vanderbilt University 3319 West End Ave. Nashville, Tn 372036917 Timing: Fiscal Year 2002; Project Start 30-SEP-2002; Project End 31-AUG-2004 Summary: (provided by applicant): The kidney is a particularly rich source for prostaglandins and prostaglandins modulate a broad range of renal functions including microvascular hemodynamics, renin release and tubular salt and water reabsorption. The normal adult mammalian kidney expresses COX2 and cyclooxygenase metabolites, and they have been implicated in functional and structural alterations in glomerular and tubulointerstitial inflammatory diseases. In experimental animal models of kidney disease, COX2 selective inhibitors decreased proteinuria and inhibited the development of glomerulosclerosis. In addition, the use of COX2 inhibitors decreased the expression of TGF-a1 in Type III and IV collagen. Clinical studies in humans have minimally examined the renal effects of the COX2 inhibitors. They have been demonstrated to

Studies

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decrease the urinary excretion of prostaglandins, reduce urinary sodium excretion and have conflicting results on acute changes in GFR. Nonsteroidal anti-inflammatory agents, which work less specifically than COX2 inhibitors in the kidney have been demonstrated to decrease proteinuria in subjects with refractory nephrotic syndrome. In this study, we propose to extend the animal and human data suggesting a potential beneficial effect of COX2 inhibitors in renal disease as manifested by its acute hemodynamic effects decreasing proteinuria and perhaps initially single nephron GFR. Recognizing there may be safety concerns in regards to hyperkalemia and acute renal failure in a subject population with preexisting diabetes and renal disease given COX2 inhibitors, we propose a short-term pilot study in humans with diabetes and modest chronic renal insufficiency and proteinuria. We will randomly assign 30 subjects with diabetic nephropathy already on ACE inhibitor therapy to a crossover design of either placebo (6 wks) - washout (3 wks) - COX2 inhibitor(6 wks) - washout (3 wks) or COX2 inhibitor (6 wks) - washout (3 wks) - placebo (6 wks) - washout (3 wks). This will allow us to both collect safety data in this population of subjects as well as examine the acute effects of COX2 inhibitors on proteinuria. We propose to use a decrease in proteinuria as a surrogate for renal function in this short-term pilot study. A decline in proteinuria in subjects randomized to COX2 inhibitors would support consideration of a larger, longterm trial to examine the efficacy of COX2 inhibitors in preserving renal function. Website: http://crisp.cit.nih.gov/crisp/Crisp_Query.Generate_Screen

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

Prolonged cholestasis associated with irbesartan. by Hariraj R, Stoner E, Jader S, Preston DM.; 2000 Sep 2; http://www.pubmedcentral.gov/articlerender.fcgi?tool=pmcentrez&artid=27470

The National Library of Medicine: PubMed One of the quickest and most comprehensive ways to find academic studies in both English and other languages is to use PubMed, maintained by the National Library of Medicine.6 3 4

Adapted from the National Library of Medicine: http://www.pubmedcentral.nih.gov/about/intro.html.

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

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Irbesartan

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

24-hour blood pressure control by once-daily administration of irbesartan assessed by ambulatory blood pressure monitoring. Irbesartan Multicenter Investigators' Group. Author(s): Fogari R, Ambrosoli S, Corradi L, Degli Esposti E, Mos L, Nami R, Nicrosini F, Pessina AC, Salvetti A, Vaccarella A, Zanchetti A, Martin A, Reeves RA. Source: Journal of Hypertension. 1997 December; 15(12 Pt 1): 1511-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9431859

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A look through the new therapeutic window: irbesartan. Author(s): Waeber B, Brunner HR. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1998 September; 16(7): S11-6. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9855026

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A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorizacion Ambulatoria Presion Arterial APROVEL). Author(s): Coca A, Calvo C, Garcia-Puig J, Gil-Extremera B, Aguilera MT, de L, MartinHidalgo A, Marin R; MAPAVEL Investigators (Monitorizacion Ambulatoria Presion Arterial APROVEL). Source: Clinical Therapeutics. 2002 January; 24(1): 126-38. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11833827

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A multicenter, randomized, double-blind study of the antihypertensive efficacy and tolerability of irbesartan in patients aged > or = 65 years with mild to moderate hypertension. Author(s): Lacourciere Y. Source: Clinical Therapeutics. 2000 October; 22(10): 1213-24. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11110232

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.

Studies

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A randomised, double-blind comparison of the angiotensin II receptor antagonist, irbesartan, with the full dose range of enalapril for the treatment of mild-to-moderate hypertension. Author(s): Mimran A, Ruilope L, Kerwin L, Nys M, Owens D, Kassler-Taub K, Osbakken M. Source: Journal of Human Hypertension. 1998 March; 12(3): 203-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9579771

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A study of the efficacy and safety of irbesartan in combination with conventional therapy, including ACE inhibitors, in heart failure. Irbesartan Heart Failure Group. Author(s): Tonkon M, Awan N, Niazi I, Hanley P, Baruch L, Wolf RA, Block AJ. Source: Int J Clin Pract. 2000 January-February; 54(1): 11-4, 16-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10750252

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Additional effects of irbesartan when compared to captopril in the prevention of post-infarction left ventricular dilatation. Author(s): Parkhomenko AN, Irkin OI, Kushnir SP, Bryl ZV, Soliarik O, Shkliar LV. Source: Acta Cardiol. 2002 February; 57(1): 61-3. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11918155

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Aldosterone synthase (CYP11B2) -344 C/T polymorphism is related to antihypertensive response: result from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. Author(s): Kurland L, Melhus H, Karlsson J, Kahan T, Malmqvist K, Ohman P, Nystrom F, Hagg A, Lind L. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 May; 15(5): 389-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12022239

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An ambulatory blood pressure monitoring study of the comparative antihypertensive efficacy of two angiotensin II receptor antagonists, irbesartan and valsartan. Author(s): Mancia G, Korlipara K, van Rossum P, Villa G, Silvert B. Source: Blood Pressure Monitoring. 2002 April; 7(2): 135-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12048432

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An economic evaluation of irbesartan in the treatment of patients with type 2 diabetes, hypertension and nephropathy: cost-effectiveness of Irbesartan in Diabetic Nephropathy Trial (IDNT) in the Belgian and French settings. Author(s): Palmer AJ, Annemans L, Roze S, Lamotte M, Rodby RA, Cordonnier DJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2003 October; 18(10): 2059-66. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=13679481

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Irbesartan

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An elective-titration study of the comparative effectiveness of two angiotensin IIreceptor blockers, irbesartan and losartan. Author(s): Bunt T. Source: Clinical Therapeutics. 1999 March; 21(3): 611-2. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10321426

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An elective-titration study of the comparative effectiveness of two angiotensin IIreceptor blockers, irbesartan and losartan. Irbesartan/Losartan Study Investigators. Author(s): Oparil S, Guthrie R, Lewin AJ, Marbury T, Reilly K, Triscari J, Witcher JA. Source: Clinical Therapeutics. 1998 May-June; 20(3): 398-409. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9663357

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Angiotensin AT1 receptor antagonist irbesartan decreases lesion size, chemokine expression, and macrophage accumulation in apolipoprotein E-deficient mice. Author(s): Dol F, Martin G, Staels B, Mares AM, Cazaubon C, Nisato D, Bidouard JP, Janiak P, Schaeffer P, Herbert JM. Source: Journal of Cardiovascular Pharmacology. 2001 September; 38(3): 395-405. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11486244

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B2 bradykinin receptor (B2BKR) polymorphism and change in left ventricular mass in response to antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. Author(s): Hallberg P, Lind L, Michaelsson K, Karlsson J, Kurland L, Kahan T, Malmqvist K, Ohman KP, Nystrom F, Melhus H. Source: Journal of Hypertension. 2003 March; 21(3): 621-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12640257

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Biotransformation of irbesartan in man. Author(s): Chando TJ, Everett DW, Kahle AD, Starrett AM, Vachharajani N, Shyu WC, Kripalani KJ, Barbhaiya RH. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1998 May; 26(5): 408-17. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9571222

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Cardiac autonomic tone during trandolapril-irbesartan low-dose combined therapy in hypertension: a pilot project. Author(s): Franchi F, Lazzeri C, Foschi M, Tosti-Guerra C, Barletta G. Source: Journal of Human Hypertension. 2002 August; 16(8): 597-604. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12149667

Studies

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Cardiovascular outcomes in the Irbesartan Diabetic Nephropathy Trial of patients with type 2 diabetes and overt nephropathy. Author(s): Berl T, Hunsicker LG, Lewis JB, Pfeffer MA, Porush JG, Rouleau JL, Drury PL, Esmatjes E, Hricik D, Parikh CR, Raz I, Vanhille P, Wiegmann TB, Wolfe BM, Locatelli F, Goldhaber SZ, Lewis EJ; Irbesartan Diabetic Nephropathy Trial. Collaborative Study Group. Source: Annals of Internal Medicine. 2003 April 1; 138(7): 542-9. Summary for Patients In: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667024

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Cholestatic hepatitis related to use of irbesartan: a case report and a literature review of angiotensin II antagonist-associated hepatotoxicity. Author(s): Andrade RJ, Lucena MI, Fernandez MC, Vega JL, Garcia-Cortes M, Casado M, Guerrero-Sanchez E, Pulido-Fernandez F. Source: European Journal of Gastroenterology & Hepatology. 2002 August; 14(8): 887-90. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172412

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Clinical overview of irbesartan: a new angiotensin II receptor antagonist. Author(s): Pouleur HG. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1997 December; 10(12 Pt 2): 318S-324S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9438776

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Clinical overview of irbesartan: expanding the therapeutic window in hypertension. Author(s): Man in't Veld AJ. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1997 December; 15(7): S27-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9532518

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Comparative cost effectiveness of angiotensin II receptor blockers in a US managed care setting: olmesartan medoxomil compared with losartan, valsartan, and irbesartan. Author(s): Simons WR. Source: Pharmacoeconomics. 2003; 21(1): 61-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12484804

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Comparative effects of Irbesartan on ambulatory and office blood pressure: a substudy of ambulatory blood pressure from the Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria study. Author(s): Rossing K, Christensen PK, Andersen S, Hovind P, Hansen HP, Parving HH; Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study. Source: Diabetes Care. 2003 March; 26(3): 569-74. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12610003

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Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricaemia and gout. Author(s): Wurzner G, Gerster JC, Chiolero A, Maillard M, Fallab-Stubi CL, Brunner HR, Burnier M. Source: Journal of Hypertension. 2001 October; 19(10): 1855-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11593107

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Comparative effects of losartan and irbesartan on serum uric acid in hypertensive patients with hyperuricemia and gout. Author(s): Liberopoulos E, Christides D, Elisaf M. Source: Journal of Hypertension. 2002 February; 20(2): 347. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11821722

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Comparative efficacy of olmesartan, losartan, valsartan, and irbesartan in the control of essential hypertension. Author(s): Oparil S, Williams D, Chrysant SG, Marbury TC, Neutel J. Source: Journal of Clinical Hypertension (Greenwich, Conn.). 2001 September-October; 3(5): 283-91, 318. Erratum In: J Clin Hypertens (Greenwich) 2001 November-December; 3(6): 395. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11588406

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Comparative efficacy of two angiotensin II receptor antagonists, irbesartan and losartan in mild-to-moderate hypertension. Irbesartan/Losartan Study Investigators. Author(s): Kassler-Taub K, Littlejohn T, Elliott W, Ruddy T, Adler E. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1998 April; 11(4 Pt 1): 445-53. Erratum In: Am J Hypertens 1998 June; 11(6 Pt 1): 736. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9607383

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Comparison of 3D structures and AT(1) binding properties of pyrazolidine-3,5-diones and tetrahydropyridazine-3,6-diones with parent antihypertensive drug irbesartan. Author(s): Le Bourdonnec B, Cauvin C, Meulon E, Yous S, Goossens JF, Durant F, Houssin R, Henichart JP. Source: Journal of Medicinal Chemistry. 2002 October 10; 45(21): 4794-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12361407

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Comparison of actions of irbesartan versus atenolol on cardiac repolarization in hypertensive left ventricular hypertrophy: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation Versus Atenolol (SILVHIA). Author(s): Malmqvist K, Kahan T, Edner M, Bergfeldt L. Source: The American Journal of Cardiology. 2002 November 15; 90(10): 1107-12. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12423712

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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 the angiotensin II receptor antagonist irbesartan with atenolol for treatment of hypertension. Author(s): Stumpe KO, Haworth D, Hoglund C, Kerwin L, Martin A, Simon T, Masson C, Kassler-Taub K, Osbakken M. Source: Blood Pressure. 1998 January; 7(1): 31-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9551875

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Dose-ranging study of the angiotensin II receptor antagonist irbesartan (SR 47436/BMS-186295) on blood pressure and neurohormonal effects in salt-deplete men. Author(s): McIntyre M, MacFadyen RJ, Meredith PA, Brouard R, Reid JL. Source: Journal of Cardiovascular Pharmacology. 1996 July; 28(1): 101-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=8797143

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Dose-related antihypertensive effects of irbesartan in patients with mild-to-moderate hypertension. Author(s): Pool JL, Guthrie RM, Littlejohn TW 3rd, Raskin P, Shephard AM, Weber MA, Weir MR, Wilson TW, Wright J, Kassler-Taub KB, Reeves RA. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1998 April; 11(4 Pt 1): 462-70. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9607385

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Dose-related beneficial long-term hemodynamic and clinical efficacy of irbesartan in heart failure. Author(s): Havranek EP, Thomas I, Smith WB, Ponce GA, Bilsker M, Munger MA, Wolf RA. Source: Journal of the American College of Cardiology. 1999 April; 33(5): 1174-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10193713

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Dose-related efficacy of irbesartan for hypertension: an integrated analysis. Author(s): Reeves RA, Lin CS, Kassler-Taub K, Pouleur H. Source: Hypertension. 1998 June; 31(6): 1311-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9622147

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Drug interactions with irbesartan. Author(s): Marino MR, Vachharajani NN. Source: Clinical Pharmacokinetics. 2001; 40(8): 605-14. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11523726

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Drug points: prolonged cholestasis associated with irbesartan. Author(s): Hariraj R, Stoner E, Jader S, Preston DM. Source: Bmj (Clinical Research Ed.). 2000 September 2; 321(7260): 547. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10968816

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Economic evaluation of the use of irbesartan and amlodipine in the treatment of diabetic nephropathy in patients with hypertension in Canada. Author(s): Coyle D, Rodby RA. Source: The Canadian Journal of Cardiology. 2004 January; 20(1): 71-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14968145

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Effectiveness and safety of the angiotensin II antagonist irbesartan in children with chronic kidney diseases. Author(s): Franscini LM, Von Vigier RO, Pfister R, Casaulta-Aebischer C, Fossali E, Bianchetti MG. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2002 December; 15(12): 1057-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12460701

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Effects and tolerability of irbesartan versus enalapril in patients with severe hypertension. Irbesartan Multicenter Investigators. Author(s): Larochelle P, Flack JM, Marbury TC, Sareli P, Krieger EM, Reeves RA. Source: The American Journal of Cardiology. 1997 December 15; 80(12): 1613-5. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9416950

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Effects of irbesartan on cloned potassium channels involved in human cardiac repolarization. Author(s): Moreno I, Caballero R, Gonzalez T, Arias C, Valenzuela C, Iriepa I, Galvez E, Tamargo J, Delpon E. Source: The Journal of Pharmacology and Experimental Therapeutics. 2003 February; 304(2): 862-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12538844

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Effects of long-term Irbesartan in reducing portal pressure in cirrhotic patients: comparison with propranolol in a randomised controlled study. Author(s): Ann Intern Med. 2003 Apr 1;138(7):I43 Source: Journal of Hepatology. 2003 April; 38(4): 455-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12667050

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Efficacy of irbesartan, a receptor selective antagonist of angiotensin II, in reducing portal hypertension. Author(s): Debernardi-Venon W, Barletti C, Alessandria C, Marzano A, Baronio M, Todros L, Saracco G, Repici A, Rizzetto M. Source: Digestive Diseases and Sciences. 2002 February; 47(2): 401-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11855558

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End-stage renal failure after irbesartan prescription in a diabetic patient with previously stable chronic renal insufficiency. Author(s): Descombes E, Fellay G. Source: Renal Failure. 2000 November; 22(6): 815-21. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11104169

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Evaluation of irbesartan effects as a function of the time of drug administration. Author(s): Ruiz-Vega H, Vargas-Espinoza JM, Huape-Arreola MS. Source: Proc West Pharmacol Soc. 2002; 45: 86-7. No Abstract Available. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12434539

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Exanthematous reaction to irbesartan. Author(s): Gambini D, Sala F, Gianotti R, Cusini M. Source: Journal of the European Academy of Dermatology and Venereology : Jeadv. 2003 July; 17(4): 472-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12834468

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Fibrinolytic/hemostatic variables in arterial hypertension: response to treatment with irbesartan or atenolol. Author(s): Makris TK, Stavroulakis GA, Krespi PG, Hatzizacharias AN, Triposkiadis FK, Tsoukala CG, Votteas VV, Kyriakidis MK. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 2000 July; 13(7): 783-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10933570

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Headache in mild-to-moderate hypertension and its reduction by irbesartan therapy. Author(s): Hansson L, Smith DH, Reeves R, Lapuerta P. Source: Archives of Internal Medicine. 2000 June 12; 160(11): 1654-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10847258

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Headache, hypertension, and irbesartan therapy. Author(s): Bensenor IM, Lotufo PA. Source: Archives of Internal Medicine. 2001 March 12; 161(5): 775-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11231724

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Hemodynamic and biochemical effects of the AT1 receptor antagonist irbesartan in hypertension. Author(s): van den Meiracker AH, Admiraal PJ, Janssen JA, Kroodsma JM, de Ronde WA, Boomsma F, Sissmann J, Blankestijn PJ, Mulder PG, Man In 't Veld AJ, et al. Source: Hypertension. 1995 January; 25(1): 22-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=7843749

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Hemodynamic effects of the angiotensin II receptor antagonist irbesartan in patients with cirrhosis and portal hypertension. Author(s): Schepke M, Werner E, Biecker E, Schiedermaier P, Heller J, Neef M, StoffelWagner B, Hofer U, Caselmann WH, Sauerbruch T. Source: Gastroenterology. 2001 August; 121(2): 389-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11487548

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High-performance liquid chromatographic assay for the quantitation of irbesartan (SR 47436/BMS-186295) in human plasma and urine. Author(s): Chang SY, Whigan DB, Vachharajani NN, Patel R. Source: J Chromatogr B Biomed Sci Appl. 1997 November 21; 702(1-2): 149-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9449566

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Human pharmacokinetic/pharmacodynamic profile of irbesartan: a new potent angiotensin II receptor antagonist. Author(s): Ruilope L. Source: Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension. 1997 December; 15(7): S15-20. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9532516

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Influence of two doses of irbesartan on non-dipper circadian blood pressure rhythm in salt-sensitive black hypertensives under high salt diet. Author(s): Polonia J, Diogo D, Caupers P, Damasceno A. Source: Journal of Cardiovascular Pharmacology. 2003 July; 42(1): 98-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12827033

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Inhibition of the acute effects of angiotensin II by the receptor antagonist irbesartan in normotensive men. Author(s): Ribstein J, Picard A, Armagnac C, Sissmann J, Mimran A. Source: Journal of Cardiovascular Pharmacology. 2001 April; 37(4): 449-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11300658

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Irbesartan does not affect the pharmacokinetics of simvastatin in healthy subjects. Author(s): Marino MR, Vachharajani NN, Hadjilambris OW. Source: Journal of Clinical Pharmacology. 2000 August; 40(8): 875-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10934672

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Irbesartan does not affect the steady-state pharmacodynamics and pharmacokinetics of warfarin. Author(s): Mangold B, Gielsdorf W, Marino MR. Source: European Journal of Clinical Pharmacology. 1999 October; 55(8): 593-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10541778

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Irbesartan effects on renal function in patients with renal impairment and hypertension: a drug-withdrawal study. Author(s): De Rosa ML, de Cristofaro A, Rossi M, Baiano A, Cardace P, Albanese L, Vigorito C. Source: Journal of Cardiovascular Pharmacology. 2001 September; 38(3): 482-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11486253

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Irbesartan reduces QT dispersion in hypertensive individuals. Author(s): Lim PO, Nys M, Naas AA, Struthers AD, Osbakken M, MacDonald TM. Source: Hypertension. 1999 February; 33(2): 713-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10024334

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Irbesartan reduces the albumin excretion rate in microalbuminuric type 2 diabetic patients independently of hypertension: a randomized double-blind placebocontrolled crossover study. Author(s): Sasso FC, Carbonara O, Persico M, Iafusco D, Salvatore T, D'Ambrosio R, Torella R, Cozzolino D. Source: Diabetes Care. 2002 November; 25(11): 1909-13. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12401731

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Irbesartan substitution for valsartan or losartan in treating hypertension. Author(s): Graham MR, Allcock NM. Source: The Annals of Pharmacotherapy. 2002 December; 36(12): 1840-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12452741

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Irbesartan treatment in hypertension. Author(s): Brown MJ. Source: Hosp Med. 1998 October; 59(10): 808-11. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9850301

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Irbesartan, an angiotensin type 1 receptor inhibitor, regulates markers of inflammation in patients with premature atherosclerosis. Author(s): Navalkar S, Parthasarathy S, Santanam N, Khan BV. Source: Journal of the American College of Cardiology. 2001 February; 37(2): 440-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11216960

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Irbesartan

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Irbesartan, an angiotensin type 1 receptor inhibitor, regulates the vascular oxidative state in patients with coronary artery disease. Author(s): Khan BV, Navalkar S, Khan QA, Rahman ST, Parthasarathy S. Source: Journal of the American College of Cardiology. 2001 November 15; 38(6): 1662-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11704378

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Irbesartan. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in the management of hypertension. Author(s): Gillis JC, Markham A. Source: Drugs. 1997 December; 54(6): 885-902. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9421695

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Irbesartan: an updated review of its use in cardiovascular disorders. Author(s): Markham A, Spencer CM, Jarvis B. Source: Drugs. 2000 May; 59(5): 1187-206. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10852648

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Irbesartan: review of pharmacology and comparative properties. Author(s): Adams MA, Trudeau L. Source: Can J Clin Pharmacol. 2000 Spring; 7(1): 22-31. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10822210

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Irbesartan-associated persistent edema of the eyelids, face, and neck. Author(s): Cohen PR. Source: J Drugs Dermatol. 2002 December; 1(3): 329-30. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12851994

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Lack of effect of food on the oral bioavailability of irbesartan in healthy male volunteers. Author(s): Vachharajani NN, Shyu WC, Mantha S, Park JS, Greene DS, Barbhaiya RH. Source: Journal of Clinical Pharmacology. 1998 May; 38(5): 433-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9602956

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Long-term effects of irbesartan and atenolol on the renin-angiotensin-aldosterone system in human primary hypertension: the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA). Author(s): Malmqvist K, Ohman KP, Lind L, Nystrom F, Kahan T. Source: Journal of Cardiovascular Pharmacology. 2003 December; 42(6): 719-26. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14639093

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Long-term safety and antihypertensive efficacy of irbesartan: pooled results of five open-label studies. Author(s): Littlejohn T 3rd, Saini R, Kassler-Taub K, Chrysant SG, Marbury T. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 1999 November; 21(8): 1273-95. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10574413

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Matrix study of irbesartan with hydrochlorothiazide in mild-to-moderate hypertension. Author(s): Kochar M, Guthrie R, Triscari J, Kassler-Taub K, Reeves RA. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1999 August; 12(8 Pt 1): 797-805. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10480473

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Novel angiotensin II AT(1) receptor antagonist irbesartan prevents thromboxane A(2)induced vasoconstriction in canine coronary arteries and human platelet aggregation. Author(s): Li P, Fukuhara M, Diz DI, Ferrario CM, Brosnihan KB. Source: The Journal of Pharmacology and Experimental Therapeutics. 2000 January; 292(1): 238-46. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10604953

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Nurse-recorded and ambulatory blood pressure predicts treatment-induced reduction of left ventricular hypertrophy equally well in hypertension: results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA) study. Author(s): Nystrom F, Malmqvist K, Ohman KP, Kahan T. Source: Journal of Hypertension. 2002 August; 20(8): 1527-33. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12172314

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Oral bioavailability and disposition characteristics of irbesartan, an angiotensin antagonist, in healthy volunteers. Author(s): Vachharajani NN, Shyu WC, Chando TJ, Everett DW, Greene DS, Barbhaiya RH. Source: Journal of Clinical Pharmacology. 1998 August; 38(8): 702-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9725545

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Pharmacodynamic studies on the angiotensin II type 1 antagonists irbesartan and candesartan based on angiotensin II dose response in humans. Author(s): Belz GG, Butzer R, Kober S, Mutschler E. Source: Journal of Cardiovascular Pharmacology. 2002 April; 39(4): 561-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11904530

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Pharmacokinetics and pharmacodynamics of irbesartan in healthy subjects. Author(s): Marino MR, Langenbacher K, Ford NF, Uderman HD. Source: Journal of Clinical Pharmacology. 1998 March; 38(3): 246-55. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9549663

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Pharmacokinetics and pharmacodynamics of irbesartan in patients with hepatic cirrhosis. Author(s): Marino MR, Langenbacher KM, Raymond RH, Ford NF, Lasseter KC. Source: Journal of Clinical Pharmacology. 1998 April; 38(4): 347-56. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9590462

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Pharmacokinetics of irbesartan are not altered in special populations. Author(s): Marino MR, Vachharajani NN. Source: Journal of Cardiovascular Pharmacology. 2002 July; 40(1): 112-22. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12072584

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Plasma atrial natriuretic peptide in essential hypertension after treatment with irbesartan. Author(s): Kotridis P, Kokkas B, Karamouzis M, Sakadamis G, Kanonidis I, Dadous G, Karantona C, Gouli O, Karadoumanis J, Papadopoulos PC, Papadopoulos CL. Source: Blood Pressure. 2002; 11(2): 91-4. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12035877

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Polymorphisms in the angiotensinogen and angiotensin II type 1 receptor gene are related to change in left ventricular mass during antihypertensive treatment: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation versus Atenolol (SILVHIA) trial. Author(s): Kurland L, Melhus H, Karlsson J, Kahan T, Malmqvist K, Ohman P, Nystrom F, Hagg A, Lind L. Source: Journal of Hypertension. 2002 April; 20(4): 657-63. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11910301

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Preliminary experience with the angiotensin II receptor antagonist irbesartan in chronic kidney disease. Author(s): von Vigier RO, Zberg PM, Teuffel O, Bianchetti MG. Source: European Journal of Pediatrics. 2000 August; 159(8): 590-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10968237

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Problems with interpreting the data in Kassler-Taub et al's article comparing irbesartan and losartan. Author(s): Bunt T. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1999 January; 12(1 Pt 1): 79-81. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10075390

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Randomized, double-blind comparison of irbesartan and enalapril for treatment of mild to moderate hypertension. Author(s): Chiou KR, Chen CH, Ding PY, Chen YT, Ting CT, Huang JL, Chiang AH, Liu CP, Tseng CJ, Chao CT, Chang MS. Source: Zhonghua Yi Xue Za Zhi (Taipei). 2000 May; 63(5): 368-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10862446

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Regression of left ventricular hypertrophy in human hypertension with irbesartan. Author(s): Malmqvist K, Kahan T, Edner M, Held C, Hagg A, Lind L, Muller-Brunotte R, Nystrom F, Ohman KP, Osbakken MD, Ostergern J. Source: Journal of Hypertension. 2001 June; 19(6): 1167-76. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11403367

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Renal response to the angiotensin II receptor subtype 1 antagonist irbesartan versus enalapril in hypertensive patients. Author(s): Pechere-Bertschi A, Nussberger J, Decosterd L, Armagnac C, Sissmann J, Bouroudian M, Brunner HR, Burnier M. Source: Journal of Hypertension. 1998 March; 16(3): 385-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9557932

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Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. Author(s): Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, Ritz E, Atkins RC, Rohde R, Raz I; Collaborative Study Group. Source: The New England Journal of Medicine. 2001 September 20; 345(12): 851-60. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11565517

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Role of cytochrome P-4502C9 in irbesartan oxidation by human liver microsomes. Author(s): Bourrie M, Meunier V, Berger Y, Fabre G. Source: Drug Metabolism and Disposition: the Biological Fate of Chemicals. 1999 February; 27(2): 288-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9929518

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Safety of irbesartan in the treatment of mild to moderate systemic hypertension. Author(s): Simon TA, Gelarden RT, Freitag SA, Kassler-Taub KB, Davies R. Source: The American Journal of Cardiology. 1998 July 15; 82(2): 179-82. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9678288

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Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma by liquid chromatography. Author(s): Erk N. Source: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences. 2003 January 25; 784(1): 195-201. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12504198

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The antihypertensive efficacy of the combination of irbesartan and hydrochlorothiazide assessed by 24-hour ambulatory blood pressure monitoring. Irbesartan Multicenter Study Group. Author(s): Howe P, Phillips P, Saini R, Kassler-Taub K. Source: Clinical and Experimental Hypertension (New York, N.Y. : 1993). 1999 November; 21(8): 1373-96. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10574419

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The antihypertensive response to irbesartan treatment from a pharmacogenetic perspective. Author(s): Kurland L. Source: Minerva Med. 2003 August; 94(4): 251-8. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=14605589

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The cost-effectiveness of irbesartan in the treatment of hypertensive patients with type 2 diabetic nephropathy. Author(s): Rodby RA, Chiou CF, Borenstein J, Smitten A, Sengupta N, Palmer AJ, Roze S, Annemans L, Simon TA, Chen RS, Lewis EJ; Collaborative Study Group. Source: Clinical Therapeutics. 2003 July; 25(7): 2102-19. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12946554

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The CYP2C9 genotype predicts the blood pressure response to irbesartan: results from the Swedish Irbesartan Left Ventricular Hypertrophy Investigation vs Atenolol (SILVHIA) trial. Author(s): Hallberg P, Karlsson J, Kurland L, Lind L, Kahan T, Malmqvist K, Ohman KP, Nystrom F, Melhus H. Source: Journal of Hypertension. 2002 October; 20(10): 2089-93. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12359989

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The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes. Author(s): Parving HH, Lehnert H, Brochner-Mortensen J, Gomis R, Andersen S, Arner P; Irbesartan in Patients with Type 2 Diabetes and Microalbuminuria Study Group. Source: The New England Journal of Medicine. 2001 September 20; 345(12): 870-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11565519

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The effects of age and gender on the pharmacokinetics of irbesartan. Author(s): Vachharajani NN, Shyu WC, Smith RA, Greene DS. Source: British Journal of Clinical Pharmacology. 1998 December; 46(6): 611-3. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9862252

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The effects of irbesartan added to hydrochlorothiazide for the treatment of hypertension in patients non-responsive to hydrochlorothiazide alone. Author(s): Rosenstock J, Rossi L, Lin CS, MacNeil D, Osbakken M. Source: Journal of Clinical Pharmacy and Therapeutics. 1998 December; 23(6): 433-40. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10048504

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The Irbesartan type II diabetic nephropathy trial: study design and baseline patient characteristics. For the Collaborative Study Group. Author(s): Rodby RA, Rohde RD, Clarke WR, Hunsicker LG, Anzalone DA, Atkins RC, Ritz E, Lewis EJ. Source: Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association. 2000 April; 15(4): 487-97. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10727543

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The long-term antihypertensive activity and tolerability of irbesartan with hydrochlorothiazide. Author(s): Raskin P, Guthrie R, Flack J, Reeves R, Saini R. Source: Journal of Human Hypertension. 1999 October; 13(10): 683-7. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10516738

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The new angiotensin II receptor antagonist, irbesartan: pharmacokinetic and pharmacodynamic considerations. Author(s): Brunner HR. Source: American Journal of Hypertension : Journal of the American Society of Hypertension. 1997 December; 10(12 Pt 2): 311S-317S. Review. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9438775

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The pharmacokinetics and pharmacodynamics of irbesartan in heart failure. Author(s): Kostis JB, Vachharajani NN, Hadjilambris OW, Kollia GD, Palmisano M, Marino MR. Source: Journal of Clinical Pharmacology. 2001 September; 41(9): 935-42. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11549097

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The pharmacokinetics of irbesartan in hypertensive children and adolescents. Author(s): Sakarcan A, Tenney F, Wilson JT, Stewart JJ, Adcock KG, Wells TG, Vachharajani NN, Hadjilambris OW, Slugg P, Ford NF, Marino MR. Source: Journal of Clinical Pharmacology. 2001 July; 41(7): 742-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11452706

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The pharmacokinetics of irbesartan in renal failure and maintenance hemodialysis. Author(s): Sica DA, Marino MR, Hammett JL, Ferreira I, Gehr TW, Ford NF. Source: Clinical Pharmacology and Therapeutics. 1997 December; 62(6): 610-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=9433389

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Time course and extent of angiotensin II antagonism after irbesartan, losartan, and valsartan in humans assessed by angiotensin II dose response and radioligand receptor assay. Author(s): Belz GG, Butzer R, Kober S, Mang C, Mutschler E. Source: Clinical Pharmacology and Therapeutics. 1999 October; 66(4): 367-73. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=10546920

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Treatment of psychogenic polydipsia: comparison of risperidone and olanzapine, and the effects of an adjunctive angiotensin-II receptor blocking drug (irbesartan). Author(s): Kruse D, Pantelis C, Rudd R, Quek J, Herbert P, McKinley M. Source: The Australian and New Zealand Journal of Psychiatry. 2001 February; 35(1): 658. Erratum In: Aust N Z J Psychiatry 2001 June; 35(3): 419. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11270459

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Treatment with irbesartan or atenolol improves endothelial function in essential hypertension. Author(s): von zur Muhlen B, Kahan T, Hagg A, Millgard J, Lind L. Source: Journal of Hypertension. 2001 October; 19(10): 1813-8. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=11593101

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Type 2 diabetes, obesity, and the renal response to blocking the renin system with irbesartan. Author(s): Price DA, Lansang MC, Osei SY, Fisher ND, Laffel LM, Hollenberg NK. Source: Diabetic Medicine : a Journal of the British Diabetic Association. 2002 October; 19(10): 858-61. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12358875

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Use of irbesartan to maintain sinus rhythm in patients with long-lasting persistent atrial fibrillation: a prospective and randomized study. Author(s): Madrid AH, Bueno MG, Rebollo JM, Marin I, Pena G, Bernal E, Rodriguez A, Cano L, Cano JM, Cabeza P, Moro C. Source: Circulation. 2002 July 16; 106(3): 331-6. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12119249

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Usefulness of quinapril and irbesartan to improve the anti-inflammatory response of atorvastatin and aspirin in patients with coronary heart disease. Author(s): Lauten WB, Khan QA, Rajagopalan S, Lerakis S, Rahman ST, Parthasarathy S, Khan BV. Source: The American Journal of Cardiology. 2003 May 1; 91(9): 1116-9. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=A bstract&list_uids=12714159

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

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

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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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Irbesartan

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

Comparison of irbesartan with captopril effects on cardiac hypertrophy and gene expression in heart failure-prone male SHHF/Mcc-fa(cp) rats. Author(s): Department of Veterinary Biosciences, The Ohio State University, Columbus, USA. Source: Carraway, J W Park, S McCune, S A Holycross, B J Radin, M J J-CardiovascPharmacol. 1999 March; 33(3): 451-60 0160-2446

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Different types of antagonism by losartan and irbesartan on the effects of angiotensin II and its degradation products in rabbit arteries. Author(s): Department of Pharmacotherapy, AMC, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, the Netherlands. Source: Li, Q Pfaffendorf, M van Zwieten, P A Fundam-Clin-Pharmacol. 2001 April; 15(2): 143-50 0767-3981

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Differential inhibition of the prejunctional actions of angiotensin II in rat atria by valsartan, irbesartan, eprosartan, and losartan. Author(s): Novartis Institute for Biomedical Research, Metabolic and Cardiovascular Diseases, Summit, New Jersey 07901-1027, USA. [email protected] Source: Shetty, S S DelGrande, D J-Pharmacol-Exp-Ther. 2000 July; 294(1): 179-86 00223565

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Prevention of hypertension by irbesartan in Dahl S rats relates to central angiotensin II type 1 receptor blockade. Author(s): Hypertension Unit, University of Ottawa Heart Institute, Ottawa, Ontario, Canada. [email protected] Source: Leenen, F H Yuan, B Hypertension. 2001 March; 37(3): 981-4 1524-4563

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The angiotensin II AT1 receptor antagonist irbesartan prevents thromboxane A2induced vasoconstriction in the rat hind-limb vascular bed in vivo. Author(s): Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina, 27157-1032, USA. [email protected] Source: Fukuhara, M Neves, L A Li, P Diz, D I Ferrario, C M Brosnihan, K B JHypertens. 2001 March; 19(3 Pt 2): 561-6 0263-6352

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Two angiotensin AT1 receptor antagonists, irbesartan and losartan, effects in cholesterol-fed rabbits. Author(s): Department of Pharmacology, School of Medicine, Complutense University, Madrid, Spain. Source: Sanz, M Ganado, P Tejerina, T Eur-J-Pharmacol. 2002 May 3; 442(1-2): 99-106 0014-2999

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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CHAPTER 3. PATENTS ON IRBESARTAN Overview Patents can be physical innovations (e.g. chemicals, pharmaceuticals, medical equipment) or processes (e.g. treatments or diagnostic procedures). The United States Patent and Trademark Office defines a patent as a grant of a property right to the inventor, issued by the Patent and Trademark Office.8 Patents, therefore, are intellectual property. For the United States, the term of a new patent is 20 years from the date when the patent application was filed. If the inventor wishes to receive economic benefits, it is likely that the invention will become commercially available within 20 years of the initial filing. It is important to understand, therefore, that an inventor’s patent does not indicate that a product or service is or will be commercially available. The patent implies only that the inventor has “the right to exclude others from making, using, offering for sale, or selling” the invention in the United States. While this relates to U.S. patents, similar rules govern foreign patents. In this chapter, we show you how to locate information on patents and their inventors. If you find a patent that is particularly interesting to you, contact the inventor or the assignee for further information. IMPORTANT NOTE: When following the search strategy described below, you may discover non-medical patents that use the generic term “irbesartan” (or a synonym) in their titles. To accurately reflect the results that you might find while conducting research on irbesartan, we have not necessarily excluded non-medical patents in this bibliography.

Patents on Irbesartan By performing a patent search focusing on irbesartan, you can obtain information such as the title of the invention, the names of the inventor(s), the assignee(s) or the company that owns or controls the patent, a short abstract that summarizes the patent, and a few excerpts from the description of the patent. The abstract of a patent tends to be more technical in nature, while the description is often written for the public. Full patent descriptions contain much more information than is presented here (e.g. claims, references, figures, diagrams, etc.). We will tell you how to obtain this information later in the chapter. The following is an 8Adapted

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

34

Irbesartan

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

Combination of an ADP-receptor blocking antiplatelet drug and antihypertensive drug and a method for preventing a cerebral infarction employing such combination Inventor(s): Blumenthal; Melvin S. (Yardley, PA), Coniglio; Anthony A. (Branchburg, NJ), Plat; Francis R. (Skillman, NJ) Assignee(s): Bristol-myers Squibb Co. (princeton, Nj), Sanofi-synthelabo (paris, Fr) Patent Number: 6,248,729 Date filed: June 9, 1999 Abstract: A method is provided for preventing a cerebral infarction by administering to a patient a combination of an ADP-receptor blocking antiplatelet drug, such as clopidogrel, in combination with an antihypertensive agent such as an angiotensin AII antagonist (for example, irbesartan), an ACE inhibitor (for example, fosinopril) or a NEP/ACE inhibitor such as omapatrilat. Excerpt(s): The present invention relates to a novel combination of an ADP-receptor blocking antiplatelet drug, such as clopidogrel, and an antihypertensive drug, for example, an angiotensin II antagonist such as irbesartan, or an ACE inhibitor such as fosinopril, or a NEP/ACE inhibitor such as omapatrilat, and to a method for preventing or inhibiting onset of a cerebral infarction employing such combination. including pharmaceutically acceptable acid addition salts thereof, preferably the hydrogen sulfate salt, and is disclosed in U.S. Pat. Nos. 4,529,596 to Aubert et al and U.S. Pat. No. 4,847,265 to Badorc et al as having blood platelet aggregation inhibiting activity and anti-thrombotic activity and thus useful in inhibiting or preventing arterial and venous thrombosis. U.S. Pat. No. 5,576,328 to Herbert et al discloses that clopidogrel may be employed in secondary prevention of ischemic events such as myocardial infarction, unstable or stable angina, acute reocclusion after percutaneous transluminal coronary angioplasty (PTCA), restenosis after PTCA, thrombotic stroke, transient ischemic attack, reversible ischemic neurological deficit, and intermittent claudication. Web site: http://www.delphion.com/details?pn=US06248729__

•

Pharmaceutical compositions containing irbesartan Inventor(s): Desai; Divyakant S. (Robbinsville, NJ), Ku; Cathy C. (Martinsville, NJ), Lang; Beth A. (Bedminster, NJ), Sprockel; Omar L. (Bridgewater, NJ) Assignee(s): Sanofi (paris, Fr) Patent Number: 5,994,348 Date filed: May 20, 1998 Abstract: Pharmaceutical compositions containing irbesartan, alone or in combination with a diuretic, providing tablets with a high relative amount of active agent and excellent wetting and disintegration properties. Excerpt(s): The present invention relates to pharmaceutical compositions containing irbesartan, preferably in the form of a tablet. The present invention also relates to tablets prepared from these compositions. Irbesartan may be administered in dosages containing a substantial quantity of the active agent (e.g., 75-300 mg). Certain physical

Patents 35

properties of the drug present a challenge in developing formulations suitable for preparing a tablet having both a substantial quantity of active agent and a small enough tablet mass to allow ease of swallowing. Irbesartan is, for example, a fluffy material, with relatively low bulk and tap densities. These properties make it difficult to formulate a large amount of the drug into a small tablet with uniformity of weight, hardness, and other desirable tablet properties. In addition, irbesartan has certain undesirable flow characteristics, for example, is sticky and can adhere to surfaces such as tablet punch faces and dies, causing problems in tableting, especially on a high speed tablet press. The low aqueous solubility of irbesartan also presents a challenge, since, to keep the tablet mass small, only limited amounts of excipients may be added to facilitate wetting, disintegration, and ultimately, rapid and complete drug release. The addition of a diuretic such as hydrochlorothiazide, which is also a fluffy material exhibiting poor flow and low aqueous solubility, can further contribute to tableting problems. Web site: http://www.delphion.com/details?pn=US05994348__

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

Method of treatment Inventor(s): Brenner, Barry M.; (Weston, MA), Shahinfar, Shahnaz; (Newton Square, PA), Zhang, Zhongxin; (Blue Bell, PA) Correspondence: Merck And CO Inc; P O Box 2000; Rahway; NJ; 070650907 Patent Application Number: 20030073705 Date filed: May 10, 2002 Abstract: This disclosure relates to a method of preventing end stage renal disease using an angiotensin II antagonist in patients with impaired renal function. Angiotensin II antagonists such as candesartan cilexetil, eprosartan, irbesartan, losartan, tasosartan, telmisartan, valsartan, 2-butyl-4-chloro-1-[(2'-tetrazol-5-yl)biphenyl-4yl)methyl]imidazolecarbo- xylic acid and 3-(2'-(tetrazol-5-yl)-1,1'-biphen-4-yl)methyl5,7-dimethyl-- 2-ethyl-3H-imidazo[4,5-b]pyridine, or pharmaceutically acceptable salts thereof are useful. Excerpt(s): Angiotensin II (AII) is a potent vasoconstrictor. Its generation in the reninangiotensin cascade results from the enzymatic action of renin on a blood plasma, 2globulin, angiotensinogen, to produce angiotensin I (AI). AI is then converted by angiotensin converting enzyme (ACE) to the octapeptide hormone, AII. AII has been implicated as a causitive agent in hypertension. Therefore, ACE inhibitiors, which inhibit the production of AII, and AII receptor antagonists, which inhibit the function of AII, are useful in the treatment of hypertension. The efficacy of these compounds in the treatment of heart failure is also being studied. Pals, et al., Circulation Research, 29, 673 (1971) describe the introduction of a sarcosine residue in position 1 and alanine in position 8 of the endogenous vasoconstrictor hormone AII to yield an (octa)peptide that

9

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

36

Irbesartan

blocks the effects of AII on the blood pressure of pithed rats. This analog, [Sar1, Ala8] AII, initially called "P-113" and subsequently "Saralasin," was found to be one of the most potent competitive antagonists of the actions of AII, although, like most of the socalled peptide-AII-antagonists, it also possesses agonistic actions of its own. Saralasin has been demonstrated to lower arterial pressure in mammals and man when the (elevated) pressure is dependent on circulating AII (Pals et al., Circulation Research, 29, 673 (1971); Streeten and Anderson, Handbook of Hypertension, Vol. 5, Clinical Pharmacology of Antihypertensive Drugs, A. E. Doyle (Editor), Elsevier Science Publishers B. V., p. 246 (1984)). However, due to its agonistic character, saralasin generally elicits pressor effects when the pressure is not sustained by AII. Being a peptide, the pharmacological effects to saralasin are relatively short-lasting and are only manifest after parenteral administration, oral doses being ineffective. Although the therapeutic uses of peptide AII-blockers, like saralasin, are severely limited due to their oral ineffectiveness and short duration of action, their major utility is as a pharmaceutical standard. Some known non-peptide antihypertensive agents act by inhibiting an enzyme, called angiotensin converting enzyme (ACE), which is responsible for conversion of angiotensin I to AII. Captopril and enalapril are commercially available ACE inhibitors (ACEI's). Based on experimental and clinical evidence, about 40% of hypertensive patients are non-responsive to treatment with ACEI's. But when a diuretic such as furosemide or hydrochlorothiazide is given together with a CEI, the blood pressure of the majority of hypertensive patients is effectively normalized. 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 irbesartan, 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 “irbesartan” (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 irbesartan. You can also use this procedure to view pending patent applications concerning irbesartan. Simply go back to http://www.uspto.gov/patft/index.html. Select “Quick Search” under “Published Applications.” Then proceed with the steps listed above.

37

CHAPTER 4. PERIODICALS AND NEWS ON IRBESARTAN Overview In this chapter, we suggest a number of news sources and present various periodicals that cover irbesartan.

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

High-dose irbesartan seems to confer long-term renal protection in diabetics Source: Reuters Industry Breifing Date: December 04, 2003

•

Irbesartan's renoprotective effect in diabetics not due to BP reduction over 24 hours Source: Reuters Industry Breifing Date: March 27, 2003

38

Irbesartan

•

Irbesartan reduces arterial pressure and proteinuria in pediatric kidney diseases Source: Reuters Industry Breifing Date: January 01, 2003

•

Irbesartan reduces albumin excretion in normotensive diabetics Source: Reuters Industry Breifing Date: November 07, 2002

•

Bristol-Myers, Sanofi earn FDA nod to market irbesartan for renal indication Source: Reuters Industry Breifing Date: September 18, 2002

•

EC grants broader indication for irbesartan Source: Reuters Industry Breifing Date: June 26, 2002

•

Addition of irbesartan to amiodarone reduces recurrence of atrial fibrillation Source: Reuters Industry Breifing Date: June 24, 2002

•

Sanofi near EU OK on wider irbesartan Source: Reuters Industry Breifing Date: March 12, 2002

•

FDA panel refuses to recommend new indication for Avapro Source: Reuters Industry Breifing Date: January 17, 2002

•

Bristol-Myers, Sanofi-Synthelabo seek expanded indications for irbesartan Source: Reuters Industry Breifing Date: August 14, 2001

•

Sanofi increases rights to antihypertensive drug Avapro Source: Reuters Industry Breifing Date: June 08, 2001

•

Irbesartan may prevent or slow atherosclerosis Source: Reuters Industry Breifing Date: February 06, 2001

•

Hypertensive patients treated with irbesartan show greater compliance Source: Reuters Industry Breifing Date: January 26, 2001

•

Irbesartan effective in lowering blood pressure in atherosclerotic renal disease Source: Reuters Industry Breifing Date: October 23, 2000

•

Irbesartan a more potent angiotensin II antagonist than valsartan, losartan Source: Reuters Medical News Date: October 27, 1999

•

Irbesartan safe and well tolerated at a wide range of doses Source: Reuters Medical News Date: July 29, 1998

Periodicals and News

39

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

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

40

Irbesartan

these sources, you can search for articles covering irbesartan 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.”

41

CHAPTER 5. 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 irbesartan. 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 irbesartan. 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

42

Irbesartan

following drugs have been mentioned in the Pharmacopeia and other sources as being potentially applicable to irbesartan: Irbesartan •

Systemic - U.S. Brands: Avapro http://www.nlm.nih.gov/medlineplus/druginfo/uspdi/203379.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.

43

APPENDICES

45

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

NIH Guidelines Commonly referred to as “clinical” or “professional” guidelines, the National Institutes of Health publish physician guidelines for the most common diseases. Publications are available at the following by relevant Institute10: •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

10

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

46

Irbesartan

•

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

Physician Resources

47

NIH Databases In addition to the various Institutes of Health that publish professional guidelines, the NIH has designed a number of databases for professionals.11 Physician-oriented resources provide a wide variety of information related to the biomedical and health sciences, both past and present. The format of these resources varies. Searchable databases, bibliographic citations, full-text articles (when available), archival collections, and images are all available. The following are referenced by the National Library of Medicine:12 •

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

11

Remember, for the general public, the National Library of Medicine recommends the databases referenced in MEDLINEplus (http://medlineplus.gov/ or http://www.nlm.nih.gov/medlineplus/databases.html). 12 See http://www.nlm.nih.gov/databases/databases.html.

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Irbesartan

•

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

•

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

The NLM Gateway13 The NLM (National Library of Medicine) Gateway is a Web-based system that lets users search simultaneously in multiple retrieval systems at the U.S. National Library of Medicine (NLM). It allows users of NLM services to initiate searches from one Web interface, providing one-stop searching for many of NLM’s information resources or databases.14 To use the NLM Gateway, simply go to the search site at http://gateway.nlm.nih.gov/gw/Cmd. Type “irbesartan” (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 514 0 152 0 1 667

HSTAT15 HSTAT is a free, Web-based resource that provides access to full-text documents used in healthcare decision-making.16 These documents include clinical practice guidelines, quickreference guides for clinicians, consumer health brochures, evidence reports and technology assessments from the Agency for Healthcare Research and Quality (AHRQ), as well as AHRQ’s Put Prevention Into Practice.17 Simply search by “irbesartan” (or synonyms) at the following Web site: http://text.nlm.nih.gov.

13

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

14

The NLM Gateway is currently being developed by the Lister Hill National Center for Biomedical Communications (LHNCBC) at the National Library of Medicine (NLM) of the National Institutes of Health (NIH). 15 Adapted from HSTAT: http://www.nlm.nih.gov/pubs/factsheets/hstat.html. 16 17

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

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

Physician Resources

49

Coffee Break: Tutorials for Biologists18 Coffee Break is a general healthcare site that takes a scientific view of the news and covers recent breakthroughs in biology that may one day assist physicians in developing treatments. Here you will find a collection of short reports on recent biological discoveries. Each report incorporates interactive tutorials that demonstrate how bioinformatics tools are used as a part of the research process. Currently, all Coffee Breaks are written by NCBI staff.19 Each report is about 400 words and is usually based on a discovery reported in one or more articles from recently published, peer-reviewed literature.20 This site has new articles every few weeks, so it can be considered an online magazine of sorts. It is intended for general background information. You can access the Coffee Break Web site at the following hyperlink: http://www.ncbi.nlm.nih.gov/Coffeebreak/.

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

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

•

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

18 Adapted 19

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

The figure that accompanies each article is frequently supplied by an expert external to NCBI, in which case the source of the figure is cited. The result is an interactive tutorial that tells a biological story. 20 After a brief introduction that sets the work described into a broader context, the report focuses on how a molecular understanding can provide explanations of observed biology and lead to therapies for diseases. Each vignette is accompanied by a figure and hypertext links that lead to a series of pages that interactively show how NCBI tools and resources are used in the research process.

51

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

52

•

Irbesartan

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

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

•

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

•

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

•

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

•

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

•

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

•

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

Patient Resources 53

Finding Associations There are several Internet directories that provide lists of medical associations with information on or resources relating to irbesartan. By consulting all of associations listed in this chapter, you will have nearly exhausted all sources for patient associations concerned with irbesartan. 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 irbesartan. 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 “irbesartan” (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 “irbesartan”. 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 “irbesartan” (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 “irbesartan” (or a synonym) into the search box, and click “Submit Query.”

55

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

Preparation Your local public library and medical libraries have interlibrary loan programs with the National Library of Medicine (NLM), one of the largest medical collections in the world. According to the NLM, most of the literature in the general and historical collections of the National Library of Medicine is available on interlibrary loan to any library. If you would like to access NLM medical literature, then visit a library in your area that can request the publications for you.21

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

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

21

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

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Irbesartan

libraries recommended by the National Library of Medicine (sorted alphabetically by name of the U.S. state or Canadian province where the library is located)22: •

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

•

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

•

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

•

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

•

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

•

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

•

California: Gateway Health Library (Sutter Gould Medical Foundation)

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

22

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

Finding Medical Libraries 57

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

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•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

•

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

Finding Medical Libraries 59

•

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

•

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

•

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

•

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

•

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

61

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

63

IRBESARTAN 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] 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] Adjustment: The dynamic process wherein the thoughts, feelings, behavior, and biophysiological mechanisms of the individual continually change to adjust to the environment. [NIH] Administration, Oral: The giving of drugs, chemicals, or other substances by mouth. [NIH] Adrenal Cortex: The outer layer of the adrenal gland. It secretes mineralocorticoids, androgens, and glucocorticoids. [NIH] Adrenergic: Activated by, characteristic of, or secreting epinephrine or substances with similar activity; the term is applied to those nerve fibres that liberate norepinephrine at a synapse when a nerve impulse passes, i.e., the sympathetic fibres. [EU] 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] Adverse Effect: An unwanted side effect of treatment. [NIH] Affinity: 1. Inherent likeness or relationship. 2. A special attraction for a specific element, organ, or structure. 3. Chemical affinity; the force that binds atoms in molecules; the tendency of substances to combine by chemical reaction. 4. The strength of noncovalent chemical binding between two substances as measured by the dissociation constant of the complex. 5. In immunology, a thermodynamic expression of the strength of interaction between a single antigen-binding site and a single antigenic determinant (and thus of the stereochemical compatibility between them), most accurately applied to interactions among simple, uniform antigenic determinants such as haptens. Expressed as the association constant (K litres mole -1), which, owing to the heterogeneity of affinities in a population of antibody molecules of a given specificity, actually represents an average value (mean intrinsic association constant). 6. The reciprocal of the dissociation constant. [EU] Age of Onset: The age or period of life at which a disease or the initial symptoms or manifestations of a disease appear in an individual. [NIH] Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. [NIH] 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

64

Irbesartan

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] Alimentary: Pertaining to food or nutritive material, or to the organs of digestion. [EU] Alkaline: Having the reactions of an alkali. [EU] 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 Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amino Acids: Organic compounds that generally contain an amino (-NH2) and a carboxyl (COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins. [NIH] Amiodarone: An antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance. [NIH] Amlodipine: 2-((2-Aminoethoxy)methyl)-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-3,5pyridinedicarboxylic acid 3-ethyl 5-methyl ester. A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. [NIH] Ampulla: A sac-like enlargement of a canal or duct. [NIH] Analog: In chemistry, a substance that is similar, but not identical, to another. [NIH] Analytes: A component of a test sample the presence of which has to be demonstrated. The term "analyte" includes where appropriate formed from the analyte during the analyses. [NIH]

Anatomical: Pertaining to anatomy, or to the structure of the organism. [EU] Angina: Chest pain that originates in the heart. [NIH] Angina Pectoris: The symptom of paroxysmal pain consequent to myocardial ischemia usually of distinctive character, location and radiation, and provoked by a transient stressful situation during which the oxygen requirements of the myocardium exceed the capacity of the coronary circulation to supply it. [NIH] Angioplasty: Endovascular reconstruction of an artery, which may include the removal of atheromatous plaque and/or the endothelial lining as well as simple dilatation. These are procedures performed by catheterization. When reconstruction of an artery is performed

Dictionary 65

surgically, it is called endarterectomy. [NIH] 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] Animal model: An animal with a disease either the same as or like a disease in humans. Animal models are used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models. [NIH] Anions: Negatively charged atoms, radicals or groups of atoms which travel to the anode or positive pole during electrolysis. [NIH] Antagonism: Interference with, or inhibition of, the growth of a living organism by another living organism, due either to creation of unfavorable conditions (e. g. exhaustion of food supplies) or to production of a specific antibiotic substance (e. g. penicillin). [NIH] Anterior Cerebral Artery: Artery formed by the bifurcation of the internal carotid artery. Branches of the anterior cerebral artery supply the caudate nucleus, internal capsule, putamen, septal nuclei, gyrus cinguli, and surfaces of the frontal lobe and parietal lobe. [NIH] Antianginal: Counteracting angina or anginal conditions. [EU] Antiangiogenic: Having to do with reducing the growth of new blood vessels. [NIH] Antiarrhythmic: An agent that prevents or alleviates cardiac arrhythmia. [EU] Antibiotic: A drug used to treat infections caused by bacteria and other microorganisms. [NIH]

Anticoagulant: A drug that helps prevent blood clots from forming. Also called a blood thinner. [NIH] Antihypertensive: An agent that reduces high blood pressure. [EU] Antihypertensive Agents: Drugs used in the treatment of acute or chronic hypertension regardless of pharmacological mechanism. Among the antihypertensive agents are diuretics (especially diuretics, thiazide), adrenergic beta-antagonists, adrenergic alpha-antagonists, angiotensin-converting enzyme inhibitors, calcium channel blockers, ganglionic blockers, and vasodilator agents. [NIH] Anti-inflammatory: Having to do with reducing inflammation. [NIH] Anti-Inflammatory Agents: Substances that reduce or suppress inflammation. [NIH] Antipsychotic: Effective in the treatment of psychosis. Antipsychotic drugs (called also neuroleptic drugs and major tranquilizers) are a chemically diverse (including phenothiazines, thioxanthenes, butyrophenones, dibenzoxazepines, dibenzodiazepines, and diphenylbutylpiperidines) but pharmacologically similar class of drugs used to treat schizophrenic, paranoid, schizoaffective, and other psychotic disorders; acute delirium and dementia, and manic episodes (during induction of lithium therapy); to control the movement disorders associated with Huntington's chorea, Gilles de la Tourette's syndrome, and ballismus; and to treat intractable hiccups and severe nausea and vomiting. Antipsychotic agents bind to dopamine, histamine, muscarinic cholinergic, a-adrenergic, and serotonin receptors. Blockade of dopaminergic transmission in various areas is thought to be responsible for their major effects : antipsychotic action by blockade in the mesolimbic

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and mesocortical areas; extrapyramidal side effects (dystonia, akathisia, parkinsonism, and tardive dyskinesia) by blockade in the basal ganglia; and antiemetic effects by blockade in the chemoreceptor trigger zone of the medulla. Sedation and autonomic side effects (orthostatic hypotension, blurred vision, dry mouth, nasal congestion and constipation) are caused by blockade of histamine, cholinergic, and adrenergic receptors. [EU] Antiviral: Destroying viruses or suppressing their replication. [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] Arachidonic Acid: An unsaturated, essential fatty acid. It is found in animal and human fat as well as in the liver, brain, and glandular organs, and is a constituent of animal phosphatides. It is formed by the synthesis from dietary linoleic acid and is a precursor in the biosynthesis of prostaglandins, thromboxanes, and leukotrienes. [NIH] Arterial: Pertaining to an artery or to the arteries. [EU] Arteries: The vessels carrying blood away from the heart. [NIH] Arteriolar: Pertaining to or resembling arterioles. [EU] Aspirin: A drug that reduces pain, fever, inflammation, and blood clotting. Aspirin belongs to the family of drugs called nonsteroidal anti-inflammatory agents. It is also being studied in cancer prevention. [NIH] Assay: Determination of the amount of a particular constituent of a mixture, or of the biological or pharmacological potency of a drug. [EU] Atenolol: A cardioselective beta-adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. [NIH] Atrial: Pertaining to an atrium. [EU] Atrial Fibrillation: Disorder of cardiac rhythm characterized by rapid, irregular atrial impulses and ineffective atrial contractions. [NIH] Atrium: A chamber; used in anatomical nomenclature to designate a chamber affording entrance to another structure or organ. Usually used alone to designate an atrium of the heart. [EU] Atypical: Irregular; not conformable to the type; in microbiology, applied specifically to strains of unusual type. [EU] Autonomic: Self-controlling; functionally independent. [EU] Base: In chemistry, the nonacid part of a salt; a substance that combines with acids to form salts; a substance that dissociates to give hydroxide ions in aqueous solutions; a substance whose molecule or ion can combine with a proton (hydrogen ion); a substance capable of donating a pair of electrons (to an acid) for the formation of a coordinate covalent bond. [EU] 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] Biliary: Having to do with the liver, bile ducts, and/or gallbladder. [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] Biochemical: Relating to biochemistry; characterized by, produced by, or involving chemical reactions in living organisms. [EU]

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Biopsy: Removal and pathologic examination of specimens in the form of small pieces of tissue from the living body. [NIH] Biosynthesis: The building up of a chemical compound in the physiologic processes of a living organism. [EU] Biotechnology: Body of knowledge related to the use of organisms, cells or cell-derived constituents for the purpose of developing products which are technically, scientifically and clinically useful. Alteration of biologic function at the molecular level (i.e., genetic engineering) is a central focus; laboratory methods used include transfection and cloning technologies, sequence and structure analysis algorithms, computer databases, and gene and protein structure function analysis and prediction. [NIH] Bladder: The organ that stores urine. [NIH] Blood Coagulation: The process of the interaction of blood coagulation factors that results in an insoluble fibrin clot. [NIH] Blood pressure: The pressure of blood against the walls of a blood vessel or heart chamber. Unless there is reference to another location, such as the pulmonary artery or one of the heart chambers, it refers to the pressure in the systemic arteries, as measured, for example, in the forearm. [NIH] Blood vessel: A tube in the body through which blood circulates. Blood vessels include a network of arteries, arterioles, capillaries, venules, and veins. [NIH] Body Fluids: Liquid components of living organisms. [NIH] Bradykinin: A nonapeptide messenger that is enzymatically produced from kallidin in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from mast cells during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter. [NIH] Branch: Most commonly used for branches of nerves, but applied also to other structures. [NIH]

Breakdown: A physical, metal, or nervous collapse. [NIH] Bronchi: The larger air passages of the lungs arising from the terminal bifurcation of the trachea. [NIH] Bronchodilator: A drug that relaxes the smooth muscles in the constricted airway. [NIH] Calcium: A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. [NIH] Calcium channel blocker: A drug used to relax the blood vessel and heart muscle, causing pressure inside blood vessels to drop. It also can regulate heart rhythm. [NIH] Calcium Channel Blockers: A class of drugs that act by selective inhibition of calcium influx through cell membranes or on the release and binding of calcium in intracellular pools. Since they are inducers of vascular and other smooth muscle relaxation, they are used in the drug therapy of hypertension and cerebrovascular spasms, as myocardial protective agents, and in the relaxation of uterine spasms. [NIH] Calculi: An abnormal concretion occurring mostly in the urinary and biliary tracts, usually composed of mineral salts. Also called stones. [NIH]

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Caloric intake: Refers to the number of calories (energy content) consumed. [NIH] Capillary: Any one of the minute vessels that connect the arterioles and venules, forming a network in nearly all parts of the body. Their walls act as semipermeable membranes for the interchange of various substances, including fluids, between the blood and tissue fluid; called also vas capillare. [EU] Capillary Permeability: Property of blood capillary walls that allows for the selective exchange of substances. Small lipid-soluble molecules such as carbon dioxide and oxygen move freely by diffusion. Water and water-soluble molecules cannot pass through the endothelial walls and are dependent on microscopic pores. These pores show narrow areas (tight junctions) which may limit large molecule movement. [NIH] 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] Cardiac: Having to do with the heart. [NIH] Cardiomyopathy: A general diagnostic term designating primary myocardial disease, often of obscure or unknown etiology. [EU] Cardioselective: Having greater activity on heart tissue than on other tissue. [EU] Cardiovascular: Having to do with the heart and blood vessels. [NIH] Cardiovascular disease: Any abnormal condition characterized by dysfunction of the heart and blood vessels. CVD includes atherosclerosis (especially coronary heart disease, which can lead to heart attacks), cerebrovascular disease (e.g., stroke), and hypertension (high blood pressure). [NIH] Case report: A detailed report of the diagnosis, treatment, and follow-up of an individual patient. Case reports also contain some demographic information about the patient (for example, age, gender, ethnic origin). [NIH] Catheterization: Use or insertion of a tubular device into a duct, blood vessel, hollow organ, or body cavity for injecting or withdrawing fluids for diagnostic or therapeutic purposes. It differs from intubation in that the tube here is used to restore or maintain patency in obstructions. [NIH] Cell: The individual unit that makes up all of the tissues of the body. All living things are made up of one or more cells. [NIH] Central Nervous System: The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. [NIH] Cerebral: Of or pertaining of the cerebrum or the brain. [EU] Cerebral Infarction: The formation of an area of necrosis in the cerebrum caused by an insufficiency of arterial or venous blood flow. Infarcts of the cerebrum are generally classified by hemisphere (i.e., left vs. right), lobe (e.g., frontal lobe infarction), arterial distribution (e.g., infarction, anterior cerebral artery), and etiology (e.g., embolic infarction). [NIH]

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]

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Cholestasis: Impairment of biliary flow at any level from the hepatocyte to Vater's ampulla. [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 renal: Slow and progressive loss of kidney function over several years, often resulting in end-stage renal disease. People with end-stage renal disease need dialysis or transplantation to replace the work of the kidneys. [NIH] Circadian: Repeated more or less daily, i. e. on a 23- to 25-hour cycle. [NIH] Claudication: Limping or lameness. [EU] Clinical study: A research study in which patients receive treatment in a clinic or other medical facility. Reports of clinical studies can contain results for single patients (case reports) or many patients (case series or clinical trials). [NIH] Clinical trial: A research study that tests how well new medical treatments or other interventions work in people. Each study is designed to test new methods of screening, prevention, diagnosis, or treatment of a disease. [NIH] Cloning: The production of a number of genetically identical individuals; in genetic engineering, a process for the efficient replication of a great number of identical DNA molecules. [NIH] Coagulation: 1. The process of clot formation. 2. In colloid chemistry, the solidification of a sol into a gelatinous mass; an alteration of a disperse phase or of a dissolved solid which causes the separation of the system into a liquid phase and an insoluble mass called the clot or curd. Coagulation is usually irreversible. 3. In surgery, the disruption of tissue by physical means to form an amorphous residuum, as in electrocoagulation and photocoagulation. [EU] Coenzyme: An organic nonprotein molecule, frequently a phosphorylated derivative of a water-soluble vitamin, that binds with the protein molecule (apoenzyme) to form the active enzyme (holoenzyme). [EU] 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] 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] 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] Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH]

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Connective Tissue: Tissue that supports and binds other tissues. It consists of connective tissue cells embedded in a large amount of extracellular matrix. [NIH] Constriction: The act of constricting. [NIH] Constriction, Pathologic: The condition of an anatomical structure's being constricted beyond normal dimensions. [NIH] Contraindications: Any factor or sign that it is unwise to pursue a certain kind of action or treatment, e. g. giving a general anesthetic to a person with pneumonia. [NIH] Control group: In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works. [NIH] Controlled clinical trial: A clinical study that includes a comparison (control) group. The comparison group receives a placebo, another treatment, or no treatment at all. [NIH] Controlled study: An experiment or clinical trial that includes a comparison (control) group. [NIH]

Conventional therapy: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional treatment. [NIH] Conventional treatment: A currently accepted and widely used treatment for a certain type of disease, based on the results of past research. Also called conventional therapy. [NIH] Coronary: Encircling in the manner of a crown; a term applied to vessels; nerves, ligaments, etc. The term usually denotes the arteries that supply the heart muscle and, by extension, a pathologic involvement of them. [EU] Coronary 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] Cortex: The outer layer of an organ or other body structure, as distinguished from the internal substance. [EU] Cortisol: A steroid hormone secreted by the adrenal cortex as part of the body's response to stress. [NIH] Creatinine: A compound that is excreted from the body in urine. Creatinine levels are measured to monitor kidney function. [NIH] Curative: Tending to overcome disease and promote recovery. [EU] Cyst: A sac or capsule filled with fluid. [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

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maximum of the a-band of the iron (II) form in pyridine, e.g., c-555. [EU] Databases, Bibliographic: Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from factual databases which is used for collections of data and facts apart from bibliographic references to them. [NIH] Degenerative: Undergoing degeneration : tending to degenerate; having the character of or involving degeneration; causing or tending to cause degeneration. [EU] Deuterium: Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus. [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] Dilatation: The act of dilating. [NIH] Dilated cardiomyopathy: Heart muscle disease that leads to enlargement of the heart's chambers, robbing the heart of its pumping ability. [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] 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] Disposition: A tendency either physical or mental toward certain diseases. [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] Dopamine: An endogenous catecholamine and prominent neurotransmitter in several systems of the brain. In the synthesis of catecholamines from tyrosine, it is the immediate precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. A family of dopaminergic receptor subtypes mediate its action. Dopamine is used pharmacologically for its direct (beta adrenergic agonist) and indirect (adrenergic releasing) sympathomimetic effects including its actions as an inotropic agent and as a renal vasodilator. [NIH] Drug Interactions: The action of a drug that may affect the activity, metabolism, or toxicity of another drug. [NIH]

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Edema: Excessive amount of watery fluid accumulated in the intercellular spaces, most commonly present in subcutaneous tissue. [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] Elastin: The protein that gives flexibility to tissues. [NIH] Elective: Subject to the choice or decision of the patient or physician; applied to procedures that are advantageous to the patient but not urgent. [EU] Electrolyte: A substance that dissociates into ions when fused or in solution, and thus becomes capable of conducting electricity; an ionic solute. [EU] Electrons: Stable elementary particles having the smallest known negative charge, present in all elements; also called negatrons. Positively charged electrons are called positrons. The numbers, energies and arrangement of electrons around atomic nuclei determine the chemical identities of elements. Beams of electrons are called cathode rays or beta rays, the latter being a high-energy biproduct of nuclear decay. [NIH] Emboli: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Embolism: Blocking of a blood vessel by a blood clot or foreign matter that has been transported from a distant site by the blood stream. [NIH] Embolization: The blocking of an artery by a clot or foreign material. Embolization can be done as treatment to block the flow of blood to a tumor. [NIH] Embolus: Bit of foreign matter which enters the blood stream at one point and is carried until it is lodged or impacted in an artery and obstructs it. It may be a blood clot, an air bubble, fat or other tissue, or clumps of bacteria. [NIH] Enalapril: An angiotensin-converting enzyme inhibitor that is used to treat hypertension. [NIH]

Endarterectomy: Surgical excision, performed under general anesthesia, of the atheromatous tunica intima of an artery. When reconstruction of an artery is performed as an endovascular procedure through a catheter, it is called atherectomy. [NIH] 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] Estrogen: One of the two female sex hormones. [NIH] Excipients: Usually inert substances added to a prescription in order to provide suitable consistency to the dosage form; a binder, matrix, base or diluent in pills, tablets, creams,

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

Fatty acids: A major component of fats that are used by the body for energy and tissue development. [NIH] Felodipine: A dihydropyridine calcium antagonist with positive inotropic effects. It lowers blood pressure by reducing peripheral vascular resistance through a highly selective action on smooth muscle in arteriolar resistance vessels. [NIH] Forearm: The part between the elbow and the wrist. [NIH] Fosinopril: A phosphinic acid-containing angiotensin-converting enzyme inhibitor that is effective in the treatment of hypertension. It is a prodrug that is converted to its active metabolite fosinoprilat. [NIH] Frontal Lobe: The anterior part of the cerebral hemisphere. [NIH] Furosemide: A sulfamyl saluretic and diuretic. It has a fast onset and short duration of action and is used in edema and chronic renal insufficiency. [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] Gastrin: A hormone released after eating. Gastrin causes the stomach to produce more acid. [NIH]

Gastrointestinal: Refers to the stomach and intestines. [NIH] Gene: The functional and physical unit of heredity passed from parent to offspring. Genes are pieces of DNA, and most genes contain the information for making a specific protein. [NIH]

Gene Expression: The phenotypic manifestation of a gene or genes by the processes of gene action. [NIH] Genotype: The genetic constitution of the individual; the characterization of the genes. [NIH] Glomerular: Pertaining to or of the nature of a glomerulus, especially a renal glomerulus. [EU]

Glomeruli: Plural of glomerulus. [NIH] Glomerulosclerosis: Scarring of the glomeruli. It may result from diabetes mellitus (diabetic glomerulosclerosis) or from deposits in parts of the glomerulus (focal segmental glomerulosclerosis). The most common signs of glomerulosclerosis are proteinuria and

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kidney failure. [NIH] Glomerulus: A tiny set of looping blood vessels in the nephron where blood is filtered in the kidney. [NIH] Glucose: D-Glucose. A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. [NIH] Glucose Intolerance: A pathological state in which the fasting plasma glucose level is less than 140 mg per deciliter and the 30-, 60-, or 90-minute plasma glucose concentration following a glucose tolerance test exceeds 200 mg per deciliter. This condition is seen frequently in diabetes mellitus but also occurs with other diseases. [NIH] Gout: Hereditary metabolic disorder characterized by recurrent acute arthritis, hyperuricemia and deposition of sodium urate in and around the joints, sometimes with formation of uric acid calculi. [NIH] Governing Board: The group in which legal authority is vested for the control of healthrelated institutions and organizations. [NIH] Gp120: 120-kD HIV envelope glycoprotein which is involved in the binding of the virus to its membrane receptor, the CD4 molecule, found on the surface of certain cells in the body. [NIH]

Growth: The progressive development of a living being or part of an organism from its earliest stage to maturity. [NIH] Habitual: Of the nature of a habit; according to habit; established by or repeated by force of habit, customary. [EU] Heart attack: A seizure of weak or abnormal functioning of the heart. [NIH] Heart failure: Loss of pumping ability by the heart, often accompanied by fatigue, breathlessness, and excess fluid accumulation in body tissues. [NIH] Heme: The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins. [NIH] Hemodialysis: The use of a machine to clean wastes from the blood after the kidneys have failed. The blood travels through tubes to a dialyzer, which removes wastes and extra fluid. The cleaned blood then flows through another set of tubes back into the body. [NIH] Hemodynamics: The movements of the blood and the forces involved in systemic or regional blood circulation. [NIH] Hemorrhage: Bleeding or escape of blood from a vessel. [NIH] Hepatic: Refers to the liver. [NIH] Hepatitis: Inflammation of the liver and liver disease involving degenerative or necrotic alterations of hepatocytes. [NIH] Hepatocyte: A liver cell. [NIH] Hepatotoxicity: How much damage a medicine or other substance does to the liver. [NIH] Heredity: 1. The genetic transmission of a particular quality or trait from parent to offspring. 2. The genetic constitution of an individual. [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] 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

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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] Hydroxylysine: A hydroxylated derivative of the amino acid lysine that is present in certain collagens. [NIH] Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ascorbic acid can result in impaired hydroxyproline formation. [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] Hyperuricaemia: Excess of uric acid or urates in the blood; it is a prerequisite for the development or gout and may lead to renal disease. Called also uricacidaemia and, formerly, lithemia. [EU] Hyperuricemia: A buildup of uric acid (a byproduct of metabolism) in the blood; a side effect of some anticancer drugs. [NIH] Id: The part of the personality structure which harbors the unconscious instinctive desires and strivings of the individual. [NIH] Immune system: The organs, cells, and molecules responsible for the recognition and disposal of foreign ("non-self") material which enters the body. [NIH] Immunity: Nonsusceptibility to the invasive or pathogenic microorganisms or to the toxic effect of antigenic substances. [NIH]

effects

of

foreign

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] Indicative: That indicates; that points out more or less exactly; that reveals fairly clearly. [EU] Induction: The act or process of inducing or causing to occur, especially the production of a specific morphogenetic effect in the developing embryo through the influence of evocators or organizers, or the production of anaesthesia or unconsciousness by use of appropriate agents. [EU] Infarction: A pathological process consisting of a sudden insufficient blood supply to an area, which results in necrosis of that area. It is usually caused by a thrombus, an embolus, or a vascular torsion. [NIH] 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] Inotropic: Affecting the force or energy of muscular contractions. [EU] Insulin: A protein hormone secreted by beta cells of the pancreas. Insulin plays a major role

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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] Intermittent: Occurring at separated intervals; having periods of cessation of activity. [EU] Interstitial: Pertaining to or situated between parts or in the interspaces of a tissue. [EU] Intoxication: Poisoning, the state of being poisoned. [EU] Intracellular: Inside a cell. [NIH] Intramuscular: IM. Within or into muscle. [NIH] Intravenous: IV. Into a vein. [NIH] 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] Isoproterenol: Isopropyl analog of epinephrine; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant. [NIH] Kallidin: A decapeptide bradykinin homolog produced by the action of tissue and glandular kallikreins on low-molecular-weight kininogen. It is a smooth-muscle stimulant and hypotensive agent that functions through vasodilatation. [NIH] Kb: A measure of the length of DNA fragments, 1 Kb = 1000 base pairs. The largest DNA fragments are up to 50 kilobases long. [NIH] 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] Kidney stone: A stone that develops from crystals that form in urine and build up on the inner surfaces of the kidney, in the renal pelvis, or in the ureters. [NIH] Lesion: An area of abnormal tissue change. [NIH] Library Services: Services offered to the library user. They include reference and circulation. [NIH]

Life Expectancy: A figure representing the number of years, based on known statistics, to which any person of a given age may reasonably expect to live. [NIH] Ligaments: Shiny, flexible bands of fibrous tissue connecting together articular extremities of bones. They are pliant, tough, and inextensile. [NIH] Lipid: Fat. [NIH] Liver: A large, glandular organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile. [NIH] Lobe: A portion of an organ such as the liver, lung, breast, or brain. [NIH] Longitudinal Studies: Studies in which variables relating to an individual or group of individuals are assessed over a period of time. [NIH] Lovastatin: A fungal metabolite isolated from cultures of Aspergillus terreus. The compound is a potent anticholesteremic agent. It inhibits 3-hydroxy-3-methylglutaryl

Dictionary 77

coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It also stimulates the production of low-density lipoprotein receptors in the liver. [NIH] Macrophage: A type of white blood cell that surrounds and kills microorganisms, removes dead cells, and stimulates the action of other immune system cells. [NIH] Malnutrition: A condition caused by not eating enough food or not eating a balanced diet. [NIH]

Manifest: Being the part or aspect of a phenomenon that is directly observable : concretely expressed in behaviour. [EU] MEDLINE: An online database of MEDLARS, the computerized bibliographic Medical Literature Analysis and Retrieval System of the National Library of Medicine. [NIH] Membrane: A very thin layer of tissue that covers a surface. [NIH] Membrane Glycoproteins: Glycoproteins found on the membrane or surface of cells. [NIH] Menopause: Permanent cessation of menstruation. [NIH] Metabolic disorder: A condition in which normal metabolic processes are disrupted, usually because of a missing enzyme. [NIH] Metabolite: Any substance produced by metabolism or by a metabolic process. [EU] Methionine: A sulfur containing essential amino acid that is important in many body functions. It is a chelating agent for heavy metals. [NIH] MI: Myocardial infarction. Gross necrosis of the myocardium as a result of interruption of the blood supply to the area; it is almost always caused by atherosclerosis of the coronary arteries, upon which coronary thrombosis is usually superimposed. [NIH] Milligram: A measure of weight. A milligram is approximately 450,000-times smaller than a pound and 28,000-times smaller than an ounce. [NIH] Modeling: A treatment procedure whereby the therapist presents the target behavior which the learner is to imitate and make part of his repertoire. [NIH] 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] 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] Myocardium: The muscle tissue of the heart composed of striated, involuntary muscle known as cardiac muscle. [NIH] Necrosis: A pathological process caused by the progressive degradative action of enzymes that is generally associated with severe cellular trauma. It is characterized by mitochondrial swelling, nuclear flocculation, uncontrolled cell lysis, and ultimately cell death. [NIH] Need: A state of tension or dissatisfaction felt by an individual that impels him to action toward a goal he believes will satisfy the impulse. [NIH] Nephron: A tiny part of the kidneys. Each kidney is made up of about 1 million nephrons,

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which are the working units of the kidneys, removing wastes and extra fluids from the blood. [NIH] Nephropathy: Disease of the kidneys. [EU] Nephrosis: Descriptive histopathologic term for renal disease without an inflammatory component. [NIH] Nephrotic: Pertaining to, resembling, or caused by nephrosis. [EU] Nephrotic Syndrome: Clinical association of heavy proteinuria, hypoalbuminemia, and generalized edema. [NIH] Normotensive: 1. Characterized by normal tone, tension, or pressure, as by normal blood pressure. 2. A person with normal blood pressure. [EU] Odds Ratio: The ratio of two odds. The exposure-odds ratio for case control data is the ratio of the odds in favor of exposure among cases to the odds in favor of exposure among noncases. The disease-odds ratio for a cohort or cross section is the ratio of the odds in favor of disease among the exposed to the odds in favor of disease among the unexposed. The prevalence-odds ratio refers to an odds ratio derived cross-sectionally from studies of prevalent cases. [NIH] Osmotic: Pertaining to or of the nature of osmosis (= the passage of pure solvent from a solution of lesser to one of greater solute concentration when the two solutions are separated by a membrane which selectively prevents the passage of solute molecules, but is permeable to the solvent). [EU] 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]

Palliative: 1. Affording relief, but not cure. 2. An alleviating medicine. [EU] Parenteral: Not through the alimentary canal but rather by injection through some other route, as subcutaneous, intramuscular, intraorbital, intracapsular, intraspinal, intrasternal, intravenous, etc. [EU] Pathologic: 1. Indicative of or caused by a morbid condition. 2. Pertaining to pathology (= branch of medicine that treats the essential nature of the disease, especially the structural and functional changes in tissues and organs of the body caused by the disease). [EU] 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] Peptide T: N-(N-(N(2)-(N-(N-(N-(N-D-Alanyl L-seryl)-L-threonyl)-L-threonyl) L-threonyl)L-asparaginyl)-L-tyrosyl) L-threonine. Octapeptide sharing sequence homology with HIV envelope protein gp120. It is potentially useful as antiviral agent in AIDS therapy. The core pentapeptide sequence, TTNYT, consisting of amino acids 4-8 in peptide T, is the HIV envelope sequence required for attachment to the CD4 receptor. [NIH] Percutaneous: Performed through the skin, as injection of radiopacque material in radiological examination, or the removal of tissue for biopsy accomplished by a needle. [EU] 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,

Dictionary 79

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

Pilot study: The initial study examining a new method or treatment. [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] Platelets: A type of blood cell that helps prevent bleeding by causing blood clots to form. Also called thrombocytes. [NIH] Polycystic: An inherited disorder characterized by many grape-like clusters of fluid-filled cysts that make both kidneys larger over time. These cysts take over and destroy working kidney tissue. PKD may cause chronic renal failure and end-stage renal disease. [NIH] Polydipsia: Chronic excessive thirst, as in diabetes mellitus or diabetes insipidus. [EU] Polymorphism: The occurrence together of two or more distinct forms in the same population. [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] Portal Pressure: The venous pressure measured in the portal vein. [NIH] Portal Vein: A short thick vein formed by union of the superior mesenteric vein and the splenic vein. [NIH] Potassium: An element that is in the alkali group of metals. It has an atomic symbol K, atomic number 19, and atomic weight 39.10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte and it plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. [NIH] Potassium Channels: Cell membrane glycoproteins selective for potassium ions. [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]

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Precursor: Something that precedes. In biological processes, a substance from which another, usually more active or mature substance is formed. In clinical medicine, a sign or symptom that heralds another. [EU] 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] Proline: A non-essential amino acid that is synthesized from glutamic acid. It is an essential component of collagen and is important for proper functioning of joints and tendons. [NIH] Prophylaxis: An attempt to prevent disease. [NIH] Proportional: Being in proportion : corresponding in size, degree, or intensity, having the same or a constant ratio; of, relating to, or used in determining proportions. [EU] 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] Prostaglandins D: Physiologically active prostaglandins found in many tissues and organs. They show pressor activity, are mediators of inflammation, and have potential antithrombotic effects. [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] Proteinuria: The presence of protein in the urine, indicating that the kidneys are not working properly. [NIH] Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion. [NIH] Psychic: Pertaining to the psyche or to the mind; mental. [EU] Psychogenic: Produced or caused by psychic or mental factors rather than organic factors. [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]

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Publishing: "The business or profession of the commercial production and issuance of literature" (Webster's 3d). It includes the publisher, publication processes, editing and editors. Production may be by conventional printing methods or by electronic publishing. [NIH]

Pulmonary: Relating to the lungs. [NIH] Pulmonary Artery: The short wide vessel arising from the conus arteriosus of the right ventricle and conveying unaerated blood to the lungs. [NIH] Pulmonary Embolism: Embolism in the pulmonary artery or one of its branches. [NIH] Radioactive: Giving off radiation. [NIH] Radiological: Pertaining to radiodiagnostic and radiotherapeutic procedures, and interventional radiology or other planning and guiding medical radiology. [NIH] Ramipril: A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. [NIH] 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] 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] Recurrence: The return of a sign, symptom, or disease after a remission. [NIH] Reductase: Enzyme converting testosterone to dihydrotestosterone. [NIH] Refer: To send or direct for treatment, aid, information, de decision. [NIH] Refractory: Not readily yielding to treatment. [EU] Regimen: A treatment plan that specifies the dosage, the schedule, and the duration of treatment. [NIH] Relative risk: The ratio of the incidence rate of a disease among individuals exposed to a specific risk factor to the incidence rate among unexposed individuals; synonymous with risk ratio. Alternatively, the ratio of the cumulative incidence rate in the exposed to the cumulative incidence rate in the unexposed (cumulative incidence ratio). The term relative risk has also been used synonymously with odds ratio. This is because the odds ratio and relative risk approach each other if the disease is rare ( 5 percent of population) and the number of subjects is large. [NIH] Remission: A decrease in or disappearance of signs and symptoms of cancer. In partial remission, some, but not all, signs and symptoms of cancer have disappeared. In complete remission, all signs and symptoms of cancer have disappeared, although there still may be cancer in the body. [NIH] Renal failure: Progressive renal insufficiency and uremia, due to irreversible and progressive renal glomerular tubular or interstitial disease. [NIH] Renin: An enzyme which is secreted by the kidney and is formed from prorenin in plasma and kidney. The enzyme cleaves the Leu-Leu bond in angiotensinogen to generate angiotensin I. EC 3.4.23.15. (Formerly EC 3.4.99.19). [NIH] Renin-Angiotensin System: A system consisting of renin, angiotensin-converting enzyme, and angiotensin II. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an 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

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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] Risk factor: A habit, trait, condition, or genetic alteration that increases a person's chance of developing a disease. [NIH] Risperidone: A selective blocker of dopamine D2 and serotonin-5-HT-2 receptors that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of schizophrenia. [NIH] Saralasin: 1-(N-Methylglycine)-5-L-valine-8-L-alanineangiotensin II. An octapeptide analog of angiotensin II (bovine) with amino acids 1 and 8 replaced with sarcosine and alanine, respectively. It is a highly specific competitive inhibitor of angiotensin II. [NIH] Sarcosine: Methylamino-acetic acid. [NIH] Schizoid: Having qualities resembling those found in greater degree in schizophrenics; a person of schizoid personality. [NIH] Schizophrenia: A mental disorder characterized by a special type of disintegration of the personality. [NIH] Schizotypal Personality Disorder: A personality disorder in which there are oddities of thought (magical thinking, paranoid ideation, suspiciousness), perception (illusions, depersonalization), speech (digressive, vague, overelaborate), and behavior (inappropriate affect in social interactions, frequently social isolation) that are not severe enough to characterize schizophrenia. [NIH] Screening: Checking for disease when there are no symptoms. [NIH] Segmental: Describing or pertaining to a structure which is repeated in similar form in successive segments of an organism, or which is undergoing segmentation. [NIH] Sequence Homology: The degree of similarity between sequences. Studies of amino acid and nucleotide sequences provide useful information about the genetic relatedness of certain species. [NIH] Serotonin: A biochemical messenger and regulator, synthesized from the essential amino acid L-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (receptors, serotonin) explain the broad physiological actions and distribution of this biochemical mediator. [NIH] Serum: The clear liquid part of the blood that remains after blood cells and clotting proteins have been removed. [NIH] 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] Simvastatin: A derivative of lovastatin and potent competitive inhibitor of 3-hydroxy-3methylglutaryl coenzyme A reductase (hydroxymethylglutaryl CoA reductases), which is the rate-limiting enzyme in cholesterol biosynthesis. It may also interfere with steroid hormone production. Due to the induction of hepatic LDL receptors, it increases breakdown of LDL-cholesterol (lipoproteins, LDL cholesterol). [NIH] Skeletal: Having to do with the skeleton (boney part of the body). [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.

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[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] 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] Steroid: A group name for lipids that contain a hydrogenated cyclopentanoperhydrophenanthrene ring system. Some of the substances included in this group are progesterone, adrenocortical hormones, the gonadal hormones, cardiac aglycones, bile acids, sterols (such as cholesterol), toad poisons, saponins, and some of the carcinogenic hydrocarbons. [EU] Stimulant: 1. Producing stimulation; especially producing stimulation by causing tension on muscle fibre through the nervous tissue. 2. An agent or remedy that produces stimulation. [EU]

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] 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] Subcutaneous: Beneath the skin. [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] Systemic: Affecting the entire body. [NIH] Systolic: Indicating the maximum arterial pressure during contraction of the left ventricle of the heart. [EU] Therapeutics: The branch of medicine which is concerned with the treatment of diseases, palliative or curative. [NIH] Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins. [NIH] 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] Thrombin: An enzyme formed from prothrombin that converts fibrinogen to fibrin. (Dorland, 27th ed) EC 3.4.21.5. [NIH] Thrombosis: The formation or presence of a blood clot inside a blood vessel. [NIH] Thrombus: An aggregation of blood factors, primarily platelets and fibrin with entrapment

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of cellular elements, frequently causing vascular obstruction at the point of its formation. Some authorities thus differentiate thrombus formation from simple coagulation or clot formation. [EU] 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] Torsion: A twisting or rotation of a bodily part or member on its axis. [NIH] Toxic: Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects. [NIH] Toxicity: The quality of being poisonous, especially the degree of virulence of a toxic microbe or of a poison. [EU] Toxicology: The science concerned with the detection, chemical composition, and pharmacologic action of toxic substances or poisons and the treatment and prevention of toxic manifestations. [NIH] Transfection: The uptake of naked or purified DNA into cells, usually eukaryotic. It is analogous to bacterial transformation. [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] Tryptophan: An essential amino acid that is necessary for normal growth in infants and for nitrogen balance in adults. It is a precursor serotonin and niacin. [NIH] Type 2 diabetes: Usually characterized by a gradual onset with minimal or no symptoms of metabolic disturbance and no requirement for exogenous insulin. The peak age of onset is 50 to 60 years. Obesity and possibly a genetic factor are usually present. [NIH] Unconscious: Experience which was once conscious, but was subsequently rejected, as the "personal unconscious". [NIH] Uremia: The illness associated with the buildup of urea in the blood because the kidneys are not working effectively. Symptoms include nausea, vomiting, loss of appetite, weakness, and mental confusion. [NIH] Urethra: The tube through which urine leaves the body. It empties urine from the bladder. [NIH]

Uric: A kidney stone that may result from a diet high in animal protein. When the body breaks down this protein, uric acid levels rise and can form stones. [NIH] Urinary: Having to do with urine or the organs of the body that produce and get rid of urine. [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] Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway. [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] Vasoconstriction: Narrowing of the blood vessels without anatomic change, for which constriction, pathologic is used. [NIH]

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Vasodilator: An agent that widens blood vessels. [NIH] Vein: Vessel-carrying blood from various parts of the body to the heart. [NIH] Venous: Of or pertaining to the veins. [EU] Venous blood: Blood that has given up its oxygen to the tissues and carries carbon dioxide back for gas exchange. [NIH] Venous Pressure: The blood pressure in a vein. It is usually measured to assess the filling pressure to the ventricle. [NIH] Venous Thrombosis: The formation or presence of a thrombus within a vein. [NIH] 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] Veterinary Medicine: The medical science concerned with the prevention, diagnosis, and treatment of diseases in animals. [NIH] Vivo: Outside of or removed from the body of a living organism. [NIH] Warfarin: An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. [NIH] White blood cell: A type of cell in the immune system that helps the body fight infection and disease. White blood cells include lymphocytes, granulocytes, macrophages, and others. [NIH]

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

87

INDEX A Acceptor, 63, 78 Acute renal, 9, 63 Adenosine, 63, 64, 79 Adjustment, 8, 63 Administration, Oral, 36, 63 Adrenal Cortex, 63, 64, 70, 82 Adrenergic, 63, 65, 66, 71, 72, 80, 83 Adrenergic beta-Antagonists, 63, 65 Adverse Effect, 63, 82 Affinity, 63, 83 Age of Onset, 63, 84 Alanine, 35, 63, 82 Albumin, 4, 19, 38, 63, 64, 79 Albuminuria, 4, 64 Aldosterone, 5, 11, 20, 64 Algorithms, 64, 67 Alimentary, 64, 76, 78 Alkaline, 64, 67 Alternative medicine, 39, 64 Amino Acids, 64, 65, 78, 79, 80, 82 Amiodarone, 38, 64 Amlodipine, 4, 6, 16, 64 Ampulla, 64, 69 Analog, 36, 64, 76, 82 Analytes, 8, 64 Anatomical, 64, 66, 70, 75 Angina, 34, 63, 64, 65, 80 Angina Pectoris, 63, 64, 80 Angioplasty, 34, 64 Angiotensin-Converting Enzyme Inhibitors, 65 Angiotensinogen, 22, 35, 65, 81 Animal model, 5, 8, 65 Anions, 64, 65, 76 Antagonism, 26, 30, 65 Anterior Cerebral Artery, 65, 68 Antianginal, 64, 65 Antiangiogenic, 5, 65 Antiarrhythmic, 64, 65 Antibiotic, 65, 78 Anticoagulant, 65, 80, 85 Antihypertensive, 7, 10, 11, 12, 14, 15, 21, 22, 24, 25, 34, 36, 38, 65 Antihypertensive Agents, 7, 36, 65 Anti-inflammatory, 9, 27, 65, 66 Anti-Inflammatory Agents, 9, 65, 66 Antipsychotic, 65, 82

Antiviral, 66, 78 Anxiety, 63, 66, 80 Aorta, 66, 85 Aqueous, 35, 66 Arachidonic Acid, 66, 80 Arterial, 10, 17, 34, 36, 38, 66, 68, 75, 80, 83 Arteries, 21, 30, 66, 67, 70, 77 Arteriolar, 66, 67, 73, 82 Aspirin, 27, 66 Assay, 18, 26, 66 Atenolol, 11, 12, 14, 15, 17, 20, 21, 22, 24, 26, 66 Atrial, 22, 27, 38, 64, 66, 85 Atrial Fibrillation, 27, 38, 66, 85 Atrium, 66, 85 Atypical, 66, 82 Autonomic, 12, 66, 73 B Base, 66, 72, 76 Bile, 66, 76, 83 Biliary, 66, 67, 69 Bilirubin, 64, 66 Bioavailability, 20, 21, 66 Biochemical, 18, 66, 82 Biopsy, 7, 67, 78 Biosynthesis, 66, 67, 77, 82 Biotechnology, 9, 39, 47, 67 Bladder, 67, 84 Blood Coagulation, 67 Blood pressure, 3, 4, 5, 6, 7, 8, 10, 11, 13, 15, 18, 21, 24, 36, 38, 65, 67, 68, 73, 75, 77, 78, 83, 85 Blood vessel, 65, 67, 68, 72, 74, 82, 83, 84, 85 Body Fluids, 67, 83 Bradykinin, 12, 67, 76, 79 Branch, 59, 67, 78, 83 Breakdown, 67, 71, 73, 82 Bronchi, 67, 72, 76 Bronchodilator, 67, 76 C Calcium, 4, 7, 64, 65, 67, 73 Calcium channel blocker, 4, 64, 65, 67 Calcium Channel Blockers, 65, 67 Calculi, 67, 74 Caloric intake, 6, 68 Capillary, 67, 68 Capillary Permeability, 67, 68

88

Irbesartan

Captopril, 11, 30, 36, 68 Cardiac, 6, 12, 14, 16, 30, 63, 65, 66, 68, 72, 77, 83 Cardiomyopathy, 68 Cardioselective, 66, 68, 80 Cardiovascular, 4, 5, 8, 12, 13, 15, 18, 19, 20, 21, 22, 30, 68, 82 Cardiovascular disease, 5, 8, 68 Case report, 13, 68, 69 Catheterization, 64, 68 Cell, 7, 67, 68, 73, 74, 76, 77, 79, 81, 85 Central Nervous System, 63, 68, 82 Cerebral, 34, 65, 68, 72, 73 Cerebral Infarction, 34, 68 Cerebrovascular, 67, 68 Cerebrum, 68 Character, 36, 64, 68, 71 Cholestasis, 9, 16, 69 Cholesterol, 8, 30, 66, 69, 70, 77, 82, 83 Chronic, 6, 8, 9, 16, 17, 22, 65, 69, 71, 72, 73, 76, 79 Chronic renal, 8, 9, 17, 69, 73, 79 Circadian, 18, 69 Claudication, 34, 69 Clinical study, 69, 70 Clinical trial, 5, 47, 69, 70, 81 Cloning, 67, 69 Coagulation, 67, 69, 79, 84, 85 Coenzyme, 69, 77, 82 Collagen, 8, 69, 79, 80 Colloidal, 64, 69 Computational Biology, 47, 69 Congestive heart failure, 6, 69 Conjugated, 69, 70 Connective Tissue, 69, 70 Constriction, 70, 84 Constriction, Pathologic, 70, 84 Contraindications, ii, 70 Control group, 6, 70 Controlled clinical trial, 5, 70 Controlled study, 16, 70 Conventional therapy, 11, 70 Conventional treatment, 70 Coronary, 20, 21, 27, 34, 64, 68, 70, 77 Coronary heart disease, 27, 68, 70 Coronary Thrombosis, 70, 77 Cortex, 70 Cortisol, 64, 70 Creatinine, 4, 5, 8, 70 Curative, 70, 83 Cyst, 5, 70 Cytochrome, 23, 70

D Databases, Bibliographic, 47, 71 Degenerative, 71, 74 Deuterium, 71, 75 Diabetes Insipidus, 71, 75, 79 Diabetes Mellitus, 7, 71, 73, 74, 76, 79 Diagnostic procedure, 33, 39, 71 Dialyzer, 71, 74 Diastole, 71 Diastolic, 6, 71, 75 Digestion, 64, 66, 71, 76, 83 Dilatation, 11, 64, 71 Dilated cardiomyopathy, 6, 71 Dilation, 67, 71 Dimethyl, 35, 71 Direct, iii, 6, 41, 71, 81 Disposition, 12, 21, 23, 71 Diuretic, 34, 35, 36, 71, 73, 74 Diuretics, Thiazide, 65, 71 Dopamine, 65, 71, 82 Drug Interactions, 42, 71 E Edema, 20, 72, 73, 75, 76, 78 Efficacy, 9, 10, 11, 14, 15, 17, 21, 24, 35, 72 Elastin, 69, 72 Elective, 12, 72, 79 Electrolyte, 64, 72, 79, 83 Electrons, 66, 72, 76, 78 Emboli, 72, 85 Embolism, 72, 81, 85 Embolization, 72, 85 Embolus, 72, 75 Enalapril, 10, 11, 16, 23, 36, 72 Endarterectomy, 65, 72 End-stage renal, 5, 6, 17, 69, 72, 79 Environmental Health, 46, 48, 72 Enzymatic, 35, 67, 72 Enzyme, 35, 69, 72, 73, 77, 79, 81, 82, 83 Epinephrine, 63, 71, 72, 76 Estrogen, 6, 72 Excipients, 35, 72 Exhaustion, 65, 73 Exogenous, 68, 73, 84 Extracellular, 69, 70, 73, 83 F Family Planning, 47, 73 Fat, 66, 70, 72, 73, 76 Fatigue, 73, 74 Fatty acids, 64, 73, 80 Felodipine, 15, 73 Forearm, 67, 73 Fosinopril, 34, 73

Index 89

Frontal Lobe, 65, 68, 73 Furosemide, 36, 73 G Ganglionic Blockers, 65, 73 Gas, 73, 75, 85 Gastrin, 73, 74 Gastrointestinal, 67, 72, 73, 82 Gene, 22, 30, 67, 73 Gene Expression, 30, 73 Genotype, 24, 73 Glomerular, 8, 73, 81 Glomeruli, 73 Glomerulosclerosis, 8, 73 Glomerulus, 73, 74 Glucose, 71, 74, 76, 81 Glucose Intolerance, 71, 74 Gout, 14, 74, 75 Governing Board, 74, 79 Gp120, 74, 78 Growth, 5, 65, 74, 84 H Habitual, 68, 74 Heart attack, 68, 74 Heart failure, 11, 15, 26, 30, 35, 65, 74 Heme, 66, 70, 74 Hemodialysis, 26, 71, 74, 76 Hemodynamics, 8, 74 Hemorrhage, 74, 83 Hepatic, 22, 64, 74, 82 Hepatitis, 13, 74 Hepatocyte, 69, 74 Hepatotoxicity, 13, 74 Heredity, 73, 74 Hormone, 7, 35, 64, 70, 72, 73, 74, 75, 82 Hydrochlorothiazide, 21, 24, 25, 35, 36, 74 Hydrogen, 34, 63, 66, 71, 75, 77, 78, 80 Hydroxylysine, 69, 75 Hydroxyproline, 69, 75 Hyperthyroidism, 75, 80 Hypertrophy, 11, 12, 14, 15, 20, 21, 22, 23, 24, 30, 75 Hyperuricaemia, 14, 75 Hyperuricemia, 14, 74, 75 I Id, 31, 52, 58, 60, 75 Immune system, 75, 77, 85 Immunity, 63, 75 Impairment, 6, 19, 69, 75 In vitro, 75 In vivo, 30, 75 Indicative, 75, 78, 84 Induction, 65, 73, 75, 82

Infarction, 11, 68, 75 Inflammation, 19, 64, 65, 66, 74, 75, 80 Inotropic, 66, 71, 73, 75 Insulin, 75, 84 Intermittent, 34, 76 Interstitial, 76, 81 Intoxication, 76, 85 Intracellular, 6, 67, 76, 79 Intramuscular, 76, 78 Intravenous, 76, 78 Ions, 66, 71, 72, 75, 76, 79 Isoproterenol, 7, 76 K Kallidin, 67, 76 Kb, 46, 76 Kidney Disease, 3, 4, 5, 8, 16, 22, 38, 46, 52, 64, 76 Kidney Failure, 52, 72, 74, 76 Kidney stone, 76, 84 L Lesion, 12, 76 Library Services, 58, 76 Life Expectancy, 5, 76 Ligaments, 70, 76 Lipid, 6, 68, 76 Liver, 23, 64, 66, 74, 76, 77, 81 Lobe, 65, 68, 76 Longitudinal Studies, 7, 76 Lovastatin, 76, 82 M Macrophage, 12, 77 Malnutrition, 64, 77 Manifest, 36, 77 MEDLINE, 47, 77 Membrane, 71, 74, 77, 78, 79 Membrane Glycoproteins, 77, 79 Menopause, 77, 80 Metabolic disorder, 71, 74, 77 Metabolite, 71, 73, 76, 77, 80, 81 Methionine, 71, 77 MI, 13, 61, 77 Milligram, 4, 77 Modeling, 8, 77 Molecular, 47, 49, 67, 69, 76, 77 Molecule, 66, 68, 69, 74, 77, 78, 81 Monitor, 70, 77 Myocardial infarction, 34, 70, 77, 80, 85 Myocardium, 64, 77 N Necrosis, 68, 75, 77 Need, 3, 53, 69, 77 Nephron, 9, 74, 77

90

Irbesartan

Nephropathy, 3, 4, 6, 7, 9, 11, 13, 16, 23, 24, 25, 76, 78 Nephrosis, 78 Nephrotic, 9, 78 Nephrotic Syndrome, 9, 78 Normotensive, 18, 38, 78 O Odds Ratio, 78, 81 Osmotic, 64, 78 Oxidation, 23, 63, 70, 78 P Palliative, 78, 83 Parenteral, 36, 78 Pathologic, 67, 70, 78 Penicillin, 65, 78, 84 Peptide, 22, 35, 78, 79, 80 Peptide T, 35, 78 Percutaneous, 34, 78 Pharmacodynamic, 18, 20, 21, 25, 78 Pharmacokinetic, 18, 20, 25, 78 Pharmacologic, 79, 84 Phosphorus, 67, 79 Physiologic, 67, 79, 81 Pilot study, 5, 9, 79 Plaque, 64, 79 Plasma, 18, 22, 24, 35, 63, 74, 76, 79, 81 Plasma protein, 63, 79 Platelet Aggregation, 21, 34, 79 Platelets, 79, 82, 83 Polycystic, 5, 79 Polydipsia, 26, 79 Polymorphism, 11, 12, 79 Polypeptide, 69, 79 Portal Pressure, 16, 79 Portal Vein, 79 Potassium, 16, 64, 71, 75, 79 Potassium Channels, 16, 79 Practice Guidelines, 48, 79 Precursor, 65, 66, 71, 72, 80, 84 Prodrug, 73, 80, 81 Progression, 3, 4, 5, 65, 80 Progressive, 5, 6, 69, 74, 77, 80, 81 Proline, 69, 75, 80 Prophylaxis, 80, 85 Proportional, 8, 80 Propranolol, 16, 66, 80 Prostaglandins, 8, 66, 80 Prostaglandins A, 8, 80 Prostaglandins D, 80 Protein C, 64, 80 Protein S, 67, 80 Proteins, 64, 69, 77, 78, 79, 80, 81, 82, 83

Proteinuria, 7, 8, 38, 73, 78, 80 Protons, 75, 80 Psychic, 80 Psychogenic, 26, 80 Public Policy, 47, 80 Publishing, 9, 81 Pulmonary, 67, 76, 81, 85 Pulmonary Artery, 67, 81, 85 Pulmonary Embolism, 81, 85 R Radioactive, 75, 81 Radiological, 78, 81 Ramipril, 6, 81 Randomized, 5, 9, 10, 19, 23, 27, 72, 81 Reabsorption, 8, 74, 81 Receptor, 3, 4, 5, 6, 7, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 30, 34, 35, 71, 74, 78, 81, 82 Recurrence, 38, 81 Reductase, 77, 81, 82 Refer, 1, 81 Refractory, 9, 81 Regimen, 72, 81 Relative risk, 4, 8, 81 Remission, 81 Renal failure, 26, 81 Renin, 3, 5, 6, 7, 8, 20, 26, 35, 65, 68, 81 Renin-Angiotensin System, 6, 65, 68, 81 Risk factor, 3, 7, 81, 82 Risperidone, 26, 82 S Saralasin, 36, 82 Sarcosine, 35, 82 Schizoid, 82, 85 Schizophrenia, 82, 85 Schizotypal Personality Disorder, 82, 85 Screening, 69, 82 Segmental, 73, 82 Sequence Homology, 78, 82 Serotonin, 65, 82, 84 Serum, 4, 5, 8, 14, 63, 82 Side effect, 7, 41, 63, 66, 75, 82, 84 Simvastatin, 18, 82 Skeletal, 76, 82 Small intestine, 74, 82 Smooth muscle, 67, 73, 82 Sodium, 9, 64, 71, 74, 75, 81, 83 Specialist, 53, 71, 83 Species, 72, 82, 83, 84, 85 Spinal cord, 68, 69, 83 Steroid, 70, 82, 83 Stimulant, 76, 83, 84

Index 91

Stomach, 73, 74, 82, 83 Stroke, 34, 46, 68, 83 Subcutaneous, 72, 78, 83 Sympathomimetic, 71, 72, 76, 83 Systemic, 4, 24, 42, 66, 67, 72, 74, 83, 84, 85 Systolic, 6, 75, 83 T Therapeutics, 10, 12, 16, 21, 24, 25, 26, 42, 83 Threonine, 78, 83 Threshold, 75, 83 Thrombin, 79, 80, 83 Thrombosis, 80, 83 Thrombus, 70, 75, 79, 83, 85 Thyroxine, 64, 84 Tissue, 63, 66, 67, 68, 69, 70, 72, 73, 76, 77, 78, 79, 82, 83, 84 Torsion, 75, 84 Toxic, iv, 75, 84 Toxicity, 71, 84 Toxicology, 48, 84 Transfection, 67, 84 Transplantation, 5, 11, 25, 69, 84 Tryptophan, 69, 82, 84 Type 2 diabetes, 3, 4, 11, 13, 23, 25, 26, 84 U Unconscious, 75, 84

Uremia, 76, 81, 84 Urethra, 84 Uric, 14, 74, 75, 84 Urinary, 4, 9, 67, 84 Urine, 3, 18, 64, 67, 70, 71, 76, 80, 84 V Valine, 82, 84 Vascular, 6, 7, 20, 30, 64, 67, 73, 75, 84 Vascular Resistance, 64, 73, 84 Vasoconstriction, 21, 30, 72, 84 Vasodilator, 65, 67, 71, 85 Vein, 76, 79, 85 Venous, 34, 68, 79, 80, 85 Venous blood, 68, 85 Venous Pressure, 79, 85 Venous Thrombosis, 34, 85 Ventricle, 6, 81, 83, 85 Ventricular, 11, 12, 14, 15, 20, 21, 22, 23, 24, 64, 85 Veterinary Medicine, 47, 85 Vivo, 85 W Warfarin, 19, 85 White blood cell, 77, 85 Withdrawal, 19, 85 X Xenograft, 65, 85

92

Irbesartan

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