Ace Inhibitors

Angiotensin converting enzyme inhibitors (ACEI) represent the first class of antihypertensive agents that was designed and developed on the basis of a well-defined physiopathological axis of arterial hypertension, a vascular dis order that is now becoming one of the major causes of morbidity/mortality, not only in developed societies but also in the highly populated developing coun tries [1]. CAPTOPRIL, the prototype of the "PRIL" family, which now comprises more than 40 molecule-species, was quite hazardous and the clinical develop ment almost failed when serious side-effects were reported in an alarmist fash ion in reputable scientific journals, such as the New England Journal of Medicine and Lancet. Squibb & Sons came very close to withdrawing CAPTOPRIL from clinical investigation [2]. However, after re-examination of the data obtained from different categories of patients and appropriate dose-adjustments, the clinical use of CAPTOPRIL turned out to be revolutionary. The prototype, as well as other members of the "PRIL" family became the starting point for numerous basic and clinical research programs, focusing on the interactions of ACEI with the kinin, endothelin, and nitric oxide systems, and the contribution of the receptors for AT I, AT 2, bradykinin Bland B , ETA and ET B to the pharmacological actions 2 of the respective peptides. This research activity led to the development of new pharmacological agents, such as the angiotensin receptor antagonists and, more recently, the neutral endopeptidase inhibitors. In the near future, bradykinin receptor antagonists also will be available to modulate ACEI phar macological actions.

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This book, published in two volumes, Volume 1 and Volume 2, respectively, represents the most comprehensive and up-to-date collection of current literature on angiotensin inhibition and related topics in medicine, nephrology and cardiovascular medicine ever compiled. Top experts in the various fields of nephrology, hypertension, cardiovascular medicine, pharmacotherapeutics and related fields from all five continents have contributed essays, original papers, reviews and editorial opinions in this volume. This book has turned out to be the most authoritative reference source on ACEIs, with contributions made by leading experts in their various fields of medicine, from the USA, Europe, including the United Kingdom, South America, Australia-New Zealand, Asia including Japan, and Africa. Critically vital clinical topics are covered in this book by top world-renowned experts in different subspecialties, including classic topics such as the efficacy of ACE inhibition as an antihypertensive among the various ethnicities and races, as written from American, African, Caribbean and European perspectives. This volume should indeed serve as a major literature reference text for physicians in general, internists, researchers, cardiologists and hypertension specialists, and especially the practitioners of the art of nephrology in all the countries around the world. Medical students and various physician training programs should reach for a copy of this volume as a research and teaching tool for many years to come. There is also a place here for research scientists in the pharmaceutical industry to review current and newly emerging indications for angiotensin inhibition and the future of reno-protection.

Meyler's Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions, Sixteenth Edition, Seven Volume Set builds on the success of the 15 previous editions, providing an extensively reorganized and expanded resource that now comprises more than 1,500 individual drug articles with the most complete coverage of adverse reactions and interactions found anywhere. Each article contains detailed and authoritative information about the adverse effects of each drug, with comprehensive references to the primary literature, making this a must–have reference work for any academic or medical library, pharmacologist, regulatory organization, hospital dispensary, or pharmaceutical company. The online version of the book provides an unparalleled depth of coverage and functionality by offering convenient desktop access and enhanced features such as increased searchability, extensive internal cross-linking, and fully downloadable and printable full-text, HTML or PDF articles. Enhanced encyclopedic format with drug monographs now organized alphabetically Completely expanded coverage of each drug, with more than 1,500 drug articles and information on adverse reactions and interactions Clearer, systematic organization of information for easier reading, including case histories to provide perspective on each listing Extensive bibliography with over 40,000 references A must–have reference work for any academic or medical library, pharmacologist, regulatory organization, hospital dispensary, or pharmaceutical company

Almost 75 million American adults-approximately one-third-have hypertension. The prevalence of hypertension increases with advancing age such that more than half of people 55 to 74 years old and approximately three-fourths of those age 75 years and older are affected. In addition to being the primary attributable risk factor for death throughout the world, hypertension results in substantial morbidity because of its impact on numerous target organs, including the brain, eyes, heart, arteries, and kidneys. Despite the high rates of morbidity and mortality attributable to hypertension, control of the condition remains suboptimal. In addition to several effective nonpharmacological interventions-including diet, exercise, and control of body weight-many people require antihypertensive medication to lower blood pressure. Among the many choices in antihypertensive therapy, some of the most common are those aimed at affecting the renin-angiotensin-aldosterone (renin) system. The renin system is an important mediator of blood volume, arterial pressure, and cardiac and vascular function. Components of this system can be identified in many tissues, but the primary site of renin release is the kidney. The renin system can be triggered by sympathetic stimulation, renal artery hypotension, and decreased sodium delivery to the distal tubule. Through proteolytic cleavage, renin acts on the oligopeptide substrate angiotensinogen to produce the decapeptide angiotensin I. In turn, two terminal peptide residues of angiotensin I are removed by the angiotensinconverting enzyme (ACE) to form the octapeptide angiotensin II. Angiotensin II acts directly on the resistance vessels to: increase systemic vascular resistance and arterial pressure; stimulate the adrenal cortex to release aldosterone, which leads to increased sodium and water reabsorption and potassium excretion; promote secretion of antidiuretic hormone, which leads to fluid retention; stimulate thirst; promote adrenergic function; and increase cardiac and vascular hypertrophy. Therapies aimed at modifying the renin system have been used extensively for treatment of hypertension, heart failure, myocardial infarction, diabetes, and renal disease. Currently, three classes of drugs that interact with this system are used to inhibit the effects of angiotensin II: the angiotensin-converting enzyme inhibitors (ACEIs), the angiotensin II receptor blockers/antagonists (ARBs), and the direct renin inhibitors. ACEIs block the conversion of angiotensin I into angiotensin II; ARBs selectively inhibit angiotensin II from activating the angiotensin-specific receptor (AT1); and direct renin inhibitors block the conversion of angiotensinogen into angiotensin I. This review summarizes the evidence on the comparative long-term benefits and harms of ACEIs, ARBs, and direct renin inhibitors, focusing on their use for treating essential hypertension in adults. In that analysis, investigators assessed the conclusions from the original comparative effectiveness review, performed a limited literature search of potentially new evidence, and solicited expert opinions concerning the state of the evidence and validity of the original report. Key Questions addressed are: Key Question 1. For adult patientsa with essential hypertension, how do ACEIs (angiotensin-converting enzyme inhibitors), ARBs (angiotensin II receptor antagonists), and direct renin inhibitorsb differ in blood pressure control, cardiovascular risk reduction, cardiovascular events, quality of life, and other outcomesc? Key Question 2. For adult patients with essential hypertension, how do ACEIs, ARBs, and direct renin inhibitors differ in safety, adverse events, tolerability, persistence with drug therapy, and treatment adherence

The emergence of an exciting new class of drugs known as ACE inhibitors is having a major impact on the treatment of hypertension and heart failure. This work provides the most complete and up-to-date investigation on the biochemistry, comparative pharmacology, and clinical utility of these powerful agents. Written by internationally respected authorities, sections offer state-of-the-art reviews, with special attention given to the potential of ACE inhibitors for established as well as new indications, either alone or in combination with older drugs. The broad range of topics includes the physiology of the renin-angiotensin system, the similarities and differences among ACE inhibitors, and the advantages of ACE inhibitors with respect to ?quality of life.? Furthermore, "Angiotensin Converting Enzyme Inhibitors" is the only review of the new and potentially promising ACE inhibitors under development.

About the Book ACE inhibitors are justly regarded as the most important advance in cardiac drug therapy since the advent of calcium channel antagonist drugs. Acting basically as inhibitors of the renin-angiotensin vasoconstrictor system, these agents have grown in importance to become among the therapeutic agents first choice for hypertension and a cornerstone of therapy in congestive heart failure. Recent studies show that they can also prevent overt heart failure and reinfarction, and beneficially influence diabetic renal lesions. The major aim of Angiotensin-Converting Enzyme Inhibitors: Scientific Basis for Clinical Use is to present the clinician with the information needed for the practical and discerning use of ACE inhibitors. When do these agents really work and in what doses? Which claims are based on promotional material and which claims have relevance for the clinician in the practical treatment of hypertension, heart failure or myocardial infarction? This Second Edition adds new material that critically reviews the recent large trials including Consensus-II, Save, V-HeFT-II, Aire, and ISIS-IV and guides the clinician toward a rational policy of use. There is an important new chapter on the use of ACE inhibitors in the metabolic cardiovascular syndrome and in diabetic nephropathy. Reviews of Other Books by the Author Drugs for the Heart—"A gem" (New England Journal of Medicine) The Heart—"The subjects are brilliantly illuminated and made exciting by excellent line diagrams" (The Lancet) Reviews of First Edition of this Book "A new milestone" (British Medical Journal) "Pathophysiology is clarified by numerous diagrams in a style well-known from Opie’s former books" (The Lancet)