Adverse Drug Reactions
This book provides the current state of knowledge of basic mechanisms of adverse drug reactions (ADRs). The main focus is on idiosyncratic drug reactions because they are the most difficult to deal with. It starts with a general description of the major t
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Volume 196
Editor-in-Chief F.B. Hofmann, München Editorial Board J.A. Beavo, Seattle, WA A. Busch, Berlin D. Ganten, Berlin J.-A. Karlsson, Singapore M.C. Michel, Amsterdam C.P. Page, London W. Rosenthal, Berlin
Jack Uetrecht Editor
Adverse Drug Reactions
Editor Jack Uetrecht Professor of Pharmacy and Medicine Canada Research Chair in Adverse Drug Reactions Faculty of Pharmacy University of Toronto Toronto, Canada M5S 2S2 [email protected]
ISSN 0171-2004 e-ISSN 1865-0325 ISBN 978-3-642-00662-3 e-ISBN 978-3-642-00663-0 DOI: 10.1007/978-3-642-00663-0 Springer Heidelberg Dordrecht London New York Library of Congress Control Number: 2009928631 # Springer-Verlag Berlin Heidelberg 2010 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permitted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permission for use must always be obtained from Springer. Violations are liable to prosecution under the German Copyright Law. The use of general descriptive names, registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every individual case the user must check such information by consulting the relevant literature. Cover design: SPi Publishing Services Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com)
Preface
Adverse drug reactions (ADRs) remain a major health issue. A recent study in the United Kingdom found that 6.5% of hospital admissions were precipitated by an ADR (Pirmohamed et al. 2004). In addition, they markedly increase the cost and uncertainty of drug development. Two decades ago, the major problem leading to drug candidate failure involved problems with metabolism and pharmacokinetics; now, the major problems are lack of efficacy and toxicity, and from 1975 to 2000, over 10% of the drugs approved by the FDA either had to be withdrawn or achieved a “black box” warning because of unexpected adverse reactions (Lasser et al. 2002). The basic mechanisms of the most common “type A” ADRs such as gastrointestinal bleeding caused by nonsteroidal antiinflammatory drugs and bleeding caused by warfarin are well known. However, the mechanisms of most ADRs, especially idiosyncratic drug reactions, are not understood, and that makes it impossible to predict which drug candidates will cause such reactions and which patients are at high risk. This is unlikely to change rapidly because the unpredictable nature and virtual lack
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