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 targets for ADRs followed by a description of what are presently believed to be mediators and biochemical pathways involved in idiosyncratic drug reactions. There is also a description of several examples of ADRs that serve to illustrate specific aspects of ADR mechanisms. Eventually the book shows that ultimately better methods are needed to predict which drug candidates are likely to cause ADRs and which patients are at increased risk. But at present research seems to be far from this goal.
Author(s): Michael Holt, Cynthia Ju (auth.), Jack Uetrecht (eds.)
Series: Handbook of Experimental Pharmacology 196
Edition: 1
Publisher: Springer Berlin Heidelberg
Year: 2010
Language: English
Pages: 552
Tags: Pharmacology/Toxicology; Immunology; Public Health/Gesundheitswesen; Hepatology; Dermatology; Allergology
Front Matter....Pages 1-9
Front Matter....Pages 1-1
Drug-Induced Liver Injury....Pages 3-27
Drug Hypersensitivity Reactions Involving Skin....Pages 29-55
Adverse Drug Reactions Affecting Blood Cells....Pages 57-76
Molecular Mechanisms of Adverse Drug Reactions in Cardiac Tissue....Pages 77-109
Mechanisms of Drug-Induced Nephrotoxicity....Pages 111-130
Receptor- and Reactive Intermediate-Mediated Mechanisms of Teratogenesis....Pages 131-162
Front Matter....Pages 164-164
Role of Reactive Metabolites in Drug-Induced Hepatotoxicity....Pages 165-194
The Role of Cytokines in the Mechanism of Adverse Drug Reactions....Pages 195-231
The Keap1-Nrf2 Cellular Defense Pathway: Mechanisms of Regulation and Role in Protection Against Drug-Induced Toxicity....Pages 233-266
Signal Transduction Pathways Involved in Drug-Induced Liver Injury....Pages 267-310
Mitochondrial Involvement in Drug-Induced Liver Injury....Pages 311-365
Front Matter....Pages 368-368
Mechanisms of Acetaminophen-Induced Liver Necrosis....Pages 369-405
Drug-Induced Liver Injury in Humans: The Case of Ximelagatran....Pages 407-418
Troglitazone....Pages 419-435
Nevirapine Hypersensitivity....Pages 437-451
Mechanisms of Adverse Drug Reactions to Biologics....Pages 453-474
Front Matter....Pages 476-476
Pharmacogenetics of Idiosyncratic Adverse Drug Reactions....Pages 477-491
The Danger Hypothesis Applied to Idiosyncratic Drug Reactions....Pages 493-509
Approaches for Minimizing Metabolic Activation of New Drug Candidates in Drug Discovery....Pages 511-544
Back Matter....Pages 1-12
