Metabolism of drugs and other xenobiotics

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Metabolism of drugs and other xenobiotics

edited by Pavel Anzenbacher and Ulrich M. Zanger

Wiley-VCH, c2012

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注記

Includes bibliographical references and index

内容説明・目次

内容説明

A practice-oriented desktop reference for medical professionals, toxicologists and pharmaceutical researchers, this handbook provides systematic coverage of the metabolic pathways of all major classes of xenobiotics in the human body. The first part comprehensively reviews the main enzyme systems involved in biotransformation and how they are orchestrated in the body, while parts two to four cover the three main classes of xenobiotics: drugs, natural products, environmental pollutants. The part on drugs includes more than 300 substances from five major therapeutic groups (central nervous system, cardiovascular system, cancer, infection, and pain) as well as most drugs of abuse including nicotine, alcohol and "designer" drugs. Selected, well-documented case studies from the most important xenobiotics classes illustrate general principles of metabolism, making this equally useful for teaching courses on pharmacology, drug metabolism or molecular toxicology. Of particular interest, and unique to this volume is the inclusion of a wide range of additional xenobiotic compounds, including food supplements, herbal preparations, and agrochemicals.

目次

Preface PART ONE: Biochemistry and Molecular Genetics of Drug Metabolism DRUG-METABOLIZING ENZYMES - AN OVERVIEW Introduction: Fate of a Drug in the Human Body Classification Systems of Drug-Metabolizing Enzymes According to Different Criteria Overview of the Most Important Drug-Metabolizing Enzyme CYTOCHROMES P450 Introduction and Historical Perspective Nomenclature and Gene Organization Regulation Polymorphisms Protein Structure Catalytic Mechanisms What Determines P450 Catalytic Selectivity? Oxidative Stress and P450s Relevance in Drug Metabolism and Clinical Medicine UDP-GLUCURONOSYLTRANSFERASES Introduction A Simple Phenotype: Unconjugated Nonhemolytic Hyperbilirubinemia and Glucuronidation Organization of UGTs and the UGT1A Gene Locus UGT1A Gene Nomenclature Human UGT1A Gene Locus and Sequence Variability Glucuronidation of Bilirubin UGT1A1 Gene Is There an Advantage or Risk Associated with UGT1A1 Variability? UGT1A1 Gene and Pharmacogenetic Protection UGT1A1 Gene and Pharmacogenetic Risks UGT1A1 Variability and Cancer Risk UGT1A3 Gene UGT1A7 Gene Transcriptional Regulation of UGT1A Genes Aryl Hydrocarbon Receptor/Aryl Hydrocarbon Receptor Nuclear Translocator Regulation of UGT1A Genes Regulation by Hepatic Nuclear Factors Regulation by the Farnesoid X Receptor Regulation by Nuclear Factor Erythroid 2-Related Factor 2 Regulation by Splice Variants Animal Models to Study UGT1A Genes Outlook SULFOTRANSFERASES Introduction Background PAPS Synthesis SULT Enzyme Family Assays for SULT Activity Structure and Function of SULT SULT Pharmacogenetics Bioactivation and the Role of SULTs in Toxicology Conclusions and Future Perspectives GLUTATHIONE S-TRANSFERASES Introduction and History Nomenclature, Structure, and Function Substrates Regulation, Induction, and Inhibition Gene Polymorphism of GSTs HYDROLYTIC ENZYMES Carboxylesterases Epoxide Hydrolases Paraoxonases Other Hydrolases TRANSPORTING SYSTEMS Introduction Classification of Drug Transporters and Transport Mechanisms Drug Transporters of the SLC Superfamily ABC Drug Transporters Drug Transporters and Disease Drug Transporters and Pharmacokinetics Role of Drug Transporters in Chemotherapy Resistance Pharmacogenomics of Drug Transporters: Implications for Clinical Drug Response TRANSCRIPTIONAL REGULATION OF HUMAN DRUG-METABOLIZING CYTOCHROME P450 ENZYMES Factors Affecting Drug-Metabolizing Cytochromes P450 Transcriptional Regulation of CYP Regulation of Drug-Metabolizing CYPs IMPORTANCE OF PHARMACOGENOMICS Introduction Pharmacogenetic Polymorphisms Polygenic and Multifactorial Aspects of Drug Metabolism Phenotype Genomics Technologies and Approaches Conclusions PART TWO: Metabolism of Drugs INTRODUCTION TO DRUG METABOLISM Introduction Historical Aspects Diversity of Drug Metabolic Pathways Influence of Drug Metabolism on Pharmacological Activity Biotoxification Extrahepatic Drug Metabolism Factors Affecting Drug Metabolism Activity Conclusions CENTRAL NERVOUS SYSTEM DRUGS Introduction Antidepressants Antipsychotics Tranquillizers and Hypnotic Agents Psychostimulants Anticonvulsants and Mood Stabilizers Agents for Dementia and Cognitive Enhancers Antimigraine Drugs Other Drugs Conclusions CARDIOVASCULAR DRUGS Introduction RAAS as a Target for Angiotensin-Converting Enzyme Inhibitors and AT1 Receptor Blockers Adrenergic Receptor Agonists Adrenergic Receptor Antagonists Diuretics Antiarrhythmics Anticoagulants Cholesterol-Lowering Drugs ANTICANCER DRUGS Introduction Alkylating Drugs Platinum-Containing Agents Antimetabolites Endocrine Therapy Histone Deacetylase Inhibitor (Vorinostat) Tyrosine Kinase Inhibitors Proteasome Inhibitor (Bortezomib) ANTIMICROBIAL AGENTS Introduction Pharmacokinetics/Pharmacodynamics of the Main Families of Antimicrobial Agents Pharmacogenetics Conclusions DRUGS AGAINST ACUTE AND CHRONIC PAIN Introduction Acute Pain Chronic Pain DRUGS OF ABUSE (INCLUDING DESIGNER DRUGS) Introduction Classic Drugs of Abuse Designer Drugs of Abuse NICOTINE METABOLISM AND ITS IMPLICATIONS Introduction Absorption and Distribution of Nicotine Excretion of Nicotine Metabolism of Nicotine Sources of Variation in Nicotine Metabolism Implications of Variation in Nicotine Metabolism and CYP2A6 Activity Conclusions METABOLISM OF ALCOHOL AND ITS CONSEQUENCES Introduction Properties and Sources of Ethanol Ethanol Absorption and Elimination Ethanol Metabolism PART THREE: Metabolism of Natural Compounds INTRODUCTION AND OVERVIEW Introduction Terpenoids: A Structurally Complex Group of Natural Products Other Classes of Natural Products Summary and Conclusions FLAVONOIDS Flavonoids - Plant Phytochemicals Absorption and Metabolism of Flavonoids Interactions of Flavonoids with Mammalian Proteins with Possible Implications for Drug Metabolism Dietary Flavonoids - Health Issues Flavonoid-Drug Interactions Conclusion - Double-Edged Sword Properties of Flavonoids ST JOHN'S WORT (HYPERICUM PERFORATUM L.) The Name Hypericum Chemical Constituents of Hypericum perforatum Clinical Pharmacology of H. perforatum Pharmacokinetics and Pharmacokinetic Interactions of H. perforatum In Vitro Studies In Vivo Studies FOOD COMPONENTS AND SUPPLEMENTS Introduction Food Contaminants Vitamins Macronutrients Secondary Plant Metabolites Probiotics and Prebiotics in the Modulation of Drug Metabolism PART FOUR: Metabolism of Unnatural Xenobiotics ENVIRONMENTAL POLLUTANTS Introduction - An Overview Overview of Environmental Pollutants Toxic and Hazardous Environmental Pollutants Interacting with Drug Metabolism Summary ENVIRONMENTAL ESTROGENS Introduction Estrogen Receptor Signaling Pathways Agonistic/Antagonistic Effects of Xenobiotics on ERs Effects of EDCs on Biosynthesis and Metabolism of Estrogens Case of Polychlorinated Biphenyls Conclusions BIOTRANSFORMATION OF INSECTICIDES Introduction to Insecticides Metabolism of Insecticides Extrahepatic Metabolism of Insecticides Factors Affecting Metabolism Conclusions

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