Details

Metabolism of Drugs and Other Xenobiotics


Metabolism of Drugs and Other Xenobiotics


1. Aufl.

von: Pavel Anzenbacher, Ulrich M. Zanger

210,99 €

Verlag: Wiley-VCH
Format: EPUB
Veröffentl.: 23.02.2012
ISBN/EAN: 9783527646326
Sprache: englisch
Anzahl Seiten: 753

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Beschreibungen

A practice-oriented desktop reference for medical professionals, toxicologists and pharmaceutical researchers, this handbook provides<br> systematic coverage of the metabolic pathways of all major classes of xenobiotics in the human body. The first part comprehensively reviews<br> the main enzyme systems involved in biotransformation and how they are orchestrated in the body, while parts two to four cover the three<br> main classes of xenobiotics: drugs, natural products, environmental pollutants. The part on drugs includes more than 300 substances from<br> five major therapeutic groups (central nervous system, cardiovascular system, cancer, infection, and pain) as well as most drugs of abuse<br> <br> 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<br> toxicology.<br> 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.
Preface<br> <br> PART ONE: Biochemistry and Molecular Genetics of Drug Metabolism<br> <br> DRUG-METABOLIZING ENZYMES -<br> AN OVERVIEW<br> Introduction: Fate of a Drug in the Human Body<br> Classification Systems of Drug-Metabolizing Enzymes According to Different Criteria<br> Overview of the Most Important Drug-Metabolizing Enzyme<br> <br> CYTOCHROMES P450<br> Introduction and Historical Perspective<br> Nomenclature and Gene Organization<br> Regulation<br> Polymorphisms<br> Protein Structure<br> Catalytic Mechanisms<br> What Determines P450 Catalytic Selectivity?<br> Oxidative Stress and P450s<br> Relevance in Drug Metabolism and Clinical Medicine<br> <br> UDP-GLUCURONOSYLTRANSFERASES<br> Introduction<br> A Simple Phenotype: Unconjugated Nonhemolytic<br> Hyperbilirubinemia and Glucuronidation<br> Organization of UGTs and the UGT1A Gene Locus<br> UGT1A Gene Nomenclature<br> Human UGT1A Gene Locus and Sequence Variability<br> Glucuronidation of Bilirubin<br> UGT1A1 Gene<br> Is There an Advantage or Risk Associated with UGT1A1 Variability?<br> UGT1A1 Gene and Pharmacogenetic Protection<br> UGT1A1 Gene and Pharmacogenetic Risks<br> UGT1A1 Variability and Cancer Risk<br> UGT1A3 Gene<br> UGT1A7 Gene<br> Transcriptional Regulation of UGT1A Genes<br> Aryl Hydrocarbon Receptor/Aryl Hydrocarbon Receptor Nuclear Translocator Regulation of UGT1A Genes<br> Regulation by Hepatic Nuclear Factors<br> Regulation by the Farnesoid X Receptor<br> Regulation by Nuclear Factor Erythroid 2-Related Factor 2<br> Regulation by Splice Variants<br> Animal Models to Study UGT1A Genes<br> Outlook<br> <br> SULFOTRANSFERASES<br> Introduction<br> Background<br> PAPS Synthesis<br> SULT Enzyme Family<br> Assays for SULT Activity<br> Structure and Function of SULT<br> SULT Pharmacogenetics<br> Bioactivation and the Role of SULTs in Toxicology<br> Conclusions and Future Perspectives<br> <br> GLUTATHIONE S-TRANSFERASES<br> Introduction and History<br> Nomenclature, Structure, and Function<br> Substrates<br> Regulation, Induction, and Inhibition<br> Gene Polymorphism of GSTs<br> <br> HYDROLYTIC ENZYMES<br> Carboxylesterases<br> Epoxide Hydrolases<br> Paraoxonases<br> Other Hydrolases<br> <br> TRANSPORTING SYSTEMS<br> Introduction<br> Classification of Drug Transporters and Transport Mechanisms<br> Drug Transporters of the SLC Superfamily<br> ABC Drug Transporters<br> Drug Transporters and Disease<br> Drug Transporters and Pharmacokinetics<br> Role of Drug Transporters in Chemotherapy Resistance<br> Pharmacogenomics of Drug Transporters: Implications for Clinical Drug Response<br> <br> TRANSCRIPTIONAL REGULATION OF HUMAN DRUG-METABOLIZING CYTOCHROME P450 ENZYMES<br> Factors Affecting Drug-Metabolizing Cytochromes P450<br> Transcriptional Regulation of CYP<br> Regulation of Drug-Metabolizing CYPs<br> <br> IMPORTANCE OF PHARMACOGENOMICS<br> Introduction<br> Pharmacogenetic Polymorphisms<br> Polygenic and Multifactorial Aspects of Drug Metabolism Phenotype<br> Genomics Technologies and Approaches<br> Conclusions<br> <br> PART TWO: Metabolism of Drugs<br> <br> INTRODUCTION TO DRUG METABOLISM<br> Introduction<br> Historical Aspects<br> Diversity of Drug Metabolic Pathways<br> Influence of Drug Metabolism on Pharmacological Activity<br> Biotoxification<br> Extrahepatic Drug Metabolism<br> Factors Affecting Drug Metabolism Activity<br> Conclusions<br> <br> CENTRAL NERVOUS SYSTEM DRUGS<br> Introduction<br> Antidepressants<br> Antipsychotics<br> Tranquillizers and Hypnotic Agents<br> Psychostimulants<br> Anticonvulsants and Mood Stabilizers<br> Agents for Dementia and Cognitive Enhancers<br> Antimigraine Drugs<br> Other Drugs<br> Conclusions<br> <br> CARDIOVASCULAR DRUGS<br> Introduction<br> RAAS as a Target for Angiotensin-Converting Enzyme Inhibitors and AT1 Receptor Blockers<br> Adrenergic Receptor Agonists<br> Adrenergic Receptor Antagonists<br> Diuretics<br> Antiarrhythmics<br> Anticoagulants<br> Cholesterol-Lowering Drugs<br> <br> ANTICANCER DRUGS<br> Introduction<br> Alkylating Drugs<br> Platinum-Containing Agents<br> Antimetabolites<br> Endocrine Therapy<br> Histone Deacetylase Inhibitor (Vorinostat)<br> Tyrosine Kinase Inhibitors<br> Proteasome Inhibitor (Bortezomib)<br> <br> ANTIMICROBIAL AGENTS<br> Introduction<br> Pharmacokinetics/Pharmacodynamics of the Main Families of Antimicrobial Agents<br> Pharmacogenetics<br> Conclusions<br> <br> DRUGS AGAINST ACUTE AND CHRONIC PAIN<br> Introduction<br> Acute Pain<br> Chronic Pain<br> <br> DRUGS OF ABUSE (INCLUDING DESIGNER DRUGS)<br> <br> Introduction<br> Classic Drugs of Abuse<br> Designer Drugs of Abuse<br> <br> NICOTINE METABOLISM AND ITS IMPLICATIONS<br> Introduction<br> Absorption and Distribution of Nicotine<br> Excretion of Nicotine<br> Metabolism of Nicotine<br> Sources of Variation in Nicotine Metabolism<br> Implications of Variation in Nicotine Metabolism and CYP2A6 Activity<br> Conclusions<br> <br> METABOLISM OF ALCOHOL AND ITS CONSEQUENCES<br> Introduction<br> Properties and Sources of Ethanol<br> Ethanol Absorption and Elimination<br> Ethanol Metabolism<br> <br> PART THREE: Metabolism of Natural Compounds<br> <br> INTRODUCTION AND OVERVIEW<br> Introduction<br> Terpenoids: A Structurally Complex Group of Natural Products<br> Other Classes of Natural Products<br> Summary and Conclusions<br> <br> FLAVONOIDS<br> Flavonoids -<br> Plant Phytochemicals<br> Absorption and Metabolism of Flavonoids<br> Interactions of Flavonoids with Mammalian Proteins with Possible Implications for Drug Metabolism<br> Dietary Flavonoids -<br> Health Issues<br> Flavonoid-Drug Interactions<br> Conclusion -<br> Double-Edged Sword Properties of Flavonoids<br> <br> ST JOHN'S WORT (HYPERICUM PERFORATUM L.)<br> The Name Hypericum<br> Chemical Constituents of Hypericum perforatum<br> Clinical Pharmacology of H. perforatum<br> Pharmacokinetics and Pharmacokinetic Interactions of H. perforatum<br> In Vitro Studies<br> In Vivo Studies<br> <br> FOOD COMPONENTS AND SUPPLEMENTS<br> Introduction<br> Food Contaminants<br> Vitamins<br> Macronutrients<br> Secondary Plant Metabolites<br> Probiotics and Prebiotics in the Modulation of Drug Metabolism<br> <br> PART FOUR: Metabolism of Unnatural Xenobiotics<br> <br> ENVIRONMENTAL POLLUTANTS<br> Introduction -<br> An Overview<br> Overview of Environmental Pollutants<br> Toxic and Hazardous Environmental Pollutants Interacting with Drug Metabolism<br> Summary<br> <br> ENVIRONMENTAL ESTROGENS<br> Introduction<br> Estrogen Receptor Signaling Pathways<br> Agonistic/Antagonistic Effects of Xenobiotics on ERs<br> Effects of EDCs on Biosynthesis and Metabolism of Estrogens<br> Case of Polychlorinated Biphenyls<br> Conclusions<br> <br> BIOTRANSFORMATION OF INSECTICIDES<br> Introduction to Insecticides<br> Metabolism of Insecticides<br> Extrahepatic Metabolism of Insecticides<br> Factors Affecting Metabolism<br> Conclusions
<p>“Overall therefore, a book which can be read in its own right for the first half and then a valuable source of reference for the second half.  A useful tome to have on the bookshelf for anyone in the field.”  (<i>British Toxicology Society</i>, 1 July 2013)</p>
Pavel Anzenbacher heads the Department of Pharmacology at Palacky University, Olomouc (Czech Republic) and is vicepresident of the Czech Society of Clinical and Experimental Pharmacology and Toxicology. Having obtained his academic degrees from Charles University, Prague and from the Academy of Sciences of the Czech Republic he joined the Faculty of Medicine at Palacky University. His scientific contacts and stays have included e.g. the Princeton University, Vanderbilt University, Nashville, University of Connecticut, INSERM Montpellier, University of Lubeck, Technical University Berlin and Jagellonian University Cracow. Professor Anzenbacher has authored over 150 original scientific publications and has, among other honours, received the Fogarty Award of the USPHS.<br> <br> Ulrich M. Zanger is deputy head of the Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart (Germany). A chemist by training, he began to work on drug metabolism at the Biocenter of the University of Basel, Switzerland, where he obtained a PhD<br> degree in biochemistry. He undertook postdoctoral studies at the Southwestern Medical Center at Dallas, Texas, before returning to Basel and later moving to Stuttgart. His major research interests are in human drug metabolizing cytochromes P450 and in basic and clinical aspects<br> of pharmacogenetics/genomics. Professor Zanger has authored more than 130 scientific articles and is lecturing in pharmacology and toxicology at the University of Tubingen.
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.<br> 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.

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