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1st ed |
| Descript |
1 online resource (756 pages) |
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text txt rdacontent |
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computer c rdamedia |
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online resource cr rdacarrier |
| Note |
Intro -- Metabolism of Drugs and Other Xenobiotics -- Contents -- Preface -- List of Contributors -- Part One: Biochemistry and Molecular Genetics of Drug Metabolism -- 1: Drug-Metabolizing Enzymes - An Overview -- 1.1 Introduction: Fate of a Drug in the Human Body -- 1.2 Classification Systems of Drug-Metabolizing Enzymes According to Different Criteria -- 1.3 Overview of the Most Important Drug-Metabolizing Enzymes -- 1.3.1 CYPs -- 1.3.2 Peroxidases -- 1.3.3 Flavin Monooxygenases -- 1.3.4 Other Oxidases: Amine Oxidases, and Molybdenum-Containing XO and AO -- 1.3.5 NADPH Oxidase, NAD(P)H Oxidoreductase, and Dihydropyridine Dehydrogenase -- 1.3.6 Reductases -- 1.3.7 Conjugating Enzymes -- Acknowledgments -- References -- 2: Cytochromes P450 -- 2.1 Introduction and Historical Perspective -- 2.2 Nomenclature and Gene Organization -- 2.3 Regulation -- 2.3.1 Transcriptional Regulation -- 2.3.2 Post-Translational and Epigenetic Regulation -- 2.3.3 Post-Translational Regulation -- 2.4 Polymorphisms -- 2.5 Protein Structure -- 2.6 Catalytic Mechanisms -- 2.7 What Determines P450 Catalytic Selectivity? -- 2.8 Oxidative Stress and P450s -- 2.9 Relevance in Drug Metabolism and Clinical Medicine -- References -- 3: UDP-Glucuronosyltransferases -- 3.1 Introduction -- 3.2 A Simple Phenotype: Unconjugated Nonhemolytic Hyperbilirubinemia and Glucuronidation -- 3.3 Organization of UGTs and the UGT1A Gene Locus -- 3.4 UGT1A Gene Nomenclature -- 3.5 Human UGT1A Gene Locus and Sequence Variability -- 3.6 Glucuronidation of Bilirubin -- 3.7 UGT1A1 Gene -- 3.8 Is There an Advantage or Risk Associated with UGT1A1 Variability? -- 3.9 UGT1A1 Gene and Pharmacogenetic Protection -- 3.9.1 Cardiovascular Disease -- 3.9.2 Cancer -- 3.10 UGT1A1 Gene and Pharmacogenetic Risks -- 3.10.1 Disposition to Drug Toxicity -- 3.10.1.1 Irinotecan Toxicity |
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3.10.1.2 Jaundice in Protease Inhibitor Therapy (Atazanavir and Indinavir) -- 3.11 UGT1A1 Variability and Cancer Risk -- 3.11.1 CRC -- 3.11.2 Breast Cancer -- 3.12 UGT1A3 Gene -- 3.13 UGT1A7 Gene -- 3.13.1 CRC -- 3.13.2 HCC -- 3.13.3 Pancreatic Cancer -- 3.14 Transcriptional Regulation of UGT1A Genes -- 3.15 Aryl Hydrocarbon Receptor/Aryl Hydrocarbon Receptor Nuclear Translocator Regulation of UGT1A Genes -- 3.16 Regulation by Hepatic Nuclear Factors -- 3.17 Regulation by the Farnesoid X Receptor -- 3.18 Regulation by Nuclear Factor Erythroid 2-Related Factor 2 -- 3.19 Regulation by Splice Variants -- 3.20 Animal Models to Study UGT1A Genes -- 3.21 Outlook -- Acknowledgments -- References -- 4: Sulfotransferases -- 4.1 Introduction -- 4.2 Background -- 4.3 PAPS Synthesis -- 4.4 SULT Enzyme Family -- 4.4.1 SULT1 Family -- 4.4.2 SULT2 Family -- 4.4.3 SULT3, 4, 5 and 6 Families -- 4.5 Assays for SULT Activity -- 4.6 Structure and Function of SULT -- 4.7 SULT Pharmacogenetics -- 4.8 Bioactivation and the Role of SULTs in Toxicology -- 4.9 Conclusions and Future Perspectives -- References -- 5: Glutathione S-Transferases -- 5.1 Introduction and History -- 5.2 Nomenclature, Structure, and Function -- 5.2.1 Cytosolic GSTs -- 5.2.1.1 GSTA, GSTM, and GSTP Classes -- 5.2.1.2 GSTS Class -- 5.2.1.3 GSTT Class -- 5.2.1.4 GSTO Class -- 5.2.1.5 GSTZ Class -- 5.2.2 Mitochondrial GSTs -- 5.2.3 Microsomal GSTs -- 5.3 Substrates -- 5.4 Regulation, Induction, and Inhibition -- 5.5 Gene Polymorphism of GSTs -- 5.5.1 GSTA Polymorphism -- 5.5.2 GSTM Polymorphism -- 5.5.3 GSTT Polymorphism -- 5.5.4 GSTP1 Polymorphism -- 5.5.5 GSTO Polymorphism -- References -- 6: Hydrolytic Enzymes -- 6.1 Carboxylesterases -- 6.1.1 Overview -- 6.1.2 Classification and Structural Features -- 6.1.2.1 Human Carboxylesterases -- 6.1.2.2 Salient Features of Carboxylesterases |
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6.1.2.3 Secondary and Crystal Structure -- 6.1.3 Catalytic Mechanism, Substrate Specificity, and Activators and Inhibitors -- 6.1.3.1 Catalytic Mechanism -- 6.1.3.2 Substrate Specificity -- 6.1.3.3 Activators and Inhibitors -- 6.1.4 Pharmacogenomics of Carboxylesterases -- 6.1.4.1 Polymorphisms -- 6.1.4.2 Interaction with the Cytochrome P450 Enzyme System -- 6.1.4.3 Interaction with UDP-Glucuronosyltransferases -- 6.1.4.4 Interactions with Drug Transporters -- 6.1.4.5 Drug-Insecticide Interactions -- 6.1.5 Comparison between Human and Animal Carboxylesterases -- 6.1.5.1 Tissue Distribution -- 6.1.5.2 Species-Specific Hydrolysis -- 6.1.5.3 Ontogenic Expression -- 6.1.5.4 Regulated Expression -- 6.2 Epoxide Hydrolases -- 6.2.1 Overview -- 6.2.2 Classification and Structural Features -- 6.2.3 Catalytic Mechanisms -- 6.2.4 Comparison among Various EHs -- 6.3 Paraoxonases -- 6.3.1 Overview -- 6.3.2 Classification and Structural Features -- 6.3.3 Catalytic Mechanism -- 6.4 Other Hydrolases -- 6.4.1 Carbonic Anhydrases -- 6.4.2 Cholinesterases -- 6.4.3 β-Glucuronidase -- 6.4.4 Lipases -- 6.4.5 Peptidases/Proteases -- 6.4.6 Valacylovirase -- References -- 7: Transporting Systems -- 7.1 Introduction -- 7.2 Classification of Drug Transporters and Transport Mechanisms -- 7.3 Drug Transporters of the SLC Superfamily -- 7.4 ABC Drug Transporters -- 7.5 Drug Transporters and Disease -- 7.6 Drug Transporters and Pharmacokinetics -- 7.6.1 Intestinal Transporters -- 7.6.2 Hepatic Transporters -- 7.6.3 Renal Transporters -- 7.6.4 Transporters at the Blood-Brain Barrier -- 7.7 Role of Drug Transporters in Chemotherapy Resistance -- 7.8 Pharmacogenomics of Drug Transporters: Implications for Clinical Drug Response -- Acknowledgments -- References -- 8: Transcriptional Regulation of Human Drug-Metabolizing Cytochrome P450 Enzymes |
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8.1 Factors Affecting Drug-Metabolizing Cytochromes P450 -- 8.1.1 Genetic Polymorphism -- 8.1.2 Physiological and Pathophysiological Factors -- 8.1.3 Environmental Factors -- 8.2 Transcriptional Regulation of CYP -- 8.2.1 Xenoreceptors, and Steroid and Nuclear Receptors -- 8.2.1.1 Aryl Hydrocarbon Receptor -- 8.2.1.2 Pregnane X Receptor -- 8.2.1.3 Constitutive Androstane Receptor -- 8.2.1.4 Steroid and Nuclear Receptors -- 8.2.2 Transcriptional Mechanisms -- 8.2.2.1 Direct Binding to the Gene Promoter -- 8.2.2.2 Indirect Binding to the Gene Promoter -- 8.2.2.3 Regulating the Regulator -- 8.2.3 Receptor Cross-Talk -- 8.2.3.1 Ligand Sharing -- 8.2.3.2 Response Element Sharing -- 8.2.3.3 Receptor Cascade -- 8.2.3.4 Coactivator Sharing -- 8.2.3.5 Metabolic Cross-Talk -- 8.2.4 Ligands-Agonists and Antagonists -- 8.3 Regulation of Drug-Metabolizing CYPs -- 8.3.1 CYP1A Subfamily -- 8.3.2 CYP1B1 -- 8.3.3 CYP2A6 -- 8.3.4 CYP2B6 -- 8.3.5 CYP2C Subfamily -- 8.3.6 CYP3A Subfamily -- Acknowledgments -- References -- 9: Importance of Pharmacogenomics -- 9.1 Introduction -- 9.2 Pharmacogenetic Polymorphisms -- 9.2.1 Lessons from Early Examples -- 9.2.2 Cytochrome P450 Polymorphisms -- 9.2.3 Polymorphisms in Further Drug-Metabolizing Enzymes -- 9.2.4 Polymorphic Drug Transporters -- 9.3 Polygenic and Multifactorial Aspects of Drug Metabolism Phenotype -- 9.3.1 Polygenic Inheritance: CYP1A2 and CYP3A4 Conundrums -- 9.3.2 Epigenetic Influences on Drug Metabolism -- 9.4 Genomics Technologies and Approaches -- 9.4.1 GWAS-A Matured Tool in Pharmacogenomics -- 9.4.2 Genetical Genomics: Identifying Novel Polymorphic ADME Genes -- 9.5 Conclusions -- References -- Part Two: Metabolism of Drugs -- 10: Introduction to Drug Metabolism -- 10.1 Introduction -- 10.2 Historical Aspects -- 10.3 Diversity of Drug Metabolic Pathways |
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10.4 Influence of Drug Metabolism on Pharmacological Activity -- 10.5 Biotoxification -- 10.6 Extrahepatic Drug Metabolism -- 10.7 Factors Affecting Drug Metabolism Activity -- 10.7.1 Genetic Polymorphism -- 10.7.2 Sex -- 10.7.3 Age -- 10.7.4 Influence of Diseases and Pathophysiological Factors -- 10.7.5 Environmental Influences -- 10.8 Conclusions -- References -- 11: Central Nervous System Drugs -- 11.1 Introduction -- 11.2 Antidepressants -- 11.2.1 Tricyclic Antidepressants and Structurally Related Compounds -- 11.2.2 SSRIs -- 11.2.3 Other Recent Antidepressants -- 11.2.4 MAO Inhibitors -- 11.3 Antipsychotics -- 11.3.1 Phenothiazines and Thioxanthenes -- 11.3.2 Butyrophenones and Related Compounds -- 11.3.3 Atypical Antipsychotics -- 11.4 Tranquillizers and Hypnotic Agents -- 11.5 Psychostimulants -- 11.6 Anticonvulsants and Mood Stabilizers -- 11.7 Agents for Dementia and Cognitive Enhancers -- 11.8 Antimigraine Drugs -- 11.9 Other Drugs -- 11.10 Conclusions -- References -- 12: Cardiovascular Drugs -- 12.1 Introduction -- 12.2 RAAS as a Target for Angiotensin-Converting Enzyme Inhibitors and AT1 Receptor Blockers -- 12.2.1 ACE Inhibitors -- 12.2.2 ARBs -- 12.3 Adrenergic Receptor Agonists -- 12.3.1 α1-Selective Adrenergic Receptor Agonists -- 12.3.2 α2-Selective Adrenergic Receptor Agonists -- 12.3.3 β-Selective Adrenergic Receptor Agonists -- 12.4 Adrenergic Receptor Antagonists -- 12.4.1 α1-Selective Adrenergic Receptor Antagonists -- 12.4.2 α2-Selective Adrenergic Receptor Antagonists -- 12.4.3 β-Selective Adrenergic Receptor Antagonists -- 12.5 Diuretics -- 12.5.1 Carbonic Anhydrase Inhibitors -- 12.5.2 Osmotic Diuretics -- 12.5.3 Na+-K+-2Cl− Symport Inhibitors -- 12.5.4 Thiazide or Thiazide-Like Diuretics -- 12.5.5 Nonspecific Cation Channel Inhibitors -- 12.5.6 Inhibitors of Renal Epithelial Na+ Channels |
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12.5.7 Mineralcorticoid Receptor Antagonists |
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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 |
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Description based on publisher supplied metadata and other sources |
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Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2020. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries |
| Link |
Print version: Anzenbacher, Pavel Metabolism of Drugs and Other Xenobiotics
Weinheim : John Wiley & Sons, Incorporated,c2012 9783527329038
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| Subject |
Drugs -- Metabolism.;Xenobiotics -- Metabolism
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Electronic books
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| Alt Author |
Zanger, Ulrich M
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