Overview

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 ...
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Metabolism of Drugs and Other Xenobiotics

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Overview

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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Editorial Reviews

Doody's Review Service
Reviewer: Feng Li, PhD (University of Kansas Medical Center)
Description: This comprehensive handbook discusses the metabolism of numerous xenobiotic chemicals such as therapeutic drugs, natural products, and food components and supplements, as well as environmental pollutants and insecticides. The authors are worldwide experts in the field from various research institutes and universities around the world; some are accomplished clinical pharmacologists.
Purpose: The goal is to provide readers with comprehensive information on xenobiotic metabolism by devoting individual chapters to substances in a given chemical class. Thus, it provides a systematic discussion on important metabolic pathways of most major classes of xenobiotics in the human body.
Audience: This book is targeted at medical professionals, toxicologists, and medicinal chemists working both in academic and industrial fields.
Features: The first part of the book covers drug metabolizing enzymes (phase I and phase II) and transporting systems in detail. This is followed by a discussion of the regulation of human CPYP450 enzymes as it relates to advances in pharmacogenomics. The second part features the metabolism of marketed drugs and is organized by drug classes, including discussions on nicotine, alcohol, and illegal abused drugs. Parts three and four address the metabolism of natural products and unnatural xenobiotics, respectively.
Assessment: Compared to the other books in this area, this one goes beyond the discussion of the metabolism of therapeutic drugs to cover many other xenobiotic chemicals including natural products from herbs and food supplements, abused drugs, industrial chemicals and environmental pollutants. Moreover, information on the metabolism of many of the xenobiotic chemicals covered in this book is rarely found in previously available books on this topic. For example, this book covers more than 300 substances found in medications used for the treatment of the central nervous system, cardiovascular system, cancer, infectious diseases, and pain. This book also illustrates the importance of general principles of drug metabolism using well-documented case studies, which renders it very valuable for those teaching courses on drug metabolism and molecular toxicology.
From the Publisher
“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.”  (British Toxicology Society, 1 July 2013)
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Product Details

  • ISBN-13: 9783527646326
  • Publisher: Wiley
  • Publication date: 2/23/2012
  • Sold by: Barnes & Noble
  • Format: eBook
  • Edition number: 1
  • Pages: 753
  • File size: 9 MB

Meet the Author

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.

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
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
of pharmacogenetics/genomics. Professor Zanger has authored more than 130 scientific articles and is lecturing in pharmacology and toxicology at the University of Tübingen.
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Table of Contents

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

NI
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