Human Drug Metabolism: An Introduction provides an accessible introduction to human drug metabolism for those who already have some understanding of the life sciences. It focuses only on essential chemical detail and includes patient case histories to illustrate the clinical consequences of changes in drug metabolism and its impact on patient welfare.
After underlining the relationship between efficacy, toxicity and drug concentration, the book then considers how metabolising systems operate and how they impact upon drug concentration, both under drug pressure and during inhibition. Factors affecting drug metabolism, such as genetic polymorphisms, age and diet are discussed and how metabolism can lead to toxicity is explained. The book concludes with the role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs.
* focuses on a conceptual understanding of drug metabolism
* takes a user-friendly approach to the chemical aspect of drug metabolism
* includes a wealth of diagrams and illustrations
* provides strategies for maximising examination performance
Human Drug Metabolism: An Introduction will be an invaluable resource for students studying pharmacology, pharmacy, bio-molecular sciences, biochemistry, molecular biology, toxicology, dentistry and medicine in addition to healthcare professionals and postgraduates.
Rezensionen / Stimmen
"...a useful introductory text for the intended audience of students studying pharmacology and toxicology..." (Veterinary Pathology, November 2006) "The author has certainly achieved his goal of providing an accessible introduction to human drug metabolism." (The Annals of Pharmacotherapy, June 2006) "Armed with the knowledge contained in this book, we should all be well on the way" (Pharmaceutical Physician, May 2006) "...useful for many who are just beginning to learn about drug metabolism...a good addition to many personal and school libraries." (Journal of Medicinal Chemistry, April 20, 2006) "...thumbs up for ambition." (Chemistry World, 1st March 2006) "Overall this is an interesting book that provides a rather comprehensive overview of drug metabolism in humans" (Journal of Medicinal Chemistry, 2006 Volume 49. No 8)
Auflage
Sprache
Verlagsort
Verlagsgruppe
Zielgruppe
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Maße
Höhe: 24.4 cm
Breite: 16.8 cm
Dicke: 21 mm
Gewicht
ISBN-13
978-0-470-86352-7 (9780470863527)
Schweitzer Klassifikation
Michael D. Coleman, DSc is a Senior Lecturer in Toxicology at Aston University. His award of the degree ofDoctor of Science from Aston University in 2005 reflects his substantial and original contribution to knowledge of Biochemical Pharmacology and Toxicology of Antiparasitic Drugs
Preface.
1. INTRODUCTION.
1.1 Therapeutic Window.
1.2 Consequences of Drug Concentration Changes.
1.3 Clearance.
1.4 Hepatic Extraction and Intrinsic Clearance.
1.5 First Pass and Plasma Drug Levels.
1.6 Drug and Xenobiotic Metabolism.
2. DRUG BIOTRANSFORMATIONAL SYSTEMS - ORIGINS AND AIMS.
2.1 Biotransforming enzymes.
2.2 Threat of Aromatic Hydrocarbons.
2.3 Cell Communication.
2.4 Potential Food Toxins.
2.5 Sites of Biotransforming Enzymes.
2.6 Biotransformation.
3. HOW PHASE I SYSTEMS METABOLISE SUBSTRATES.
3.1 Introduction.
3.2 Capture of Lipophilic Molecules.
3.3 Cytochrome P450s Basic Structure.
3.4 CYPs-Main and Associated Structures.
3.5 CYP Substrate Specificity and Regulation.
3.6 Main Human CYP Families.
3.7 Cytochrome P450 Catalytic Cycle.
3.8 Real-life Operations.
3.9 CYP Isoforms: how aims are translated into function.
3.10 Aromatic Ring Hydroxylation.
3.11 Alkyl Oxidations.
3.12 Rearrangement and Reactions.
3.13 Other Oxidation Processes.
3.14 Reduction Reactions.
3.15 Control of CYP Metabolic Function.
4. INDUCTION OF PHASE I SYSTEMS.
4.1 Introduction.
4.2 Causes of Accelerated Clearance.
4.3 Enzyme Induction.
4.4 Mechanisms of Enzyme induction.
4.5. Induction-General Clinical Aspects.
5. PHASE I ENZYME INHIBITION.
5.1 Introduction.
5.2 Inhibition of Metabolism-general aspects.
5.3 Mechanisms of Inhibition.
5.4 Cell transport systems and CYP 3A inhibitors.
5.5.Clinical Consequences of Drug Inhibition.
5.6. Use of Inhibitors for Positive Clinical Intervention.
6. PHASE II and III PROCESSES.
6.1 Introduction.
6.2 Glucuronidation.
6.3 Sulphation.
6.4 The GSH System.
6.5 Glutathione S-Transferases.
6.6 Epoxide hydrolases.
6.7 Acetylation.
6.8 Methylation.
6.9 Esterases/amidases.
6.10 Amino Acid Conjugation (Glycine or Glutamate).
6.11 Phase III Processes.
7. FACTORS AFFECTING DRUG METABOLISM.
7.1 Introduction.
7.2 Genetic Polymorphisms.
7.3 Effects of Age on Drug Metabolism.
7.4 Effects of Diet on Drug Metabolism.
7.5 Gender Effects.
7.8 Effects of Disease on Drug Metabolism.
7.9 Summary.
8. ROLE OF METABOLISM IN DRUG TOXICITY.
8.1 Adverse Drug Reactions.
8.2 Reversible Drug Adverse Effects Type A.
8.3. Irreversible Toxicity (Type B).
8.4 Type B1 Necrotic Reactions.
8.5. Type B2 Reactions: Immunotoxicity.
8.6 Type B3 Reactions: Role of Metabolism in Cancer.
8.7 Summary Of Biotransformational Toxicity.
APPENDIX A: METHODS IN DRUG METABOLISM.
A.1 Introduction.
A.2 Human liver microsomes.
A.3 Human hepatocytes.
A.4 Heterolohous systems.
A.5 Toxicological metabolism-based assays.
A.6 In silico studies.
APPENDIX B: METABOLISM OF MAJOR ILICIT DRUGS.
B.1 Introduction.
B.2 Opiates.
B.3 Cocaine.
B.4 Hallucinogens.
B.5 Amphetamines:ecstacy (MDMA).
B.6 Cannabis.
B.7 PCP.
APPENDIX C: EXAMINATION TECHNIQUES.
C.1 Introduction.
C.2 A first-class answer.
C.3 Preparation.
C.4 The day of reckoning.
APPENDIX D: SUMMARY OF MAJOR CYP ISOFORMS AND THEIR SUBSTRATES, INHIBITORS AND INDUCERS.
SUGGESTED FURTHER READING.
Index.
