 Human Drug Metabolism: An Introduction
ISBN: 978-0-470-86352-7
Hardcover
286 pages
November 2005
US $170.00
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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.
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