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Human drug metabolism / Michael D. Coleman. -- 3rd ed. -- Hoboken, NJ : Wiley-Blackwell, 2020. – (63.312 /C692 /3rd ed.) |
Contents
Preface
1 Introduction
1.1 Therapeutic window
1.2 Consequences of drug concentration changes
1.3 Clearance
1.4 First pass and drug extraction
1.5 First pass and plasma drug levels
1.6 Drug and xenobiotic metabolism
References
2 Drug Biotransformational Systems - Origins and Aims
2.1 Biotransforming enzymes
2.2 Threat of lipophilic hydrocarbons
2.3 Cell communication
2.4 False signal molecules: bioprotection
2.5 Sites of biotransforming enzymes
2.6 Biotransformation and xenobiotic cell entry
References
3 How Oxidative Systems Metabolise Substrates
3.1 Introduction
3.2 Capture of lipophilic molecules
3.3 Cytochrome P450s: nomenclature and methods of study
3.4 CYPs: main and associated structures
3.5 Human CYP families and their regulation
3.6 Main human CYP families
3.7 Cytochrome P450 catalytic cycle
3.8 Flavin monooxygenases (FMOs)
3.9 How CYP isoforms operate in vivo
3.10 Aromatic ring hydroxylation
3.11 Alkyl oxidations
3.12 Rearrangement reactions
3.13 Other oxidation processes
3.14 Control of CYP metabolic function
References
4 Induction of Cytochrome P450 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
4.6 Induction: practical considerations
4.7 Induction vs. inhibition: which 'wins'?
4.8 Induction: long-term impact
References
5 Cytochrome P450 Inhibition
5.1 Introduction
5.2 Inhibition of metabolism: general aspects
5.3 Mechanisms of reversible inhibition
5.4 Mechanisms of irreversible inhibition
5.5 Clinical consequences of irreversible inhibition
5.6 Cell transport systems and inhibition
5.7 Major clinical consequences of inhibition of drug clearance
5.8 Use of inhibitors for positive clinical intervention
5.9 Summary
References
6 Conjugation and Transport Processes
6.1 Introduction
6.2 Glucuronidation
6.3 Sulphonation
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 (mainly glycine)
6.11 Phase III transport processes
6.12 Biotransformation: integration of processes
References
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
7.6 Smoking
7.7 Effects of ethanol on drug metabolism
7.8 Artificial livers
7.9 Effects of disease on drug metabolism
7.10 Summary
References
8 Role of Metabolism in Drug Toxicity
8.1 Adverse drug reactions: definitions
8.2 Predictable drug adverse effects: type A
8.3 Unpredictable drug adverse effects: type B
8.4 Nature of drug-mediated immune responses
8.5 Type B3 reactions: role of metabolism in cancer
8.6 Summary of biotransformational toxicity
References
Appendix A Drug Metabolism in Drug Discovery
A.1 The pharmaceutical industry
A.2 Drug design and biotransformation: strategies
A.3 Animal and human experimental models: strategies
A.4 In vitro metabolism platforms and methods
A.5 Animal model developments in drug metabolism
A.6 Toxicological assays
A.7 In silico approaches
A.8 Summary
References
Appendix B Metabolism of Major Illicit Drugs
B.1 Introduction
B.2 Opiates
B.3 Cocaine
B.4 Hallucinogens
B.5 Amphetamine derivatives
B.6 Cannabis
B.7 Dissociative anaesthetics
B.8 Charlie Don't Surf!
References
Appendix C Examination Techniques
C.1 Introduction
C.2 A first-class answer
C.3 Preparation.
C.4 The day of reckoning
C.5 Foreign students
Appendix D Summary of Major CYP Isoforms and Their Substrates, Inhibitors, and Inducers
Index
