Human Drug Metabolism : An Introduction

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ISBN: 9780470742174 | 0470742178
Cover: Hardcover
Copyright: 5/17/2010

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Human Drug Metabolism, Second Edition is a completely revised and updated version of this key text. Providing an invaluable introduction to this core area of pharmacology and covering recent progress and advances in this fast moving field.

Preface	p. xi
Preface to First Edition	p. xiii
Introduction	p. 1
Therapeutic Window	p. 1
Consequences of drug concentration changes	p. 3
Clearance	p. 5
Hepatic extraction and intrinsic clearance	p. 7
First pass and plasma drug levels	p. 9
Drug and xenobiotic metabolism	p. 11
Drug Biotransformational Systems-Origins and Aims	p. 13
Biotransforming enzymes	p. 13
Threat of lipophilic hydrocarbons	p. 13
Cell communication	p. 14
Potential food toxins	p. 16
Sites of biotransforming enzymes	p. 18
Biotransformation and xenobiotic cell entry	p. 18
How Oxidative Systems Metabolize Substrates	p. 23
Introduction	p. 23
Capture of lipophilic molecules	p. 23
Cytochrome P450s classification and basic structure	p. 25
CYPs - main and associated structures	p. 27
Human CYP families and their regulation	p. 33
Main human CYP families	p. 35
Cytochrome P450 catalytic cycle	p. 43
Flavin monooxygenases (FMOs)	p. 47
How CYP isoforms operate in vivo	p. 50
Aromatic ring hydroxylation	p. 53
Alkyl oxidations	p. 54
'Rearrangement' reactions	p. 58
Other oxidation processes	p. 63
Control of CYP metabolic function	p. 64
Induction of Cytochrome P450 Systems	p. 65
Introduction	p. 65
Causes of accelerated clearance	p. 68
Enzyme induction	p. 69
Mechanisms of enzyme induction	p. 71
Induction - general clinical aspects	p. 86
Cytochrome P450 Inhibition	p. 93
Introduction	p. 93
Inhibition of metabolism - general aspects	p. 95
Mechanisms of inhibition	p. 96
Cell transport systems and inhibition	p. 111
Major clinical consequences of inhibition of drug clearance	p. 114
Use of inhibitors for positive clinical intervention	p. 119
Summary	p. 123
Conjugation and Transport Processes	p. 125
Introduction	p. 125
Glucuronidation	p. 126
Sulphonation	p. 138
The GSH system	p. 141
Glutathione S-transferases	p. 144
Epoxide hydrolases	p. 149
Acetylation	p. 151
Methylation	p. 152
Esterases/amidases	p. 152
Amino acid conjugation (glycine or glutamate)	p. 153
Phase III transport processes	p. 153
Biotransformation-integration of processes	p. 156
Factors Affecting Drug Metabolism	p. 159
Introduction	p. 159
Genetic polymorphisms	p. 159
Effects of age on drug metabolism	p. 192
Effects of diet on drug metabolism	p. 196
Gender effects	p. 200
Smoking	p. 201
Effects of ethanol on drug metabolism	p. 202
Artificial livers	p. 210
Effects of disease on drug metabolism	p. 210
Summary	p. 212
Role of Metabolism in Drug Toxicity	p. 213
Adverse drug reactions: definitions	p. 213
Reversible drug adverse effects: Type A	p. 213
Irreversible drug toxicity: Type B	p. 220
Type B1 necrotic reactions	p. 224
Type B2 reactions: immunotoxicity	p. 236
Type B3 reactions: role of metabolism in cancer	p. 251
Summary of biotransformational toxicity	p. 266
Methods in Drug Metabolism	p. 269
Introduction	p. 269
Analytical techniques	p. 271
Human liver microsomes	p. 272
Human hepatocytes	p. 273
Human cell lines	p. 275
Heterologous recombinant systems	p. 276
Animal model developments in drug metabolism	p. 276
Toxicological metabolism-based assays	p. 278
In silico studies	p. 281
Summary	p. 282
Metabolism of Major Illicit Drugs	p. 285
Introduction	p. 285
Opiates	p. 285
Cocaine	p. 292
Hallucinogens	p. 294
Amphetamines	p. 298
Cannabis	p. 304
Dissociative anaesthetics	p. 307
Examination Techniques	p. 311
Introduction	p. 311
A first-class answer	p. 311
Preparation	p. 312
The day of reckoning	p. 314
Summary of Major CYP Isoforms and their Substrates, Inhibitors and Inducers	p. 317
Suggested Further Reading	p. 319
Index	p. 329
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Human Drug Metabolism : An Introduction

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