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Expert report writing in toxicology : forensic, scientific, and legal aspects / / Michael D. Coleman
Expert report writing in toxicology : forensic, scientific, and legal aspects / / Michael D. Coleman
Autore Coleman Michael D.
Pubbl/distr/stampa Chichester, West Sussex, United Kingdom : , : John Wiley & Sons, , 2014
Descrizione fisica 1 online resource (226 p.)
Disciplina 614/.13
Soggetto topico Evidence, Expert
Self-poisoning
ISBN 1-118-43233-9
1-118-43236-3
1-118-43235-5
Formato Materiale a stampa
Livello bibliografico Monografia
Lingua di pubblicazione eng
Nota di contenuto Expert Report Writing in Toxicology: Forensic, Scientific and Legal Aspects; Copyright; Contents; Preface; 1 A brief history of occupational toxicology; 1.1 Occupational toxin exposure in antiquity; 1.2 The Middle Ages and the Renaissance: The beginnings of modern occupational toxicology; 1.3 The Industrial Revolution; 1.4 Petrochemicals: The beginnings; 1.5 Petrochemicals and mass production; 1.6 Aromatic amines: Tyres, dyes, explosives and cigarettes; 1.7 Contemporaneous knowledge; 1.8 The pursuit of truth; 1.9 The 'Mad Hatter'; 1.10 The 'Radium Girls'; 1.11 Asbestos
1.12 Occupational toxicity: Medicine and science1.13 Health and safety today; References; 2 The expert report process in legal context; 2.1 The would-be claimant's initial position; 2.2 Industrial injuries disablement benefit; 2.3 The legal process: First steps; 2.4 Legal advice: Who pays?; 2.5 Claim progression and possible outcomes; 2.6 Pre-action protocols; 2.7 Case initiation: Legal steps; 2.8 Expert reports: Medical; 2.9 Causality: The scientific report; 2.10 Recruiting the scientific expert; 2.11 Expectations of the expert: The court
2.12 Expectations of the expert: The solicitor/expert relationship2.13 The expert report: The contract; 2.14 Compiling the report; 2.15 The toxin or toxins; 2.16 Toxin entry; 2.17 Toxin chemical nature; 2.18 Exacerbating factors in toxin absorption; 2.19 Causation: Mechanisms; 2.20 Contemporaneous knowledge; 2.21 The initial draft; 2.22 Silence in court; 2.23 Report writing in the real world; References; 3 Acute toxicity: Case histories of solvent exposure; 3.1 Introduction; 3.2 Solvents in adhesives; 3.3 Solvent toxicity; 3.4 The real-world confusion of symptoms
3.5 Case histories: General format3.6 Case history 1: Mr A and volatile petroleum mixture exposure; 3.6.1 Case comment; 3.7 Case history 2: Mr B and dichloromethane exposure; 3.7.1 Case comment; 3.8 Mr B and dichloromethane: Further developments; 3.8.1 Further case comment; 3.9 Case history 3: Mr C and chronic solvent exposure and behaviour; 3.9.1 Case comment; 3.10 Summary of chronic solvent toxicity and behaviour; References; 4 Chronic and permanent injury: Bladder cancer and occupation; 4.1 Bladder cancer; 4.2 The patient's perspective; 4.3 Bladder cancer: Causes and risks
4.4 Bladder cancer and occupation: Industrial injury benefit claims4.5 Case history 1: Mr D; 4.6 Case history 2: Mr E; 4.7 Case history 3: Mr F; 4.8 Case history 4: Mrs G; 4.9 Bladder cancer and occupation: Legal claims for compensation; 4.10 Mr H: bladder cancer and the car industry; 4.10.1 Case comment; 4.11 Mr J: Bladder cancer; crankcase oils and diesel; 4.11.1 Case comment; 4.11.2 Further comment; 4.12 Summary; References; 5 Chronic and acute toxicity of herbicides and pesticides; 5.1Introduction; 5.2Herbicide/pesticide toxicity evaluation; 5.3Herbicides: Toxicity
5.4Case history 1: Mr K and Roundup©
Record Nr. UNINA-9910787860803321
Coleman Michael D.  
Chichester, West Sussex, United Kingdom : , : John Wiley & Sons, , 2014
Materiale a stampa
Lo trovi qui: Univ. Federico II
Opac: Controlla la disponibilità qui
Expert report writing in toxicology : forensic, scientific, and legal aspects / / Michael D. Coleman
Expert report writing in toxicology : forensic, scientific, and legal aspects / / Michael D. Coleman
Autore Coleman Michael D.
Pubbl/distr/stampa Chichester, West Sussex, United Kingdom : , : John Wiley & Sons, , 2014
Descrizione fisica 1 online resource (226 p.)
Disciplina 614/.13
Soggetto topico Evidence, Expert
Self-poisoning
ISBN 1-118-43233-9
1-118-43236-3
1-118-43235-5
Formato Materiale a stampa
Livello bibliografico Monografia
Lingua di pubblicazione eng
Nota di contenuto Expert Report Writing in Toxicology: Forensic, Scientific and Legal Aspects; Copyright; Contents; Preface; 1 A brief history of occupational toxicology; 1.1 Occupational toxin exposure in antiquity; 1.2 The Middle Ages and the Renaissance: The beginnings of modern occupational toxicology; 1.3 The Industrial Revolution; 1.4 Petrochemicals: The beginnings; 1.5 Petrochemicals and mass production; 1.6 Aromatic amines: Tyres, dyes, explosives and cigarettes; 1.7 Contemporaneous knowledge; 1.8 The pursuit of truth; 1.9 The 'Mad Hatter'; 1.10 The 'Radium Girls'; 1.11 Asbestos
1.12 Occupational toxicity: Medicine and science1.13 Health and safety today; References; 2 The expert report process in legal context; 2.1 The would-be claimant's initial position; 2.2 Industrial injuries disablement benefit; 2.3 The legal process: First steps; 2.4 Legal advice: Who pays?; 2.5 Claim progression and possible outcomes; 2.6 Pre-action protocols; 2.7 Case initiation: Legal steps; 2.8 Expert reports: Medical; 2.9 Causality: The scientific report; 2.10 Recruiting the scientific expert; 2.11 Expectations of the expert: The court
2.12 Expectations of the expert: The solicitor/expert relationship2.13 The expert report: The contract; 2.14 Compiling the report; 2.15 The toxin or toxins; 2.16 Toxin entry; 2.17 Toxin chemical nature; 2.18 Exacerbating factors in toxin absorption; 2.19 Causation: Mechanisms; 2.20 Contemporaneous knowledge; 2.21 The initial draft; 2.22 Silence in court; 2.23 Report writing in the real world; References; 3 Acute toxicity: Case histories of solvent exposure; 3.1 Introduction; 3.2 Solvents in adhesives; 3.3 Solvent toxicity; 3.4 The real-world confusion of symptoms
3.5 Case histories: General format3.6 Case history 1: Mr A and volatile petroleum mixture exposure; 3.6.1 Case comment; 3.7 Case history 2: Mr B and dichloromethane exposure; 3.7.1 Case comment; 3.8 Mr B and dichloromethane: Further developments; 3.8.1 Further case comment; 3.9 Case history 3: Mr C and chronic solvent exposure and behaviour; 3.9.1 Case comment; 3.10 Summary of chronic solvent toxicity and behaviour; References; 4 Chronic and permanent injury: Bladder cancer and occupation; 4.1 Bladder cancer; 4.2 The patient's perspective; 4.3 Bladder cancer: Causes and risks
4.4 Bladder cancer and occupation: Industrial injury benefit claims4.5 Case history 1: Mr D; 4.6 Case history 2: Mr E; 4.7 Case history 3: Mr F; 4.8 Case history 4: Mrs G; 4.9 Bladder cancer and occupation: Legal claims for compensation; 4.10 Mr H: bladder cancer and the car industry; 4.10.1 Case comment; 4.11 Mr J: Bladder cancer; crankcase oils and diesel; 4.11.1 Case comment; 4.11.2 Further comment; 4.12 Summary; References; 5 Chronic and acute toxicity of herbicides and pesticides; 5.1Introduction; 5.2Herbicide/pesticide toxicity evaluation; 5.3Herbicides: Toxicity
5.4Case history 1: Mr K and Roundup©
Record Nr. UNINA-9910813757003321
Coleman Michael D.  
Chichester, West Sussex, United Kingdom : , : John Wiley & Sons, , 2014
Materiale a stampa
Lo trovi qui: Univ. Federico II
Opac: Controlla la disponibilità qui
Expert Report Writing in Toxicology
Expert Report Writing in Toxicology
Autore Coleman Michael D.
Pubbl/distr/stampa John Wiley & Sons, Inc
Descrizione fisica 1 online resource (224 p.)
Disciplina 614.13
Soggetto non controllato Toxicology
Medical
Formato Materiale a stampa
Livello bibliografico Monografia
Lingua di pubblicazione eng
Altri titoli varianti Expert report writing in toxicology
Record Nr. UNINA-9910830406203321
Coleman Michael D.  
John Wiley & Sons, Inc
Materiale a stampa
Lo trovi qui: Univ. Federico II
Opac: Controlla la disponibilità qui
Expert Report Writing in Toxicology
Expert Report Writing in Toxicology
Autore Coleman Michael D.
Pubbl/distr/stampa John Wiley & Sons, Inc
Descrizione fisica 1 online resource (224 p.)
Disciplina 614.13
Soggetto non controllato Toxicology
Medical
Formato Materiale a stampa
Livello bibliografico Monografia
Lingua di pubblicazione eng
Altri titoli varianti Expert report writing in toxicology
Record Nr. UNINA-9910877398303321
Coleman Michael D.  
John Wiley & Sons, Inc
Materiale a stampa
Lo trovi qui: Univ. Federico II
Opac: Controlla la disponibilità qui
Human drug metabolism / / Michael D. Coleman
Human drug metabolism / / Michael D. Coleman
Autore Coleman Michael D.
Edizione [3rd ed]
Pubbl/distr/stampa Hoboken, N.J., : Wiley Blackwell, 2020
Descrizione fisica 1 online resource (683 pages)
Disciplina 615.1
Soggetto topico Drugs -- Metabolism
Drugs -- Metabolic detoxication
ISBN 1-119-45861-7
1-119-65801-2
1-119-45860-9
Classificazione 491.5
615.1
Formato Materiale a stampa
Livello bibliografico Monografia
Lingua di pubblicazione und
Nota di contenuto Preface -- 1 Introduction -- 1.1 Therapeutic window -- 1.1.1 Introduction -- 1.1.2 Therapeutic index -- 1.1.3 Changes in dosage -- 1.1.4 Changes in rate of removal -- 1.2 Consequences of drug concentration changesh -- 1.2.1 Drug failure -- 1.2.2 Drug toxicity -- 1.3 Clearance -- 1.3.1 Definitions -- 1.3.2 Clearance and elimination -- 1.3.3 Biotransformation prior to elimination -- 1.3.4 Intrinsic clearance -- 1.3.5 Clearance: influencing factors -- 1.4 First pass and drug extraction -- 1.4.1 First pass: gut contribution -- 1.4.2 First pass: hepatic contribution -- 1.4.3 First pass: low‐extraction drugs -- 1.5 First pass and plasma drug levels -- 1.5.1 Introduction -- 1.5.2 Changes in clearance and plasma 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 -- 2.3.1 Signal molecule evolution -- 2.3.2 Lipophilic hydrocarbons as signal molecules -- 2.4 False signal molecules: bioprotection -- 2.4.1 Endocrine disruption -- 2.4.2 Endocrine disruption: problems and solutions -- 2.4.3 Endocrine disruption: cosmetic and nutraceutical aspects -- 2.4.4 Endocrine disruption: microRNAs -- 2.5 Sites of biotransforming enzymes -- 2.6 Biotransformation and xenobiotic cell entry -- 2.6.1 Role of the liver -- 2.6.2 Drug and xenobiotic uptake: transporter systems -- 2.6.3 Hepatic and gut uptake (influx) transporter systems -- 2.6.4 Aims of biotransformation -- 2.6.5 Task of biotransformation -- 2.6.6 Phase's I-III of biotransformation: descriptions and classifications -- 2.6.7 Biotransformation and drug action -- 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 -- 3.3.1 Classification -- 3.3.2 Methods of analysis -- 3.3.3 CYP key features and capabilities -- 3.4 CYPs: main and associated structures -- 3.4.1 General structure -- 3.4.2 Haem moiety -- 3.4.3 CYP flexible regions -- 3.4.4 Substrate binding in CYPs -- 3.4.5 Homotropic binding in CYPs -- 3.4.6 Heterotropic binding in CYPs -- 3.4.7 CYP complex formation -- 3.4.8 CYP REDOX partners (i): P450 oxidoreductase (POR) -- 3.4.9 CYP REDOX partners (ii): Cytochrome b5 -- 3.5 Human CYP families and their regulation -- 3.5.1 CYP regulation: lifespan -- 3.5.2 CYP regulation: transcriptional -- 3.5.3 CYP regulation: post‐translational -- 3.6 Main human CYP families -- 3.6.1 CYP1A series -- 3.6.2 CYP2 series -- 3.6.3 CYP3A series -- 3.7 Cytochrome P450 catalytic cycle -- 3.7.1 Substrate binding -- 3.7.2 Oxygen binding -- 3.7.3 Oxygen scission (splitting) -- 3.7.4 Insertion of oxygen into substrate -- 3.7.5 Release of product -- 3.7.6 Reductions -- 3.8 Flavin monooxygenases (FMOs) -- 3.8.1 Introduction -- 3.8.2 Structure -- 3.8.3 Mechanism of catalysis -- 3.8.4 Variation and expression -- 3.8.5 FMOs in drug development -- 3.9 How CYP isoforms operate in vivo -- 3.9.1 Illustrative use of structures -- 3.9.2 Primary purposes of CYPs -- 3.9.3 Role of oxidation -- 3.9.4 Summary of CYP operations -- 3.10 Aromatic ring hydroxylation -- 3.10.1 Nature of aromatics -- 3.10.2 Oxidation of benzene -- 3.11 Alkyl oxidations -- 3.11.1 Saturated alkyl groups -- 3.11.2 Unsaturated alkyl groups -- 3.11.3 Pathways of alkyl metabolism -- 3.12 Rearrangement reactions -- 3.12.1 Dealkylations -- 3.12.2 Deaminations -- 3.12.3 Dehalogenations -- 3.13 Other oxidation processes -- 3.13.1 Primary amine oxidations -- 3.13.2 Oxidation of alcohol and aldehydes -- 3.13.3 Monoamine oxidase (MAO) -- 3.14 Control of CYP metabolic function -- References -- 4 Induction of Cytochrome P450 Systems -- 4.1 Introduction -- 4.1.1 How living systems self‐regulate: overview -- 4.1.2 Self‐regulation in drug metabolism -- 4.1.3 Self‐regulatory responses to drugs: summary -- 4.2 Causes of accelerated clearance -- 4.3 Enzyme induction -- 4.3.1 Types of inducers -- 4.3.2 Common features of inducers and clinical significance -- 4.4 Mechanisms of enzyme induction -- 4.4.1 Introduction -- 4.4.2 CYPs 1A1/1A2 and 1B1 induction -- 4.4.3 CYP 2B6 2C8/2C9/C19 and 3A4 induction -- 4.4.4 CYP 2E1 induction -- 4.4.5 CYP2D6 -- 4.4.6 Reversal of induction -- 4.4.7 Cell transport systems and induction: P‐glycoprotein -- 4.4.8 Induction processes: summary -- 4.5 Induction: general clinical aspects -- 4.5.1 Introduction -- 4.5.2 Anti‐epileptic agents -- 4.5.3 OTC (over the counter) and online herbal preparations -- 4.5.4 Anticoagulant drugs -- 4.5.5 Oral contraceptives/steroids -- 4.5.6 Antiviral/antibiotic drugs -- 4.5.7 Anticancer drugs -- 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 -- 5.3.1 Introduction -- 5.3.2 Competitive inhibition -- 5.3.3 Noncompetitive inhibition -- 5.3.4 Uncompetitive inhibition -- 5.4 Mechanisms of irreversible inhibition -- 5.4.1 Introduction -- 5.4.2 Mechanism‐based quasi‐irreversible inhibitors -- 5.4.3 Mechanism‐based irreversible inhibitors -- 5.5 Clinical consequences of irreversible inhibition -- 5.5.1 Introduction -- 5.5.2 Quasi‐irreversible inhibitors: the SSRIs -- 5.5.3 Mechanism‐based inhibitors: grapefruit juice -- 5.5.4 Mechanism‐based inhibitors: other juice products -- 5.5.5 OTC herbal remedy inhibitors -- 5.6 Cell transport systems and inhibition -- 5.6.1 Uptake (Influx) transporters: OATPs -- 5.6.2 Efflux transporters: P‐glycoprotein (P‐gp) -- 5.7 Major clinical consequences of inhibition of drug clearance -- 5.7.1 Introduction -- 5.7.2 Torsades de pointes (TdP) -- 5.7.3 Sedative effects -- 5.7.4 Muscle damage (rhabdomyolysis) -- 5.7.5 Excessive hypotension -- 5.7.6 Ergotism -- 5.7.7 Excessive anticoagulation -- 5.8 Use of inhibitors for positive clinical intervention -- 5.8.1 Introduction -- 5.8.2 CYP inhibitors and female hormone‐dependent tumours -- 5.8.3 CYP inhibitors and male hormone‐dependent tumours -- 5.8.4 CYP inhibitors and manipulation of prescription drug disposition -- 5.8.5 Use of inhibitors to increase drug efficacy -- 5.8.6 Use of inhibitors to reduce toxic metabolite formation -- 5.8.7 Use of inhibitors to reduce drug costs -- 5.8.8 Use of inhibition in alcoholism -- 5.9 Summary -- References -- 6 Conjugation and Transport Processes -- 6.1 Introduction -- 6.2 Glucuronidation -- 6.2.1 UGTs -- 6.2.2 UGT mode of operation -- 6.2.3 UGT isoforms -- 6.2.4 UGTs and bilirubin -- 6.2.5 UGTs and bile acids -- 6.2.6 Role of glucuronidation in drug clearance -- 6.2.7 Types of glucuronides formed -- 6.2.8 Control of UGTs -- 6.2.9 Induction of UGTs: clinical consequences -- 6.2.10 UGT inhibition: bilirubin metabolism -- 6.2.11 UGT inhibition: drug clearance -- 6.2.12 Microbiome and drug metabolism: passengers or crew? -- 6.3 Sulphonation -- 6.3.1 Introduction -- 6.3.2 SULT structure related to catalytic operation -- 6.3.3 Control of SULT enzymes -- 6.3.4 SULTs and cancer -- 6.4 The GSH system -- 6.4.1 Introduction -- 6.4.2 GSH system maintenance -- 6.5 Glutathione S‐transferases -- 6.5.1 Structure and location -- 6.5.2 Mode of operation -- 6.5.3 GST classes -- 6.5.4 Control of GSTs: overview -- 6.5.5 Control of GSTs and reactive species -- 6.5.6 Control of GSTs: the nrf2 system -- 6.6 Epoxide hydrolases -- 6.6.1 Nature of epoxides -- 6.6.2 Epoxide hydrolases -- 6.6.3 Epoxide hydrolases: structure, mechanisms of action, and regulation -- 6.7 Acetylation -- 6.8 Methylation -- 6.9 Esterases/amidases -- 6.10 Amino acid conjugation (mainly glycine) -- 6.11 Phase III transport processes -- 6.11.1 Introduction -- 6.11.2 ABC Efflux transporters -- 6.11.3 RLIP76 -- 6.12 Biotransformation: integration of processes -- References -- 7 Factors Affecting Drug Metabolism -- 7.1 Introduction -- 7.2 Genetic polymorphisms -- 7.2.1 Introduction -- 7.2.2 Clinical implications -- 7.2.3 Genetic polymorphisms in CYP systems -- 7.2.4 Genetic polymorphisms in nonconjugative systems -- 7.2.5 Conjugative polymorphisms: acetylation -- 7.2.6 Conjugative polymorphisms: methylation -- 7.2.7 Conjugative polymorphisms: UGT 1A1 -- 7.2.8 Conjugative polymorphisms: sulphonation.
7.2.9 Other conjugative polymorphisms: Glutathione S‐transferases -- 7.2.10 Transporter polymorphisms -- 7.2.11 Polymorphism detection: clinical and practical issues -- 7.3 Effects of age on drug metabolism -- 7.3.1 The elderly -- 7.3.2 Drug clearance in neonates and children -- 7.4 Effects of diet on drug metabolism -- 7.4.1 Polyphenols -- 7.4.2 Barbecued meat -- 7.4.3 Cruciferous vegetables -- 7.4.4 Other vegetable effects on metabolism -- 7.4.5 Caffeine -- 7.4.6 Diet: general effects -- 7.5 Gender effects -- 7.6 Smoking -- 7.7 Effects of ethanol on drug metabolism -- 7.7.1 Context of ethanol usage -- 7.7.2 Ethanol metabolism -- 7.7.3 Ethanol and inhibitors of ALDH -- 7.7.4 Mild ethanol usage and drug clearance -- 7.7.5 Heavy ethanol usage and paracetamol -- 7.7.6 Alcoholic liver disease -- 7.7.7 Effects of cirrhosis on drug clearance -- 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 -- 8.2.1 Intensification of pharmacologic effect: type A1 -- 8.2.2 Off‐target reversible effects and methaemoglobin formation: type A2 -- 8.2.3 Predictable overdose toxicity: type A3 -- 8.3 Unpredictable drug adverse effects: type B -- 8.3.1 Idiosyncratic and overdose toxicity: similarities and differences -- 8.3.2 Type B1 necrosis: troglitazone -- 8.3.3 Type B1 necrosis: trovafloxacin -- 8.3.4 Type B2 reactions: immunotoxicity -- 8.4 Nature of drug‐mediated immune responses -- 8.4.1 Anaphylaxis -- 8.4.2 DRESS/Anticonvulsant hypersensitivity syndrome (AHS) -- 8.4.3 Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) -- 8.4.4 Blood dyscrasias -- 8.4.5 Prediction of idiosyncratic reactions -- 8.5 Type B3 reactions: role of metabolism in cancer -- 8.5.1 Sources of risks of malignancy -- 8.5.2 Risks of malignancy and drug development -- 8.5.3 Environmental carcinogenicity risks -- 8.5.4 Occupational carcinogens -- 8.5.5 Dietary carcinogens: acrylamide -- 8.5.6 Dietary carcinogens: aflatoxins -- 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.4.1 Analytical techniques -- A.4.2 Human liver microsomes -- A.4.3 Heterologous recombinant systems -- A.4.4 Liver slices -- A.4.5 Human hepatocytes -- A.5 Animal model developments in drug metabolism -- A.5.1 Introduction -- A.5.2 Genetic modification of animal models -- A.5.3 'Humanized' mice -- A.6 Toxicological assays -- A.6.1 Aims -- A.6.2 Cell viability assays -- A.6.3 'One compartment' cell models -- A.6.4 'Two compartment' models -- A.6.5 DNA and chromosomal toxicity assays -- A.6.6 The Ames test -- A.6.7 Comet assay -- A.6.8 Micronucleus test -- A.6.9 Toxicology in drug discovery -- 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.
Record Nr. UNINA-9910829804703321
Coleman Michael D.  
Hoboken, N.J., : Wiley Blackwell, 2020
Materiale a stampa
Lo trovi qui: Univ. Federico II
Opac: Controlla la disponibilità qui
Human drug metabolism / / Michael D. Coleman
Human drug metabolism / / Michael D. Coleman
Autore Coleman Michael D.
Edizione [3rd ed]
Pubbl/distr/stampa Hoboken, N.J., : Wiley Blackwell, 2020
Descrizione fisica 1 online resource (683 pages)
Disciplina 615.1
Soggetto topico Drugs -- Metabolism
Drugs -- Metabolic detoxication
ISBN 1-119-45861-7
1-119-65801-2
1-119-45860-9
Classificazione 491.5
615.1
Formato Materiale a stampa
Livello bibliografico Monografia
Lingua di pubblicazione und
Nota di contenuto Preface -- 1 Introduction -- 1.1 Therapeutic window -- 1.1.1 Introduction -- 1.1.2 Therapeutic index -- 1.1.3 Changes in dosage -- 1.1.4 Changes in rate of removal -- 1.2 Consequences of drug concentration changesh -- 1.2.1 Drug failure -- 1.2.2 Drug toxicity -- 1.3 Clearance -- 1.3.1 Definitions -- 1.3.2 Clearance and elimination -- 1.3.3 Biotransformation prior to elimination -- 1.3.4 Intrinsic clearance -- 1.3.5 Clearance: influencing factors -- 1.4 First pass and drug extraction -- 1.4.1 First pass: gut contribution -- 1.4.2 First pass: hepatic contribution -- 1.4.3 First pass: low‐extraction drugs -- 1.5 First pass and plasma drug levels -- 1.5.1 Introduction -- 1.5.2 Changes in clearance and plasma 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 -- 2.3.1 Signal molecule evolution -- 2.3.2 Lipophilic hydrocarbons as signal molecules -- 2.4 False signal molecules: bioprotection -- 2.4.1 Endocrine disruption -- 2.4.2 Endocrine disruption: problems and solutions -- 2.4.3 Endocrine disruption: cosmetic and nutraceutical aspects -- 2.4.4 Endocrine disruption: microRNAs -- 2.5 Sites of biotransforming enzymes -- 2.6 Biotransformation and xenobiotic cell entry -- 2.6.1 Role of the liver -- 2.6.2 Drug and xenobiotic uptake: transporter systems -- 2.6.3 Hepatic and gut uptake (influx) transporter systems -- 2.6.4 Aims of biotransformation -- 2.6.5 Task of biotransformation -- 2.6.6 Phase's I-III of biotransformation: descriptions and classifications -- 2.6.7 Biotransformation and drug action -- 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 -- 3.3.1 Classification -- 3.3.2 Methods of analysis -- 3.3.3 CYP key features and capabilities -- 3.4 CYPs: main and associated structures -- 3.4.1 General structure -- 3.4.2 Haem moiety -- 3.4.3 CYP flexible regions -- 3.4.4 Substrate binding in CYPs -- 3.4.5 Homotropic binding in CYPs -- 3.4.6 Heterotropic binding in CYPs -- 3.4.7 CYP complex formation -- 3.4.8 CYP REDOX partners (i): P450 oxidoreductase (POR) -- 3.4.9 CYP REDOX partners (ii): Cytochrome b5 -- 3.5 Human CYP families and their regulation -- 3.5.1 CYP regulation: lifespan -- 3.5.2 CYP regulation: transcriptional -- 3.5.3 CYP regulation: post‐translational -- 3.6 Main human CYP families -- 3.6.1 CYP1A series -- 3.6.2 CYP2 series -- 3.6.3 CYP3A series -- 3.7 Cytochrome P450 catalytic cycle -- 3.7.1 Substrate binding -- 3.7.2 Oxygen binding -- 3.7.3 Oxygen scission (splitting) -- 3.7.4 Insertion of oxygen into substrate -- 3.7.5 Release of product -- 3.7.6 Reductions -- 3.8 Flavin monooxygenases (FMOs) -- 3.8.1 Introduction -- 3.8.2 Structure -- 3.8.3 Mechanism of catalysis -- 3.8.4 Variation and expression -- 3.8.5 FMOs in drug development -- 3.9 How CYP isoforms operate in vivo -- 3.9.1 Illustrative use of structures -- 3.9.2 Primary purposes of CYPs -- 3.9.3 Role of oxidation -- 3.9.4 Summary of CYP operations -- 3.10 Aromatic ring hydroxylation -- 3.10.1 Nature of aromatics -- 3.10.2 Oxidation of benzene -- 3.11 Alkyl oxidations -- 3.11.1 Saturated alkyl groups -- 3.11.2 Unsaturated alkyl groups -- 3.11.3 Pathways of alkyl metabolism -- 3.12 Rearrangement reactions -- 3.12.1 Dealkylations -- 3.12.2 Deaminations -- 3.12.3 Dehalogenations -- 3.13 Other oxidation processes -- 3.13.1 Primary amine oxidations -- 3.13.2 Oxidation of alcohol and aldehydes -- 3.13.3 Monoamine oxidase (MAO) -- 3.14 Control of CYP metabolic function -- References -- 4 Induction of Cytochrome P450 Systems -- 4.1 Introduction -- 4.1.1 How living systems self‐regulate: overview -- 4.1.2 Self‐regulation in drug metabolism -- 4.1.3 Self‐regulatory responses to drugs: summary -- 4.2 Causes of accelerated clearance -- 4.3 Enzyme induction -- 4.3.1 Types of inducers -- 4.3.2 Common features of inducers and clinical significance -- 4.4 Mechanisms of enzyme induction -- 4.4.1 Introduction -- 4.4.2 CYPs 1A1/1A2 and 1B1 induction -- 4.4.3 CYP 2B6 2C8/2C9/C19 and 3A4 induction -- 4.4.4 CYP 2E1 induction -- 4.4.5 CYP2D6 -- 4.4.6 Reversal of induction -- 4.4.7 Cell transport systems and induction: P‐glycoprotein -- 4.4.8 Induction processes: summary -- 4.5 Induction: general clinical aspects -- 4.5.1 Introduction -- 4.5.2 Anti‐epileptic agents -- 4.5.3 OTC (over the counter) and online herbal preparations -- 4.5.4 Anticoagulant drugs -- 4.5.5 Oral contraceptives/steroids -- 4.5.6 Antiviral/antibiotic drugs -- 4.5.7 Anticancer drugs -- 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 -- 5.3.1 Introduction -- 5.3.2 Competitive inhibition -- 5.3.3 Noncompetitive inhibition -- 5.3.4 Uncompetitive inhibition -- 5.4 Mechanisms of irreversible inhibition -- 5.4.1 Introduction -- 5.4.2 Mechanism‐based quasi‐irreversible inhibitors -- 5.4.3 Mechanism‐based irreversible inhibitors -- 5.5 Clinical consequences of irreversible inhibition -- 5.5.1 Introduction -- 5.5.2 Quasi‐irreversible inhibitors: the SSRIs -- 5.5.3 Mechanism‐based inhibitors: grapefruit juice -- 5.5.4 Mechanism‐based inhibitors: other juice products -- 5.5.5 OTC herbal remedy inhibitors -- 5.6 Cell transport systems and inhibition -- 5.6.1 Uptake (Influx) transporters: OATPs -- 5.6.2 Efflux transporters: P‐glycoprotein (P‐gp) -- 5.7 Major clinical consequences of inhibition of drug clearance -- 5.7.1 Introduction -- 5.7.2 Torsades de pointes (TdP) -- 5.7.3 Sedative effects -- 5.7.4 Muscle damage (rhabdomyolysis) -- 5.7.5 Excessive hypotension -- 5.7.6 Ergotism -- 5.7.7 Excessive anticoagulation -- 5.8 Use of inhibitors for positive clinical intervention -- 5.8.1 Introduction -- 5.8.2 CYP inhibitors and female hormone‐dependent tumours -- 5.8.3 CYP inhibitors and male hormone‐dependent tumours -- 5.8.4 CYP inhibitors and manipulation of prescription drug disposition -- 5.8.5 Use of inhibitors to increase drug efficacy -- 5.8.6 Use of inhibitors to reduce toxic metabolite formation -- 5.8.7 Use of inhibitors to reduce drug costs -- 5.8.8 Use of inhibition in alcoholism -- 5.9 Summary -- References -- 6 Conjugation and Transport Processes -- 6.1 Introduction -- 6.2 Glucuronidation -- 6.2.1 UGTs -- 6.2.2 UGT mode of operation -- 6.2.3 UGT isoforms -- 6.2.4 UGTs and bilirubin -- 6.2.5 UGTs and bile acids -- 6.2.6 Role of glucuronidation in drug clearance -- 6.2.7 Types of glucuronides formed -- 6.2.8 Control of UGTs -- 6.2.9 Induction of UGTs: clinical consequences -- 6.2.10 UGT inhibition: bilirubin metabolism -- 6.2.11 UGT inhibition: drug clearance -- 6.2.12 Microbiome and drug metabolism: passengers or crew? -- 6.3 Sulphonation -- 6.3.1 Introduction -- 6.3.2 SULT structure related to catalytic operation -- 6.3.3 Control of SULT enzymes -- 6.3.4 SULTs and cancer -- 6.4 The GSH system -- 6.4.1 Introduction -- 6.4.2 GSH system maintenance -- 6.5 Glutathione S‐transferases -- 6.5.1 Structure and location -- 6.5.2 Mode of operation -- 6.5.3 GST classes -- 6.5.4 Control of GSTs: overview -- 6.5.5 Control of GSTs and reactive species -- 6.5.6 Control of GSTs: the nrf2 system -- 6.6 Epoxide hydrolases -- 6.6.1 Nature of epoxides -- 6.6.2 Epoxide hydrolases -- 6.6.3 Epoxide hydrolases: structure, mechanisms of action, and regulation -- 6.7 Acetylation -- 6.8 Methylation -- 6.9 Esterases/amidases -- 6.10 Amino acid conjugation (mainly glycine) -- 6.11 Phase III transport processes -- 6.11.1 Introduction -- 6.11.2 ABC Efflux transporters -- 6.11.3 RLIP76 -- 6.12 Biotransformation: integration of processes -- References -- 7 Factors Affecting Drug Metabolism -- 7.1 Introduction -- 7.2 Genetic polymorphisms -- 7.2.1 Introduction -- 7.2.2 Clinical implications -- 7.2.3 Genetic polymorphisms in CYP systems -- 7.2.4 Genetic polymorphisms in nonconjugative systems -- 7.2.5 Conjugative polymorphisms: acetylation -- 7.2.6 Conjugative polymorphisms: methylation -- 7.2.7 Conjugative polymorphisms: UGT 1A1 -- 7.2.8 Conjugative polymorphisms: sulphonation.
7.2.9 Other conjugative polymorphisms: Glutathione S‐transferases -- 7.2.10 Transporter polymorphisms -- 7.2.11 Polymorphism detection: clinical and practical issues -- 7.3 Effects of age on drug metabolism -- 7.3.1 The elderly -- 7.3.2 Drug clearance in neonates and children -- 7.4 Effects of diet on drug metabolism -- 7.4.1 Polyphenols -- 7.4.2 Barbecued meat -- 7.4.3 Cruciferous vegetables -- 7.4.4 Other vegetable effects on metabolism -- 7.4.5 Caffeine -- 7.4.6 Diet: general effects -- 7.5 Gender effects -- 7.6 Smoking -- 7.7 Effects of ethanol on drug metabolism -- 7.7.1 Context of ethanol usage -- 7.7.2 Ethanol metabolism -- 7.7.3 Ethanol and inhibitors of ALDH -- 7.7.4 Mild ethanol usage and drug clearance -- 7.7.5 Heavy ethanol usage and paracetamol -- 7.7.6 Alcoholic liver disease -- 7.7.7 Effects of cirrhosis on drug clearance -- 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 -- 8.2.1 Intensification of pharmacologic effect: type A1 -- 8.2.2 Off‐target reversible effects and methaemoglobin formation: type A2 -- 8.2.3 Predictable overdose toxicity: type A3 -- 8.3 Unpredictable drug adverse effects: type B -- 8.3.1 Idiosyncratic and overdose toxicity: similarities and differences -- 8.3.2 Type B1 necrosis: troglitazone -- 8.3.3 Type B1 necrosis: trovafloxacin -- 8.3.4 Type B2 reactions: immunotoxicity -- 8.4 Nature of drug‐mediated immune responses -- 8.4.1 Anaphylaxis -- 8.4.2 DRESS/Anticonvulsant hypersensitivity syndrome (AHS) -- 8.4.3 Stevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) -- 8.4.4 Blood dyscrasias -- 8.4.5 Prediction of idiosyncratic reactions -- 8.5 Type B3 reactions: role of metabolism in cancer -- 8.5.1 Sources of risks of malignancy -- 8.5.2 Risks of malignancy and drug development -- 8.5.3 Environmental carcinogenicity risks -- 8.5.4 Occupational carcinogens -- 8.5.5 Dietary carcinogens: acrylamide -- 8.5.6 Dietary carcinogens: aflatoxins -- 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.4.1 Analytical techniques -- A.4.2 Human liver microsomes -- A.4.3 Heterologous recombinant systems -- A.4.4 Liver slices -- A.4.5 Human hepatocytes -- A.5 Animal model developments in drug metabolism -- A.5.1 Introduction -- A.5.2 Genetic modification of animal models -- A.5.3 'Humanized' mice -- A.6 Toxicological assays -- A.6.1 Aims -- A.6.2 Cell viability assays -- A.6.3 'One compartment' cell models -- A.6.4 'Two compartment' models -- A.6.5 DNA and chromosomal toxicity assays -- A.6.6 The Ames test -- A.6.7 Comet assay -- A.6.8 Micronucleus test -- A.6.9 Toxicology in drug discovery -- 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.
Record Nr. UNINA-9910876645903321
Coleman Michael D.  
Hoboken, N.J., : Wiley Blackwell, 2020
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