Thieme / Hemmersbach Doping in Sports

1. Auflage 2009
ISBN: 978-3-540-79088-4
Verlag: Springer Berlin Heidelberg
Format: PDF
Kopierschutz: 1 - PDF Watermark

E-Book, Englisch, Band 195, 542 Seiten

Reihe: Handbook of Experimental Pharmacology

Doping in sports and the fight against it has gained increasing attention in recent years. The pharmacological basis for a possible performance enhancement in competitive sport through the administration of prohibited substances and methods as well as the analytical disclosure of such practices are comprehensively covered in 21 contributions by outstanding and distinctive authors.

Autoren/Hrsg.

Thieme, Detlef

Hemmersbach, Peter

Inhaltsverzeichnis

2;152640_1_En_1_Chapter_OnlinePDF;12
2.1;Chapter : History of Doping and Doping Control;12
2.1.1;The Expression ``Doping´´;12
2.1.2;Early Attempts of Doping;13
2.1.3;Doping and its Emerging Prohibition;13
2.1.3.1;Stimulants;16
2.1.3.2;Anabolic Agents;16
2.1.3.3;Fatalities with Presumptive Correlation to Doping;18
2.1.4;Development of General Anti-Doping Regulations;18
2.1.5;Doping Analysis and Accreditation of Anti-Doping Laboratories;20
2.1.6;Doping and the Cold War;22
2.1.7;Developments from the 1990s Onward;23
2.1.8;Appendix 1 Historical Definitions of Doping;26
2.1.9;References;29
3;152640_1_En_2_Chapter_OnlinePDF;35
4;152640_1_En_3_Chapter_OnlinePDF;75
4.1;Chapter : Phase-II Metabolism of Androgens and Its Relevance for Doping Control Analysis;75
4.1.1;Phase-II Metabolism of Androgens;76
4.1.1.1;Glucuronide Conjugation;76
4.1.1.2;Sulphonation;79
4.1.1.3;Genetic Polymorphism;80
4.1.2;Relevance of Phase-II Metabolism in Doping Control Analysis;81
4.1.3;In Vitro Production of Phase-II Metabolites;81
4.1.4;References;83
5;152640_1_En_4_Chapter_OnlinePDF;86
5.1;Chapter : Detecting the Administration of Endogenous Anabolic Androgenic SteroidsAnabolic Androgenic SteroidsEndogenous;86
5.1.1;Introduction;87
5.1.1.1;Testosterone;87
5.1.1.2;Historical Background;88
5.1.2;General Approach to the Measurement of Urinary Steroids;89
5.1.2.1;From Immunoassays to Mass Spectrometry;89
5.1.2.2;Sample Preparation for GC/MS Analyses;90
5.1.2.3;Stability of Urinary Steroid Conjugates;90
5.1.3;Testosterone and Epitestosterone;91
5.1.3.1;Reference Ranges;91
5.1.3.2;Stability of Individual Parameters;93
5.1.4;Alteration of the Urinary Steroid Profile;93
5.1.4.1;Testosterone;93
5.1.4.2;Dihydrotestosterone, Androstenedione and Dehydroepiandrosterone;95
5.1.5;Measurement of the delta13C Values of Urinary Steroid Metabolites;97
5.1.5.1;Principle of the GC/C/IRMS Analysis;97
5.1.5.2;IRMS for Determining the Origin of Organic Compounds;98
5.1.5.3;delta13C Values of Urinary Steroid Metabolites;98
5.1.6;External Factors Influencing the GC/MS Steroid Profile;99
5.1.6.1;Anabolic Agents and Inhibitors of Reductase;99
5.1.6.2;Ethanol;100
5.1.6.3;Supplements;101
5.1.7;From Population-Based to Subject-Based Testing Approach;101
5.1.8;References;102
6;152640_1_En_5_Chapter_OnlinePDF;108
6.1;Chapter : Synthetic Anabolic Agents: Steroids and Nonsteroidal Selective Androgen Receptor Modulators;108
6.1.1;Introduction;109
6.1.2;Pharmacological Aspects and Mode of Action of AAS;110
6.1.2.1;Mode of Action of AAS;111
6.1.2.2;Metabolism of AAS;111
6.1.2.2.1;Methyltestosterone and Metandienone;113
6.1.2.2.2;Stanozolol;117
6.1.2.3;Undesirable Effects of AAS;117
6.1.2.3.1;Cardiovascular Issues;117
6.1.2.3.2;Endocrine Issues;118
6.1.2.3.3;Hepatic Issues;118
6.1.2.3.4;Psychiatric Issues;118
6.1.2.3.5;Musculoskeletal Issues;119
6.1.3;Pharmacological Aspects and Mode of Action of SARMs;119
6.1.3.1;Metabolism of SARMs;120
6.1.3.2;Clinical Applications;121
6.1.3.3;Undesirable Effects of SARMs;121
6.1.4;Detection Strategies for AAS and SARMs;123
6.1.4.1;Sample Preparation and Analysis of AAS;123
6.1.4.1.1;GC-MS Analyses;124
6.1.4.1.2;LC-MS(/MS) Analyses;126
6.1.4.2;Sample Preparation and Analysis of SARMs;126
6.1.5;Conclusions;129
6.1.6;References;129
7;152640_1_En_6_Chapter_OnlinePDF;136
8;152640_1_En_7_Chapter_OnlinePDF;164
8.1;Chapter : Designer Steroids;164
8.1.1;Introduction;165
8.1.1.1;Exogenous SteroidsSteroidsExogenous;165
8.1.1.2;Endogenous SteroidsSteroidsEndogenous;166
8.1.1.3;BALCO, an Insight into Conspiracy;167
8.1.2;Anabolic Steroid Chemistry;169
8.1.3;Detection Methods;178
8.1.3.1;Use of Gas Chromatography-Mass Spectrometry (GC-MS);180
8.1.3.2;Use of LC-MS(/MS);183
8.1.4;The Supplement Market;187
8.1.5;Conclusion;191
8.1.6;References;192
9;152640_1_En_8_Chapter_OnlinePDF;195
9.1;Chapter : Growth Hormone;195
9.1.1;Intended Pharmacological Effect;196
9.1.1.1;Effects on Bone and GrowthHuman Growth HormoneEffects on Bone and Growth;197
9.1.1.2;Effects on Substrate Metabolism and Body Composition;197
9.1.1.3;Effects on Protein TurnoverHuman Growth HormoneEffects on Protein Turnover, Muscle Mass and Strength;198
9.1.1.4;Effects on Cardiac and Pulmonary FunctionHuman Growth HormoneEffects on Cardiac Function;198
9.1.2;Analytical Procedures;199
9.1.3;Screening and Confirmation Strategy;200
9.1.3.1;The Marker Approach;201
9.1.3.2;The Isoform Approach;202
9.1.4;References;204
10;152640_1_En_9_Chapter_OnlinePDF;209
10.1;Chapter : Mass Spectrometry-Based Analysis of IGF-1 and hGH;209
10.1.1;Introduction;209
10.1.2;IGF-1;209
10.1.3;Human Growth Hormone;209
10.1.4;References;214
11;152640_1_En_10_Chapter_OnlinePDF;216
11.1;Chapter : Insulin;216
11.1.1;Introduction;217
11.1.2;Pharmacological Aspects and Mode of Action;218
11.1.2.1;Endogenous Insulin Production and Storage;218
11.1.2.2;Insulin Secretion;219
11.1.2.3;Insulin Actions;220
11.1.3;Clinical Applications;221
11.1.4;Insulin Metabolism;222
11.1.5;Analytical Assays in Doping Control;224
11.1.5.1;Mass Spectrometry of Peptides and Proteins;224
11.1.5.2;Confirmation Methods for Synthetic Insulins;225
11.1.6;Case Reports;227
11.1.7;Conclusions;230
11.1.8;References;230
12;152640_1_En_11_Chapter_OnlinePDF;234
12.1;Chapter : beta-Adrenergic Stimulation;234
12.1.1;Introduction;235
12.1.2;Noradrenaline and the Nervous System;235
12.1.3;Receptor Agonists Capacities;236
12.1.4;Sympathomimetic Amines;237
12.1.4.1;Amphetamines and Related Compounds;238
12.1.4.2;Ephedrines;239
12.1.4.3;Strychnine and Cocaine;240
12.1.4.4;Modafinil and Adrafinil;241
12.1.4.5;Methamphetamine - Isomers: The Baxter Case;241
12.1.4.6;Bromantane;243
12.1.4.7;Pemoline;243
12.1.4.8;Methylphenidate;244
12.1.5;beta2-Agonists;244
12.1.6;Detection;246
12.1.7;Liquid Chromatography Mass Spectrometry (LC-MS);250
12.1.8;References;253
13;152640_1_En_12_Chapter_OnlinePDF;257
13.1;Chapter : Erythropoietin and Analogs;257
13.1.1;Introduction;258
13.1.2;Pharmacology and Mode of Action;259
13.1.2.1;Production of Erythrocytes;259
13.1.2.2;EPO Synthesis;259
13.1.2.3;Erythropoietin Receptor;260
13.1.2.4;Isolation, Expression and Production;261
13.1.2.5;Clearance;262
13.1.2.6;Benefits and Adverse Effects;262
13.1.3;Erythropoietin and Analogs;263
13.1.3.1;EPO Structure;263
13.1.3.2;EPOEPOAnalogs Analogs;264
13.1.3.3;Production of Recombinant Human Erythropoietin;268
13.1.3.4;Performance Enhancement;268
13.1.4;Analytical Procedures and Instrumental Techniques;270
13.1.4.1;ON/OFF Model;270
13.1.4.2;Electrophoretic Methods;271
13.1.4.2.1;Zone Electrophoresis in Agarose Suspension;271
13.1.4.2.2;Isoelectric Focusing in Solution;272
13.1.4.2.3;Isoelectric Focusing in Polyacrylamide Slab-Gels;272
13.1.4.2.3.1;4.2.3.1General Description;272
13.1.4.2.3.2;4.2.3.2Criteria for Positivity - WADA Technical Document TD2007EPO;274
13.1.4.2.3.3;4.2.3.3Specificity of the Antibody;276
13.1.4.2.4;SDS-PAGE;277
13.1.4.2.5;2D-Electrophoresis;278
13.1.4.3;Chromatographic Methods;278
13.1.4.4;Mass Spectrometric Methods;280
13.1.4.5;Proteolytic Digestion of EPO;289
13.1.4.6;Miscellanous;290
13.1.4.6.1;Epo Detection Using MAIIA Technology;290
13.1.5;Case Report: Detection of Dynepo Administration;291
13.1.6;References;292
14;152640_1_En_13_Chapter_OnlinePDF;301
15;152640_1_En_14_Chapter_OnlinePDF;311
16;152640_1_En_15_Chapter_OnlinePDF;333
16.1;Chapter : Masking and Manipulation;333
16.1.1;Introduction;334
16.1.2;Diuretics;335
16.1.2.1;Pharmacological Mode of Action of Representative Compounds;335
16.1.2.2;Intended Pharmacological Effects;335
16.1.2.3;Biotransformation;339
16.1.2.4;Analytical Procedures, ScreeningScreening and ConfirmationConfirmation Strategy;339
16.1.3;Epitestosterone;344
16.1.3.1;Potential as Masking Agent;344
16.1.3.2;Biological Disposition;345
16.1.3.3;Testing for Epitestosterone Abuse in Sport;346
16.1.4;Probenecid;347
16.1.5;Inhibitors of 5a-Reductase;348
16.1.5.1;Pharmacological Aspects and Intended Use for Doping Purposes;348
16.1.5.2;Analytical Determinations;350
16.1.6;Plasma Expanders;350
16.1.6.1;Pharmacological Action;350
16.1.6.2;Molecular Characteristics;351
16.1.6.3;Simple Screening Approaches;351
16.1.6.4;Chromatographic and Mass Spectrometric Analysis;352
16.1.7;Conclusion;353
16.1.8;References;354
17;152640_1_En_16_Chapter_OnlinePDF;361
17.1;Chapter : Hormonal Growth Promoting Agents in Food Producing Animals;361
17.1.1;Introduction;362
17.1.2;Hormones in Use as Growth Promoters;363
17.1.3;Pharmacology and Withdrawal Times;364
17.1.4;Control Strategies;367
17.1.5;Conclusions;371
17.1.6;References;372
18;152640_1_En_17_Chapter_OnlinePDF;374
18.1;Chapter : Some Aspects of Doping and Medication Control in Equine Sports;374
18.1.1;Introduction;375
18.1.2;Technological Advances in Drug Detection;377
18.1.3;Knowledge of Drug MetabolismDrug Metabolism and its Significance to Drug Surveillance Programmes;378
18.1.4;Quality Systems and Drug Control in Sport;379
18.1.5;Typical Laboratory Testing Process;380
18.1.5.1;Screening;381
18.1.5.2;Confirmatory Analysis;382
18.1.6;The Approaches Adopted by the Racing Industry to Address Endogenous Substances and Substances of Dietary Origin;382
18.1.6.1;Salicylic Acid Threshold;384
18.1.6.2;Arsenic Threshold;385
18.1.6.3;Nandrolone Threshold;386
18.1.6.4;Theobromine Threshold;387
18.1.6.5;The Carbon Dioxide Threshold;388
18.1.6.6;Threshold Values and Article 6 of the International Agreement on Breeding, Racing and Wagering;388
18.1.6.7;Managing Threshold Values;390
18.1.6.7.1;Isotope Ratio Mass SpectrometryIsotope Ratio Mass Spectrometry•;391
18.1.7;An Approach for the Control of Therapeutic Substances in Thoroughbred Horseracing;393
18.1.7.1;Pharmacokinetic/Pharmacodynamic Assessment of Irrelevant Drug Concentrations in Equine Plasma and Urine;394
18.1.7.2;Administration and Analytical Assay Validation Studies;395
18.1.7.3;The Irrelevant Urinary Concentration and Risk Management;396
18.1.7.4;The Determination of Detection Times;396
18.1.8;Anabolic Steroids in the Horse;397
18.1.9;LC-MS Analysis in Equine Drug Testing and Metabolism;403
18.1.10;The Future;406
18.1.11;References;408
19;152640_1_En_18_Chapter_OnlinePDF;415
19.1;Chapter : Androgenic Anabolic Steroid Abuse and the Cardiovascular System;415
19.1.1;Introduction;416
19.1.2;Echocardiographic Studies;420
19.1.2.1;Summary;430
19.1.3;Hypertension;430
19.1.3.1;Summary;435
19.1.4;Vascular Reactivity and Vascular Function;436
19.1.5;Coronary CalcificationCoronary Calcification;438
19.1.6;Blood Platelet Function and Haemostasis;439
19.1.7;Lipids;444
19.1.8;Arrhythmias and Sudden Death;448
19.1.9;References;451
20;152640_1_En_19_Chapter_OnlinePDF;462
20.1;Chapter : Side Effects of Anabolic Androgenic Steroids: Pathological Findings and Structure-Activity Relationships;462
20.1.1;Methodological Limitations;463
20.1.2;Mechanisms of Action and Substance Specificity;463
20.1.3;Anabolic Effects;466
20.1.3.1;Correlation of Steroid Structure and Anabolic Effects;466
20.1.3.2;Pathological Findings;467
20.1.4;Bioconversion of Steroids to Characteristic Androgens and Estrogens;471
20.1.4.1;Conversion to Androgens;471
20.1.4.2;Conversion to Estrogens;472
20.1.4.3;Suppression of Endogenous Steroid Biosynthesis and Pathological Effects on the Endocrine and Reproductive System;473
20.1.4.4;Metabolic Suppression and Hepatotoxic Effects;474
20.1.4.4.1;Pathological Findings in the Liver;475
20.1.4.4.2;Lipid Metabolism;476
20.1.5;Neurosteroids and Psychiatric Effects;477
20.1.5.1;Biosynthesis of Neurosteroids;477
20.1.5.2;Behavioral-Psychiatric Side Effects;479
20.1.6;Reference;482
21;152640_1_En_20_Chapter_OnlinePDF;488
22;152640_1_En_21_Chapter_OnlinePDF;516
22.1;Chapter : Science and the Rules Governing Anti-Doping Violations;516
22.1.1;WADA Anti-Doping Program;519
22.1.1.1;WADA CodeWADA Code;519
22.1.1.1.1;Definitions of DopingDefinitions of Doping;520
22.1.1.1.2;Rights of Athletes;521
22.1.1.1.3;Antidoping Violation Resolutions;522
22.1.1.2;WADA International Standards;523
22.1.1.2.1;Prohibited ListProhibited List International Standard;523
22.1.1.2.2;International Standard for LaboratoriesInternational Standard for Laboratories;525
22.1.1.3;WADA Models of Best PracticeModels of Best Practice;527
22.1.2;UNESCO ConventionUNESCO Convention;527
22.1.3;Arbitration of Doping Rule Violations;527
22.1.3.1;Court of Arbitration for Sport;530
22.1.4;Evidence in Doping Rule ArbitrationArbitration;531
22.1.5;Laboratory Documentation of Adverse Analytical Findings;532
22.1.6;References;533
23;152640_1_En_BM2_OnlinePDF;535
23.1;: Index;535