In the news…. ► Sinkewitz (sacked in TdF for +ve testosterone test in training) admits using banned blood transfusions and EPO since 2003 ► Kashechkin (+ve TdF for homologous blood doping)  Privately run sports bodies (UCI and WADA) no legitimate right to test athletes  Contravenes Europes declaration Human Rights  Only public bodies (eg. Governments) have legitimate right to test athletes ► Watch this space……

Prohibited Substances ► In and out of comp.  Other Anabolic Agents  Other Peptide Hormones  Beta-2 Agonists  Agents with anti-oestrogenic activity  Diuretics and other Masking Agents ► In comp.  Stimulants  Narcotics  Cannabinoids  Glucocorticosteroids

Other Anabolic agents ► E.g clenbuterol ► A Β 2 Agonist – similar to salbutamol. Used tx asthma (not in UK). ► Numerous positive cases ► Evidence promotes skeletal muscle growth (10- 12%) in rats with 2 weeks tx (Yang and McElliott 1989) ► But effect in animals is with 100x tolerable dose in humans ► Inhibits protein catabolism ► Equivocal results in human studies ► Side effects – tremor, restlessness, ↑ bp, headache  Purported to reduce after 8-10d  Downregulation of receptors

Peptide Hormones ► Corticotrophins (ACTH) to increase corticosteroid levels – anti-inflammatory and mood enhancing; ► Gonadotrophins to counter androgenic anabolic steroid effects; ► hGH – used for anabolic properties, able to train harder and promote recovery; ► Insulin (unless certified IDDM) ► EPO – separate lecture.

Human Growth Hormone ► Increases growth in pre-adolescents (clinical use) ► Stimulates production of insulin-like growth factors (IGLF-1 and IGLFD-2) ► Some effect on muscle growth (via IGF-1) ► Increases amino acid and glucose uptake into muscle ► Increases fat breakdown (glycogen sparing) ► hGH increases following exercise ► Detection difficult due to similarity between endogenous and rhGH – short ½ life (20 mins) – returns to baseline within 16 – 20 hrs

Why take hGH? ► Few controlled studies:  Deyssig et al., (1993) reduction fat mass, no diff strength;  Yarasheski et al., (1993) no increase muscle protein synthesis in weight lifters cf. placebo ► Adverse effects – acromegaly, DM, hypertension, reduced HDL, osteoporosis, menstrual irregularities, impotence

Narcotics ► Act on brain to reduce pain from injury & go thru pain threshold ► Addictive ► Illegal in most countries ► Illegal opiates – morphine, heroine, pethidine, dextropropoxyphene ► Legal – Dextromethorphan, codeine (analgesics and diarrhoea suppressants)

Cannabinoids ► Tetrahydrocannabinol (THC) ► Renaud and Cormier (1986) – reduction in max performance ► Doping? Calming, improved sleep

Β 2 Agonists ► Used in treatment of asthma, EIA as potent bronchodilators. ► Eg. Salbutamol (Ventalin), short acting, also eg. Clenbuterol, long-acting ► Some reclassified into ‘Other anabolic agents’ due to poss. anabolic effect ► Use restricted to inhaler only with TUE from physician prior to competition  Formoterol, salbutamol, salmeterol, terbutaline  Salbutamol >1000ng.ml adverse finding

Do inhaled β 2 agonists affect performance?

Do β 2 agonists affect performance? ► Oral admin of salbutamol may increase  muscle strength (Martineau et al., 1992; van Baak et al., 2000)  Endurance (van Baak et al., 2000, Collomp et al., 2000)  But much larger dose (10 – 20x inhalation)

Hormone antagonists and modulators ► Aromatase inhibitors ► Ostrogen receptor modulators eg. tamoxifen ► Anti-oestrogenic substances  E.g. Clomiphene, cyclofenil – used after steroids to stimulate own production of testosterone ► Agents modifying myostatin function: myostatin inhibitors

Masking Agents ► Eg. Acetazolamide – diuretic decreases urinary output of some drugs for short periods ► Epitestosterone ► Probenecid – anti-gout banned by IOC but not banned by IOC but not UCI until after 1988 tour ► Plasma expanders

Diuretics

Diuretics Elimination of fluid from the body Used illegally in sport to: ► Meet weight limit; ► Overcome fluid retention from use of anabolic steroids; ► Increase volume of urine Side effects: dehydration, faint, muscle cramps, headaches, nausea.

Glucocorticosteroids ► Eg. Cortisol, cortisone ► Produced by adrenal cortex (from cholesterol) ► Feedback mech between  hypothalamus (corticotropin releasing factor);  ant pit (adrenocorticotropic hormone (ACTH)); and  adrenal cortex (cortisol) ► Widely used for injuries - Potent anti-inflammatories despite limited evidence of benefits of glucocorticosteroid use in acute injuries in sport (Dvorak et al., 2006) ► Open airways, mask injury, increase ability to train. ► Stim gluconeogenesis, mobilisation amino acids and fatty acids ► Prohibited orally, rectally, iv or intramuscular – unless with TUE (common request) ► Allowed – dermatological, aural/otic, nasal, buccal cavity, opthalmologic disorders ► Serious toxic effects with prolonged use. ► Soetens et al., (1995) – no evidence of ACTH on max performance ► Insufficient evidence for substantial benefits of glucocorticosteroids in tx of sport related injuries

Prohibited Methods ► Enhancement of oxygen transfer – separate lecture; ► Pharmacological, chemical and physical manipulation; ► Gene doping.

Substances prohibited in particular sports ► Alcohol ► Beta-blockers

Beta-2 Agonists What are beta and alpha receptors ? Adrenaline  1  2  1  2  3 Pupil dilation Vasoconstriction Increased heart rate bronchodilation lipolysis Note adrenalin = epinephrine

Comparison of hormones and neurotransmitters

How a receptor mediates an effect

How alpha and beta agents work

How beta blockers work

Beta-2 agonists  Banned unless have therapeutic use exemption  Cannot use at poolside Salbutamol, terbutaline  2 bronchodilation

Beta-2 agonists  Known cases of bans  British weightlifters 1992 Olympics  Katrine Krabbe (German 100 m sprinter). 4 year ban reduced to 2 years on appeal Clenbuterol (asthma medication in Europe, not UK)  2 Bronchodilation and anabolic effects (increases muscle mass and fat metabolism in animals)

Refs ► British Journal Sports Med (2006) 40 (Suppl I)