In the news….In the news….

► Sinkewitz (sacked in TdF for +ve testosterone Sinkewitz (sacked in TdF for +ve testosterone test in training) admits using banned blood test in training) admits using banned blood transfusions and EPO since 2003transfusions and EPO since 2003

► Kashechkin (+ve TdF for homologous blood Kashechkin (+ve TdF for homologous blood doping)doping) Privately run sports bodies (UCI and WADA) no Privately run sports bodies (UCI and WADA) no

legitimate right to test athleteslegitimate right to test athletes Contravenes Europes declaration Human RightsContravenes Europes declaration Human Rights Only public bodies (eg. Governments) have Only public bodies (eg. Governments) have

legitimate right to test athleteslegitimate right to test athletes► Watch this space……Watch this space……

Prohibited SubstancesProhibited Substances

► In and out of comp.In and out of comp. Other Anabolic AgentsOther Anabolic Agents Other Peptide HormonesOther Peptide Hormones Beta-2 AgonistsBeta-2 Agonists Agents with anti-oestrogenic activityAgents with anti-oestrogenic activity Diuretics and other Masking AgentsDiuretics and other Masking Agents

► In comp.In comp. StimulantsStimulants Narcotics Narcotics CannabinoidsCannabinoids GlucocorticosteroidsGlucocorticosteroids

Other Anabolic agentsOther Anabolic agents

► E.g clenbuterolE.g clenbuterol► A A ΒΒ22 Agonist – similar to salbutamol. Used tx asthma Agonist – similar to salbutamol. Used tx asthma

(not in UK).(not in UK).► Numerous positive casesNumerous positive cases► Evidence promotes skeletal muscle growth (10- 12%) Evidence promotes skeletal muscle growth (10- 12%)

in rats with 2 weeks tx (Yang and McElliott 1989)in rats with 2 weeks tx (Yang and McElliott 1989)► But effect in animals is with 100x tolerable dose in But effect in animals is with 100x tolerable dose in

humanshumans► Inhibits protein catabolismInhibits protein catabolism► Equivocal results in human studiesEquivocal results in human studies► Side effects – tremor, restlessness, ↑bp, headacheSide effects – tremor, restlessness, ↑bp, headache

Purported to reduce after 8-10dPurported to reduce after 8-10d Downregulation of receptors Downregulation of receptors

Peptide HormonesPeptide Hormones

►Corticotrophins (ACTH) to increase Corticotrophins (ACTH) to increase corticosteroid levels – anti-corticosteroid levels – anti-inflammatory and mood enhancing;inflammatory and mood enhancing;

►Gonadotrophins to counter Gonadotrophins to counter androgenic anabolic steroid effects;androgenic anabolic steroid effects;

►hGH – used for anabolic properties, hGH – used for anabolic properties, able to train harder and promote able to train harder and promote recovery;recovery;

► Insulin (unless certified IDDM)Insulin (unless certified IDDM)►EPO – separate lecture.EPO – separate lecture.

Human Growth HormoneHuman Growth Hormone

► Increases growth in pre-adolescents (clinical use)Increases growth in pre-adolescents (clinical use)► Stimulates production of insulin-like growth factors Stimulates production of insulin-like growth factors

(IGLF-1 and IGLFD-2)(IGLF-1 and IGLFD-2)► Some effect on muscle growth (via IGF-1)Some effect on muscle growth (via IGF-1)► Increases amino acid and glucose uptake into Increases amino acid and glucose uptake into

musclemuscle► Increases fat breakdown (glycogen sparing)Increases fat breakdown (glycogen sparing)► hGH increases following exercisehGH increases following exercise► Detection difficult due to similarity between Detection difficult due to similarity between

endogenous and rhGH – short ½ life (20 mins) – endogenous and rhGH – short ½ life (20 mins) – returns to baseline within 16 – 20 hrsreturns to baseline within 16 – 20 hrs

Why take hGH?Why take hGH?

► Few controlled studies:Few controlled studies: Deyssig et al., (1993) reduction fat mass, no Deyssig et al., (1993) reduction fat mass, no

diff strength;diff strength; Yarasheski et al., (1993) no increase muscle Yarasheski et al., (1993) no increase muscle

protein synthesis in weight lifters cf. placeboprotein synthesis in weight lifters cf. placebo

► Adverse effects – acromegaly, DM, Adverse effects – acromegaly, DM, hypertension, reduced HDL, hypertension, reduced HDL, osteoporosis, menstrual irregularities, osteoporosis, menstrual irregularities, impotenceimpotence

NarcoticsNarcotics►Act on brain to reduce pain from Act on brain to reduce pain from

injury & go thru pain thresholdinjury & go thru pain threshold►AddictiveAddictive► Illegal in most countriesIllegal in most countries► Illegal opiates – morphine, heroine, Illegal opiates – morphine, heroine,

pethidine, dextropropoxyphenepethidine, dextropropoxyphene►Legal – Dextromethorphan, Legal – Dextromethorphan,

codeine (analgesics and diarrhoea codeine (analgesics and diarrhoea suppressants)suppressants)

CannabinoidsCannabinoids

► TetrahydrocannabinTetrahydrocannabinol (THC)ol (THC)

► Renaud and Renaud and Cormier (1986) – Cormier (1986) – reduction in max reduction in max performanceperformance

► Doping? Calming, Doping? Calming, improved sleepimproved sleep

ΒΒ22 Agonists Agonists

► Used in treatment of asthma, EIA as potent Used in treatment of asthma, EIA as potent bronchodilators.bronchodilators.

► Eg. Salbutamol (Ventalin), short acting, also Eg. Salbutamol (Ventalin), short acting, also eg. Clenbuterol, long-actingeg. Clenbuterol, long-acting

► Some reclassified into ‘Other anabolic Some reclassified into ‘Other anabolic agents’ due to poss. anabolic effectagents’ due to poss. anabolic effect

► Use restricted to inhaler only with TUE from Use restricted to inhaler only with TUE from physician prior to competitionphysician prior to competition Formoterol, salbutamol, salmeterol, terbutalineFormoterol, salbutamol, salmeterol, terbutaline Salbutamol >1000ng.ml adverse finding Salbutamol >1000ng.ml adverse finding

Do inhaled Do inhaled ββ22 agonists affect agonists affect performance?performance?

Do Do ββ22 agonists affect performance? agonists affect performance?

►Oral admin of salbutamol may Oral admin of salbutamol may increaseincrease muscle strength (Martineau et al., 1992; muscle strength (Martineau et al., 1992;

van Baak et al., 2000)van Baak et al., 2000) Endurance (van Baak et al., 2000, Endurance (van Baak et al., 2000,

Collomp et al., 2000)Collomp et al., 2000)

But much larger dose (10 – 20x But much larger dose (10 – 20x inhalation)inhalation)

Hormone antagonists and Hormone antagonists and modulatorsmodulators

►Aromatase inhibitorsAromatase inhibitors►Ostrogen receptor modulators eg. Ostrogen receptor modulators eg.

tamoxifentamoxifen►Anti-oestrogenic substancesAnti-oestrogenic substances

E.g. Clomiphene, cyclofenil – used after E.g. Clomiphene, cyclofenil – used after steroids to stimulate own production of steroids to stimulate own production of testosteronetestosterone

►Agents modifying myostatin function: Agents modifying myostatin function: myostatin inhibitorsmyostatin inhibitors

Masking AgentsMasking Agents►Eg. Acetazolamide – diuretic Eg. Acetazolamide – diuretic

decreases urinary output of some decreases urinary output of some drugs for short periodsdrugs for short periods

►EpitestosteroneEpitestosterone►Probenecid – anti-goutProbenecid – anti-gout

banned by IOC but not banned by IOC but not

UCI until after 1988 tourUCI until after 1988 tour►Plasma expandersPlasma expanders

DiureticsDiuretics

DiureticsDiureticsElimination of fluid from the bodyElimination of fluid from the body

Used illegally in sport to:Used illegally in sport to:► Meet weight limit;Meet weight limit;► Overcome fluid retention from use of Overcome fluid retention from use of

anabolic steroids;anabolic steroids;► Increase volume of urineIncrease volume of urine

Side effects: dehydration, faint, muscle Side effects: dehydration, faint, muscle cramps, headaches, nausea.cramps, headaches, nausea.

GlucocorticosteroidsGlucocorticosteroids► Eg. Cortisol, cortisoneEg. Cortisol, cortisone► Produced by adrenal cortex (from cholesterol)Produced by adrenal cortex (from cholesterol)► Feedback mech between Feedback mech between

hypothalamus (corticotropin releasing factor); hypothalamus (corticotropin releasing factor); ant pit (adrenocorticotropic hormone (ACTH)); andant pit (adrenocorticotropic hormone (ACTH)); and adrenal cortex (cortisol)adrenal cortex (cortisol)

► Widely used for injuries - Potent anti-inflammatories despite Widely used for injuries - Potent anti-inflammatories despite limited evidence of benefits of glucocorticosteroid use in acute limited evidence of benefits of glucocorticosteroid use in acute injuries in sport (Dvorak et al., 2006) injuries in sport (Dvorak et al., 2006)

► Open airways, mask injury, increase ability to train.Open airways, mask injury, increase ability to train.► Stim gluconeogenesis, mobilisation amino acids and fatty acidsStim gluconeogenesis, mobilisation amino acids and fatty acids► Prohibited orally, rectally, iv or intramuscular – unless with TUE Prohibited orally, rectally, iv or intramuscular – unless with TUE

(common request)(common request)► Allowed – dermatological, aural/otic, nasal, buccal cavity, Allowed – dermatological, aural/otic, nasal, buccal cavity,

opthalmologic disordersopthalmologic disorders► Serious toxic effects with prolonged use.Serious toxic effects with prolonged use.► Soetens et al., (1995) – no evidence of ACTH on max Soetens et al., (1995) – no evidence of ACTH on max

performanceperformance► Insufficient evidence for substantial benefits of Insufficient evidence for substantial benefits of

glucocorticosteroids in tx of sport related injuriesglucocorticosteroids in tx of sport related injuries

Prohibited MethodsProhibited Methods

►Enhancement of oxygen transfer – Enhancement of oxygen transfer – separate lecture;separate lecture;

►Pharmacological, chemical and Pharmacological, chemical and physical manipulation;physical manipulation;

►Gene doping.Gene doping.

Substances prohibited in particular Substances prohibited in particular sportssports

► AlcoholAlcohol► Beta-blockersBeta-blockers

Beta-2 AgonistsBeta-2 Agonists

What are beta and alpha receptors ?

Adrenaline

12

1 23

Pupil dilation

Vasoconstriction

Increased heart rate

bronchodilation

lipolysis

Note adrenalin = epinephrine

Comparison of hormones and Comparison of hormones and neurotransmittersneurotransmitters

How a receptor mediates an How a receptor mediates an effecteffect

How alpha and beta agents How alpha and beta agents workwork

How beta blockers workHow beta blockers work

Beta-2 agonistsBeta-2 agonists

Banned unless have therapeutic use exemption

Cannot use at poolside

Salbutamol, terbutaline

2

bronchodilation

Beta-2 agonistsBeta-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)

RefsRefs

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