Transcript Drug_others

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.
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Other Anabolic Agents
Other Peptide Hormones
Beta-2 Agonists
Agents with anti-oestrogenic activity
Diuretics and other Masking Agents
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Stimulants
Narcotics
Cannabinoids
Glucocorticosteroids
► In
comp.
Other Anabolic agents
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E.g clenbuterol
A Β2 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
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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
Β2 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 β2 agonists affect performance?
Do β2 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
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
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 hypothalamus (corticotropin releasing factor);
 ant pit (adrenocorticotropic hormone (ACTH)); and
 adrenal cortex (cortisol)
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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
Pupil dilation
lipolysis
Vasoconstriction
bronchodilation
Increased heart rate
a-1
a-2
b-1
b-3
b-2
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
Salbutamol, terbutaline
bronchodilation
b-2
Banned unless have therapeutic use exemption
Cannot use at poolside
Beta-2 agonists
Clenbuterol
(asthma medication in Europe, not UK)
Bronchodilation and anabolic effects (increases muscle mass and fat metabolism in animals)
b-2
Known cases of bans
British weightlifters 1992 Olympics
Katrine Krabbe (German 100 m sprinter). 4 year ban reduced to 2 years on appeal
Refs
► British
I)
Journal Sports Med (2006) 40 (Suppl