IN THE NAME OF GOD Drugs & Sport
Session 5
Prohibited Substances
S3. Beta agonists
S4. Hormone antagonists &
S5. Diuretics & other
All beta-2 agonists including their D- and L-
isomers are prohibited.
As an exception, formoterol, salbutamol,
salmeterol and terbutaline when administered by
inhalation, require an abbreviated Therapeutic
Use Exemption.
Despite the granting of any form of Therapeutic
Use Exemption, a concentration of salbutamol
(free plus glucuronide) greater than 1000 ng/mL
will be considered an Adverse Analytical Finding
unless the Athlete proves that the abnormal
result was the consequence of the therapeutic
use of inhaled salbutamol.

They can be divided into two groups:
Short-Acting Beta2 Agonists

Salbutamol (albuterol)
Bitolterol mesylate

Long-Acting Beta2 Agonists
Salbutamol or albuterol is a short-acting β2
adrenergic receptor agonist used for the relief of
bronchospasm in conditions such as asthma and
Salbutamol sulphate is usually given by the
inhaled route for direct effect on bronchial smooth
muscle. This is usually achieved through a
metered dose inhaler, nebuliser or other proprietary
delivery devices. In these forms of delivery, the
maximal effect of Salbutamol can take place within
five to twenty minutes of dosing, though some relief
is immediately seen. Salbutamol can also be given
orally or IV.
Salbutamol became available in the UK in 1969
and in the USA in 1980 under the trade name
Formula: C H NO
Half life: 1.6 hours
Clinical use
acute asthma symptom relief during maintenance therapy of asthma and other conditions with reversible airways obstruction (including COPD)protection against EIA Hyperkalemia, especially in patients with RF can be aerosolized with a nebulizer for patients with cystic fibrosis, along with ipratropium bromide and pulmozyme. As a β-2agonist, salbutamol also finds use in obstetrics. Intravenous salbutamol can be used as a tocolytic to relax the uterine smooth muscle to delay premature labour. Its role has largely been replaced by the calcium-channel blocker nifedipine which is more effective, better tolerated and orally administered Diet and bodybuilding use
Salbutamol is
taken by some as
an alternative to
Clenbuterol for
purposes of fat
Mode of action
Salbutamol binds to β-2adrenergic receptors
with a higher affinity than β-1receptors. In the
airway, activation of β-2receptors results in
relaxation of bronchial smooth muscle
resulting in a widening of the airway. Inhaled
salbutamol sulfate has a rapid onset of
action, providing relief within 5-15 minutes of

In tocolysis, the activation of β-2receptors
results in relaxation of uterine smooth
muscle, thus delaying labour.

Adverse effects
There exists the potential for adverse drug
reactions to occur - especially when in high
doses, or when taken orally or intravenously.
Common: tremor, palpitations and headache.
Infrequent: tachycardia, muscle cramps,
agitation, hypokalemia, tinnitus,
hyperactivity in children, and insomnia.
The (S) isomer of salbutamol can inhibit the
anti-inflammatory effect of steroids
prescribed to treat asthma. However, the (R)
isomer can stimulate the steroid's effect and
the overall effect of the two isomers is

Brand names
Prohibited substances most commonly
reported by IOC- accredited
laboratories, in order of frequency
Prohibited substances most commonly
reported by IOC- accredited
laboratories, in order of frequency
For documentation of asthma, and/or EIA, or exercise induced bronchoconstriction the following tests are considered appropriate by the International Olympic Committee (IOC):bronchodilator test—increase in FEV1 of at least 12% of the baseline FEV1 after the administration of a b2 agonist by inhalationbronchial provocation tests—eucapnic voluntary hyperpnea test, exercise challenge in the laboratory or in the field, hypertonic aerosol, methacholine test.
A urine salbutamol concentration of 1000 ng/ml is considered as positive doping test because this concentration cannot be achieved by inhalation alone.
Do inhaled β agonists affect athletic 20 randomised, placebo controlled studies (19 double blind, 1 single blind) that addressed the effect of inhaled b agonists on physical performance in nonasthmatic athletes with documented normal resting pulmonary function. Eighteen of these included endurance athletes such as cyclists, middle and long distance runners, cross country skiers, and triathletes, one study was in power athletes, and one in recreational subjects.
In most of the studies, b2 agonists were inhaled between 15 and 30 minutes prior to the onset of exercise. High doses, between 800 mg and 1200 mg, of salbutamol were given in four studies. Moreover, three studies were performed in cross-country skiers at ambient temperatures of -10°C and -15°C, which closely resembled a typical situation for the onset of EIA. In 15 studies salbutamol was the substance investigated and salmeterol in 4, formoterol in 2, and terbutaline in 1; two investigations compared two different b2 agonists.
Ergogenic effects were demonstrated in three studies only.
Signorile et al, in a frequently cited investigation, observed increased peak power outputs during repeated 15 s Wingate tests. However, their subjects were not competitive but recreational athletes. This lower fitness status might be linked to different exercise limitations during repetitive anaerobic exercise bouts that can be overcome by bronchodilation. Bedi et al found cycling time increased after the inhalation of 180 mg salbutamol during a trial including an exhaustive final sprint. However, they included two recreational cyclists in their study. In a subsequent study of similar design, these results could not be confirmed.
van Baak et al found that the inhalation of a supratherapeutic dose of 800 mg salbutamol improved cycling time trial performance by 2%. The largest improvements, however, were found in the subjects with the worst performance. Of 16 subjects, performance in 11 improved after inhalation of salbutamol, but the effect remained rather small in 5 of them. In contrast, in two studies running time until exhaustion was reduced under salbutamol and salmeterol. Even high doses of salbutamol had no ergogenic effect in three of four studies. Furthermore, inhaled b2 agonists did not influence physical performance under cold conditions. In contrast with inhalation of b2 agonists, oral administration of salbutamol can improve muscle strength and endurance performance. However, the dose needed to obtain such an effect is 10–20-fold greater than the dose used for inhalation.
Altogether, inhaled b2 agonists do not seem to affect physical performance in non-asthmatic competitive athletes.
In addition, there is no evidence for anabolic effects of inhaled b2 agonists. It is noteworthy that after inhalation of b2 agonists, lung function improved in most studies (typically measured by an increase in FEV1). Apparently, inhaled b2 agonists also induce some degree of bronchodilation in healthy athletes. This improved lung function, however, does not lead to performance enhancement in competitive athletes, perhaps because the ease of ventilation is generally not a limiting factor during maximal exercise in young nonasthmatic subjects. During maximal exercise pulmonary ventilation is not as high as the maximal achievable ventilation during clinical tests of ventilation.
Do Inhaled β -Agonists have an Ergogenic
Potential in Non-Asthmatic Competitive
In 17 of 19 randomised placebo-controlled trials in non-asthmatic competitive athletes, performance-enhancing effects of the inhaled β -agonists formoterol, salbutamol, salmeterol and terbutaline could not be proved. This is particularly true for endurance performance, anaerobic power and strength performance. In three of four studies, even supratherapeutic doses of salbutamol (800-1200μg) had no ergogenic effect. In contrast to inhaled β -agonists, oral administration of salbutamol seems to be able to improve the muscle strength and the endurance performance. Endocrinol Metab Clin N Am 39 (2010) 75–87
A number of non-asthmatic athletes consider inhaled b2 agonists ergogenic although scientific evidence clearly disregards a performance enhancing effect. Drug intake by these athletes, thus, can be labelled ‘‘misuse''. However, several other (permitted) substances such as acetylsalicylic acid and other analgesics (for example, diclofenac) with well known side effects are used much more frequently without indication. It is therefore questionable if the documented misuse of inhaled b2 agonists is a sufficient argument to prohibit their use. The prevalence of asthma in athletes has been demonstrated to be higher than in the non-athletic population, which implies a more frequent indication for the use of b2 agonists. The requirement for TUEs obviously leads to considerable administrative workload for athletes, physicians, and associations. This may even interfere with appropriate drug therapy in some althletes. It is highly questionable if such expenditures are necessary and if they really promote the fight against doping. Campaigns to educate athletes and coaches about the appropriate use of asthma sprays and their lack of performance enhancing efficacy seem more promising. In summary, the inclusion of b2 agonists on the Prohibited List should be newly discussed becaused of their lacking ergogenic effects. Furthermore, the limited financial and human resources of the fight against doping may be better focused on substances and methods which have a proved performance enhancing effect and, therefore, a much larger potential to elicit unfair competition—anabolic steroids, erythropoietin, human growth hormone, insulin-like growth factor, blood doping, and similar substances and methods.
It is not justified that the bronchial obstruction criteria are different if the patient is an athlete, particularly as there is no evidence that inhaled b2 agonists have ergogenic effects at therapeutic doses, although they may do if administered orally at doses very much higher than therapeutic ones. Excessive control can lead to situations of inequality for asthmatic athletes. In the current situation, the physician who has to treat an asthmatic athlete is often denied the most effective therapeutic option. For all of these reasons, these aspects of the antidoping regulations must be reviewed. Measures could be adopted such as including a fall of 70% in FEV1% as the indication for a bronchodilation test and extending the definition of a positive result for the methacholine test to a PC20 of 8 mg/ml.
The following classes are prohibited:
1. Aromatase inhibitors including, but not limited to:
anastrozole, letrozole, aminoglutethimide,
exemestane, formestane, testolactone.

2. Selective estrogen receptor modulators (SERMs)
including, but not limited to: raloxifene,
tamoxifen, toremifene.

3. Other anti-estrogenic substances including, but
not limited to: clomiphene, cyclofenil, fulvestrant.
4. Agents modifying myostatin function(s) including
but not limited to: myostatin inhibitors.
Selective estrogen receptor
A class of medication that acts on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues SERMs are used dependent on their pattern of action in various tissues:Clomifene is used in anovulation. Raloxifen is used for osteoporosis and reducing risk of invasive breast cancer. Tamoxifen and Toremifene are used for breast cancer. Ormeloxifene is used for contraception. Some SERMs may be good replacements for hormone replacement therapy (HRT), which recent studies have called into question, although the above agents still have an unacceptably high risk of thrombosis and other side-effects to allow for widespread use.
Mechanism of action
Estrogenic compounds span a spectrum of activity ranging from:full agonists (agonistic in all tissues) such as the natural endogenous hormone estrogen. mixed agonists/antagonistics (agonistic in some tissues while antagonist in others) such as tamoxifen (a SERM) pure antagonists (antagonistic in all tissues) such as Fulvestrant.
Mechanism of action
The mechanism of mixed agonism/antagonism may differ depending on the chemical structure of the SERM, but for at least for some SERMs, it appears to be related to (1) the ratio of co-activator to co-repressor proteins in different cell types and (2) the conformation of the estrogen receptor induced by drug binding which in turn determines how strongly the drug/receptor complex recruits co-activators (resulting in an agonist response) relative to co-repressors (resulting in antagonism). For example, the prototypical SERM tamoxifen acts as an antagonist in breast and conversely an agonist in uterus. The concentration of steroid receptor co-activator 1 is higher in uterus than in breast, therefore SERMs such as tamoxifen are more agonistic in uterus than in breast. In contrast, raloxifene behaves as an antagonist in both tissues. It appears that raloxifene more strongly recruits co-repressor proteins and consequently is still an antagonist in the uterus despite the higher concentration of co-activators relative to co-repressors.
Actions of SERMs
Pituitary gland - clomifene blocks estrogen action, leading to an increase of FSH. Uterus- tamoxifen may increase endometrial carcinoma risk, but raloxifene does not. Data on toremifene and clomifene is insufficient. Breast- all SERMs decrease breast cancer risk, and tamoxifen is mainly used for its ability to inhibit growth in estrogen receptor-positive breast cancer. Deep venous thrombosis- the risk may be elevated in all SERMs. Cholesterol and triglycerides- levels respond favorably to SERMs. Bone turnover and postmenopausal osteoporosis -respond favorably to SERMs. Hot flashes- are increased by all SERMs. Tamoxifen is an orally active selective estrogen
receptor modulator (SERM) which is used in the
treatment of breast cancer and is currently the
world's largest selling drug for that purpose.
Tamoxifen was discovered by ICI
Pharmaceuticals now Asterazeneca and is sold
under the trade names NolvadexIstubal
and Valodex
However, the drug, even before its patent
expiration, was and still is widely referred to by
its generic name "tamoxifen."
Tamoxifen Drug characteristics
Formula: C H NO
Half life: 5-7 days
Breast cancer treatment Tamoxifen is currently used for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancer in pre- and post-menopausal women. It is also approved by the FDA for the prevention of breast cancer in women at high risk of developing the disease. It has been further approved for the reduction of contralateral breast cancer.
At the conclusion of the large STAR clinical study, it was reported in 2006 that raloxifen is equally effective in reducing the incidence of breast cancer, but caused fewer side effects (e.g., endometrial cancer) Other uses
Tamoxifen is used to treat infertility in women with anovulatory disorders. A dose of 10–40 mg per day is administered in days 3–7 of a woman's cycle. In addition, a rare condition occasionally treated with tamoxifen is retroperitoneal fibrosis.
In men, tamoxifen is sometimes used to treat gynecomastia which arises for example as a side effect of antiandrogen prostate cancer treatment.
Tamoxifen is also used by bodybuilders to prevent or reduce drug-induced gynecomastia caused by the estrogenic metabolites of AAS. Finally tamoxifen is used as a research tool to trigger tissue selective gene expression in genetically modified animals.
Tamoxifen itself is a prodrug, having very little affinity for its target protein, the estrogen receptor. It must first be metabolized in the liver by the cytochrome P450 isoform CYP2D6 into the active metabolites 4-hydroxytamoxifen and des-N-methyl-4-hydroxytamoxifen (endoxifen).
These active metabolites compete with estrogen in the body for binding to the estrogen receptor. In breast tissue, 4-hydroxytamoxifen acts as an antagonist so that transcription of estrogen-responsive genes is inhibited. Side effects
endometrial cancer in some womenrapid increase in triglyceride concentration in the bloodincreased risk of thromboembolism especially during and immediately after major surgery or periods of immobilityis also a cause of fatty liverreduction of libidoA beneficial side effect of tamoxifen is that behaves as an agonist in bone, preventing bone loss by inhibiting osteoclasts, and therefore it prevents osteoporosis. S5. DIURETICS AND OTHER
Masking agents are prohibited. They include:
Diuretics*, epitestosterone, probenecid,
alpha-reductase inhibitors (e.g. finasteride,
dutasteride), plasma expanders (e.g.
albumin, dextran, hydroxyethyl starch) and
other substances with similar biological

* A Therapeutic Use Exemption is not valid if an
Athlete's urine contains a diuretic in association
with threshold or sub-threshold levels of a
Prohibited Substance
Acetazolamide,amiloride, bumetanide,
canrenone, chlortalidone, etacrynic
acid, furosemide, indapamide,
metolazone, spironolactone, thiazides
(e,g. bendroflumethiazide,
chlorothiazide, hydrochlorothiazide)
and triamterene, and other substances
with similar chemical structure or
similar pharmacological effects.
Diuretics are used to treat heart failure, liver cirrhosis, hypertension and certain kidney diseases. Some diuretics, such as acetazolamide, help to make the urine more alkaline and are helpful in increasing excretion of substances such as aspirin in cases of overdose or poisoning. Diuretics are often abused by sufferers of eating disorders, especially bulimics, in attempts at weight loss.
These drugs may be misused for 3 main reasons: 1- To effect acute reduction of weight to meet weight- class limits ( in sports such as wrestling, boxing, weight lifting and …) 2- To overcome fluid retention induced by AAS (body building).
3- To modify the excretion rate of urine and to alter urinary concentrations of prohibited drugs.
Is used to mask the use of doping substances, anabolic drugs in particular, by delaying their elimination. The medical application of Probenecid is to treat gout rheumatism. It may cause the following undesirable effects:CephalgiaAnorexiaNauseaStomach achesVertigoFrequent micturitionAnemiaPossible anaphylactic-like reactions with feverDermatitis and other skin irritations Apurina; Benecid; Benemid; Benuryl; Col-Probenecid; Colbenemid; Ethamide; Polycillin-Prb; Principen W/ Probenecid; Probalan; Probampacin; Probecid; Proben; Proben-C; Probenecid; Probenecid Acid; Probenecid W/ Colchicine; Probenecid and Colchicine; Probenemid; Probexin; Prolongine; Synergid R; Tubophan; Uricosid Drug Category (FDA):
Uricosuric Agents


Microsoft word - afghan political parties-a short outline

Afghan Political Parties: a short outline By René Teijgeler Summary Political parties are controversial in Afghanistan. Associated with recent conflict and ethnic or military factions, they are not considered a potentially positive force by the public or the Afghan Government. Strong ties to tribal, regional, religious, or ethnic identities, the lack of class awareness, and the very small size of the intelligentsia limited the formation of political parties in Afghanistan. Besides patron-client relationships (qawm) are still striving and stalling the full development of political parties. As a matter of fact qawm is so important that is overrides any ethnic, religious or family ties. Therefore, the term ‘political party' has a number of connotations. It does not necessarily denote an organization that is politically active in the way parties are in established democracies. While distinguishable, ideological currents of political activity exist today, few parties hold individualized, identifiable platforms or have cohesive internal structures. Many have connections to ex-mujahidin military factions previously active in Afghanistan's civil conflict. A more accurate term for these parties is ‘proto parties', as they lack the institutionalization more commonly associated with parties in the conventional sense. The New Democratic Parties (NDP) that came into being after the Bonn Conference in 2001 are different from the mujahideen parties in that they are more likely to embrace moderate state-building or national unity platforms. They have no direct ties to the power structures from the former resistance movement but in the contrary are supported by NGOs, lawyers or socio-political associations. After the 2005 parliament elections the NDPs, however, did not manage to get any seats upon which the International Community (IC) decided not to support them anymore. The mujahideen parties won these elections based on their effective military-based organization. Yet, before the 2009 elections the IC realized that the NDPs are the only parties that give hope for a more democratic Afghanistan in the future. Subsequently they decided to assist the NDPs in party development and organization. Party in general is hindered by inadequate legislative. The government feared that in the beginning party development might entice ethnic and religious strives thus decided, also for practical reasons, to organize the first elections on basis of the Single Non-Transferable Vote (SNTV) system. This now still stands in the way of democratization through party development. Other steps to stimulate this process are: state funding of parties, independent party registration and altering the Parliamentary Rules of Procedures. Early Afghan Parties The modernization policies of King Zahir Shah (1933-1973) in the 1940s led to the formation of a number of parties. The development of mature political parties in

RALEIGH DISABILITY DETERMINATION SERVICES PSYCHOLOGICAL EVALUATION CLAIMANT: DOE, JONATHAN CLAIMANT#: 156332 DATE SEEN: 10/12/2010 EXAMINER: Dr. Ken Smith 100 Main Street Cary, North Carolina 27518 ADJUDICATOR: CLARK MILLER ARRIVAL INFORMATION:The claimant arrived early for his scheduled appointment at 10:00 AM on Tuesday, October 12, 2010.Jonathan arrived for the appointment by bus. The claimant does not have a driver's license. Jonathanshowed the examiner his North Carolina photo I.D. card. He stated he has never had a driver license inthe past. Jonathan's group home manager was supposed to accompany the claimant on his bus trip tothe office, but a last minute scheduling change forced Jonathan to get on the bus alone today. Given theclaimant's poor performance and unstable presentation during the interview, the examiner accompaniedthe claimant out of the office at the end of the session. Assistance was provided in crossing the streetand helping the claimant get on the city bus. The bus driver was alerted that this man may needassistance in getting off at his destination. The claimant was unable to provide an estimate of travel toreach the office today. The claimant was given total assistance by office staff in completing thecomputerized intake process. Jonathan stated that he does not know how to use computers. Althoughhe has access to a computer in the group home where he resides, he has never used the system.