Drugs Used in Atheletic

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The use of stimulants to improve athletic performance is prevalent in both college and Olympic sports, and likely in professional sports as well. In a 2001 study of 21,225 college athletes who responded to a survey, the use of amphetamines and ephedrine was reported to be 3.3% and 3.9%, respectively. This is an increase in comparison with similar surveys conducted in prior years.Claims have been made that the majority of Major League Baseball (MLB) players use amphetamines or other stimulants. Amphetamine-like sympathomimetics stimulate the central

nervous system (CNS), as well as the cardiovascular system.[30] In addition, they increase glycogen and fatty acid metabolism. Such compounds have been shown to improve athletic performance to various degrees in strength and endurance exercises, improve reaction times, and reduce fatigue.[14,31] Amphetamine and its analogues can cause euphoria, boost confidence, and intensify aggression. Adverse effects of these compounds include tachycardia, palpitations, hypertension, nervousness, restlessness, irritability, insomnia, seizures, life-threatening arrhythmias, stroke, thermogenesis, and death.[14,15,30] Particularly problematic in this group is ephedrine, which is available in the United States and

abroad, and is often found in combination allergy and cold products and in dietary supplements (see also Ephedra, below). The NCAA prohibits the use of ephedrine, and the National Football League (NFL) added ephedrine to its list of banned substances in 2001.[22,32] WADA prohibits the "in-competition" use of ephedrine.[12]

Caffeine has been used in sports as a stimulant, to counter drowsiness, to improve endurance, and to enhance bodybuilding workouts.[14] Caffeine stimulates the CNS to increase mental alertness and increases adrenaline release.[33-35] It also increases the hydrolysis and utilization of fats in the body for energy, while its effect on muscle glycogen has been mixed.[35] Caffeine is also believed to enhance muscular contraction. Studies have indicated that caffeine in doses of 3-13 mg/kg can potentially improve performance in endurance events, particularly for trained athletes.

Studies on the ergogenic benefit of caffeine for power and

sprint events either have shown no benefitor have been inconsistent.[38] However, by increasing endurance, caffeine may enhance the efficacy of training in these events since training often consists of performing multiple repetitions.

Adverse reactions to caffeine are similar to those of other stimulants and include insomnia, tremors, nervousness, restlessness, tachycardia, and palpitations.[14] Caffeine is also a diuretic, which can potentially cause electrolyte imbalances and hasten dehydration. As of January 2004, WADA removed caffeine from its list of prohibited substances; previously caffeine was a banned substance when urinary concentrations exceeded 12 mcg/mL.[12] Caffeine is a restricted substance by the NCAA, which allows urine concentrations of 15 mg/L or less.[22] The amount of caffeine intake that would yield such concentrations can vary widely, however, a general guide is that the limits will be exceeded if about 500 mg or more of caffeine is ingested within a few hours of the drug test in an average sized, healthy man; this is equivalent to about 5 cups of regular coffee (about 100 mg/cup).[15] Athletes must be made aware of the caffeine content in prescription and over-the-counter medications, soft drinks, sport and energy drinks, herbal products, and other dietary supplements. Herbal or natural products and dietary supplements can be particularly problematic as some contain hidden sources of caffeine.[39]

Anabolic-Androgenic Steroids
Anabolic-androgenic steroids are synthetic analogues of

testosterone, and as the name suggests, their actions are both anabolic (muscle building) and androgenic (masculinizing) in nature. Testosterone and anabolic-androgenic steroids have widespread physiologic effects. With regard to ergogenic properties, these agents promote the growth of skeletal muscle, increase strength, and promote healing of muscle tissue.[14,40-44] They also enhance erythropoiesis and cause aggression. These agents are the most abused class of banned drugs documented in modern Olympic athletes.[14,27,28] The previous Summer Olympics yielded multiple reports of athletes testing positive for these banned substances, even though drug testing had become routine and was expected by the competitors.[8] The use of anabolicandrogenic steroids is prevalent among bodybuilders,[40] and as many as 55% of elite power lifters had admitted to using these agents in one study.[45] MLB players have admitted to the use of anabolic-androgenic steroids, and some claim that the use of these drugs in MLB is rampant.[29] Various studies have reported that as high as 20% of college athletes have used anabolic-androgenic steroids.[46] Alarmingly, 4% to 11% of high school males and 0.5% to 2.5% of high school females have reportedly tried these agents.

Moreover, in one study, 1.9% and 2.8% of 7th and 8th

graders, respectively, responded to a survey that they had used anabolic-androgenic steroids in the previous 30 days.[52] Most of the adolescents who use anabolic-androgenic steroids participate in sports, and a primary reason for taking these agents is reportedly to improve athletic performance.[49,53] Abusers of androgenic-anabolic steroids take these agents by "stacking" (taking more than one androgenic-anabolic steroid at a time, including both oral and injectable forms) and "cycling" (taking them for periods of time, usually 6-12 weeks, and then stopping for a similar period of time), and they take high doses (as much as 10-100 times the normal therapeutic dose); and they combine this with intense physical workouts and high-protein diets.[14,40,41,54] The rationale for cycling is to allow the body to recover from reversible adverse effects. Another method of administration is "pyramiding" in which the user initiates the drug at a low dose, gradually increases the dose over several weeks, then tapers back down. It should be emphasized that anabolicandrogenic steroids alone are not necessarily effective in producing gains in strength. It is the combination of anabolic-androgenic steroids, intense physical training, and a high-protein diet that is most efficacious in building strength and muscle.[40,41,43,44]

In terms of adverse effects from anabolic-androgenic steroids, generalizations and extrapolations can be made based on information from anecdotal case reports and some limited studies. However, the severity and extent of adverse effects in humans is not truly known for athletes taking such high doses and when cycling, stacking, and pyramiding. Controlled studies simulating those conditions are unethical. In males, the administration of anabolic-androgenic suppression hormone, of agents results in a negative-feedback luteinizing endogenous inhibition of the hypothalamic-pituitary-testicular axis, and a gonadotropin-releasing hormone, and follicle-stimulating hormone,

testosterone production.[55-58] Adverse effects associated with anabolic-androgenic drugs in men include acne, testicular atrophy, prostate enlargement, decreased spermatogenesis, infertility, impotence, and changes in libido.

Gynecomastia can also occur secondary to some of the

various peripheral metabolites of the steroid compounds that exert estrogenic effects, and this may be irreversible or require surgical treatment. Some users of anabolic-androgenic steroids take tamoxifen to treat or prevent gynecomastia.[58,59] In females, adverse effects include potentially irreversible masculinization (e.g., hirsutism, male-pattern baldness, deepening of the voice),

acne, enlargement of the clitoris, menstrual irregularities, and changes in libido.[14,41,47,48,57] Other adverse effects associated with anabolic-androgenic steroids include cholesterol and lipid disorders, hypercalcemia, edema due to electrolyte and fluid retention, hypertension, thrombolic events (e.g., emboli, myocardial infarction, stroke) presumably due to an increase in platelet aggregation and erythrogenesis, liver dysfunction, psychiatric effects (e.g., aggression, psychosis, manic episodes, panic disorders, depression), cancer, and premature mortality.[40,41,54,58,60,61] Due to their promotion of aggression, they can cause hostility and extreme rage ("roid rage").[41,60] Adolescents who take these drugs can also experience premature closure of the epiphyseal plates, potentially resulting in shorter stature in adulthood.[57] Addiction and dependence to these drugs can also occur, and withdrawal can result in depression and suicidal thoughts.[54]

Peptide Hormones
A variety of peptide hormones have been used by athletes. These include human growth hormone (HGH), erythropoietin, human chorionic gonadotrophin (HCG), corticotrophin, and pituitary and synthetic gonadotrophins. These agents, as well as their respective

releasing factors, are banned by both the NCAA and WADA, and may be by other sporting organizations as well.[12,22] HGH stimulates lipolysis in adipose tissue and gluconeogenesis in the liver; its anabolic effects are believed to be mediated by insulin-like growth factors.[62] Athletes have used HGH to increase muscle mass and strength. Although several studies did not observe an increase is muscle growth with HGH administration alone, athletes have been known to combine the use of HGH with androgenic-anabolic steroids.[63-67] Potential adverse effects of longterm HGH administration include antisocial behavior, depression, psychosis, glucose intolerance, hyperlipidemia, hypothyroidism, heart disease, and other symptoms associated with acromegaly and gigantism.[15,62] Epoetin alfa and darbepoetin alfa are recombinant human erythropoietins used to boost the body's production of red blood cells. These compounds can increase the red blood cell count, the hematocrit, and the blood hemoglobin concentration.[68,69] These effects can be ergogenic for endurance athletes by supplying more oxygen to the muscles and other organs. Potential risks of abusing erythropoiesis-stimulating agents include iron deficiency, hypertension, seizures, and thrombosis, including stroke and myocardial infarction, by increasing the blood viscosity.[15,69,70]

HCG can boost the production of testosterone in men by stimulating the Leydig cells in the testes.[15] HCG is also used to regenerate suppressed testicular function after the use of anabolicandrogenic steroids. Abusers of anabolic-androgenic steroids have used HCG to prevent or reverse gynecomastia; however, this can potentially aggravate the situation since testosterone itself is partially converted to estrogenic compounds.[15,59] Corticotropins stimulate the adrenal cortex to secrete hormones, including glucocorticoids, mineralocorticoids, androstenedione, and dehydroepiandrosterone.[71] Adverse effects of corticotropins include cardiac hypertrophy, hypertension, fluid retention, electrolyte imbalances, Cushing's syndrome, and adrenal insufficiency upon abrupt withdrawal after long-term use.

Beta-blockers are used to improve performance in anaerobic events that require steadiness and control, such as in shooting and archery.

These drugs are used to improve aim by decreasing tremors and

shaking and to improve steadiness.[72] Further, beta-blockers will reduce the heart rate, and elite shooters are trained to shoot between heartbeats to avoid any vibration that may occur. A reduced heart rate provides these athletes with a longer interval to pull the trigger. In addition to shooting and archery, beta-blockers

are banned in a number of other Olympic sports, such as bobsled, curling, diving, gymnastics, ski jumping, football (soccer), and wrestling.[12] Adverse effects of beta-blockers include fatigue, lethargy, bradycardia, hypotension, impotence, and bronchospasm.

In low doses or amounts, alcohol can reduce essential tremor, and is therefore used for similar reasons as beta-blockers.[14,73] However, in higher amounts, alcohol can have a negative effect on athletic performance, particularly for events that require endurance, speed, quick reaction times, balance, and coordination. Adverse effects of alcohol include drowsiness, sedation, impaired balance, psychologic and physical dependence, impaired judgment, and impaired psychomotor skills. Obviously, long-term use of alcohol can result in other alcohol-related problems such as liver damage. The NCAA and WADA ban the use of alcohol for certain events, such as rifle and archery, respectively.[12,22]

Beta-2 Agonists
Beta-2 agonists have become increasingly popular with Olympic athletes claiming that they have asthma or exercise inducedasthma.[13,74-78] However, many of these agents are considered to be stimulants by some sports-governing agencies, and others (e.g.,

clenbuterol) are considered anabolic. WADA and the NCAA permit the use of certain beta-2 agonists by inhalation only, including terbutaline, albuterol, and salmeterol; oral and injectable beta-2 agonists are not permitted.[12,22] Written verification by a qualified physician may be required prior to competition. At the 2002 Winter Olympic Games, athletes wishing to use beta-2 agonists were required to submit to the IOC Medical Commission clinical and laboratory documentation that demonstrated the need for these medications. If the information was considered insufficient or doubtful, an independent panel of experts was authorized to require appropriate testing.[76]

Athletes use diuretics for a variety of reasons. Since these agents result in a loss of fluid from the body, they are sometimes used to "make weight" for a particular sport such as boxing, weightlifting and wrestling.[15,79] In addition, drug-abusing athletes use diuretics to dilute their urine in an attempt to mask a drug test, since assays require a minimum concentration to detect the presence of a substance.[15,79] However, requiring that athletes produce an adequate specimen with acceptable pH and specific gravity counters the dilutional effect; furthermore, the detection of a diuretic in a urine drug test constitutes a positive test.[3]

Acetazolamide has been used both to alleviate the effects of performing at high altitude and to diminish the excretion of basic stimulants by altering the pH of the urine.[14] Complications from the use of diuretics include fluid and electrolyte imbalance, dehydration, muscle cramps, weakness, nausea, and impairment of the body's heat-regulatory mechanisms. Both WADA and the NCAA ban the use of diuretics.[12,22]

Masking Agents
Masking agents are substances that athletes might use to prevent detection of drugs in the urine. These include substances ingested by the athlete as well as adulterants that are surreptitiously added to a urine specimen in an attempt to fool the drug assay. In 1987, the IOC requested that urine samples be screened for the presence of probenecid at the Pan American Games, because probenecid was suspected of being used to prevent the excretion of certain anabolic-androgenic steroids in an attempt to cheat on a drug test.

After probenecid was indeed detected in a number of urine

samples of strength athletes, it was subsequently added to the banned substance list by the IOC. The mechanism of action is believed to be an inhibition of renal tubular secretion of these drugs. Both the NCAA and WADA now ban probenecid.[12,22]

By taking a substance to alkalinize the urine, the urinary excretion rate of basic compounds (e.g., amphetamine analogues) can be reduced.[80] By decreasing the excretion of the drug, the urine concentration may be too low for the analysis to detect. For this reason, strict drug-testing protocols require a urine sample to have a pH of 7.5 or less.[3,15] Furthermore, alkalinizing agents, such as acetazolamide, are banned by the NCAA and WADA, and they can be detected by the drug tests.[12,22] Adulterants have been used by athletes to mask the use of banned substances, either by adding something that degrades or denatures the drug and its metabolites or by interfering with the analysis in some manner to deceive it. Such adulterants are surreptitiously added to a urine specimen by an athlete after the specimen has been produced. Examples of such adulterants -- which may or may not be effective masking agents -- are bleach, vinegar, lemon juice, salt, hand soap, Drano, and various acids.[81-83] A number of products are marketed, particularly on the Internet, to assist athletes in beating a drug test.[82] These products attempt to interfere with the analysis by various mechanisms, but strict specimen collection procedures (e.g., observed collections) and counterdetection methods used in certified laboratories will generally detect such attempts at deception. Tampering, adulterating, or manipulating a urine specimen is banned, and

evidence of such can constitute a positive drug test, depending on the sports-governing body.

Street Drugs
Marijuana, cocaine, heroin, methylenedioxymethamphetamine (MDMA, Ecstasy), lysergic acid diethylamide (LSD), mescaline, phencyclidine (PCP), and other psychedelics and hallucinogens are banned by many amateur and professional sports organizations.

Although these drugs would not be considered performance

enhancing, they are generally banned for legal reasons and to protect the health and safety of the athlete and competitors.

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