Pharm 100 - Lesson E.5

• Performance-enhancing substances have been used by athletes for centuries. Athletes havesought that extra edge over their competitors. Recorded history and legend reveals that the ancient Greeks ingested mushrooms to increase performance. Legend has it that the Aztec people ate the hearts of human sacrifices to improve performance. Early Belgian racers used sugar cubes dipped in ether as a performance enhancer. In the early 1900’s, boxers ingested brandy and cocaine. Other drugs used in the early part of this century include caffeine, alcohol, nitroglycerin, ethyl ether,strychnine, and opium.
• The modern era of performance-enhancing substances started in the early 1950’s with the use of amphetamines and anabolic steroids and use increased rapidly until the sports regulatory bodiesbanned these substances. The rationale behind the ban is that use of performance-enhancingsubstances is unethical. All athletes should compete on their own abilities. Competition shouldcompare the athletes, not the team of doctors, biochemists and pharmacologists behind the athlete. Toenforce the ban, most sports regulatory bodies have introduced random doping control.

• 1. Reduce pain and inflammation. The drugs in this group include local anesthetics, narcotics, andanti-inflammatory steroids (cortisone).
• 2. Increase endurance and speed. The drug most widely used is amphetamine and its derivatives. Blood doping would also be included in this category.
• 3. Increase strength. Anabolic steroids and growth hormone are the major drugs in this class.
• 4. Alter heart rate. The beta adrenoceptor blocking drugs (propranolol) are used in some of theprecision sports.
• 5. Reduce body weight. Diuretics are used to reduce body water, and in turn, body weight.
• 6. Sedatives. The benzodiazepines (diazapam, also known as Valium) are the drugs used.

It is difficult to obtain an accurate estimate of the extent of drugs used as athletes are not willing to admit to cheating. In 1972, the following estimates of anabolic steroid use revealed that: 100% ofOlympic weight lifters used steroids, 100% of body builders, and 75% of professional football players. Estimates of steroid use in the 1990’s are: 4-12% of high school males, 14% in U.S. college sports,and 30-75% in professional sports. A recent survey suggests that 10% of high school aged males havetaken anabolic steroids to look good for the opposite sex.

Stacking is the process of using several different drugs in the same class, e.g. simultaneous useof three anabolic steroids. The body may eliminate each drug at a rate independent of the other, andby using smaller doses of three separate drugs, the athlete can stop the drugs closer to the competition and they will be removed from the body prior to the competition.

Pyramiding is the process of starting with small doses and building to a large dose for maximaleffect, then tapering to smaller doses and stopping the drug just before the competition. The lowerdose is eliminated quickly and the athlete is drug-free at competition.

Doping control is the process of measuring the drug in urine

Masking is the process of taking a second drug to "mask" the detection of the banned drug in urine.

• The pharmacology of the amphetamines is discussed in more detail in another lesson. In terms ofperformance, amphetamines are powerful, psychomotor stimulants producing increased alertness and afeeling of power. It is well known that amphetamines increase both endurance and speed, thus overallperformance.
• In a British study, the effect on endurance was clearly demonstrated. Athletic performance was measured on an exercise bicycle. The duration of performance was extended by about 40% when 10mg of methamphetamine was administered. That is, as the athletes were nearing exhaustion, 10 mg ofmethamphetamine allowed them to continue. Several other studies have reported similar data.
• Similar studies have examined the effect of amphetamines on speed. When given amphetamines,14 of 15 swimmers were faster, 73% of runners improved their times, and most shot putters increasedtheir throwing distance.
• What is the magnitude of performance? The following data demonstrate the small but significantincrease in performance

• 
• The dose of amphetamine was kept at an acceptable level. Higher doses may give a greater response.
• To put this magnitude of change in perspective, let us consider the evolution of the four-minutemile. Records have been kept since 1850 where the record holder of the mile had a time of five minutes. In 1954, Bannister broke the four-minute barrier for the mile. In 1975, Walker held the world record, and in the intervening years there were six others who held the world record, each worldrecord separated by less than one second. It is easy to envision what a one percent increase in performance produced by amphetamines would have done to the progression of world records in the one-mile event.
• The two to three percent increase produced by amphetamines, especially in the elite athlete at the peak of training, may move the athlete from 6th or 10th position to the gold medal.

Amphetamines increase the activity of the central and peripheral nervous system. This results in central nervous system excitation and euphoria. As the drug wears off, the user experiences a low or "crashes". There are significant increases in heart rate and blood pressure. Large doses can lead to fatal increases in blood pressure. Amphetamines also produce dependence, and tolerance to the drug develops quickly.

• These are compounds with reduced androgenic effects but maintaining anabolic effects, i.e. the building of muscle mass. Androgenic effect of a compound is the effect on secondary male sex characteristics. Testosterone, the male sex hormone, has both androgenic and anabolic properties. Anabolic steroids are compounds that have reduced androgenic effects compared to testosterone, but this separation is by no means complete.
• Anabolic steroids are used by athletes to increase muscle mass and strength in a large variety ofsports, including football, weight lifting, running, and gymnastics. In addition, they are used toenhance physical appearance.
• Do anabolic steroids enhance strength and performance? It has been assumed that these agents increase muscle mass and strength and produce a more masculine appearance, but early studies failedto show a clear response. At least half of the clinical trials conducted in the 1970’s and 1980’s failedto show any response, and those trials that did show a response had serious limitations in design
• The studies conducted prior to the 1990’s did not demonstrate a clear response of the anabolicsteroids for a number of reasons, but most notably the dose utilized was low – athletes use large doses. Ethics prevents the use of these large doses in a study. In addition, most studies did not use conditioned athletes and it is now known that the trained athlete may respond differently than the untrained individual. The sports world knew that anabolic steroids enhanced performance as they were used in that milieu, but scientists did not have the studies which conclusively demonstrated abenefit. However, even from the early study, it was apparent that weight lifters benefited, especially in the single repetition events where they could lift a greater weight. The other observation that was important was that the recovery period between training sessions was reduced. The athlete could train harder and longer.

• Recent studies have demonstrated that anabolic steroids can increase both the size and thestrength of the athlete, but not aerobic performance (e.g. long distance running). There are at least three potential mechanisms whereby anabolic steroids produce this effect:
• 1 They produce an anti-catabolic response. As the athlete trains, he/she reaches a plateau or pointwhere more muscle is used as fuel or broken down as is produced in response to training. The athlete trains so hard that he/she uses protein from the muscle to fuel that training. This action is blocked by the anabolic steroids.
• 2. Anabolic effects follow the anti-catabolic effects and the drugs produce new protein. These responses may be more important or have great effects at the high doses used by athletes.
• 3. Motivational responses also contribute to the overall effect. Anabolic steroids can produceaggressive behaviour, a condition called “roid rage”. This aggressive behaviour is beneficial formost sports, especially football.

• 1. Low to moderate doses have modest effects on the average adult.
• 2. Effect on inexperienced weight lifters is less than a good exercise program.
• 3. Large doses yield significant increases in lean body mass and increase in strength (in trained athlete at plateau).
• 4. The aggressive behaviour induced by the anabolic steroids contribute to their performance enhancement effects.
• 5. A diet high in protein is required for the anabolic steroids to be fully effective.

• Reduced testosterone levels. The anabolic steroids block the release of GNRH and hence FSHand LH, leading to a reduction in sperm production and testosterone levels. The reduced testosteronelevels can lead to infertility, reduced libido and impotence.
• Altered liver function. The anabolic steroids are associated with altered liver function –hepatitis, liver failure and liver cancer.
• Mood swings. Users of anabolic steroids have experienced aggressive behaviour and moodswings.
• Cardiovascular disease. The anabolic steroids increase the plasma levels of low density lipoproteins (bad cholesterol) and decrease the levels of high density lipoproteins (good cholesterol). This places the user at a higher risk for cardiovascular disease.

This has been less studied in females than males, but they should have the same effects on performance as in males. In the female, several deleterious effects occur, including an increase in facial and body hair, a lowered voice, enlarged clitoris, and courser skin. Other effects include amenorrhea, increased libido, increased aggression, and acne. These effects may or may not be reversible upon cessation of the drug.

A number of designer steroids have been used by athletes. Drugs such as tetrahydrogetrinone havebeen developed in an attempt to circumvent detection. Marion Jones a US athlete and winner ofseveral gold medals was recently found guilty of using these products. The company (Balco Labs) wasalso found guilty

Propranolol blocks the beta adrenoceptor in the heart and regulates the heart beat. The heart beatbecomes slower and steadier and not influenced by the anxiety of competition. It is used by precisionsports such as shooting; they attempt to pull the trigger between heart beats in order that the heart beatdoes not alter the precision of the shot.

Drugs such as Valium are used to reduce anxiety during competition. These drugs are reportedto be taken by ski jumpers. Presumably they calm the nerves before the jump.

Human growth hormone will increase muscle mass and, in turn, strength. It is probably not as effective as the anabolic steroids, but if used in appropriate doses, gives a response. It is not easily detected as it is cleared by the body rapidly. Thus, an athlete could take growth hormone to build muscle mass, and if the drug was stopped two days before the competition, it would not be detected. Newer techniques are better at detecting the drug a bit longer.

This technique involves collecting the athletes own blood which is infused just before thecompetition. This leads to enhanced hemoglobin concentrations and enhanced oxygen carrying capacity of the blood.

Erythropoietin is a protein hormone that stimulates red blood cell formation. Administration ofthis agent leads to formation of more than the normal amount of red blood cells and to enhanced oxygen carrying capacity of the blood. Darbepoietin, a modified erythropoetin, was the red cellstimulant of choice during the Salt Lake City Olympics.

Diuretics are used to reduce body water to be able to compete at a lower weight class.

• A large number of other drugs are used by athletes to enhance performance or to preventdetection of drug use. Drugs such as probenecid block the urinary excretion of other drugs and thus reduces their levels in the urine to concentrations which may not be detected.
• Caffeine cannot be found in blood in levels that exceed those expected from the ingestion of acouple of cups of coffee. All mild stimulants are banned, including ephedrine.
• Food supplements may contain banned substances. Dehydroepiandrosterone (DHEA) is aprecursors to testosterone and testosterone is the performance enhancer. In Canada, DHEA is a drugand is banned for athletic use.
• Creatine is a protein supplement that is widely used as an agent in body building. The efficacy has not been established but reports suggest a modest benefit in brief high intensity activities.