1. Performance Enhancing Drugs Kristin Zenker Revised by Corey Behrens: 3/07 CBE 555

2. Overview History History Types Types Methods and Function Methods and Function Regulation Regulation Availability Availability Questions? Questions?

3. History Stories date back thousands of years to Ancient Olympic games Stories date back thousands of years to Ancient Olympic games Ground horse hooves and sheep testicles Ground horse hooves and sheep testicles In Chinese traditional medicine to bolster male body. In Chinese traditional medicine to bolster male body. deer antler deer antler tiger bone tiger bone bear gall bladder bear gall bladder ginseng and other roots ginseng and other roots Athletes in Late 19 th /Early 20 th century Athletes in Late 19 th /Early 20 th century Caffeine and strychnine Caffeine and strychnine Dutch cyclist death in 1960 Olympic game Dutch cyclist death in 1960 Olympic game International Olympic Committee came out with first list of prohibited drugs. International Olympic Committee came out with first list of prohibited drugs.

4. Types Steroids (Anabolic-Androgenic and THG) Steroids (Anabolic-Androgenic and THG) Blood Boosting Enhancers Blood Boosting Enhancers Erythropoietin (EPO) Erythropoietin (EPO) Transfusions Transfusions Autologous Autologous Homologous Homologous Health Supplements Health Supplements Androstenedione Androstenedione Creatine Creatine Human Growth Hormone (hGH) Human Growth Hormone (hGH) Stimulants Stimulants Amphetamines Amphetamines Ephedra Ephedra

5. Steroids Lipid produced naturally by the human body Lipid produced naturally by the human body Testosterone Testosterone Estrogen Estrogen Progesterone Progesterone Cholesterol Cholesterol Synthetic steroids Synthetic steroids “Anabolic” “Anabolic” Greek : “to build up” Greek : “to build up” “Anabolic-Androgenic” “Anabolic-Androgenic” Greek: “masculine, masculinity” Greek: “masculine, masculinity”

6. Steroids - History First produced in late 1930’s First produced in late 1930’s hypogandism (testosterone deficiency) hypogandism (testosterone deficiency) Commonly prescribed for medical reasons Commonly prescribed for medical reasons Prevent loss of bone density Prevent loss of bone density osteoporosis osteoporosis Counter-acting body-wasting effects of HIV/AIDS Counter-acting body-wasting effects of HIV/AIDS 30% HIV infected men, 50% men with AIDS are hypoganadal 30% HIV infected men, 50% men with AIDS are hypoganadal Late 1950’s, weightlifters discovered the athletic benefits Late 1950’s, weightlifters discovered the athletic benefits 1991 – Congress adds anabolic steroids to U.S. Schedule III of the Controlled Substances Act (CSA) 1991 – Congress adds anabolic steroids to U.S. Schedule III of the Controlled Substances Act (CSA) Used at least once in lifetime: Used at least once in lifetime: 2.5 percent of 8th graders 2.5 percent of 8th graders 3.0 percent of 10th graders 3.0 percent of 10th graders 3.5 percent of 12th graders 3.5 percent of 12th graders

7. Steroids – How do they work? Taken by injection or in pill form Taken by injection or in pill form Stimulates certain proteins involved in the building of muscle tissue Stimulates certain proteins involved in the building of muscle tissue Results in fat free muscle mass Results in fat free muscle mass Blocks action of bodily chemicals that signal muscle fatigue Blocks action of bodily chemicals that signal muscle fatigue “Cycling” and “Stacking” “Cycling” and “Stacking” Cycling: period of 6-14 weeks of steroid use, then reduction Cycling: period of 6-14 weeks of steroid use, then reduction Stacking: multiple drugs concurrently Stacking: multiple drugs concurrently

8. Steroids – Side Effects Liver tumors and cancer Liver tumors and cancer Jaundice Jaundice Fluid retention Fluid retention High Blood Pressure High Blood Pressure Increase in LDL, decrease in HDL Increase in LDL, decrease in HDL Elevated risk of heart attack and stroke Elevated risk of heart attack and stroke Kidney tumors Kidney tumors Severe acne Severe acne

9. Steroids –Side Effects, cont’d Differing side-effects by gender Differing side-effects by gender Men Men increased breast size increased breast size shrinkage of testicles shrinkage of testicles Baldness Baldness reduced sperm count reduced sperm count possible impotence possible impotence Women Women development of masculine features development of masculine features facial hair facial hair deepening of the voice deepening of the voice reproductive abnormalities reproductive abnormalities Emotional – increase in aggressive behavior, “roid rage” Emotional – increase in aggressive behavior, “roid rage” Depression/Withdrawal symptoms from addiction Depression/Withdrawal symptoms from addiction

10. Tetrahydrogestrinone (THG) Oct 16, 2003 – US Anti-Doping Agency discloses existence, not FDA approved Oct 16, 2003 – US Anti-Doping Agency discloses existence, not FDA approved Performance Factors: Performance Factors: In-competition strength In-competition strength Recovery from rigorous training/fatigue Recovery from rigorous training/fatigue Steroid Alternative Steroid Alternative gestrinone gestrinone trenbolone trenbolone “Designer” steroid “Designer” steroid Manipulated by chemists Manipulated by chemists Previously undetectable Previously undetectable Bay Area Lab Co-operative (BALCO Scandal) Bay Area Lab Co-operative (BALCO Scandal) 2003 - Four US Track and Field Athletes 2003 - Four US Track and Field Athletes

11. Erythropoietin (EPO) Glycoprotein Hormone (protein w/ sugar attached) Glycoprotein Hormone (protein w/ sugar attached) Signal compound for production of red blood cells Signal compound for production of red blood cells MW: 30,000 amu MW: 30,000 amu 165 Amino acid chain 165 Amino acid chain 4 Oligosaccharide side chains 4 Oligosaccharide side chains In blood plasma (Conc: 5 pmol/L) In blood plasma (Conc: 5 pmol/L) Produced in kidneys, some in liver Produced in kidneys, some in liver Prod. Stimulated by low O 2 levels in blood (hypoxia) Prod. Stimulated by low O 2 levels in blood (hypoxia) Function Function Binds to receptor on red blood cell precursor in bone marrow Binds to receptor on red blood cell precursor in bone marrow Transform precursor to mature cell Transform precursor to mature cell Source: Source: Initially isolated from human urine 1977 Initially isolated from human urine 1977 r-HuEPO (synthetic) from animal recombinant DNA techn. r-HuEPO (synthetic) from animal recombinant DNA techn.

12. EPO Medical Applications Medical Applications Anemia Anemia Chronic renal failure Chronic renal failure Cancer chemotherapy Cancer chemotherapy Blood transfusion Blood transfusion Surgery with excessive blood loss Surgery with excessive blood loss Polycythemia Polycythemia Excess of red blood cells Excess of red blood cells Methods Methods intravenous intravenous Side-effects Side-effects Fever Fever Blood clots Blood clots Headache, Nausea, Vomiting, Delirium Headache, Nausea, Vomiting, Delirium Cardiovascular complications Cardiovascular complications

13. EPO Abuse Abuse among endurance sports Abuse among endurance sports Cycling Cycling Triathlons Triathlons Marathons Marathons Available starting in late 1980’s Available starting in late 1980’s No detection methods No detection methods Dosing Dosing 3 injections per week for six weeks. 3 injections per week for six weeks. Vials contain varying concentrations Vials contain varying concentrations doses are likely to vary considerably doses are likely to vary considerably Competitive Advantages Competitive Advantages Increase oxygen carrying capacity of blood Increase oxygen carrying capacity of blood offset the decrease in red blood cells that occurs over several weeks of racing offset the decrease in red blood cells that occurs over several weeks of racing

14. EPO Abuse cont’d Complications Complications Extreme overuse leads to thickening of blood Extreme overuse leads to thickening of blood Paired with increased blood viscosity from exercise related dehydration Paired with increased blood viscosity from exercise related dehydration Strains the heart, especially during sleep (i.e. low heart rate) Strains the heart, especially during sleep (i.e. low heart rate) Excessive increase in heamatocrit detrimental to O 2 capacity Excessive increase in heamatocrit detrimental to O 2 capacity Low flow rate, not deliverable Low flow rate, not deliverable Symptons akin to chronic altitude sickness Symptons akin to chronic altitude sickness Detection Detection Animal (synthetic) vs. endogenous residue Animal (synthetic) vs. endogenous residue Difficult because short half-life (5-6 hours) Difficult because short half-life (5-6 hours) Detection in blood and/or urine Detection in blood and/or urine Reliability heavily disputed Reliability heavily disputed

15. Health Supplements OTC health supplements OTC health supplements Common Common Readily available Readily available Not regulated by the FDA Not regulated by the FDA Examples Examples Androstenedione Androstenedione Creatine Creatine SOBE Adrenaline Rush: Sugar Free SOBE Adrenaline Rush: Sugar Free

16. Androstenedione (Andro) Initially categorized as a testosterone precursor Initially categorized as a testosterone precursor chemical from which body synthesizes testosterone chemical from which body synthesizes testosterone NFL banned in 1997 NFL banned in 1997 Mark McGwire admitted to using in 1998 when he set the HR record for most in one-season Mark McGwire admitted to using in 1998 when he set the HR record for most in one-season FDA reclassified as a steroid in 2004 FDA reclassified as a steroid in 2004

17. Androstenedione – Side Effects Gender differences Gender differences Men Men decrease in testosterone prod. decrease in testosterone prod. increase in estrogen production increase in estrogen production Acnes Acnes decreased sperm count decreased sperm count Women Women Acne Acne masculinity masculinity

18. Creatine Occurs naturally in the body in skeletal muscle Occurs naturally in the body in skeletal muscle Helps to supply energy to muscle cells Helps to supply energy to muscle cells Made in the liver from 3 amino acids Made in the liver from 3 amino acids Glycine Glycine Arginine Arginine Methionine Methionine When taken as a nutritional supplement, increases the body’s supply of adenosine triphosphate (ATP) When taken as a nutritional supplement, increases the body’s supply of adenosine triphosphate (ATP)

19. ATP and Creatine

20. Creatine – History Usage documented back to the early 20 th century Publicity after 1992 Olympics Linford Christie (gold metal 100 m dash), Sally Gunnel (gold metal 400 m hurdles), Britain’s rowing team At time, low potency dosage supplements available in UK 1993 – Company Experimental Applied Sciences (EAS) introduced compound to sports nutrition market under Phosphagen label

21. Creatine – What does it do? Can be taken in as a powder mixed into a drink or as a pill Can be taken in as a powder mixed into a drink or as a pill Creatine changed into molecule called “phosphocreatine” – reservoir for energy Creatine changed into molecule called “phosphocreatine” – reservoir for energy During intense exercise, broken down into creatine and phosphate During intense exercise, broken down into creatine and phosphate Energy released is used to regenerate ATP Energy released is used to regenerate ATP Bigger storage of phosphocreatine in muscles reduces fatigue Bigger storage of phosphocreatine in muscles reduces fatigue

22. Creatine Some studies suggest that… creatine provides a boost for short bursts of maximal effort creatine provides a boost for short bursts of maximal effort Helps with anaerobic exercise, no significant effect for aerobic exercise Helps with anaerobic exercise, no significant effect for aerobic exercise Ingesting creatine can increase the level of phosphocreatine in the muscle by 20% Ingesting creatine can increase the level of phosphocreatine in the muscle by 20% Increases in both total and fat free body mass Increases in both total and fat free body mass Buffer the lactic acid produced during anaerobic work outs Buffer the lactic acid produced during anaerobic work outs

23. Human Growth Hormone (hGH) Naturally produced in the body – synthesized in the pituitary gland Naturally produced in the body – synthesized in the pituitary gland Synthetic version of hGH originally marketed in the 1980’s to treat kids with stunted growth Synthetic version of hGH originally marketed in the 1980’s to treat kids with stunted growth Recent years promoted as anti-aging from drug companies Recent years promoted as anti-aging from drug companies Currently banned by the governing bodies of major sports, including the Olympics Currently banned by the governing bodies of major sports, including the Olympics

24. hGH – How does it work? Influences a variety of metabolic process involving carbohydrates, proteins, and fatty tissues Influences a variety of metabolic process involving carbohydrates, proteins, and fatty tissues Stimulates the body’s synthesis of the proteins that form bone and muscle tissue Stimulates the body’s synthesis of the proteins that form bone and muscle tissue Stimulates collagen – necessary for strengthening cartilage, bones, tendons, and ligaments Stimulates collagen – necessary for strengthening cartilage, bones, tendons, and ligaments Increases testosterone levels Increases testosterone levels Stimulates the liver to produce growth factors Stimulates the liver to produce growth factors

25. hGH – Side Effects Abnormal growth of facial hair and skeletal features, liver problems, irregularities in the processing of insulin, and heart disease Abnormal growth of facial hair and skeletal features, liver problems, irregularities in the processing of insulin, and heart disease If taken before or during puberty – leads to gigantism If taken before or during puberty – leads to gigantism Taken excessively as an adult – leads to diabetes Taken excessively as an adult – leads to diabetes

26. Stimulants – In General Athletes use to provide a boost in energy and alertness Athletes use to provide a boost in energy and alertness Caffeine and Cocaine are 2 well known stimulants Caffeine and Cocaine are 2 well known stimulants Affect the nervous system – causes temporary increase in the heart rate and blood pressure Affect the nervous system – causes temporary increase in the heart rate and blood pressure Negative effects – heart attack, stroke, hypertension, agitation, physical addiction, sudden cardiac death Negative effects – heart attack, stroke, hypertension, agitation, physical addiction, sudden cardiac death World Anti-Doping Agency (WADA) has a list of banned substances – includes more than 40 stimulants World Anti-Doping Agency (WADA) has a list of banned substances – includes more than 40 stimulants

27. Stimulants Commonly Used by Athletes Amphetamines “speed” “crank” Amphetamines “speed” “crank” Used by cyclists and baseball players since 19 th century Used by cyclists and baseball players since 19 th century Stimulant used to diminish the appetite, control weight, and treat disorders including narcolepsy and ADD Stimulant used to diminish the appetite, control weight, and treat disorders including narcolepsy and ADD Releases stores of norepinephrine and dopamine from nerve endings Releases stores of norepinephrine and dopamine from nerve endings Prevents the transporters of norepinephrine and dopamine from recycling them Prevents the transporters of norepinephrine and dopamine from recycling them Increases the concentration of the respective neurotransmitters – promotes nerve impulse transmission Increases the concentration of the respective neurotransmitters – promotes nerve impulse transmission

28. Stimulants, con’t Side Effects of Amphetamines Physiological Physiological Short term – decreased appetite, increased stamina and energy, nausea, irregular heart beat, jitteriness Short term – decreased appetite, increased stamina and energy, nausea, irregular heart beat, jitteriness Long term – tremors, restlessness, anxiety, weakened immune system Long term – tremors, restlessness, anxiety, weakened immune system Psychological Psychological Short term – alertness, euphoria, increased concentration, rapid talking Short term – alertness, euphoria, increased concentration, rapid talking Long term – Insomnia, schizophrenia, aggressiveness, addiction, paranoia Long term – Insomnia, schizophrenia, aggressiveness, addiction, paranoia

29. Stimulants, con’t Methylphendate “ritalin” and Modafinil Methylphendate “ritalin” and Modafinil Very similar to amphetamines Very similar to amphetamines Ephedra Ephedra Derived from a plant that contains the chemical ephedrine – stimulant similar to amphetamines Derived from a plant that contains the chemical ephedrine – stimulant similar to amphetamines Increases the metabolic burning of fatty tissues Increases the metabolic burning of fatty tissues Popular weight loss drug in late 1990’s early 2000’s Popular weight loss drug in late 1990’s early 2000’s Stimulant effects the nervous system to enhance performance and help with activities of longer duration Stimulant effects the nervous system to enhance performance and help with activities of longer duration

30. Stimulants, con’t Ephedra, con’t Ephedra, con’t Late 2003, FDA announced ban of ephedra from the marketplace because of health concerns Late 2003, FDA announced ban of ephedra from the marketplace because of health concerns Generated thousands of complaints and linked to more than 150 deaths in the US Generated thousands of complaints and linked to more than 150 deaths in the US Pulled off the market Pulled off the market Side Effects Side Effects Strokes, seizures, heart attacks, death, raise in blood sugar, irregular heart rhythm Strokes, seizures, heart attacks, death, raise in blood sugar, irregular heart rhythm

31. Regulation Sports rules and regulations vary by level and league Sports rules and regulations vary by level and league 3 most popular professional leagues – NFL, NBA, MLB all have different drug policies 3 most popular professional leagues – NFL, NBA, MLB all have different drug policies Most prominent effort to make uniform drug policies – 1999 IOC created WADA Most prominent effort to make uniform drug policies – 1999 IOC created WADA Coordinated and administered extensive drug testing of athletes in the different Olympic sports Coordinated and administered extensive drug testing of athletes in the different Olympic sports WADA published a list of hundreds of banned drugs WADA published a list of hundreds of banned drugs Violators face heavy penalties Violators face heavy penalties

32. Availability of PED Steroids Steroids 1990’s most US producers stopped making and marketing anabolic steroids within the US 1990’s most US producers stopped making and marketing anabolic steroids within the US Eastern Europe still producing steroids in quantity Eastern Europe still producing steroids in quantity European anabolic steroids are the source of most medical grade steroids sold in the US European anabolic steroids are the source of most medical grade steroids sold in the US Creatine, Ephedra, hGH Creatine, Ephedra, hGH Found websites that it is possible to purchase Found websites that it is possible to purchase

33. Availability

34. References http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookATP.html http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookATP.html http://www.emc.maricopa.edu/faculty/farabee/biobk/BioBookATP.html http://www.nida.nih.gov/Infofacts/Steroids.html http://www.nida.nih.gov/Infofacts/Steroids.html http://www.nida.nih.gov/Infofacts/Steroids.html http://www.drugabuse.gov/ResearchReports/Steroids/anabolicsteroids2.ht ml#anchor http://www.drugabuse.gov/ResearchReports/Steroids/anabolicsteroids2.ht ml#anchor http://www.drugabuse.gov/ResearchReports/Steroids/anabolicsteroids2.ht ml#anchor http://www.drugabuse.gov/ResearchReports/Steroids/anabolicsteroids2.ht ml#anchor http://en.wikipedia.org/wiki/Steroid http://en.wikipedia.org/wiki/Steroid http://en.wikipedia.org/wiki/Steroid http://www.mayoclinic.com/health/performance-enhancing- drugs/SM00045 http://www.mayoclinic.com/health/performance-enhancing- drugs/SM00045 http://www.mayoclinic.com/health/performance-enhancing- drugs/SM00045 http://www.mayoclinic.com/health/performance-enhancing- drugs/SM00045 http://encarta.msn.com/encyclopedia_701765667/Performance- Enhancing_Drugs.html http://encarta.msn.com/encyclopedia_701765667/Performance- Enhancing_Drugs.html http://encarta.msn.com/encyclopedia_701765667/Performance- Enhancing_Drugs.html http://encarta.msn.com/encyclopedia_701765667/Performance- Enhancing_Drugs.html http://en.wikipedia.org/wiki/Creatine http://en.wikipedia.org/wiki/Creatine http://en.wikipedia.org/wiki/Creatine http://en.wikipedia.org/wiki/Amphetamine http://en.wikipedia.org/wiki/Amphetamine http://en.wikipedia.org/wiki/Amphetamine http://en.wikipedia.org/wiki/Anabolic_steroid http://en.wikipedia.org/wiki/Anabolic_steroid http://en.wikipedia.org/wiki/Anabolic_steroid http://www.4-men.org/steroids/thg.html http://www.4-men.org/steroids/thg.html http://www.4-men.org/steroids/thg.html Kennedy, Michael. “Newer drugs to enhance sporting performance.” Medical Journal of Australia. 173 (6): 314-317 SEP 18 2000 Kennedy, Michael. “Newer drugs to enhance sporting performance.” Medical Journal of Australia. 173 (6): 314-317 SEP 18 2000 http://www.medterms.com/script/main/art.asp?articlekey=7032 http://www.medterms.com/script/main/art.asp?articlekey=7032 http://www.medterms.com/script/main/art.asp?articlekey=7032 http://www.usdoj.gov/dea/pubs/abuse/10-steroids.htm http://www.usdoj.gov/dea/pubs/abuse/10-steroids.htm http://www.usdoj.gov/dea/pubs/abuse/10-steroids.htm

35. Performance Enhancing Drugs Questions???? Questions????