SUBJECT Paper No. and Title Module No. and Title Module Tag FORENSIC SCIENCE PAPER No. 9: Drugs of Abuse MODULE No. 28: Drug Abuse in Sports FSC_P9_M28
TABLE OF CONTENTS 1. Learning Outcomes 2. Introduction 3. Forensic Issues 4. Classification of Prohibited Substances in Sports 5. Some Notable Drugs used in Sports 6. Analytical Approach to detect Dope Drugs 7. Summary
1. Learning Outcomes After studying this module, you shall be able to know about The commonly use Drugs in sports. Classification and nature of the Drugs used in Sports. The techniques for detection of these drugs. 2. Introduction Drug abuse in sport is habitually called as doping. The universal word dope is being used both as a noun and as a verb. The word does not appear in this context before the twentieth century regardless of the practice of horse nobbling, which was known well before this time. For example, the story of the famous trial of Daniel Dawson, publicly executed at Cambridge in 1812 for poisoning racehorses with arsenic. The abuse of drugs in an attempt to enhance performance in human sporting competitions is not new. For example, the Greek authors Phylostratos and Galen stated on the ethics of participants in the Olympics who would take any preparation to improve their performance. Roman gladiators were often intoxicated to make their fights more vigorous and gruesome as demanded by the spectators. The effect of drugs on performance is often exceptionally difficult to determine, and there is little conclusive available work for any species. The results that have been published are often contradictory as some of the workers advocate an increase in the competitor s performance and others suggest no improvement. The assessment systems used to evaluate the effect of drugs may not sufficiently relate to the appropriate sporting performance, such as increase in muscle strength and sprint running. Moreover, athletes may take far larger amounts of drugs than would be ethically acceptable in most human experiments. The toxic side-effects of drugs are less difficult to ascertain, but the conclusions drawn from the available data are often contingent. However, there is sufficient evidence of the harmful effects when certain drugs are misused to validate their prohibition from sports competitions. In human sports, the main monitoring body is International Olympic Committee (IOC). Nevertheless, since 1999, doping concerns have been taken over by the World Anti-Doping Agency (WADA).
3. Forensic Issues For most substances, the mere presence of the substance or an analytic metabolite in the biological fluid sampled constitutes an offence, but for some substances there is a reporting threshold. If the drug is detected, but it is less than the reporting threshold, no offence is reasoned to have occurred. Multifaceted rules apply to some of the substances, not least because some have therapeutic uses. The obligation is on the athlete to obtain a Therapeutic Use Exemption for certain categories of substances, with the substances covered under this possible exemption made clear in the WADA list. The WADA list also recognizes that some anabolic agents and hormones are produced endogenously. The fundamental rationale is that, an offence is considered to have occurred if one or more of these prohibited substances are detected in an athlete s specimen at a level outside of that which is considered to be the normal range in humans for the substance. For some substances, offences apply both in-competition or out of- competition, whereas for others an offence applies only if the substance is detected in-competition. For some sports, specific classes of substances are prohibited. For example, beta-blockers are prohibited in-competition in sports such as shooting, billiards and gymnastics. Alcohol is prohibited in-competition for sports such as motorcycling, power boating and archery. The emphasis when prohibiting use of a substance is on whether or not the use of a substance or method is proposed to enhance sport performance. The position regarding excessive quantities of normal nutrients is much argued. Although they are not currently included in a prohibited list, there is no hesitation that certain vitamins, notably B1, C and E and also Creatine have been used in large doses with the purpose of affecting performance. 4. Classification of Prohibited Substances in Sports 4.1 Stimulants This group of drugs includes psychomotor stimulants, sympathomimetic amines and other diverse CNS stimulants. They may produce alertness, wakefulness and an increase in the ability to concentrate. In addition they may improve the competence to exercise strenuously or produce a decreased sensitivity to pain. These effects are potentially of benefit to a wide variety of sports involving sustained physical and mental activity.
4.1.1 Amphetamines: Amphetamines are stimulants that include several structurally related drugs dextroamphetamine, methamphetamine, Phenmetrazine, and methyl phenidate. Physicians prescribe these drugs on a short term basis for treatment of obesity and also to treat narcolepsy and minimal brain dysfunction in children. 4.1.2 Cocaine: Cocaine, also a Central Nervous System Stimulant, when snorted, affects the brain within few minutes, the peak effect come within 15 20 minutes. When injected cocaine takes about 15 seconds to affect the brain. The euphoria following cocaine use is in some ways similar to the intense euphoria following an outstanding athletic performance. Both are in part facilitated through the pleasure brain. The individual feels energetic and hyper alert. 4.1.3 Sympathomimetic Amines: Sympathomimetic Amines are group of stimulants of which ephedrine is an example. However, Pseudoephedrine and phenylpropanolamine, which used to be in banned list of WADA is no more in the same category. The ephedrine is also found in low doses in cough, cold and sinus medications. Because these medicines are broadly used by the people as over the counter drugs, they are effortlessly abused by competing athletes for their stimulant effects. Prohibited stimulants: Adrafinil, Adrenaline, Amfepramone, Amphetamine, Amfetaminil, Amiphenazole, Benzfetamine, Benzylpiperazine, Bromantane, Cathine, Clobenzorex, Cocaine, Cropropamide, Crotetamide, Cyclazodone, Dimethylamphetamine, Ephedrine, Etamivan, Etilamphetamine, Etilefrine, Famprofazone, Fenbutrazate, Fencamfamin, Fencamine, Fenetylline, Fenfluramine, Fenproporex, Furfenorex, Heptaminol, P-Hydroxyamphetamine, Isometheptene, Levmethamphetamine, Meclofenoxate, Mefenorex, Mephentermine, Mesocarb, Methylenedioxyamphetamine, Methamphetamine, Methylephedrine, Methylphenidate, Modafinil, Nikethamide, Norfenefrine, Norfenfluramine, Octopamine, Ortetamine, Oxilofrine, Pemoline, Pentetrazol, Phendimetrazine, Phenmetrazine, Phenpromethamine, Phentermine, 4- Phenylpiracetam, Prolintane, Propylhexedrine, Selegiline, Sibutramine, Strychnine, Tuaminoheptane and other substances with a similar chemical structure or similar biological effect(s).
4.2 Narcotics Analgesics Narcotics are derivatives of Opium and consist of powerful painkiller drugs. Narcotics are not perceived as ergogenic drug. However, their use, misuse and abuse potential in sports may be high because of pressures on the athlete to perform competitively despite varied musculo-skeletal injuries. The pressure on the athletes to perform well is so intense that they sometimes turn to narcotics as an emotional escape. These drugs are banned so as to decrease the risk of tragic conditions. Prohibited Narcotics analgesics: Buprenorphine, Dextromoramide, Diamorphine (Heroin), Fentanyl and its derivatives, Hydromorphone, Methadone, Morphine, Oxycodone, Oxymorphone, Pentazocine, Pethidine 4.3 Anabolic Steroids Anabolic steroids are synthetic derivatives of the natural male hormones Testosterone, which is produced principally by testes in males and is responsible for androgenic (masculinizing) and anabolic (tissue- building) effects. The abuse of anabolic steroids has historic foundations in man s aspiration to create a body building wonder drug. This group of drugs is responsible for the most pervasive abuse of drugs in sports. In human sport, anabolic steroids are used as bodybuilding drugs, occasionally in very large quantities, in events such as weightlifting and shot-putting. There are generally two chemical types based upon the androstane and estrane ring systems: those with a 17α-alkyl group, which are active orally but possess hepatotoxicity, and 19-nor derivatives administered by injection. Although steroidal estrogens and some stilbenes reputedly possess anabolic activity and are engaged in beef production, they do not appear to be used as doping agents. Anabolic Steroids reverse the negative or catabolic effects of exercise have on muscle. During exercise the adrenal glands naturally secrete glucocorticoids that induce muscle breakdown. Anabolic Steroids minimize this catabolism and thus build muscles.
4.3.1 Exogenous Anabolic Agents: Androstenediol, Androstenedione, Bolandiol, Bolasterone, Boldenone, Boldione, Calusterone, Clostebol, Danazol, Dehydrochlormethyltestosterone, Desoxymethyltestosterone, Drostanolone, Ethylestrenol, Fluoxymesterone, Formebolone, Furazabol, Gestrinone, 4- Hydroxytestosterone, Mestanolone, Mesterolone, Metenolone, Metandienone, Methandriol, Methasterone, Methyldienolone, Methyl-1-Testosterone, Methylnortestosterone, Methyltrienolone, Methyltestosterone, Mibolerone, Nandrolone, 19-Norandrostenedione, Norboletone, Norclostebol, Norethandrolone, Oxabolone, Oxandrolone, Oxymesterone, Oxymetholone, Prostanozol, Quinbolone, Stanozolol, Stenbolone, 1-Testosterone, Tetrahydrogestrinone, Trenbolone and other substances with a similar chemical structure or similar biological effect(s) 4.3.2 Endogenous anabolic agents: Androstenediol, androstenedione, Dihydrotestosterone, Prasterone, Testosterone and metabolites and isomers 4.3.3 Other anabolic agents: Clenbuterol, Selective Androgen Receptor Modulators (SARMs), Tibolone, Zeranol, Zilpaterol 4.4 Masking agents & Diuretics Masking agents are the products that have a potential to impair the excretion of prohibited substances, to conceal their presence in urine or other samples used in doping control, or to change hematological parameters and Diuretics are one of them. Diuretics are the drugs that increase the rate of urine formation. In general, the diuretics act directly on the kidney tubules to yield the desired clinical effects. Clinically, diuretics are used to control hypertension, to reduce oedema and as an adjunct in treating congestive heart failure. Athletes use diuretics for acute reduction of weight to meet weight limits in weight categories to gain advantage in sports like boxing, judo or weightlifting, etc. Prohibited Diuretics: Acetazolamide, Amiloride, Bumetanide, Canrenone, Chlortalidone, Etacrynic Acid, Furosemide, Indapamide, Metolazone, Spironolactone, Thiazides, Triamterene and other substances with a similar chemical structure or similar biological effect(s), Epitestosterone, Probenecid, Alpha-Reductase inhibitors, plasma expanders and other substances with similar biological effect.
4.5 Hormones and related substances There has been significant apprehension in recent years over the use of peptide hormones such as Erythropoietin (EPO) and darbepoietin. Athletes recognized the potential for Erythropoietin to increase erythrocyte production and hence oxygen uptake. Human Chorionic Gonadotropin (hcg) is a glycoprotein hormone produced in the body, particularly during pregnancy. Administration of hcg stimulates testosterone production but does not raise the testosterone/ epitestosterone ratio. Peptide hormones act as messengers from one organ to another to stimulate growth, influence sex drive and behaviour. Prohibited Hormones and related Substances: Corticotrophins (ACTH), Erythropoietin (EPO), Human Chorionic Gonadotropin (hcg), Human Growth Hormone (hgh), Insulins, Insulin-Like Growth Factors (e.g. IGF-1), Mechano Growth Factors (MGFs), Luteinising Hormone (LH), Anti-Estrogenic Substances, aromatase inhibitors, Selective Estrogen Receptor Modulators (SERMs), agents modifying myostatin function(s). 4.6 Beta- Blockers Beta Blockers or Beta- 2 Antagonists as well as their dextro and levo isomers are prohibited. Their use entails a therapeutic use exemption. As an exception, Formoterol, Salbutamol, Salmetarol and Terbutaline when administered by inhalation to prevent or treat asthma and exercise induced asthma describes an abbreviated Therapeutic use exemption. A beta antagonist increases skeletal muscle mass, lipolysis, decreases fat deposition and thereby increasing lean body mass. They also increase non shivering thermogenesis via Beta receptors in brown adipose tissue. Prohibited Beta Blockers: Acebutolol, Alprenolol, Atenolol, Betaxolol, Bisoprolol, Bunolol, Carteolol, Carvedilol, Celiprolol, Esmolol, Labetalol, Levobunolol, Metipranolol, Metoprolol, Nadolol, Oxprenolol, Pindolol, Propranolol, Sotalol, Timolol and related compounds.
5. Some Notable Drugs used in Sports 5.1 Nandrolone Nandrolone is an anabolic steroid. Anabolic steroids are natural or synthetic versions of testosterone, a hormone that is produced naturally in males and, to a lesser extent, in females. Anabolic steroids are used in combination with appropriate diet and moderate exercise to promote a gain of protein in the body and to increase lean body mass (including muscle tissue). Nandrolone Nandrolone increases production and urinary excretion of erythropoietin. It may also have a direct action on bone marrow. Nandrolone binds to the androgen receptor to a greater degree than testosterone, but due to its inability to act on the muscle in ways unmediated by the receptor, has less overall effect on muscle growth.
5.2 Dehydroepiandrsterone (DHEA) Dehydroepiandrsterone (DHEA) is a steroid hormone secreted in greater quantity by the adrenal glands. It is released when adrenal cortex gets a message from Adrenocorticotropic hormone (ACTH). ACTH is released by the pituitary gland of the brain. Dehydroepiandrsterone (DHEA) DHEA is a week androgen that circulates in two inter convertible forms unconjugated Dehydroepiandrsterone (DHEA) and Dehydroepiandrsterone Sulphate (DHEAS). Athlete use DHEA for several reasons, like as an anti- catabolic agent to increase levels of androgens such as androstenediol and testosterone. It is challenging to detect because DHEA is a precursor in testosterone formation. It would increase the concentration of both testosterone and epitestosterone 5.3 Human Growth Hormone (hgh) Human Growth Hormone (hgh) is a hormone that is synthesized and secreted by cells in the pituitary gland located at the base of the brain. hgh is known to act on many aspects of cellular metabolism and is also essential for skeletal growth in humans.
The reason for hgh abuse appears to be based in deceitful promises that it is as effective as anabolic steroids, with fewer side effects, is less possible to be detected and may protect the athlete who has abused anabolic steroid and wishes to stop muscle meltdown. Commonly, hgh is abused in sports to increase muscle mass and strength, to increase slender body mass, to improve the appearance of musculature and to increase final adult height. 5.4 Erythropoietin Erythropoietin (EPO) is a glycoprotein produces by the kidney that functions to regulate Red Blood Corpuscles (RBC) production. This glycoprotein has a half- life of 6-8 hours. Approximately, 90% of Erythropoietin is synthesized in the renal cortical cells, whereas, the rest is synthesized in extrarenal sites, mainly liver. Erythropoietin is now potentially available in mass quantities through the process of genetic engineering. Experts speculate that the potential use and abuse of erythropoietin may be vast. Erythropoietin and Recombinant Erythropoietin (r-epo) is used precisely by endurance athletes to increase aerobic endurance with effects similar to that of blood doping. Erythropoietin is a major factor in the stimulation, proliferation and maturation of the bone marrow stem cell, which in turn increases rate of RBC production. 5.5 Gonadotrophins Human chorionic gonadotropin (hcg) is a glycoprotein hormone produced in the body by placental trophoblast cells, chiefly during pregnancy. Administration of hcg stimulates testosterone production but does not increase the testosterone/ epitestosterone ratio. Initially, this made hcg administration challenging to detect, but methods of detection have now been developed for use in human sports drug testing. Its major physiological role is stimulation of corpus luteum, to maintain synthesis and secretion of hormone progesterone during pregnancy. Abuse of hcg has become popular because it stimulates secretion of both testosterone and epitestosterone resulting in urinary excretion ratio set by WADA.
5.6 Androstenedione More recently, scientists involved in doping in sports have noted the use of so-called prohormones. An example is the use of Androstenedione, which has been promoted to body builders in dietary supplements and claimed to have an anabolic effect. Androstenedione or Andro is a hormone produced by the adrenal glands, ovaries and testes. It is a hormone that is normally converted to testosterone and estradiol in both men and women. Androstenedione is accessible legally only in prescription form, and is a controlled substance. Manufacturers and bodybuilding magazines peddle its ability to allow athletes to train harder and recuperate more rapidly. However, its use as a performance-enhancing drug is illegal. Serum concentrations of estrogen in men can increase with androstenedione administration, giving rise to an increased risk of gynaecomastia. 6. Analytical Approach to detect Dope Drugs Dope is generally administered at or proximate the therapeutic dose, which results in relatively low concentrations in biological fluids. Consequently, screening procedures must be both sensitive and comprehensive. Generally, the screening procedures depend upon the detection of either the unchanged drug or its metabolites. The identification of the corresponding metabolites is often advantageous supplementary evidence to support the identification of the parent drug. Instrumental methods Gas Chromatography using Nitrogen Phosphorus Detection (GC- NPD), High Performance Liquid Chromatography using Ultraviolet Detection (HPLC- UV), Gas Chromatography- Mass Spectroscopy (GC- MS) and Liquid Chromatography- Mass Spectroscopy (LC-MS) are the predominant analytical methods in most human sports drug-testing laboratories. Even if not routinely used for screening, some kind of TLC technology is sporadically used by many laboratories to isolate or purify a compound of interest followed by the analysis of the scrape from the TLC plate by GC- MS, LC-MS, etc.
7. Summary The usage of performance enhancing drugs is banned in sports. However, physical exercise and exertion impose upon the body an increased demand of nutrients and oxygen. The body can meet the demand only upto a certain level beyond which exhaustion sets in. A sports person needs to keep himself vigorous, energetic, full of vitality and endurance. To achieve all this, some sports persons resort to pills and injections as shortcuts to success. According to International Olympic Committee (IOC), Doping is the administration of or use by a contending athlete of any substance foreign to the body or any physiological substance taken in abnormal quantity or taken by an abnormal route of entry into a body with a sole purpose for increasing in an artificial and unfair manner his performance in competition. Dope testing in Olympics began in 1968, but till 1983, drug testing and detection in international competitions were very ineffective, due to non- availability of standard technology. The World Anti-Doping Code International Standard for Testing pronounces the procedure for sample collection. The two matrices specified for testing are Urine and Blood. Urine is the preferred body fluid in all species. Its collection is non-invasive; it is generally available in sufficient quantity; and the drugs or their metabolites tend to be present in relatively high concentrations. The disadvantages are that a drug may be present as its metabolites or in a conjugated form, and the parent drug may be present only in a relatively low concentration. Drug concentrations in blood are interpreted more effortlessly than those in urine, and certain drugs that are not excreted in urine in detectable quantities (e.g. reserpine, or Human Growth Hormone) can be detected in blood.