drug abuse among athletes

Drug abuse among athletes

Rome Games of 1960Knud Enemark JensenAmphetamine

1904 GamesThomas HicksStrychnine

S. Parasuraman M.Pharm., Ph.D.,Senior Lecturer, Faculty of Pharmacy,

AIMST University, Bedong 08100, Malaysia.

Drug abuse among athletes• The misuse of drugs and medicines by athletes has been a

problem for more than 30 years.• Doping is considered to have occurred when substances

belonging to prohibited classes of pharmacological agents are administered, or when prohibited methods are used.

• Doping (DOP referred to an alcoholic drink used in South Africa) is not a new phenomenon. Ancient Greek athletes tried to enhance performance by ingestion of alcoholic drinks and sheep testicles.

Athletes take drugs

By purpose

Accidentally

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Why do performers take drugs by sports man or women?

Physiological reasons– Increase oxygen transport– To build muscle, increase

energy– Mask injury and reduce

tiredness– Lose weight, train harder– To increase motivation– To steady nerves– To increase aggression

Social reasons– They are prepared to win at all

costs

– Belief that everyone else is doing it

– Pressure to win from coaches, peers and the media

– By winning they can earn big money

– Fear of not winning

• At the end of 19th century, athletes experimented with cocaine, heroin, and strychnine.

• In the 1904, Thomas Hicks nearly died using strychnine in combination with brandy during a bicycle race.

• Nowadays health and sports ethics have become a major concern of the medical committee of the International Olympic Commission (IOC).

• The medical committee of the IOC has created a list of forbidden substances and prohibited methods, that are included in the IOC’s medical code.

• Doping control is performed by a network of IOC accredited laboratories, which analyze urine samples collected after or out of competition.


• “World Anti-Doping Agency” (WADA) was created in 1999 at Lausanne (Switzerland) ‘The World Anti-Doping Conference’

• Objective of the WADA is to produce a World anti-doping code (Code) and to harmonize the fight against doping around the world.

Drug abuse among athletes“World Anti-Doping Agency”

• The anti-doping Code works in conjunction with four International Standards aimed at harmonization among anti-doping organizations:– Prohibited list of substances and methods– International standards for testing– International standards for laboratories– Therapeutic use exemptions (TUES)


Prohibited Substance Classes• The Prohibited List was first published in 1963 under the

leadership of the International Olympic Committee. Since 2004, it had been updated and published by the WADA.

• It lists substances and methods prohibited in and out of competition, as well as substances prohibited for particular disciplines.

1. Anabolic Agents:– Anabolic Androgenic Steroids (AAS), e.g., testosterone,

nandrolone, methandienone, stanozolol, etc.– Other anabolic agents, e.g., Clenbuterol

Prohibited Substance Classes2. Hormones and related substances:

– Erythropoietin (EPO)– Growth hormone (GH), insulin-like growth factor (IGF-1), mechano

growth factors (MGFs)– Gonadotrophins (LH, HCG)– Insulin– Corticotrophins

3. Beta2 agonists4. Agents with anti-estrogenic activity

– Aromatase inhibitors, including anastrazole, letrozole, etc.– Selective estrogen receptor modulators (SERMs), including tamoxifène,

toremifene, etc.– Other anti-estrogenic substances, including clomiphene, cyclofenyl, etc.

Prohibited Substance Classes5. Diuretics and other masking agents– Masking agents, including epitestosterone, probenecid,

plasma expanders.– Diuretics, including acetazolamide, furosemide, etc.

6. Stimulants– Examples: Amphetamine, ethylefrine, modafinil, ephedrine,

cathine, methylephedrine, etc.7. Narcotics– Examples: Buprenorphine, fentanyl, methadone, etc.

8. Cannabinoids9. Glucocorticoids10. Alcohol and Beta-blockers are prohibited in some specific

sports

Prohibited Methods1. Enhancement of oxygen transfer

– Blood doping, (homologous or autologous blood transfusion)

E.g.: PFCs (perfluorocarbons), modified hemoglobins, ect. The

oxygen capacity of blood increases on the addition of PFC

emulsion

– Artificial transport of oxygen

2. Chemical and physical manipulation

– Tampering with the sample

– Intravenous infusions

3. Gene doping

Testing Methods• International Standards for Testing

– The purpose of the International Standards for Testing is to plan for effective testing and to maintain the integrity and identity of samples throughout the testing process, from notifying the athlete to transport of the samples for analysis.

• International Standard for Laboratories– The purpose of the International Standard for Laboratories (ISL) is to

ensure production of valid test results and evidentiary data, and to achieve uniform and harmonized results and reporting from all accredited laboratories.

– In 2009 there were 35 WADA-accredited laboratories, conducting a combined total of 277,928 analyses. A total of 5,610 samples - or 2.02% of the complete sample - produced either “adverse” or “atypical” findings.

International Standard for Therapeutic Use Exemptions (TUE)

• The purpose of the International Standard for TUE is to ensure that the process of granting TUEs is harmonized across sports and countries all over the world.

• Athletes, like all others, may have illnesses or conditions that require them to take particular medications. If the medication happens to fall under the Prohibited List, a TUE authorizes the athlete to take the needed drug.

• criteria to grant a TUE are– The athlete would experience significant health problems

without taking up the prohibited substance or method.– The therapeutic use of the substance would not produce

significant enhancement of performance– There is no reasonable therapeutic alternative to the use of

the prohibited substance or method

Widely abused agents/ Commonly used agents or drugs

• Steroids – Anabolic steroids are harm if athletes consuming them

– Prevention of testosterone abuse is particularly difficult because it is identical to testosterone produced by the body.

– Most oral-anabolic-androgenic steroids (AAS) preparations are 17- β alkylated derivatives of testosterone that are resistant to hepatic inactivation.

– Esterification of the 17-β hydroxyl group makes the molecule more soluble in lipid vehicles for injection.

– 17-β alkyl derivatives: Stanozolol, danazol, fluoxymesterone fluoxymestenolone, methyltestosterone, methandrostenolone, oxandrolone, and oxymetholone

– 17-β ester derivatives: Nandrolone decanoate, boldenone, trenbolone, methenolone, and testosterone enanthate.


• Glycoprotein Hormones– This category includes chorionic gonadotrophin (hCG), erythropoietin

(EPO), and human growth hormone (hGH).– These drugs are rapidly metabolized and generally have a very short

half-life. Only very small amounts of unmetabolized drug are excreted in the urine. Most detection techniques employ immunoassays that lack specificity.

• Method of erythropoietin (EPO) doping detection– blood analysis of transferrin receptors and morphology of red blood

cells– Distinction of recombinant EPO from natural EPO in both blood and

urine by electrophoresis and radioimmunoassay– Distinction of recombinant EPO from natural EPO in urine by

isoelectrofocusing with monoclonal antibodies used for separation and detection


• Stimulants– These drugs stimulate the central nervous system (CNS) and may be used

to reduce fatigue, increase alertness, competitiveness, and aggression.

– They produce a performance enhancing effect in explosive power activities and endurance events, since the capacity to exercise strenuously is increased and sensitivity to pain is reduced.

– Because of their short half-life, stimulants are mostly used on the day of a competition.

– They may also be used in training, to allow an increase in intensity of the training session.

– E.g.: caffeine, amphetamines, ephedrine, and cocaine

• Detection of doping agents– Urine

• Chromatography

– Blood• Instrumental analysis• Immunoassay

• Quality assurance– Internal quality assurance (GLP)– The regulations issued by the International Olympic Committee– External– quality assurance is a required accreditation procedure of the IOC

Drug abuse among athletes-2

Individual agents

Ephedrine• It is a sympathomimetic alkaloid, and acts as a stimulant in the

CNS by enhancing the release of norepinephrine from sympathetic neurons.

• Filipinos have, for many years, smoked a mixture of ephedrine and caffeine called shabu (in Japan the same word is used to describe amphetamines in general).

• In the late 1980s, shabu smoking gave way to the practice of smoking methamphetamine.

• Afterwords hundreds of “food supplement” producers started selling ephedrine combined with caffeine and nowadays ephedrine has been largely replaced by more effective decongestants in the treatment of asthma, but it is still widely used for the prophylaxis and treatment of hypotension caused by spinal anesthesia.

Ephedrine• Routes of Administration:

– Ephedra may be taken orally, injected, or smoked (primarily in the Philippines). Act on both alpha and beta recepotor and produce an inconsistent, and insignificant, ergogenic benefit for power, endurance, strength, or speed.

– The IOC not entirely banned ephedrine consumption. It has ruled by urine levels of < 10 μg/ml indicate abuse and are grounds for disqualification.

Ephedrine• WADA can issue TUEs for use of ephedrine.– Nasal spray (roughly 14 mg) of ephedrine in healthy

volunteers were found to have urine levels ranging from 0.09 to 1.65 mg/mL.

– Occasionally, innocent non-abusers may find themselves falsely accused of ephedra abuse

– A Dutch professional cyclist who thought he was using a perfectly a legal, ephedra containing food supplement found to his surprise that he was taking cathine (d-norpseudoephedrine), a weak stimulant present in ephedra. (Urine ephedrine levels of Dutch cyclist was 20.2 mg/mL )

Erythropoietin — blood doping• EPO is a 30,400 D glycoprotein hormone produced mainly in the

kidney, in the liver (<10%), and, in very small quantities, in the brain.

• The physiological stimulus for EPO production is tissue hypoxia. The EPO increases circulating erythrocytes in the blood. In a normal individual, any loss of erythrocytes, such as by bleeding or hemolysis, decreases delivery of oxygen to the tissues.

• When tissue hypoxia is sensed by cells capable of producing EPO in the kidney and liver, they produce and secrete EPO into the plasma. The increased numbers of circulating erythrocytes in turn deliver more oxygen to the tissues. This increased oxygen delivery is sensed by the EPO-producing cells, which then reduce EPO production so that the normal steady-state number of erythrocytes is restored.

Erythropoietin — blood doping• Detecting Recombinant EPO (rHuEPO) Abuse in Sports:

• rHuEPO became available in 1987, it was clear that this ergogenic hormone would be used illicitly in endurance sports. Therefore, the IOC Medical Commission decided specifically to ban it in 1990.

• Two approaches were developed for the detection of rHuEPO abuse. The first was based on the detection of indirect blood markers, and the second one was based on the direct detection of rHuEPO in urine.

Figure: Anti-doping urine analysis demonstrating the presence of rHuEPO in urine: 1. rHuEPO standard. 2. Positive urine (control). 3. Negative urine (control). 4. Sample declared positive.5. Darbepoietine (standard).

GH as a Doping Agent• The effectiveness of rGH for improving sport performance

is still a subject of debate among abusers. • The anabolic effect of GH is not the only one explored by

athletes, as GH is also used in endurance sport in combination with oxygen transport enhancing methods.

• It is difficult to draw any conclusions regarding the effects of excessive GH administration on skeletal muscle function.

GH as a Doping Agent• Several factors complicate the detection of doping with

GH:• GH is a peptide with a very short half-life in blood, and low

concentration in urine. • Secretion of GH by the pituitary gland is pulsatile, leading

to highly fluctuating levels in circulation, influenced by factors such as sleep, nutritional status, exercise, and emotion.

• Secretion of GH shows high intra - and inter -individual variability.

GH as a Doping Agent• Several factors complicate the detection of doping with

GH:• In urine, the average concentration of GH is between 100

and 1000 times lower than in blood. • An extremely sensitive immune test was used to quantify

the total amount of the hormone in urine, but lack of sensitivity and specificity of the result made the urinary test less promising than blood testing.

Cannabinoids• There exists high prevalence of cannabis use among young

adults. Cannabis smoking causes impairs cognition, psychomotor, and exercise performance, it is considered an ergolytic drug.

• Marijuana smoking reduces maximal exercise performance.• Heavy use of marijuana has been linked to impairment in

memory, concentration, motivation, health, interpersonal relationships, and employment, as well as decreased participation in conventional roles of adulthood, history of psychiatric symptoms and hospitalizations, and participation in deviant activities

Ethanol use in sport and interaction with other doping agents

• Alcohol (ethanol) is prohibited in-competition only, in a limited number of sports (e.g., automobile, archery, modern pentathlon for disciplines involving shooting).

• Sport federations have set up cutoff limits in blood, which are regularly updated. They range between 0.1 and 0.3 g/L for 2006.

• The basis of the ban is the anti-tremor effect of low-dose ethanol that may enhance shooting performance.

• Even at low concentrations, alcohol disrupts many motor performances

• and can interfere with complex activities such as skiing or driving.

drug abuse among athletes

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