1. Drug abuse among athletes
Rome Games of 1960
Knud Enemark Jensen
Amphetamine
1904 Games
Thomas Hicks
Strychnine
S. Parasuraman M.Pharm., Ph.D.,
Senior Lecturer, Faculty of Pharmacy,
AIMST University,
Bedong 08100, Malaysia.

2. 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.

3. Athletes take drugs
By purpose Accidentally
Self-Administration Quacks
Couch Advice Doctors Paramed

4. 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

5. • 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.
Drug abuse among athletes

6. • “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”

7. • 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)
Drug abuse among athletes

8. 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, st
anozolol, etc.
– Other anabolic agents, e.g., Clenbuterol

9. Prohibited Substance Classes
2. 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 agonists
4. 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.

10. Prohibited Substance Classes
5. 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. Cannabinoids
9. Glucocorticoids
10. Alcohol and Beta-blockers are prohibited in some specific
sports

11. Prohibited Methods
1. 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

12. 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.

14. 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

15. 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.

16. Widely abused agents/ Commonly used
agents or drugs
• 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

17. Widely abused agents/ Commonly used
agents or drugs
• 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

18. • 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

19. Drug abuse among
athletes-2
Individual agents

20. 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.

21. 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.

22. 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 )

23. 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.

24. 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.

25. 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).

26. 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.

27. 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.

28. 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.

29. 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

30. 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.