Principal doping substances and t by liaoxiuli

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									Principal doping substances and their side effects
A compilation prepared for the International Cycling Union


Laurent RIVIER, Ph.D., chemist and toxicologist, Scientific Director of the Swiss
Institute of Doping Analysis, Martial SAUGY, Ph.D., biochimiste, Technical Director
of the Swiss Institute of Doping Analysis, and Professor Patrice MANGIN Md Ph.D.,
forensic scientist, Director of the Swiss University Institute of Forensic Medicine,
Lausanne, Switzerland.


Introduction
Any sport may be defined as a game of intelligence and a challenge of ideas combined with
the expression of perfection of the human body and its movement. There are no sports which
involve a course on pharmacology. Unfortunately, the misuse and abuse of
pharmacologically active substances have become so widespread in present day sports that
the safety, the health and the longevity of far too many athletes are now compromised. In a
sense, the initial pursuit of the sporting activity has been perverted.

Even the youngest athletes, both professionals and amateurs, have not been spared. Their
trainers, physicians and other assistants have already given them countless pills, tablets,
ointments, injections, vitamins and other potions. The goals are numerous: to stimulate, to
calm, to numb the pain caused by a wound, to enhance performance, to reduce
inflammation, sometimes to suppress anxiety. As a result, many athletes have come to
believe that successful development in the world of sports is impossible without
pharmacologically active substances. There are not many drugs that such athletes wouldn't
take in order to improve performance, to feel calm or to feel better. Some people say that is
simply impossible to resist…

It is thus essential that all athletes, beginners and professionals alike, fully understand that
the use of a forbidden substance may have severe consequences. Indeed, athletes often
have no knowledge about the immediate and delayed toxic effects of many medical drugs.
On the one hand, it has become very easy to obtain both approved substances and illicit
drugs. On the other hand, the seemingly medical information that is available is often of
pseudo-scientific nature. As a result, it has become difficult to differentiate acceptable
practices from hazardous techniques. In writing this document, our wish was to provide the
reader with simple and straightforward information, based on our current objective
understanding of the relationship between the principal doping substances and the
occasionally toxic side effects commonly observed in cases of abuse and utilization outside
the commonly accepted medical context.

According to G.-I. Wadler et B. Hainline (authors of L’athlète et le dopage, drogues et
médicaments (The Athlete and Doping, Drugs and Medication), Collection Sport et
enseignement, Editions Vigot, Paris, 1993), athlete doping and drug addiction have their
roots in pharmacological research aimed at improving athletic performance with ergogens.
Conversely, doping testing in athletes is an attempt to prevent any artificial ergogen
advantage conferred by an illicit drug, as well as the associated immediate or delayed impact
on the athlete’s health.

An athlete consumes ergogens to gain an advantage in the face of physical and emotional
challenges in a sports competition. However, as seen in the table below, the advantages
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conferred by a particular substance must be seriously evaluated in terms of the performance-
health damage ratio.

Because of practical, legal and ethical considerations, it is difficult to evaluate the effects that
a substance may have on an athlete’s performance. Indeed, one cannot carry out
pharmacological experiments on healthy individuals without a therapeutic justification.
Moreover, volunteers cannot be subjected to the same conditions experienced by athletes
engaged in doping. This limitation is explained by the fact that the levels of drugs that are
used in doping are 10-, 50- and sometimes even 100-fold higher than the accepted
therapeutic values. The cheaters do not seek the therapeutic activity of a substance but
secondary effects that appear only at levels that are never reached during normal treatment.
Finally, it is usually difficult to extrapolate the standard pharmacological parameters because
of many variables, such as the degree of purity of the drug, mode of intake, the dose-
response effect and the relation between time of intake and time of effort.

There are three main categories of drugs that are used by athletes today :

1. Ergogen substances or techniques that are aimed at improving performance. Typical
   examples include testosterone, anabolic steroids, stimulants such as amphetamines, and
   peptide hormones such as growth hormone and erythropoietin.
2. Medical drugs. This category includes substances prescribed for treating specific medical
   conditions and that are used in manners that are contrary to conventional clinical
   practice.
3. Uncontrolled substances sold on the open market for recreational purposes or pleasure.
   This category includes illegal drugs or drugs that are taken at very high doses relative to
   standard prescription levels. The result is a modification in the mood and in the
   perception of the athlete.


List of substances and associated side effects:

The list presented below includes the main substances or classes of substances that cause
well documented side effects on the human organism. The knowledge about certain PFCs is
still very fragmentary and we have omitted them form our compilation. Moreover, besides the
substances listed here, there are many other pharmacologically active compounds or
medical drugs that also have sepcific side effects (see J.-P. de Mondenard : Dictionnaire des
substances et procédés dopants en pratique sportive (Dictionary of doping substances and
behaviors) ; Editions Masson, Paris, 1990). It is important to realize that the substances
presented here are normally used to treat specific diseases or serious health conditions:
they have strong biological activity and are not to be consumed without forethought as if they
were some nutritional supplement, such as vitamins or amino acid concentrates. As a rule,
any plan to use a pharmacologically active substance must always be validated by a
physician, who in turn must confirm the rightfulness of the approach, regardless of dosage
and the health condition of the athlete.


ACTH or Corticotrophin

ACTH is used in an attempt to increase the corticosteroid levels in the blood, and to produce
the associated euphoric effects on the organism. The use of these products may cause an
allergic reaction, in particular in individuals that have a predisposition towards asthma,
urticaria, eczema, etc. Drug injections can cause severe reactions, such as anaphylactic
shock. Undesirable side effect of ACTH include many different reactions such as:
                                                                                                 3



Water retention, edema
Hyperglycemia
Blood hypertension
Modification in the psyche
Osteoporosis
Decrease in resistance to infections


Amphetamines

Amphetamines were first synthesized in 1887. In addition to their principal effects,
amphetamines have different activities on different levels, mediated by more or less specific
receptors in the organism. The desired effects include a sense of well-being, a decrease in
the perception of fatigue, an increase in self-confidence, in motor function and a decrease in
appetite.

In contrast to anabolic drugs which are used during the athlete's training, amphetamines are
usually consumed just prior to competition. Indeed, there are no positive long term effects. In
fact, most of the main pharmacological effects of amphetamines resemble those of cocaine.
One athlete may want to increase his concentration and awareness, another one will
consume massive doses to become more aggressive and develop endurance, and a runner,
for instance, may feel ready to deploy more instant energy and speed.

An individual may be inclined to increase the doses of amphetamines to obtain the same
stimulating effects experienced in the very beginning. This results in rapid addiction. The
initial use, the extended use and high-dosage use of amphetamines may all provoke severe
side effects, as shown in the table below:


             Acute or early onset side effects                      Chronic use side effects
           Average                       Severe

Impatience                      Confusion                         Addiction
Vertigo                         Fights                            Weight loss
Tremors                         Delirium                          Psychosis
Irritability                    Paranoia                          Paranoid delirium
Insomnia                        Hallucinations                    Dyskinesia
Euphoria                        Convulsions                       Behavioral disorders :
                                                                  compulsive / stereotypical /
                                                                  repetitive
Uncontrolled movements          Cerebral hemorrhage               Vascularity
Cephalgia                       Angina pectoris / infarction of   Neuropathies
                                the myocardium
Palpitations                    Blood hypertension
Anorexia                        Circulatory collapse
Nausea
Vomiting

A brutal withdrawal after repeated use of amphetamines may result in chronic fatigue,
lethargy, somnolence and depression.

An amphetamine user may display the following external signs:
                                                                                          4



Changes in one's judgement capacity
Repeated occurrence of wounds
Increase in recuperation time
Side effects that penalize a sports activity (see above)
Repeated variations in the mood (stimulation of anxiety)
The face of amphetamine: external signs of the amphetamine user
- Facial expression of anxiety
- Pinched nose
- Dilated pupils
- Teeth grinding (bruxism)
- Dry mouth
- A nauseous state
- Paleness of mucous membranes and on the finger tips (nails)
- Cold extremities
- Goose bumps
- Sudation
- Palpitations
- Accelerated or lowered heartbeat
- Hyper or hypotension
- Erection
- Loss of vision in the absence of visible eye alterations (amaurosis)
- Nervousness
- Tics: frequent touching of one's face
- Disorientation relative to people and places
- Mistrust of one's entourage and the impression of being constantly watched
- Incoherent speech
- Violent acts
- Psychosis (severe personality problem which alters the perception and understanding of
    reality)
Addiction
The habit is essentially psychological
There is a tendency to use dangerous associations of medical drugs


Anabolic substances (steroids)

This class of doping substances includes all steroids that possess anabolic properties,
meaning that they cause an extensive increase in the muscular mass. This effect is never
isolated: a more or less pronounces androgen activity is also present. This chapter also
deals with testosterone.

These ergogen substances are generally used without interruption and during several weeks
preceeding a competition. The preferred method is "piling up" oral ingestion and injections.
The amount of the substances used exceeds dramatically the standard doses recommended
in a therapeutic procedure.

There has been a report of an athlete diagnosed with AIDS and whose sole risk factor was
sharing needles to inject anabolic steroids. It is not uncommon to discover that anabolic
steroids bought on the black market have not been adequately sterilized and are deliberately
mislabeled. The possible complications arising from the use of such unknown and impure
preparations are unimaginable.
                                                                                             5

The side effects associated with the use of anabolic steroids have been scientifically
observed and documented:

Anomalies in the function of the liver
Benign and malignant liver tumors (liver cancer)
Hypercholesterolemia (excessive blood cholesterol levels)
Prostate Adenocarcinoma (prostate cancer)
Hypertension spells
Infarction of the myocardium
Diabetes
Sleep apnoea syndrome
Hypogonadotropic hypogonadism and testicular atrophy (decrease in the size of testicles)
Azoospermia (disappearance of sperm in the semen), reversible sterility
Feminization : gynecomastia (breast development in men) and high-pitched, castrato-like
voice
Behavioral modifications (aggressiveness, groundless violence) – psychiatric troubles
(addiction to anabolic products)
Humoral immunity problems
Acne
Muscular rupture
Hair loss
Premature suture of the epithelial cartilage in the prepubescent child which results in an
arrest of growth in the young athletes.
Irreversible virilization or masculinization in women
- Husky voice (which can also become screeching)
- Hirsutism : appearance of body hair in regions that are normally hairless (face, regions
     between and around nipples, back, shoulders, the back of thighs, infra-umbilical and
     intergluteal regions): the average life span of body hair is two years and excessive body
     hair may sometimes appear as late as one year after the end of hormone absorption
- development of male pattern baldness
Virilization of the female fetus

In addition to the above-mentioned symptoms, there are subjective reactions to the intake of
anabolic substances:

Modifications in sex drive (increases and decreases)
Fainting and vertigo
Headaches
Lethargy or excessive aggressiveness
Psychiatric effects: steroid-induced rage or spells of extreme violence
Tics
Dependence


Non steroid anti-inflammatory drugs (NSAIDs)

Severe undesirable side effects of NSAID drugs are rare. The common side effects include
irritations and bleeding of the gastric mucous membranes.

The other undesirable effects are :

Skin eruptions
Ear ringing
                                                                                             6

Edemas
Bronchial spasms
Sever diarrhea is a classic side effect of mefenamic acid (Ponstan).


Asthma and sports, see Ephedrine, beta-2 stimulants and corticosteroids


Barbiturates et Benzodiazepines

Barbiturates such as benzodiazepines and alcohol are usually not considered as ergogen
drugs.
However, there is scientific evidence that barbiturates and benzodiazepines may have
beneficial effects in some specific situations. Indeed, both substances are effective in
reducing tremors, which is important in some easily identified sports activities. This soothing
action has been extensively studied in cases of epileptic spells.




The side effects of theses substances are significant:

Sedation
Reduced acuteness of vision
Lowered vigilance (very important when driving a motorized vehicle)
Problems with walking and keeping balance
Decrease in memorization capacity
Euphoria
Withdrawal insomnia
Dependence
Tolerance
Clinical withdrawal syndrome
Respiratory distress
Coma


Beta-blockers

The undesirable effects of beta-blockers stem from their inhibitory properties. Asthma
sufferers in particular should avoid products belonging to this category since they can cause
bronchial spasms. Certain beta-blockers, such as propranolol, may cause insomnia,
nightmares and even a depression syndrome.

Some male users also experience sexual difficulties, such as impotence and weakened
erection.

The use of beta-blockers should be strictly prohibited in case of asthma, cardiac
insufficiency, digestive tract hemorrhages, occult bleeding, significant bradycardia (above 50
heartbeats per minute) and insulin-dependent diabetes.
The following undesirable effects are observed when these drugs are used :

Hypoglycemia
Troubles with digestion
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Asthenia
Cramps
Cephalgia, vertigo, diplopia
Raynaud’s disease : circulation problems in the extremities upon exposure to cold ; the
fingers turn pale
Insomnia, nightmares
Mood alterations (depressive tendencies) and changes in the libido
Hypothernia
Cardiac insufficiency
Cardiac rhythm problems
Anaphylactic shock after a hymenoptera sting (bee, wasp, etc.)
Numerous drug interactions




Caffeine

Caffeine resembles cocaine and amphetamines in that it essentially stimulates the central
nervous system in a dose-dependent fashion. Caffeine is known to have many deleterious
effects on the health consulting the table below, one should distinguish the chronic effects of
caffeine from acute effects following absorption of this stimulant (which may constitute
doping behavior).

 Acute intoxication, severe        Acute intoxication, less           Chronic intoxication
                                           severe

Peptic ulcer                     Nervousness, excitation          Increase in cholesterolemia
Delirium                         Irritability                     Increased risk of ischemic
                                                                  cardiopathy
Convulsions                      Insomnia                         Teratogenic activity
Coma                             Tachycardia                      Carcinogenic activity
Arrhythmia                       Blood hypertension               Risk of breast fibrocystic
                                                                  lesions
Palpitations                     Problems with digestion , in
                                 particular when coffee is
                                 mixed with milk
Death (the lethal dose is        Headaches
approximately 6 liters
depending on the brewing
strength of coffee or caffeine
content of the liquid)
                                 Tremors
                                 Exaggerated fear or anxiety
                                 Increased levels of
                                 cholesterol and higher risk of
                                 heart attack


Cannabis (Marijuana, Hashish, Kif, …)
                                                                                                 8

Cannabis has been cultivated for centuries but cannabis-derived products have been
available world-wide only starting second world war. The interest in this plant stems from its
psychotropic properties. Most countries consider cannabis as an illegal drug. Over the recent
past, the quality of the drug has improved dramatically : the levels of active substances in
plants bred nowadays are 10- to 30-fold higher than 15 years ago. Hence, it is difficult to still
consider cannabis as a harmless product. Indeed, certain preparations found on the present
day market are extremely potent. Consequently, there is a corresponding increase in the
principal undesirable side effects which are listed below :

Psychiatric effects                              Cardiovascular effects

Panic attacks                                    Tachycardia
Delirium                                         Orthostatic hypotension
Psychosis                                        Increase in carboxyhemoglobin
Loss of motivation syndrome
                                                 Broncho-pulmonary effects
Immunological effects
                                                 Rhinitis
Decrease in cellular immunity                    Pharyngitis
Decrease in monocyte maturity                    Bronchitis
                                                 Bronchial spasms
Endocrinological effects                         Squamous bronchial metaplasia
                                                 Pulmonary fibrosis
Decrease in sperm production                     Pneumomediastinum
Inhibition of ovulation in women
Gynecomastia in men

Negative effects affecting performance

Increase in recuperation time after exercise     Bloodshot and light-sensitive eyes
and in the duration of muscle aches .
A faster onset of fatigue during exercise        Mood hyper-instability: rapid switch from
                                                 euphoria to depression
Acceleration of cardiac rhythm                   Hallucinations
Enhanced feeling of thirst                       Deterioration in vigilance and coordination :
                                                 dangerous when driving a vehicle !
Loss of motivation


Cocaine

Cocaine abuse in the adult represents a significant risk. Competition merely increases the
cardiovascular side effects through cardiac hyper-stimulation accompanied by arrhythmia
and heart attacks.

The principal side effects caused by cocaine are listed in the table below :

Cardiovascular                   Cerebrovascular                 Neuropsychiatric
complications                    complications                   complications

Ventricular arrhythmia           Cerebral infarction             Convulsions
Sudden death                     Brain Hemorrhage                Exacerbation of the Gilles de
                                                                 la Tourette syndrome
                                                                                             9

Angina pectoris                  Meningeal hemorrhage           Cephalgia
Infarction of the myocardium     Transitory cerebral ischemia   Visual scotoma
Aortic dissection                                               Blindness
Myocarditis                                                     Optical neuritis
Tachycardia                      gyneco-obstetrical
                                 complications
                                                                Habit formation
                                 Premature detachment of        Insomnia
                                 placenta
Ear-Nose-Throat                  Spontaneous abortion           Mental confusion
complications
                                 Congenital malformations       Aggressiveness
Osteolytic sinusitis             Transplacental or milk-        Paranoid delirium
                                 mediated Mother-infant
                                 transfer and secondary
                                 withdrawal syndrome
Necrosis et perforation of the                                  Visual and tactile
nose septum                                                     hallucinations
Loss of sense of smell                                          Repetitive behaviors
                                 Miscellaneous                  Stereotyped movements of
                                 complications                  the mouth and tongue

Complications related to         Liver toxicity                 Anorexia
drug addiction
                                 Gastrointestinal ischemia      Specific delirium
HIV infection                    Pneumomediastinum              Thymic troubles linked to
                                                                hallucinogens
Bacterial infections             Hyperthermia                   Sex problems
Viral hepatitis


Codeine, opiates and other morphine derivatives

The use of pain killers is frequent in sports, especially among athletes engaged in violent
activities (such as boxing for instance). Often, the fear of losing a place or not fulfilling a
contractual obligation leads to an obsession to keep the fight in spite of any type of wound or
handicap. The most common effect of this class of substances is sedation, providing habitual
doses are used. One must be aware of physical and psychological addiction induced by
many opiates which are justly classified as narcotics:

Nausea
Vomiting
Vertigo
Memory loss
Mood problems
Pruritus
Constipation
Delirium
Convulsion crises
Addiction
Withdrawal syndrome
                                                                                          10


Corticosteroids

As seen in the table, the undesirables side effects associated with these substances are so
severe that they should never be administered in the absence of a medical imperative:

Hydro-electrolytic imbalance leading to edemas and increase in body weight
Increase in glycemia (blood sugar levels) and appearance of glycosuria (presence of glucose
in the urine)
Increase in blood pressure
Decrease in antibodies and natural defense mechanisms leading to higher susceptibility
towards infections
Gastric pyrosis (heartburn and regurgitation) and gastrointestinal ulceration
Diffuse osteoporosis with an increased risk of fractures and delayed bone repair
Alterations in the walls of blood vessels with possible formation of blood clots leading to
embolism
Decrease in muscle nutrition, risk of severer muscular atrophy
Eye disorders : keratitis, glaucoma, cataract
Dangerous effects on the fetus
Disorders of the nervous system: convulsions, muscular cramps
Psychiatric disorders: mood alterations, insomnia, sometimes even genuine maniac-
depressive psychoses
Decrease or even arrest in the growth in young athletes


Diuretics

All diuretics have the same side effects: dehydration, hypovolemia, muscular cramps, and
orthostatic hypotension. Biochemical shifts in potassium levels (kaliemia) may be life
threatening if strong modification are induced by diuretics.


Ephedrine (and phenylpropanolamines)

They are present in many innocuous pharmaceutical preparations used to treat benign
conditions such as a cold. One must be very cautious in examining this class of substances
since there are over 50 derivatives which have similar effects. The table shows the acute
side effects caused by ephedrine analogs (effects are ordered by severity)

Moderate effects                              Severe effects

Nervousness                                   Agitation
Irritability                                  Confusion
Insomnia                                      Paranoia
Anorexia                                      Mania
Vertigo                                       Hallucinations
Cephalgia                                     Ictus / Transitory ischemic attack
Tachycardia                                   Cerebral vascularisation
Palpitations                                  Cerebral hemorrhage
Slight increase in blood tension              Severe hypertension
                                              Myocardial ischemia
Intolerance reactions                         Ventricular arrhythmia
                                              Rhabdomyolysis
Should never be combined with an anti-        May cause convulsive crises in epileptics
                                                                                               11

depressant


Erythropoietin

This peptide hormone is used in medical practice in cases of severe anemia and during
treatment of chronic renal insufficiency, such as in dialysis patients. In each case, there is a
specific evaluation of the benefits vs. the dangers of this type of treatment. The first clinical
trials involving erythropoietin started in 1985 and it is hence premature to draw a clear picture
of the side effects. Nevertheless a few undesirable consequences have already been
identified:

Hypertension thrusts when the substance is introduced too rapidly
Vascular thrombosis
Convulsions
Influenza-like symptoms, bone aches et shivering following the injection
Skin reactions, Allergy-like edema at the site of injection
Polyglobulism


Chorionic gonadotropin (hCG)

This natural product is classified as a stimulant because it causes an increase in the
production of endogenous testosterone. The associated dangers depend on dosage and
vary according to sex:

In women                                         In men

Salt retention                                Allergic manifestations
Ovarian hyperstimulation and risk of multiple Nausea, vomiting
pregnancies
Ovarian cysts                                 Novel distribution of fat throughout the body
                                              Gynecomastia and possible secretion of milk
Hypercoagulability                            See also the chapter on anabolic drugs


Pregnancy

In terms of doping, the desired effect is the increase in cardiac capacity during the first
months of pregnancy. Later there is an increase in blood volume, in the number of red blood
cells and in hemoglobin. Apparently the resulting enhancement in oxygen delivery to the
muscles translates into a 10% increase in the deployment of effort.

The risks stem from the vulnerability of the fetus starting with the third month of pregnancy.
A abortion planned after the key competition represents a significant danger for the woman if
it is carried out in a non-medical environment by unexperienced hands. There may also be a
great psychological impact.


Growth hormone (somatotropic hormone or somatotropin)

Uncertainties remain about the safety of exogenous hGH as a therapeutic treatment. We still
do not know what influence it may have on normal individuals, even though there is a good
                                                                                                 12

deal of information about side effects of endogenous hGH hypersecretion in acromegaly.
This condition has an associated 50% mortality at age 50 and 89% mortality at age 60.

The table below summarizes the side effects linked to the presence of high hGH levels in the
adult (the same side effects are noticed in children; in addition, there is an occurrence of
gigantism due to the increase in the linear growth of bone tissue).

Tumefaction of soft tissue (may be irreversible)
Hypertrophy and bone protuberance (may be irreversible), arthritis, induced acromegaly
Thickening of the skin
Hirsutism (hair growth over the entire body)
Hypersecretion of sebaceous glands
Increase in perspiration
Peripheral neuropathies
Myopathies
Hypertrophy of the viscera : spleen, salivary glands, liver, kidneys, heart
Colon polyps
Cardiovascular diseases such as coronary disease, cardiomyopathy and blood hypertension
Glucose intolerance / diabetes mellitus

There have also been reports of the development of anti-growth hormone anti-bodies after
administration of exogenous growth hormone. This causes an interference with endogenous
hormone activity and necessitates an immunological surveillance. In order to avoid
hyperglycemia, it is also necessary to monitor blood glucose levels. An injection of this
hormone affects very fundamental processes of regulation. It may upset the balance of
thyroid and corticotropic hormones, which will have a major impact on the individual's health.

One should point out that a bovine growth hormone may be found on the market and that a
horse growth hormone may soon become available as well. These substances have no
activity on the human organism but they may cause an irreversible sensitization which can
lead to severe consequences (anaphylactic shock) if the exposure is repeated. Yet another
type of hormone may be found on the black market: the extractive growth hormone. It is
actually extracted from the pituitary gland of corpses. In this particular scenario, the industrial
method used to purify the hormone does not guarantee the removal of other biological
molecules such as prions. Based on the well-known scenario of contamination that led to the
mad cow disease, which is transmitted by a prion, one cannot exclude a similar
contamination by a prion present in an extractive hGH preparation from an individual that
died from the Creutzfeldt-Jakob's disease. This type of encephalitis, believed to be caused
by an infectious agent resembling a slow virus, has an incubation period in humans that is
close to 15 years !


Insulin (and diabetes)

Insulin causes hypoglycemia. If the organism does not produce insulin in sufficient amounts,
as is the case in certain types of diabetes, additional insulin is injected to reach normal
physiological balance. In this scenario, physical sports activities are entirely acceptable.
Unfortunately, this state of balance is so difficult to maintain that many physicians
recommend that diabetics abstain from any serious physical activity, especially sports that
demand a high energy input. The international sports regulating bodies prohibit the non-
therapeutic use of insulin for one main reason: insulin induces growth hormone release. In
itself, insulin causes a number of side effects some of which are listed below:

Tremors, sweat, anxiety, agitation
                                                                                             13

Asthenia, hypothermia, cravings
Cardiovascular problems, infarction of the myocardium
Anaphylactic shock, insulin allergy
Numerous drug interactions (it is absolutely necessary to consult a physician because there
are many dangerous associations)
Alcohol consumption should be restrained, since it enhances hypoglycemia and may lead to
a hypoglycemic coma
Overdose: hypoglycemia may result from poorly estimated insulin dosage, a mistake in
feeding or a unforeseen physical effort that is not compensated. The symptoms of
hypoglycemia include hunger, sweat, asthenia, tremors, confusion, problems with vision,
headaches, etc). Unless treated promptly, hypoglycemia may result in a coma.


Nicotine

In the present context, we will only deal with the toxic effects of passive smoking. Indeed,
athletes do not consume tobacco in large amounts (passive smoking, in a closed space
shared with smokers, is a marginal toxicological occurrence in terms of doping behavior). On
the other hand, chewing tobacco or snuff are popular practices in certain countries which
often cause serious diseases.

Periodontal decay
Teeth abrasion
Hyperkeratosis of the mouth mucous membranes
Gingivitis
Leukoplasia
Anomalies of the sense of taste : dysgeusia
Problems with olfaction : dysosmia
Spinocellular epithelioma of the oral cavity
Dependence and withdrawal syndrome
Halitosis: bad breath


PFCs (Perfluorocarbons)

These substances are all composed of fluorine, carbon and hydrogen atoms, but have
important structural differences. Unlike erythropoietin, all PFCs are synthetic and hence
never occurr naturally in the organism. Although they are in principle inert molecules, PFCs
can dissolve large quantities of gas, including oxygen. Various PFC preparations (emulsions
containing egg yolk lecithin or phospholipid) are currently undergoing clinical tests. The goal
is to provide temporary oxygen supply to the brain and other tissues in patients that have lost
important amounts of blood and whose vital functions are in danger. Little is known about the
long-term effects of these substances on the human organism. The toxicity of repeated
treatment is also unclear in situations other than extensively invasive surgical operations. In
terms of tolerance by the organism, the physical and chemical state of the preparation is as
important as its biological purity. Indeed, intra-venous injection is the only means to make
PFCs participate in gas exchange. The clinical preparations currently tested have been found
to have the following side effects:

Increase in body temperature above 40°C, fever et cold
Diarrhea
Kidney, liver and lung toxicity; the lesions are probably irreversible in most cases
                                                                                              14

Blood infections if the preparations are bacteriologically impure
Embolism and thromboses (thrombocytopenia)
Risk of Aids virus transmission if needles are shared

Because of the lack of published scientific evidence, it is a completely unconscious act to
attempt to use PCFs outside of the specific clinical context described above. this is true even
if the patient is closely and continuously monitored. Unfortunately, the world of sports is also
inhabited by unscrupulous hotheads who do not worry about the aftereffects of their
"experiments" on the "human guinea pigs". A hospital context is quite different from a sports
context. One can imagine for instance that PCFs, which already very volatile at ambient
temperatures, may form gas bubbles once injected into the blood vessels. Indeed, an
increase in body temperature is inevitable during intense physical exercise, the warm season
or upon long exposure to the sun. Given the current state of knowledge, one must absolutely
refrain from using these products in the absence of close and extensive medical surveillance.


Probenecid

This substance is used to mask the use of doping substances, anabolic drugs in particular,
by delaying their elimination. The medical application of Probenecid is to treat gout
rheumatism. It may cause the following undesirable effects:

Cephalgia
Anorexia
Nausea
Stomach aches
Vertigo
Frequent micturition
Anemia
Possible anaphylactic-like reactions with fever
Dermatitis and other skin irritations


Blood procedures (see also Erythropoietin)

Because of possible HIV infection, blood transfusions performed outside a hospital context
are simply too dangerous to be even considered as an option. This is common knowledge. It
is important to emphasize the risk of a shock if the donor and the recipient are incompatible.
While homologous transfusions are safer, they also represent a significant hazard. Only
medical surroundings can ensure the absolutely sterile conditions required by transfusion.


Testosterone : see Anabolic drugs


Vitamins

An excessive uptake of vitamin leads to well known side effects which vary with each
vitamin. The following effects are worth mentioning:


Diarrhea
Nausea
                                                                                                 15

Urticaria
Muscular weakness
Fatigue
Cephalgia
Anorexia
Blood hypertension
Cardiac Arrhythmia
Cirrhosis
Teratogen activity



Conclusions

The conclusion is clear: one should never use medication or pharmacologically active
substances without appropriate advice from a physician. If the medical drugs available today
are very potent and effective in treating disease, they also strongly affect healthy individuals
which may be tempted to use them, even though there is absolutely no therapeutic need.
One must never forget that the side effects of a drug are always present but that the
beneficial effects are felt only in case of a disease that has to be treated. The magnitude of
the side effects is of course dependent on the amount of the drug that is consumed.
Unfortunately, this amount is often excessive. The athlete that relies on doping is under
pressure to obtain quick results. Naturally, there is a strong temptation to increase the doses
to really push one's luck. We wish to emphasize yet another point: it is necessary to check
the purity of all substances of uncertain origin. Some products on the black market are
grossly mislabeled and preparations for injection are often contaminated with bacteria or
even viruses. In such cases, there is a significant risk to develop a serious condition and put
a definitive end to one's athletic career. Clearly, the game of doping is not worth playing.


Glossary of principal medical terms:

(The majority of the definitions below are taken from the Dictionnaire français de Médecine et
de Biologie en 4 volumes (French Dictionary of Medicine and Biology in 4 Volumes) A.
Manuila, L. Manuila, M, Nicole et H. Lambert. Paris : Masson, 1971)

Anaphylactic shock                          The combination of acute morbid manifestations
                                            resulting from the reintroduction of a particular
                                            substance into an already sensitive organism.
                                            This shock may be an extremely dramatic event
                                            leading to imminent death, or to a giant urticaria
                                            with congested respiratory mucous membranes
                                            (asthma). Anaphylactic shock often occurs in
                                            sensitive individuals following injections of
                                            therapeutic sera, allergens, peptide hormones,
                                            or penicillin, etc. or after insect bites.

Anemia                                      Individual or combined decrease below normal
                                            levels in the number of red blood cells per cubic
                                            milliliter of blood, in the hematocrit or in
                                            hemoglobin. Anemia may show various general
                                            symptoms: paleness of skin and of mucous
                                            membranes, nervous disorders (fainting, vertigo,
                                            etc), dyspnea, tachycardia, digestion problems.
                                                                           16

                    It may be caused by a hemorrhage, hemolysis
                    (extensive destruction of red blood cells), a
                    deficiency (in protein, vitamin B12, etc.), a
                    disorder interfering with red blood cell
                    development (infectious diseases, effects of
                    toxic substances, etc.), or a congenital illness.

Angina pectoris     A painful constructive syndrome, which
                    develops as a crisis during a specific effort or a
                    walk. It is localized in the retrosternal region and
                    may irradiate into the shoulders, arms, and jaws.
                    It causes severe distress and an interruption of
                    effort. Coronary arteriosclerosis is the most
                    common etiology. The pain is caused by the
                    reduction of blood flow to the heart. Possible
                    outcome includes chronic angina pectoris,
                    sudden death, heart attack, and progressive
                    cardiac insufficiency.

Anorexia            A partial or complete loss of appetite.

Aortic dissection   Formation of a pocket within the wall of an artery
                    caused by the splitting of the internal membrane
                    of the vessel and subsequent intra-pericardial
                    hemorrhage (synonym: dissecting aneurysm of
                    the aorta). The associated pain is intense and
                    violent. Survival is rare.

Arrhythmia          Irregularities in a rhythm. By extension, an
                    anomaly in the heart rhythm resulting in irregular
                    heart beats.

Arthritis           Inflammation of a joint. May be acute or chronic.

Asthenia            Weakening of the general state of health, of the
                    functions of an organ or a system. Decrease in
                    the vitality of an organism.

Carboxyhemoglobin   The form of hemoglobin which fixes carbon
                    dioxide thus allowing the transport of this gas
                    from various tissues to the lungs.

Cecity              Blindness.

Cephalgia           Diffuse or widespread pain located in the cranial
                    region, and exacerbated by external factors
                    (light, noise, jolts), internal factors (emotions,
                    intellectual effort) or movement and physical
                    effort.

Cholesterolemia     Concentration in cholesterol of the circulating
                    blood, usually measured in grams per liter of
                    serum. Normal values oscillate around 2.5
                    grams per liter of serum. Pathological values
                    may point to various metabolic disorders and
                                                                              17

                       liver diseases.

Circulatory collapse   Side effect linked to a collapse in blood pressure
                       and a significant slow-down in blood circulation.
                       Also called cardio-circulatory collapse. The
                       symptoms          are      prostration, loss    of
                       consciousness, cold sweat, rapid, weak and
                       occasionally indiscernible pulse. Could lead to
                       death if it isn’t treated.

Cirrhosis              Term invented by Laennec to describe the
                       disease which causes reddish granulation in the
                       liver. This liver sclerosis may have many
                       different      origins  (alcohol       intoxication,
                       malnutrition, viral hepatitis, etc.). It results in
                       liver insufficiency.

Dependence             A state resulting from periodic and repeated
                       absorption of a psychotropic substance (such as
                       narcotics, anabolic and related substances).
                       The subject feels the need to continue drug
                       intake and to increase dosage to reach the
                       same or more pronounced effects. An
                       interruption in consumption leads to a
                       withdrawal syndrome which is more or less
                       severe, depending on the substance.

Dermatitis             Skin inflammation. More generally, a skin
                       disorder which may not be inflammatory in
                       nature.

Drug interactions      Influence of two or more medicinal substances
                       on the biochemical phenomenon at the basis of
                       their mode of action. Drug interactions can be
                       beneficial, additive, multiplicative or detrimental.

Dyskinesia             Any disruption of movement: absence of
                       coordination, spasms, tremors, etc.
Epithelioma            Malignant cancerous tumour formed by the
                       epithelium (one of the skin tissues).

Ergogen                Which lies at the basis of and improves the
                       efficiency of muscular work.

Gynecomastia           In men, hypertrophy of mammary glands
                       (breasts).

Hemorrhage             A more or less important discharge of blood
                       from a blood vessel.

Hypercoagulability     Increase in the normal ability to coagulate of a
                       biological fluid, mainly blood.

Hyperglycemia          Increase in the amount of glucose in blood.
                       Depending on the measurement method used,
                                                                               18

                        the increase is considered significant above 7.8
                        mmol/L. With the exception of transient
                        hyperglycemia caused by food ingestion, cold,
                        emotions and altitude, most occurrences are
                        pathologic and involve the pancreas (diabetes
                        mellitus), the hypophysis (acromegaly) or the
                        adrenal gland (tumours).

Hypoglycemia            Decrease in the amount of sugar in blood ,
                        below the threshold of 2.8 mmol/L. A medicinal
                        cause for hypoglycemia usually involves
                        excessive insulin absorption.

Hypovolemia             Decrease in the volume of circulating blood.

Ictus                   In neuropathology,          a    sudden     morbid
                        occurrence.

Ischemia                Decrease in blood flow to a particular part of the
                        organism.    It  can     be   caused      by     a
                        vasoconstriction, an obstruction or arterial
                        compression.

Ischemic cardiopathy    A disease caused by a low blood flow to the
                        heart.

Keratosis               More or less pronounced thickening of skin
                        epidermis.

Lethargy                Pathological state of prolonged and deep sleep,
                        which can be avoided by the affected individual
                        only partially and during brief periods of time. An
                        apparent state of death, but without loss of vital
                        functions, which may last a few hours or several
                        years.

Micturition             Urination.

Motor function          The sum of activities carried out by the organism
                        necessary for motion

Myocardial infarction   Necrosis of the cardiac muscle, caused by an
                        acute coronary thrombosis, and involving one or
                        several limited, isolated foci. The overall clinical
                        picture is more or less dramatic, with a
                        prominent characteristic pain and a drop in
                        tension. The affected person is at all times
                        exposed to lethal complications.

Myocarditis             Acute or chronic inflammation of the heart
                        muscle (myocardium). It may be caused by an
                        infection (bacteria, viruses, parasites, fungi),
                        chemical or medicinal agents, or other factors.
                        The     symptoms     are   variable.   Frequent
                        manifestation include tachycardia, palpitations,
                                                                                      19

                               signs of cardiac insufficiency, and muffled
                               heartbeat sounds during auscultation, including
                               gallop rhythm.

Neuropathy                     A disorder affecting the central or peripheral
                               nervous system. Usually degenerative.

Optical neuritis               An inflammatory disorder of the optical nerve.

Orthostatic hypotension        A drop in blood tension measuring 2 cm of
                               mercury or more, which takes place during the
                               transition from decubitus (horizontal, resting
                               position) to a standing, vertical position.

Osteolytic sinusitis           Inflammation of the mucous membranes of the
                               facial sinuses. This type of sinusitis may be
                               frontal, maxillary or sphenoidal. There are acute,
                               chronic, purulent or non-purulent forms.
                               Osteolytic sinusitis has a destructive action on
                               the proximal bones.

Osteoporosis                   A bone lesion characterized by the thinning and
                               rarefaction of bone traveculae which is
                               visualized as a decrease in the radiological
                               opacity of the skeleton. Localized or diffuse
                               osteoporosis implies the weakening of bones.

Ovarian cyst                   A benign tumor of the ovaries of variable size
                               and of many types.

Paranoia (paranoid delirium)   From the times of Hippocrates and through the
                               Middle Ages, paranoia was a synonym of mental
                               disease. Until the 1920's and under the
                               influence of the German school, paranoia
                               referred to mental disorders affecting the
                               intelligence, as opposed to emotions. Today, it
                               designates a hallucinatory or interpretative
                               systematic delirium.

Pharyngitis                    Inflammation of the pharynx (schematically, the
                               pharynx corresponds to the respiratory tract
                               between the mouth and the lungs on the one
                               hand, and the tract between the mouth and the
                               stomach, on the other hand). Pharyngitis may
                               have many causes (influenza, common cold,
                               other viral diseases, intoxication, etc.). The
                               clinical manifestations involve signs of local
                               irritation (feelings of dryness, burns, irritations,
                               etc.).

Pneumomediastinum               A rare condition caused by physical efforts of
                               different nature and first described by Laennec
                               in 1837. It corresponds to the presence of air in
                               the mediastinum (a region located in the median
                               part of the rib cage, between the two lungs).
                                                                                      20


Polyglobulism                   Increase in the number of circulating red blood
                                cells resulting in a higher corpuscular volume,
                                higher levels of hemoglobin and increased blood
                                viscosity.

Pruritus                        An itchy skin feeling caused by a skin disease, a
                                general disorder or an allergic reaction to a
                                foreign substance.

Pulmonary fibrosis              Pathological formation of fibrous tissue in the
                                lungs. The clinical signs include irritated cough,
                                halting respiration and cyanosis. The outcome is
                                invariably fatal.

Respiratory distress            A decrease in the extent of respiration that can
                                lead to death.

Rhabdomyolysis                  Muscle breakdown caused by an exceptionally
                                intense physical effort or intoxication. It results
                                in abnormal levels of myoglobin in the urine
                                (synonym: paroxystic myoglobinuria).

Rhinitis                        Catarrhal inflammation of the nasal mucous
                                membrane, sometimes a synonym of a cold.


Side effects                    The effect of a medical drug which is not related
                                to its primary activity or therapeutic effects. By
                                extension, all undesirable and often toxic effects
                                of medication.

Squamous bronchial metaplasia   Transformation of the alveolar lung tissue. It is
                                often linked to an inflammatory process and
                                implies a pre-cancerous state.

Tachycardia                     Acceleration of the heart rate above 100 beats
                                per minute.

Teratogen                       Which causes deformities.

Thrombosis                      Formation of a firm or gelatinous mass inside a
                                blood vessel or a heart cavity , which causes
                                complete or partial obstruction.

Tolerance                       The capacity of the organism to tolerate physical
                                or chemical aggressions, without apparent
                                damage. Tolerance may be acquired after
                                repeated exposure to a particular medicine.

Tumefaction                     Any increase in the size of a cell, a tissue, an
                                organ or an organism. Usually pathological.

Urticaria                       Skin condition characterized by the eruption of
                                pinkish or whitish papules, accompanied by a
                                                                     21

                 burning sensation. The cause is often an
                 allergy (sensitization of the organism to medical
                 drugs, parasites, physical agents, etc.).

Vasculitis       Inflammation of blood vessels.

Visual scotoma   Blind spots in the field of view which correpond
                 to insensitive regions of the retina. The usual
                 cause is a lesion of the opitcal nerve.

								
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