Illegal substances in sports

Stimulants

Canabinoids

Narcotics

Testosterone

AAS

DHEA

Other anabolic agences

 Erythropoetine

Growth hormone

 IGF-1

 hHG

Pituitary and sinthetic gonadotropins

Insulin

 ACTH

Peptide hormones

 Beta-2 agonists

Anti-estrogene activity agences

Masking agences

Glycocorticoids

Alcohol(etanol)

Beta-blockers

Ergogenic aids and sport

Substances of phenomena( e.g. hypnosis) that improve an athlete’s performance are reffered to as ergogenic aids. The variety of potential ergogenic aids is immense, and the effects of many ergogenic(work producing) substances are shrouded in myth. Most athletes have received tips about ergogenic aids from a friend or coach and assume that the information is accurate, but this is not always the case. Some athletes experiment with substances, hoping for even a slight performance improvement regardless of possible harmful consequences. In the quest of performance perfection, a concern only with maximizing performance coupled with a lack of knowledge about ergogenic substances can lead an athlete to make unwise decisions.

The list of possible ergogenic aids is long, but the number that actually possess ergogenic properties is much shorter. In fact, some allegedly ergogenic substances or phenomena actually can impair performance. These are usually drugs, and Eichner has termed them ergolytic(work decreasing) drugs. Ironically and sometimes tragically, several ergolytic agents have been promoted as ergogenic aids.

Many athletes indiscriminately take nutritional supplements and ingest drugs and other substances in the belief that they will improve their performance. In one study of 53 Division I university coaches and trainers, 94% provided their athletes with nutritional supplements. This might seem totally harmless; but high percentage of nutritional supplements are contaminated, and some have been found to contained banned substances. Anecdotal stories suggest that anywhere from 20% to 90% of athletes in certain sports are using, or have used, anabolic steroids. Scientific studies, however, suggest a much lower estimate of 6%. Anabolic steroid use has even been reported in the general high school population in the United States, varying from 4% to 11% in boys and up to 3% in girls.

Table below provides a selected listing of substances and agents proposed to have ergogenic properties. This table also lists mechanisms of action by which these ergogenic aids have been proposed to work. These have been studied in sufficient depth to establish their efficacy. Many other substances have been proposed but not adequately researched.

Proposed ergogenic aids and mechanisms through which they might work
Age nt	Influ- ence heart, blood, circula- tion and aerobic endu- rance	Incre- ase oxy- gen deli- very	Supply the fuel for muscle and general muscle function	Act on muscle mass and strength	Result in weight loss or weight gain	Counteract or delay onset or sensa- tion fatique	Counteract central ner- vous system inhibition	Aid in relaxa- tion and stress redu- ction
Pharmacological
1	+					+	+
2	+							+
3	+		+			+
4	+				+
Hormones
5				+	+
6				+	+
Physiological
7						+
8	+	+				+
9	+	+				+
10	+	+				+
11	+	+				+
Nutritional
12	+		+	+	+	+
13			+	+	+	+
14			+			+

1 – amphetamines

2 – beta-blockers

3 – caffeine

4 – diuretics

5 – anabolic steroids

6 – human growth hormone

7 – bicarbonate loading

8 – blood doping

9 – erythropoetine

10 – oxygen

11 – phosphate loading

12 – amino acids

13 – creatine

14 – L-carnitine

Illegal methods in sport

Methods that increase oxygen transfer

Methods that are used to increase oxygen transfer are:

a)      blood doping – blood transfusion

b)     use of products that enable intake, transport or release of oxygen

Blood transfusion

The goal of blood transfusion appliance in sport is to influent on athletes abilities to increase blood capacity for connecting and transporting oxygen to the tissues. This increase in aerobic capacity can be specially useful in sports that are type endurance. For needs of athletes is not done intake of whole blood, but special technique is used to separate erythrocytes and insert them into blood circulation through transfusion.

Procedure

Autologous transfusion – procedure starts few weeks before important sports competition, through intake of 1-4 blood units(1 unit=450ml of blood). Through reinfusion plasma is returned to the athlete, and separated erythrocytes are depoed on responsible way to the moment where through infusion will be returned to the blood circulation, which is usually happened 1-7 days before competition. Level of haemoglobine and erythrocytes can be increased that way for over 20%.

Homologous transfusion means appliance of blood or blood derivates of other donor.

Harmful effects

Increase in blood viscosity created by transfusion of separated erythrocytes can be the cause of serious complications.

One of them is decrease in heart minute and hitting volume, which causes fall in blood circulation velocity, reduction of oxygen in peripheral tissues, or aerobic capacity. Other possible complications are trombosis and flebitis, heart damage, septicemia, air embolia and death.

Homologous transfusions can also be the cause of transfusion reactions(increased body temperature, urticaria, anaphylactic shock), hepatitis, HIV, malaria.

Today is thought that intake of 900-1300ml of blood through autologous transfusion can be the safe procedure.

Methods that increase flow, transport and oxygen release

Artephicial carriers of oxygen

Artephicial carriers of oxygen are products that increase blood oxygenation.

The most significant representors of these substances are:

• erythropoetine
• perfluorochemicals(PFCs)
• haemoglobin based oxygen carriers(HBOCs)
• liposome encapsulated haemoglobins(LEHs).

These substances are still in the phase of testing and development, which is placed as the condition for appliance at people in clinical medicine. Their appliance would have excuse, if responsive blood is missing or there is a risk of other donor’s blood appliance.

Appliance in sport

There are some reports of use this rimifons at the athletes in the goal of blood oxygenation increase, but they are not concrete to be able to talk more about these tries.

Harmful effects

It is thought that harmful effects can be very serious, due to difficulties in doses measuring.

Harfmul effects of PFCs are:

• transitively increase in body temperature
• reduction of trombocytes number
• potential load of fagocyte cells.

Harmful effects of HBOCs are:

• blood pressure increase
• vasoconstriction
• kidney damage
• iron overload.

Detection

PFCs can be detected through breath test of through techniques gas chromatography- mass spectrometry.

Pharmacological, chemical and physical manipulations

Pharmacological, chemical and physical manipulations means substances or methods which use has a goal to alter or substitute urine sample, that should be given to doping control.

Examples of illegal methods are:

• catheterization( procedure where by appliance of catheters is emptied urethra)
• urine substitution or tampering
• inhibition of kidney excretory function
• alteration of testosterone/epitestosterone concentration

Gene doping

Progress of medicine science enabled introduction of structure and functions of human genome. Through recognition of genoms responsible for increase of psychophysical abilities important for various sports and technology progress, that would apply everything more adjustable, presents real danger for the sport. On this way theoretically, it would be possible to increase the power through stimulation of growth hormone, increase blood capacity for oxygen transport, through stimulating synthesis of erythropoetine and similar. Technique that would be used here  looks really simple. Appliance of proper injection of DNA responsible for releasing of substances written in the body of the athlete few days or weeks before competition would give wished result. Today is generally talked about two types of gene intake into the organism. Transduction means giving DNA with assistance of viral vector, while transfection is non-viral intake, where liposome-DNA or DNA-protein complex are used. Non-viral technique is less toxic and less immunogene, but not as effective as viral. In any case, today bioengineering has to resolve problems of effective and safe DNA transduction. Progress of research and techniques in this area of medicine, would lead to successful healing of hard diseases like: haemophilia, anemia, muscle distrophia… That would mark new era in medicine. Opinions of many researchers say that these progress would be used in non-therapeutic way, as a doping in sport. There is fear cause possibility of detection would be really hard to be developed.

Beta-blockers

Beta-blockers are substances that use competition mechanism to block all effects of adrenergic substances (catecholamines and drugs- adrenergic stimulators) that are done over adrenergic beta-receptors.

The most of beta-receptors are thought to be isoprenaline derivates. The most significant beta-blockers are: propranolol, sotalol, oksprenolon, alprenolon and pindolol.

The most significant pharmacological effects of beta-blockers are manifested on: cardiovascular system, bronchias and metabolism.

Cardiovascular system

Beta-blockers decrease frequency of heart rate, miocard contractility, and it comes to decrease in heart minute volume. Decrease in arterial blood pressure is caused by beta-blockers, which is the result of influence of these substances on beta-blockers of various organs.

Bronchias

Through blocking of beta-2 adrenergic receptors, these substances enable effect of parasympaticus that is manifested through bronchoconstriction. At healthy people this effect is very weakly manifested. Through use of selective beta-1 or beta-2 blockers only effects on specific organs would be given depending on receptor type.

Metabolism

Beta-blockers inhibit glicogenolysis, lypolysis and calorigenesis.

Therapy indications – Beta-blockers are used in healing cardiovascular system illnesses( angina pectoris, increased blood pressure and heart arrhythmia) and thyrotoxycosis(thyroid glandula hyperfunction).

Appliance in sport

Decrease of glycogenolysis, tonus and blood circulation in muscles, decrease of heart hitting/minute volume and blood pressure are the effect of beta-blockers, that are used in sports where fine neuro-muscular control is needed, preciseness and energy reserves keeping.

Use is not allowed in competitive period in soccer.

Harmful effects

The biggest harmful effects are:

• Bronchospasm
• Bradycardia
• Acute renal infarction

Other harmful effects are: circulatory shock, hypoglycemia, pulmonary edema, nausea, diarrhea and allergy reactions.

Detection

Beta-blockers can be detected in urine through appliance of gas chromatography-mass spectrometry methods. Concentration of phenylpropranolamine bigger than 25 µg/ml is thought to be illegal.

Non-allowed beta-blockers are:

Acetobutolol, alprenolol, atenolol, betaxolol, bisoprolol, bunolol, carteolol, carvedilol, celiprolol, esmolol, labetolol, levobunolol, metipranolol, nadolol, oxprenolol, pindolol, propranolol, sotalol and timolol.

“Doping in sport”, Marina Djordjevic Nikic

Alcohol(ethanol)

The most significant ethanol effects are exposed as depression of cerebellum functions.

Ethanol effects on central nervous system(CNS):

• Decrease of visual acuity

This ethanol effect is spotted already when very small amounts of ethanol are present(3-11mmol), that don’t cause signs of drunkness. Use of bigger ethanol amounts leads to emphasized decrease in visual acuity.

• Reaction time increase

Alcohol concentration of over 23 mmol significantly increases reaction time.

• Skeletal muscles coordination disorder

Disorders of skeletal muscles central coordination occurs under the effect of ethanol. Small amounts effect on delicate movements, like hand coordination.

• Euphoria

Already when small amounts of alcohol are present, signs of euphoria are present. Positive mood that happens under the influence of alcohol is one of the reasons that leads to addiction.

• Inhibitions removal

      Self-confidence, free behaviour, and tension removal are the result of central cortical              inhibition removing.

Effects on cardio-vascular system are manifested through peripheral vasodilatation and toxic ethanol effect on miocard. Gastric and liver illnesses are often manifestations of long-term intake of big alcohol amounts. Inhibitory effect of ethanole on antidiuretic hormone secretion leads to increased diuresis.

Appliance in sport

Alcohol is the most widespread substance, the most often used and abused substance in recreative and competitive sport. Euphoria, inhibitions and tension removal, self-confidence increase are basic motive to use this substance in sport. All other effects are unwished effects at athletes. Increased diuresis and termoregulation disorder, like coordination muscles disorder, can influent badly to the result and lead to higher injury rate.

Detection

Alcohol in urine can be detected through techniques of gas chromatography-mass spectrometry. Analysis of air that is breathed-out or blood can be applied in detection.

If threshold is not written, any alcohol amount will be considered as offence. Alcohol is not prohibited in all sports, but in soccer it is prohibited.

“Doping in sport”, Marina Djordjevic Nikic

Glycocorticoids

Glycocorticoids are hormones that are synthetized in the cortex of adrenal glandula. Cortisole is the most significant glycocorticoid at humans. Glycocorticoids have many various effects on tissues in organism:

• Anti-inflammatory, anti-alergic and immunosuppressive effect;
• Gluconeogenesis stimulation;
• Antagonism of vitamin D effects in organism(osteoporosis);
• Stimulation of hydrochloric acid in gaster( gastric ulcer);
• Changing of cell processes regulation(influence on gene expression);
• Stimulus of central nervous system(euphoria) and other effects.

Therapy glycocorticoids are synthetized with goal to emphasize some of this substance effects, and especially its anti-inflammatory and anti-alergic effect.

Appliance in sport

Anti-inflammatory(pain removal) and stimulative effect on CNS are basic motives to use these substances as doping in sport.

In 1975 Medic commission(International Olympic Comitee) defined therapy appliance of corticosteroids at athletes during competition.

Allowed local use means appliance in ophtamology, dermatology and otorinolaringology. But, intraarticular use is also allowed, just as the appliance of inhalation therapy in the cases of astma or other opstructive illnesses of airways.

If there is therapeutic excuse for use of this hormone, it is necessary that in proper way, in written form, before competition, to inform the commission.

Every other administration is not allowed in sport(oral, vein, muscular and rectal).

Rectal administration can also lead to increase in these hormone level, just as the oral use.

Harmful effects

Long-term use of bigger corticosteroids dose(with sudden stop in use) can lead to following effects:

• Adrenal glandula suppression(these leads to inhibitory effect of applied corticosteroids on ACTH secretion. In the case of sudden stop, addinamia is reported)
• Cushing’s syndrome( hyperglycemia, diabetes, osteoporosis, acne, insomnia, body mass increase, increased hair growth at females…)
• Gastric ulcer
• Decrease of organism resistance to infections
• Psychosis and other effects.

Detection

Glycocorticoids in urine can be detected through methods gas chromatography-mass spectrometry.

“Doping in sport”, Marina Djordjevic Nikic

Masking agences

In the group of masking agences are the substances that use various mechanisms to influent the time and amount of excreted doping and disable doping control.

Masking agences are thought to be the following substances: diuretics, epitestosterone, probenecid and plasma expanders.

Diuretics

Diuretics are drugs that stop natrium tubular resorption and increase the volume of excreted urine. In therapy also osmotic diuretics are used, that connect for themselves bigger amount of water and lead to increasing of urine excreted.

Diuretics share is done according to their effect:

• Fast and hard action diuretics: furosemide, ethacrynic acid
• Diuretics that spare potassium: aldosterone antagonists and triamterene
• Osmotic diuretics
• Anhydrase inhibitors
• Other diuretics: mercury rimifons, ammonium chloride…

According to their strength, three groups are found:

• Strong: furosemide and ethacrynic acid( action comes very quick, and lasts 4-8 hours)
• Moderate: thiazides( action goes slower than in fast diuretics, but lasts longer – 6-12-24 hours)
• Weak: triamterene, amiloride, spironolactone

Mutual features of strong and weak diuretics are increased excretion of potassium and natrium. Weak diuretics have advantage compared to this two groups, cause their diuretic effect is not followed by hard potassium loss.

Tiazides are the group of diuretics that is very widespread today in therapy(hypertension, edems…). These substances decrease natrium reabsorption in distal tubules of kidneys, causing that way increased fluid secretion, and in the same time potassium loss. The most important unwished effects are hypocalemia and hyperuricaemia.

Furosemide and ethacrynic acid manifest diuretics effect by decreasing natrium reabsorption on the level of Henle’s loop, which creates strong and fast diuretics effect. These rimifons cause dehydration, potassium loss, temporary deafness and some other disorders.

Spironolactone is the rimifon that, by antagonizing effects of aldosterone, causes increased natrium excretion, with, at the same time, potassium retention. Its effect comes slowly, reaching its maximum in 2-3 days.

Triamterene and amiloride have same effects like spironolactone, but their effect mechanism is different.

Mannitol is the most significant representor of osmotic diuretics. It is applied only through infusions in special medical indications.

List of most often used diuretics: acetazolomid, hydrochlorothiazide, bumetanide, mannitol, chlorthalidone, mersalil, ethacrynic acid, spironolactone, furosemide, triamterene and  similar substances.

Appliance in sport

Athletes that have categories most often use this methods, in order to reduce body mass fast.

Increased urine excretion and following dilution effect of other illegal substances in urine is the important reason for diuretics abuse.

Harmful effects

There is a risk of hypocalemia and dehydration. Fluid loss from the organism absolutely negatively influences of psychophysical abilities of the athletes. The hardest consequences are: heart arrhythmia, muscle weakness, parestesia…

Detection

Diuretics can be detected by methods of gas chromatography-mass spectrometry.

Epitestosterone

Epitestosterone is applied as a try to change relation testosterone/epitestosterone in urine, and mask illegal amount of testosterone. Finding of epitestosterone that is bigger than 200ng/ml is thought to be doping.

Plasma expanders

These substances belong to the group of plasma substitutors. Today there is no device that can fulfill all demands of plasma substitutors. Dextrans represent the group of substances that has advantage comparing to all other devices.

Dextrans are glycopolysaccharides in which molecules of glucose are connected with glycoside connections.

Most often used are dextran 70(molecule mass 70000) and dextran 40(molecule mass 40000) in combination with 5% glucose solution or 0,9% natrium-chloride solution.

One gram of dextrane can contain in circulation 20-25ml of water or to pull the same amount of water from tissues into blood vessels.

After the infusion of dextrane following effects come very fast: increased heart minute volume, hypervolemia, diuresis. Dextranes are used in medicine in various types of shock.

Appliance in sport

Through increase of plasma volume and diuresis, plasma expanders decrease concentration of doping substance in urine and blood.

Harmful effects

Dextrans can cause allergic reactions and anafilactic shock.

Detection

Dextranes are mostly excreted through kidneys, half-time of holding in plasma for dextrane 40 is about 6 hours, and for dextrane 70 over 24 hours.

“Doping in sport”, Marina Djordjevic Nikic