A popular African proverb says:
>Since men have learned to shoot without missing, the bird has learned to fly without perching.

Chinua Achebe in Things Fall Apart.

![Goeland_leucophee_Olbia.jpg](https://steemitimages.com/DQmXGHYnFgbjVvkBumudFardFFeN269T4pu7SYQ7VWcKk3R/Goeland_leucophee_Olbia.jpg)

*A bird in flight*
Source: [Gzzz](https://commons.wikimedia.org/wiki/File:Goeland_leucophee_Olbia.jpg)

This proverb is the best description of the bittersweet relationship sportsmen and women have with performance-enhancing drugs. In the last post, we learned about the Goldman’s Dilemma. In his research, Publicist Robert Goldman asked athletes if they would risk being caught and bear the dangers in using performance-enhancing drugs for the glory and the adulation sports brings. An overwhelmingly high number of athletes gave an affirmative response. 

Like the bird in the proverb, as the World Anti-doping Agency and other relevant sports bodies tighten the screws and increase their vigilance with regards to doping in sports, the athletes have found ways to jump through the hoops, use performance-enhancing drugs and avoid detection.

In this third instalment of this ongoing series, the chemistry, physiology and mode of action of stimulants, ergogenic aids, masking agents and the pivotal position Russia seats in the doping scandals will be discussed.

## <center>Stimulants</center>

The most popular performance-enhancing substances used in the sports are those that alter the biological and physiological make up of the body systems to confer an advantage in games. Less common but also actively abused in the sports where they confer advantages are stimulants. 

Stimulants are a class of drugs that act mainly at synapses and on select areas in the central nervous system to bring about effects that improve sports performance in different ways. 

Examples of stimulant performance-enhancing drugs

- Amphetamines
- Cocaine
- Ephedrine
- Mesocarb
- Ephedrine
- pseudoephedrine hydrochloride (Sudafed)
- Phenylpropanolamine
- Crotetamide
- Fencamine

Some of these stimulants have their positive uses in the real world. For example, most drugs for treating cold contain ephedrine, pseudoephedrine hydrochloride (Sudafed) and phenylpropanolamine. Methamphetamine and amphetamine are sometimes used medically to treat attention deficit hyperactivity disorder ADHD.

Perhaps due to their actions as neuromodulators, at synapses and neurotransmitters, they improve athlete’s focus, mental alertness and preparedness, stimulants while being less common have ironically found more use in non-sporting circles.

### <center>Chemistry of Performance enhancing drug stimulant: Cocaine</center>

![209px-Cocaine.svg.png](https://steemitimages.com/DQmPcHyniJrko1HCb6GofvmViZrLYW2d3kJJpNCt546EV8Y/209px-Cocaine.svg.png)

*Chemical Structure of Cocaine*
Source: [Ayacop](https://commons.wikimedia.org/w/index.php?curid=1263769)

Cocaine is one of the most commonly abused doping agents probably because of its extensive use as a recreational drug. Like most stimulants, cocaine acts on specific areas on the nervous system to improve alertness and focus.

Cocaine is an alkaloid. 

An alkaloid is a naturally occurring class of chemical compounds. Unlike other family of chemical compounds, alkaloids are structurally diverse. While most are expected to have the requisite Nitrogen element at their base, some do not. The different types of alkaloids might contain a Nitrogen atom and originate from amino acid, might not originate from amino acids or be a peptide or cyclopeptide alkaloids.

This confusion has been neutralized to some extent by use of the ending ‘ine’ in naming alkaloids.
Alkaloids serve lots of medical functions as they are used as anticancer, antimalarial and antibiotic agents.

Examples are morphine, caffeine, cocaine etc.
Benzoyl-methyl-ecgonine as cocaine is chemically called is an alkaloid with a lipophilic, aliphatic and hydrophilic part.

### <center>Pharmacology of cocaine action</center>

Cocaine acts at neurotransmitters by binding to the dopamine transporter.  Dopamine transporter is responsible for clearing dopamine out of the synaptic cleft. By binding to the dopamine transporter, cocaine causes a build-up of dopamine thereby increasing their action on the central nervous system.
Cocaine mediates its 'euphoric' effect by increasing dopaminergic effects in the mesolimbic system or the reward pathway.

Cocaine also blocks sodium channels and affects some serotonin receptors. This action potentiates its 'neuro-affecting' function and causes some of the physiologic response which will be discussed shortly.

Cocaine has a half-life of 0.7-1.5 hours before it is cleared from the circulatory system. Depending on the amount consumed, the cocaine metabolites might remain in the urine for four hours or even eight days after consumption. Clearance by the liver and in urine is particularly crucial for cheating athletes and led to the use of masking agents to avoid detection. 

### <center>Physiology of Stimulant action</center>

The human body produces its own stimulants and releases it at the times it deems appropriate. An example is the natural stimulant adrenaline, released especially during the flight or fight response. The human body is so well-engineered it rarely makes a mistake in its time and duration of release. Only in cases of abnormality that can be treated by the use of stimulants prescribed by a physician.

Stimulants as a performance enhancer induces the following:

- Increased mental alertness.
- Increased focus.
- Since many stimulants are sympathomimetic drugs (mimicking the sympathetic nervous system), they cause vascular constriction, increase heart rate and the contractility of the cardiac muscle.
- Their sympathomimetic actions lead to increased glycolysis and glycogenolysis, increasing the concentration of circulating glucose.
- Their vasoconstricting effect and increased force of heart muscle contraction increases blood pressure.
- Apart from their actions on the nervous system, their sympathomimetic activity serves to increase energy and the strength of the muscular tissue.

### <center>Side effects</center>

- Death- an interaction between these stimulants, especially the sympathomimetic ones and the natural sympathetic nervous system can be fatal.
-  Many have reported complaints of abdominal pain, headache, insomnia, anxiety, weight loss, dependence and addiction, dehydration and tremors.
-  There is increased heart rate and blood pressure.
- There is also an increased risk of stroke, heart attack, and cardiac arrhythmia


### <center>Athletes and stimulants</center>

A positive use for adverse situations can be seen in one of my favourite athletes, the legendary swimmer Michael Phelps. Michael was in the sixth grade when he was diagnosed with attention deficit hyperactivity disorder. Exercise was recommended as treatment for ADHD. His exercise of choice was swimming. Channelling his expansive energy into the sport transformed him to the legend we know today.

![Phelps_400m_IM_Missouri_GP_2008.jpg](https://steemitimages.com/DQmXUwdxqLagduwXV5XDCHhcbyL4EW7kBj21w73mfQEF77N/Phelps_400m_IM_Missouri_GP_2008.jpg)

*Phelps during the 400m in Missouri, 2008*
Source: [Karen Blaha](https://commons.wikimedia.org/wiki/File%3APhelps_400m_IM_Missouri_GP_2008.jpg)
 
In 2013, 100m sprinters, Asafa Powell and Tyson Gay tested positive for a banned stimulant. 

Female sprinter Sherone Simpson tested positive for a banned substance in 2013. 

Nigerians, Davidson and Osmond Ezinwa tested positive for a banned stimulant in 1996. 

Pole vaulter Piotr Lisek in 2012.

## <center>Ergogenic Aids</center>

The efforts of the World Anti-Doping Agency in championing clean sports cannot be overemphasized. In fulfilling their objective to make sports clean, fun and fair for all, they release an updated list of banned substances yearly, update every athlete’s biological passport and ensure constant monitoring is maintained in and out of competition. 

Despite their best efforts, the world of performance enhancing drugs is littered with ‘gray’ areas. One of which is ergogenic aid.

An ergogenic aid has been defined to cover a broad spectrum of techniques, nutrition, physiology, psychological, biological and any instrument that can confer an advantage in sports performance.

And, wait for this…not all are banned by the World Anti-Doping Agency. This confusion creates room for a lot of controversies.

Ergogenic aids are classified into the following:
 - Mechanical Aids
- Psychological Aids, which could include hypnosis. Some of these psychological aids have a ‘placebo effect’, infusing a ‘sports enhancer’ belief in the athlete while doing nothing physiologically.
- Physiologic aids, such as "blood doping. Most physiologic aids are on the banned list.
- Pharmacological aids, which includes anabolic steroids. Most pharmacology aids are on the banned list.
- Nutritional aid- Here even more controversy arises. Included are substances like hydroxymethylbutyrate (HMB), Conjugated linoleic acid (CLA), Chromium and Creatine.

## <center>Masking agents</center>

Just like the adage in the opening paragraph illustrates, athletes have found different ways to cheat the system. Some of these ways are:

- Lying

This might sound simple, but it’s not. An athlete may say the positive test is as a result of a food they ate or something they took; it requires a thorough investigation to tell the lie from the truth.
An example is that of MMA fighter, Jon Jones who tested positive for hydroxy-clomiphene, an anti-estrogen drug. His excuse? He couldn’t have taken the drug because he didn’t even know how to pronounce the name.

Maria Sharapova, the tennis player, is just coming out of a ban for testing positive for the drug meldonium. During the appeal, she said she took the drug for health reasons when it wasn’t on the banned list. 
A look at these two cases shows the kind of uphill battle WADA is up against.

- Athletes can also avoid detection by missing blood or urine tests or failing to provide samples. 
This comes with its own penalty, so athletes have turned to the next best thing: Masking agents.

Masking agents like the name implies are drugs used to ‘hide’ or ‘mask’ the presence of another drug. They are mostly diuretics. Diuretics are a class of chemical compounds that increase urine formation to up to 6 litres per day by reducing the rate of water reabsorption by the kidneys.

By increasing the rate of urine formation and passage, the drugs and its metabolites can be quickly cleared from the system. Even if some of the drugs are present, their concentration in the urinary sample will be so small it might be negligible.

Examples of masking agents as culled from the World Anti-doping Agency banned list are:

Desmopressin, probenecid, plasma expanders, e.g. intravenous administration of albumin, dextran, hydroxyethyl starch and mannitol.

Acetazolamide, amiloride, bumetanide, canrenone, chlortalidone, etacrynic acid, furosemide, indapamid, metolazone, spironolactone, thiazides, e.g. bendroflumethiazide and chlorothiazide.

### <center>The Masking Agent: Diuretic Acetazolamide</center>

Diuretics causes increased urine production. An example is acetazolamide. Medically used in the treatment of glaucoma and edema, as a diuretic, acetazolamide is a carbonic anhydrase inhibitor. Carbonic anhydrase is the enzyme that catalyzes the breakdown of carbonic acid to water and carbon (iv) oxide in tissues with high hydrogen ion concentration. Hence lowering the concentration of hydrogen ions in the blood. 

H<sub>2</sub>CO<sub>3</sub>⇌ H<sub>2</sub>O + CO<sub>2</sub>

In tissues with high carbon (iv) oxide concentration, carbonic anhydrase catalyzes the reaction between carbon (iv) oxide and water to produce carbonic acid.

 H<sub>2</sub>O + CO<sub>2</sub>⇌H<sub>2</sub>CO<sub>3</sub>

When the hydrogen ion concentration is low, the carbonic acid can be broken down to produce hydrogen ion and bicarbonate ion. 



H<sub>2</sub>CO<sub>3</sub>⇌HCO<sub>3</sub><sup>-</sup> + H<sup>+</sup>

In the proximal tubules of the kidney, Acetazolamide inhibits carbonic anhydrase and reduces H<sup>+</sup> secretion and the resorption of HCO3 <sup>-</sup>. This leads to an increased excretion of sodium, potassiun, bicarbonate and water. Hence, an increased urine volume.
The increased urine volume 'masks' doping agents by diluting them and increasing their excretion in the urine.


Apparently, the lure of the glory is too much for the athletes to resist. There will always be cheats. The World Anti-doping Agency is determined to sift out the cheats and maintain a clean and fair sport.

This is war.
Who do you think will win?


References

[Acetazolamide](https://en.wikipedia.org/wiki/Acetazolamide)
[Acetazolamide mode of action](https://www.openanesthesia.org/acetazolamide_mechanism_of_action/)
[Alkaloid](https://en.wikipedia.org/wiki/Alkaloid)
[Chinua Achebe](https://en.wikiquote.org/wiki/Chinua_Achebe)
[Diuretics and masking agents](http://www.doping-prevention.com/substances-and-methods/diuretics-and-other-masking-agents/diuretics-and-other-masking-agents.html)
[Diuretic](https://en.wikipedia.org/wiki/Diuretic)
[Doping in sports](https://en.wikipedia.org/wiki/Performance-enhancing_substance)
[Dopamine transporter](https://en.wikipedia.org/wiki/Dopamine_transporter)
[Doping cases in athletics](https://en.wikipedia.org/wiki/List_of_doping_cases_in_athletics)
[Effect of PEDs](https://www.usada.org/substances/effects-of-performance-enhancing-drugs/)
[Goldman’s Dilemma](https://en.wikipedia.org/wiki/Goldman%27s_dilemma)
Guyton, Arthur C, and John Hall, Textbook of Medical Physiology. 
[How serious was Maria Sharapova’s doping?](https://www.theguardian.com/sport/2016/jun/10/how-serious-was-tennis-player-maria-sharapova-doping)
[Methoide](http://methoide.fcm.arizona.edu/infocenter/index.cfm?stid=169)
[Michael Phelps](https://en.wikipedia.org/wiki/Michael_Phelps)
[Nonsteroid performance-enhancing agents in sports competition](https://www.medscape.com/viewarticle/408596_5)
[What are stimulants](https://sportsanddrugs.procon.org/view.answers.php?questionID=001213)
[The use of ergogenic aids by athletes](https://www.livestrong.com/article/104856-benefits-steroids-athletes/)
[The World Anti-Doping Agency Prohibited List](https://www.wada-ama.org/sites/default/files/prohibited_list_2018_en.pdf)
[Sprinting in drug storm as Gay, Powell and Simpson face bans after failing tests](http://www.dailymail.co.uk/sport/othersports/article-2362943/Tyson-Gay-Asafa-Powell-Sherone-Simpson-test-positive-banned-substance-drug.html)
[Performance Enhancing Substances](https://en.wikipedia.org/wiki/Performance-enhancing_substance)
[Performance Enhancers: The safe and deadly](https://www.healthline.com/health/performance-enhancers-safe-deadly)
[Why Athletes Will Win the War Against Performance Enhancing Drugs](https://gizmodo.com/why-athletes-will-win-the-war-against-performance-enhan-1784540778)


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I will discuss the Russian Doping Scandal in the next installment. Thanks for following this series especially with your comments. I enjoy reading them and answering the questions that crop up.

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