Effects of Performance Enhancing Drugs

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ADHD Medications

As the number of people receiving medication for ADHD is ever expanding, it is becoming exceedingly important to understand how these medications affect the body during exercise. Currently the most common forms of medication used to tread ADHD symptoms are stimulants. These increase the levels of some neurotransmitters in the brain by inhibiting them from being reabsorbed as they naturally would. The increase in the level of neurotransmitters, especially dopamine and norepinephrine, helps control ADHD symptoms by temporarily improving focus and other cognitive functions.

Alcohol

Alcohol is a mind-altering drug that reduces thinking ability, distorts judgment, and acts as a depressant on the body. Research has suggested that alcohol leads to increased dopamine release in the human brain, bringing on feelings of relaxation and happiness. Although this drug is often used during recreation for the purpose of feeling good, it should not be used in combination with exercise because of the serious negative physiological effects that it has on the body.

One of the most easily observable effects of alcohol on the body is dehydration. When alcohol is consumed, anti-diuretic hormone (ADH) is inhibited, causing less water to be absorbed back into the nephrons in the kidneys when urine is cycling through. This causes urine levels to increase, in turn increasing the frequency of urination. With higher levels of water exiting the body, dehydration is likely to occur. This is especially a problem during exercise, when the body is expelling water in the form of sweat as well. It is important to be fully hydrated for a workout; therefore, it is dangerous to consume alcohol before or during exercise. Research has suggested that beverages containing up to 4% alcohol can delay the recovery process from dehydration to rehydration. Alcohol does not only lead to dehydration; it also prevents humans from reaching rehydration in a timely manner, which could be deadly in a situation regarding exercise.

Another important physiological effect that alcohol has on the body deals with blood pressure. Alcohol consumption increases blood and plasma volume, which in turn increases blood pressure. Exercise has a similar effect; the sympathetic immune system is stimulated, leading to vasoconstriction and ultimately increasing blood pressure. To practice safe exercise, it is important not to elevate blood pressure too high beforehand. Research has recommended that alcohol consumption be reduced in order to maintain healthy and safe blood pressure levels. Likewise, it is unsafe to consume alcohol before or during exercise because blood pressure levels may rise to dangerous levels.

Perhaps the most important physiological effect that alcohol has on the body is that which concerns the heart. Research has shown that intoxication by alcohol directly relates to impairment of cardiac contractility. Depending on how much alcohol was consumed, cardiac contractility was impaired at varying levels; a lighter intoxication lead to less impairment while a heavier intoxication lead to greater impairment. Exercise causes heart rate to increase, requiring a great deal of cardiac contractility. If the heart is impaired because of alcohol intoxication, blood may not be pumped sufficiently throughout the body during exercise. Therefore, if a person plans on exercising, they should either drink lightly or not at all in an attempt to keep their heart working properly.

Alcohol is the most popular drug in the world consumed by athletes, negatively affecting their exercise performance in terms of skeletal muscle performance, metabolic function, and immune system function. Alcohol consumption impairs metabolic processes during exercise because skeletal muscles decrease their use of glucose and amino acids, thereby adversely affecting their energy supply and metabolism. As a result of the alterations in metabolism, alcohol consumption has been shown to cause muscular atrophy and neurogenic damage. In addition to these physiological changes, alcohol consumption also impairs the host defence mechanism of the immune system. It does this by decreasing lymphocytic cell numbers in the blood and by impairing macrophage phagocytic processes. Lastly, alcohol consumption has been shown to damage the liver, resulting in possible cirrhosis. In turn, people with cirrhosis commonly have impaired exercise capacity and oxygen consumption. Many of the adverse effects of alcohol consumption can be lessened by participating in exercise, but alcohol use immediately prior to, during, or following a bout of exercise should be avoided. If a person does drink alcohol, the person should only drink during times of general relaxation and not near their normal times of exercise.

Anabolic Steroids

Anabolic steroids are drugs that have many neuropsychiatric effects in addition to the more commonly known effects they have on skeletal muscles. Anabolic steroids cause not only negative feelings like intense anger, but also some positive moods. Some of the negative feelings people have resulting from the use of anabolic steroids include irritability, mood swings, violent feelings, anger, and hostility. Among the positive feelings related to steroid use include euphoria, increased energy, and sexual arousal. Steroids are also linked to other cognitive symptoms like distractibility, forgetfulness, and confusion. All of these effects result from steroid use alone, without exercise. These impacts on mood could have either positive or negative effects on exercise, depending on feelings of the person exercising.

Steroids have not been shown to increase creatine concentrations in the muscle, red blood cell concentration, or serum liver enzyme concentrations as some have postulated. In addition one study found that injection of 600 mg of testoterone in adult males who did not exercise, resulted in more fat free mass and a greater increase in strength than individuals who did incorporate resistance training but only took a placebo. Some commonly reported side effects of steroid use, such as acne and breast tenderness resulted in some of the subjects as well, but most did not. This would seem to indicate that individual physiological differences have a profound impact on how a person reacts to steroids.

Analgesic Medication

Analgesic medication is a category of drug that is meant to cause the cessation of pain within an individual. Because of the effect that analgesic have on the body, these types of medication are more commonly referred to as painkillers. They can come in both prescription form and over the counter form, and are typically used by individuals who have experienced some type of injury or who suffer from painful diseased.

As with all medication, there are positives and negatives associated with usage, and one study set out to determine the effects of opioid usage on activities of daily living (ADL). The medication in that was used in the study was buprenorphine transdermal delivery system (BTSD), and it was evaluated for its effectiveness in helping patients with chronic low back pain (CLBP) perform ADL’s. The results showed that those individuals with CLBP who wore the BTSD patch experienced a reduction in pain and a significant improvement in abilities to carry out ADL’s . This medication could benefit those who wish to implement a strengthening or stretching regime because it ultimately reduces pain and allows increased participation in ADL’s.

Caffeine/Stimulants

Caffeine is the most widely used stimulant in the world. This is because caffeine consumption is completely legal, socially acceptable, and is consumed daily by a large majority of the world population. Daily morning staples, such as coffee and tea, as well as soda pop and energy drinks contain caffeine. Much research has been conducted to determine how caffeine consumption effects one’s body systems and processes during exercise. Many studies support the findings that caffeine enhances both physical and cognitive performances. Physically, caffeine specifically improves aerobic performance— extending the time that an activity can be sustained prior to fatigue. Mixed results exist as to whether caffeine significantly improves performance in resistance training. Several mechanisms work on different systems of the body to produce the overall enhancement of exercise performance that caffeine causes.

A neuromuscular mechanism that aides in causing caffeine’s ergogenic effects is its influence on the ryanodine receptors in the sarcoplasmic reticulum of muscles. The function of these receptors is to open to allow Ca²⁺ to flow out of the sarcoplasmic reticulum. Ca²⁺ facilitates the contraction of muscle fibers. Ca²⁺ binds to troponin, which moves tropomyosin aside so that myosin can bind to the actin myofilaments and muscle contraction can occur. Therefore, the effect that caffeine has on this system is to make Ca²⁺ more readily available, which allows for stronger contractions of muscles than is typical at a given level of stimulation.

Caffeine has also been shown to enhance exercise performance by reducing pain thresholds. Many studies have looked at caffeine's effect on the aspect of fatigue during a muscle contraction and attributed the increase force maintenance to decreaced pain perception. One study found that plasma b-endorphin levels almost doubled after two hours of cycling with caffeine consumption, while the control group had no increase. Therefore, caffeine's effect to lower pain perception is beneficial to endurance exercise performance. 

Caffeine also acts on the nervous system. Specifically, it affects normal neurotransmitter release, increasing both the amount of noradrenaline (NA) and dopamine (DA) released in the brain during exercise. Dopamine has widespread functions, but a few of these include influences on motivation, cognition, reward, motor control, and mood. Many studies have shown that an increase in DA release results in enhanced endurance. One such study showed that muscle pain perception and perceived exertion was much lower in a group that received caffeine prior to resistance training, as opposed to when those same subjects were administered a placebo on a separate date. When the individuals ingested the caffeine, they performed significantly more repetitions before failure than when they were given the placebo.

Although research supports the ergogenic effects of caffeine on endurance, it has been less conclusive as to whether caffeine has the same type of effects on resistance training. Data from several studies supports an increase in resistance training performance following caffeine ingestion; however, researchers have been unable to isolate the exact physiological mechanism responsible for this. Therefore, the increased performance could potentially be due only to the decreased pain & exertion perception of the subject [as previously explained].

One other substantial mechanism by which caffeine positively effects athletic performance is by increasing the rate that lipolysis occurs. Lipolysis is the process human bodies use to break apart fats and produce ATP (our primary usable form of energy) to fuel our body. Each triglyceride (fat molecule) that is broken down produces approximately 300-400 ATP (depending on how many carbons form the specific fat being used). The increase in fats being used to produce energy results in a decrease in carbohydrates used for that same purpose. This greatly increases efficiency because carbohydrate molecules produce far fewer ATP than triglycerides.

There are many factors in the methods of caffeine studies that cause confounded results. One factor that must be considered is the dose of caffeine administered. The many studies use different doses when investigating the effects that caffeine has on exercise. Researchers use doses of anywhere from 2-8 mg/kg, but the methods of most studies call for doses of 5-6 mg/kg. Doses of 2-5 mg/kg improve athletic performance by approximately 3%, whereas doses of 5-7mg/kg improve performance by approximately 7%. Other factors include the form of caffeine used, other ingredients in the caffeine source and their possible physiological effects, diet, time and intensity of exercise tested, and length of time prior to exercise that the caffeine is administered. These variables, in addition to many others, increase the complexity of research of caffeine and exercise performance.

The adverse effects of caffeine consumption in athletes who use it conservatively are minimal, if at all present. However, if the consumer is sedentary, or if the caffeine intake exceeds 7mg/kg, many negative side effects occur. In a sedentary person, caffeine interferes with the role of insulin, and therefore, also effects the metabolism of fats and carbohydrates. Most sources of caffeine are also high in glucose, which is a combination that leads to a decline in glucose disposal. Therefore, in the sedentary person, decreased glucose disposal often leads to obesity, which can cause many diseases, such as type 2 diabetes and metabolic syndrome. If caffeine intake exceeds 7mg/kg (even in the active individual), side effects such as nausea, jitters, headaches, and tachycardia present themselves. Additionally, these large doses do not improve athletic performance any more than the 7% improvement caused by doses of 5-7 mg/kg.

Another negative side effect that can occur from caffeine intake is its effect on Polycystic Kidney Disease. Polycystic Kidney Disease is the most common kidney disease in adults. It is an inherited disease that currently has no cure. Cysts are formed in the kidneys and grow in number and size overtime. The disease can lead to many more health problems and eventually kidney failure. There has been suggestive research that caffeine plays a role in PKD. A nucleotide known as cAMP stimulates the growth of cysts and the secretion of cyst fluid. One study showed that caffeine promotes the accumulation of cAMP in the kindeys, which leads to an increase in the size and number of cysts. The study noted that caffeine has this effect on the kidneys in only those who have PKD. If a person has PKD, they should avoid drinks such as coffee, tea, soda, or pre-workout drinks that contain a high amount of caffeine.  Water could work as a substitute and also gatorade after a workout to replenish their electrolytes.  

Creatine

There are many benefits associated with the use of creatine such as increased strength, increased lean body mass, and enhanced fatigue resistance which is crucial to the elderly population.  Creatine supplementation plus resistance training translates into a larger increase in bone mineral density than just resistance training alone. It has been shown that with higher brain creatine, there comes with an improved neuropsychological performance.  Many athletes utilize creatine for body building and for the use of working out as well. It's become a more frequently used supplement by many people around the world. For older adults, the use of creatine can improve their quality of life and may reduce the disease burden on their cognitive dysfunction. Creatine is a safe and cheap supplement that has both central and peripheral effects for adults. 

              Creatine supplementation has been associated with increased water retention and consuming 20 grams for as little as six days significantly reduces urine output when controlling for other factors . Creatine supplementation also results in a small but significant increase in IGF-I and IGF-II growth factors which are associated with human growth hormone . After prolonged bed rest, creatine supplementation results in a faster recovery of both muscle cross sectional area and maximul power ouput when compared with a placebo alone . Reports that creatine supplementation results in increased incidences of cramping are not supported by current research .

Although creatine has been shown to have many benefits associated with exercising, it also has some side effects. One major side effect is its effect on the kidneys. The research regarding this topic is inconclusive because many studies show different results of creatine and its effect on the kidneys. In one study, a prolonged creatine supplementation of 12 weeks did not have any adverse effects on the kidneys. The subjects were taking part in a resistance training program and consuming a high-protein diet, like most athletes. This study supports the use of creatine;however, in a case study on an 18 year old male, creatine did have adverse effects on the kidneys. The subject was taking the recommended amount of creatine (20g/day for 5 days (loading phase) and 1g/day for 6 weeks (maintenance phase)) and still experienced acute kidney failure. The subject was hospitalized and stopped the consumption of creatine and after 12 days his health returned to normal.  Since research is inconclusive on whether creatine causes adverse effects on the kidneys, individuals should be aware that kindey damage is a possibility while consuming creatine. 

Human Growth Hormone (HGH)

Human growth hormone (HGH), also known as somatotropin, is peptide hormone secreted by the anterior pituitary gland . HGH is an anabolic hormone that builds and repairs tissue, such as collagen and muscle tissue, throughout the body. HGH release is stimulated from the release of growth hormone releasing hormone (GHRH), which is released as a result of exercise. HGH promotes the release of IGF-1, which promotes anabolic effects within the body. HGH is an important component of metabolism by increasing lean body mass and promoting lipolysis. Groth Hormone also increases synthesis of of muscle protein via amino acid transport and amino acid availibility. It also helps facilitate body's response to exercise, however it's effects are not restricted to protein alone. HGH is only released periodically, such as during certain stages of sleep, certain parts of the day, and with exercise. The periodic release of HGH combined with its positive anabolic and metabolic effects on the body has lead to supplementation of HGH to improve exercise performance.

HGH injections and supplements are widely abused by athletes to enhance performance. Nevertheless, there is not enough definititive evidence that HGH improves performance. Meinhardt et al. (2010) investigated the impact growth hormones have on body composition and measurable performance in recreational athletes. The authors argued that growth hormone injections increase athletic exercise performance when given alone or with testosterone. In addition, participants that received growth hormones retained more body fluid and frequent joint pain than control group  Zajac, Wilk, Socha, Maszczyk, and Chycki (2014) analyzed the impact of recombinant human growth hormones and testosterone injections on aerobic and anaerobic fitness, body mass, and lipid profile in adult men. The data demonstrates that recombinant human growth hormones and testosterone injections significantly increased aerobic and anaerobic capacity, led to changes in body compositions, and decreased total body fat and increased free-fat muscle.

Liu et al. (2008) conducted a systematic review to explore the effects of growth hormone on athletic performance. The aggregated results revealed that lean body mass increased and basal metabolic rate was higher after HGH supplementation. The results of the study shows why athletes look to HGH as a means to improving body composition. The increase in lean body mass can often lead to an increase in metabolism due to the body needing to build and repair the additional lean body mass. The study did not find any significant results in muscular strength or improvement in aerobic exercise.

There are serveral side effects seen when supplementing HGH. According to findings in the systematic review by Liu et al. (2008) these side effects include sweating, joint pain, swelling, and possibly carpal tunnel syndrome. Other side effects of concern include risk of diabetes in elderly populations because of the elevation of glucose in the blood it causes. Long term saftey of HGH supplemetation is still under investgation, but preliminary studies on mice show that there is not an increased risk to survival, longevity, or tumor development, but it is unknown if these findings will transfer to humans. High doses of HGH supplemetation can cause functionally weaker muscles depsite increases in hypertophy. Consistantly high levels of GH may also result in hypertension, cardiac, and metabolic complications. Abuse of Groth Hormone can cause significan health risks when taken with other drugs. Unfortunately, the extent of these health risks are unknown because of ethical delemas in doing studies on drug abuse. Despite these negative side effects, HGH is still one of the most commonly abused drugs especially among athletes and atheltic populations.   

Marijuana

Marijuana use affects various physiologic processes through its most active substance, tetrahydrocannabinol, otherwise known as THC. Marijuana use has a direct effect on the central nervous system because it contains the receptor sites for THC. Although marijuana does possess some ergogenic effects in certain situations, it impacts the body oppositely during exercise. The drug has a sedative effect during exercise, resulting in decreased exercise and psychomotor performance like slower reaction time. In terms of the cardiovascular system, marijuana has been shown to increase heart rate and blood pressure while decreasing overall cardiac output. This is important for clinicians to consider when treating patients who use marijuana, as it is an ergolytic drug when used in combination with exercise that will negatively affect the patient’s exercise performance and overall health.

Tetrahydrocannabinol is the primary constituent of marijuana that binds to G-Protein-Coupled CB1 receptors which are found throughout the brain in the frontal and and medial temporal lobe. Marijuana is one of the most frequently used drugs among young adults. Marijuana induces tachycardia which can decrease the maximal work capacity after smoking this drug.  Marijuana creates an increase in carboxyhemoglobin concentration of blood due to large amount of carbon monoxide created from the smoking of this drug.  Some other factors that coudl affect the maximal work capacity after smoking marijuana are bronchodilation, decrease in perception of dyspnea, and increase blood flow to exercising muscles.  The utilization of marijuana with exercise has a negative correlation that affects their overall health greatly. 

Methamphetamine

Amphetamines are a group of drugs with mind-altering capabilites. Methamphetamines are the most potent of the amphetamine group of drugs.  Methamphetamine falls under the classification of a stimulant. Typically, stimulants will increases and individuals sensations such as mental awareness while also increasing one's ability to respond to the environment. Users of stimulants may also find an increase in energy levels. The effects that users feel while on methamphetamine (METH) causes this drug to be highly addictive. The physiological effect of METH is achieved by increasing the quantitiy and release of stimulatory neurotransmitters dopamine, noradrenaline and serotonin and decreasing their synaptic breakdown.  

A primary clinical consideration for methamphetamine is its use with other medications. Acute use of METH with other stimulants can overstimulate the sympathetic nervous system, potenitally resulting in cardiac arrythmia, seizures, cardiovascular collapse, and death.  Therefore, physical therapists should take special consideration when prescribing exercise to patients who present with signs suggestive of use. Characteristic presentation of METH use includes restlessness, weight loss, heightened alertness, violent behavior, and pupillary dilation.  

An acute response to METH use is hyperthermia.  Although the exact mechanism though which this is achieved is unknown, literature suggests that methamphetamine-induced hyperthermia results from heat generation as well as an inhibition in heat loss.  One study conducted in 2009 aimed to explore the effects of brain hyperthermia brought on by METH. The reaserachers of this study injected rodents with differing amounts of METH, and then proceeded to measure how dosages and enviromental factors impacted brain hyperthermia . METH, especially in large doses, influences the metabolic activity of the brain due to oxidative stress which is what occurs when the body is unable to rid itself of free radicals at a rate to maintain a homeostatic balance . Temperatures inside of the brain also increase due to "enhanced release of meluiple neuroactive substance, lipid peroxidation.... and numerous changes combined as oxidative stress" . Increases in the metabolic brain activation paried with internal head production by the brain cells seem to be the driving force behind brain hyperthermia . Ingesting METH at increased tempertures or during social gatherings when an individual is more likely to be active such as with exercise only exacerbates this increase in core body temperture. Even slight increases in cell tempertures can cause denaturation, which can then lead to impaired cell function or ultimately death of the cell.

Thus, combining therapeutic exercise when an individual is experiencing methamphetamine-induced hyperthermia could result in serious harm. The current practice for cooling methamphetamine-induced hyperthermia is placing the individual in a cool environment to try to bring that person back into a homeostatic balance .

Chronic METH use results in a range of physiologic disturbances. An adaptation with the greatest relevance to physical therapists is the presence of congestive heart failure in chronic users.  Impaired oxygen delivery to tissues would result in an inability to safely engage in treatment on the part of the patient. Moreover, attempting to engage in such an activtiy could result in cardiogenic shock. If the practitioner engages the patient in these activities without knowing about METH use, the outcome could be fatal. Another clinical implication is that chronic METH use can break down the blood-brain barrier (BBB) over time, and it has been shown that increased permeability in the BBB can lead to damage of myelin . Without myelin, the nervous system is unable to communicate effectively to different systems, including muscular, which could have an impact on exercise prescriptions and individual expectations.

Muscle Relaxants

Muscle relaxers are a class of drug that effectively decreases skeletal muscle function which in turn produces a tranquilizing effect. Botulinum toxin type-A (BoNT-A) is one type of muscle relaxer that could be commonly seen within a rehabilitation type setting. Research has shown that BoNT-A injections can produce positive outcomes when it comes to controlling spasticity and muscle tone. When considering the effects of exercise and BoNT-A, children who have cerebral palsy (CP) are a good target population to consider given the spasticity that often accompanies the disease. Research has shown that children who receive BoNT-A injections and strength training programs show both an increase in muscle volume as well as a rise in strength . The timing of the injections in relation to strength training did not seem to be a factor in strength improvement, and overall children with CP who received this injection had positive outcomes in their functional ability . This is clinically significant because therapists will be able to increase strength in areas that may be contracted with the assistance of BoNT-A injections.

Another Study looked at the effects of BoNT-A injections for treating spasticity in individuals who had suffered a stroke. As one could imagine, spasticity in the lower extremities can have detrimental effects on an individual’s ability to walk, and this can directly influence their ability to ambulate and gain back independence in life. Many individuals who have been affected by a stroke will have BoNT-A injections to reduce spasticity, but do not include therapeutic activities to either increase strength or function. The results of this study show that those who receive BoNT-A injections and a self-rehabilitation program improve their maximal gait speed, distance covered and max speed during 6MWT-modifeid (6 minute walk test), and time taken to go up or down a flight of stairs in comparison to those who only receive the injections. This research shows that a home stretching and strengthening program can help prevent muscle wasting, and can also improve gait patterns which will then increase an individual's ability to move around independently.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), including acetaminophen (asprin) and ibuprophen, simply put, reduce inflammation and pain. NSAIDs are widely and commonly used, which is why researchers are continuously studying the risks and benefits of their effects on the human body. 

NSAIDs work by inhibiting the activity of an enzyme called cyclooxygenase (COX), which is crucial in the formation of prostaglandins. Prostaglandins play a role in the generation of pain and in the inflammatory response, however they also have roles in many other bodily functions. When NSAID’s inhibit prostaglandin synthesis they can reduce pain and inflammation, but they can also hamper gastrointestinal functions and post-exercise protein synthesis, as well as cause a number of other positive and negative side effects. Interestingly, evidence shows that certain side effects are age dependent. 

Smoking

Aerobic exercise challenges the body's ability to supply and handle oxygen. For example, when performing high-intensity aerobic exercise, mitochondrial reactice oxygen species' (ROS) grow in number. ROS, is left unchecked, have have the ability to cause genetic mutations. However, several enzymes -- including superoxide dismutase -- are present to handle this oxidatve stress caused by ROS.The body responds to chronic aerobic exercise by enhancing its ability to cope with ROS.  

Smoking also induces an oxidative stress; however, smoking-induced oxidative stress also inhibits the body's abiltiy to cope by suppressing the genes responsible for antioxidant production.  The net result of smoking-induced oxidative stress is vascular and arteriolar inflammation -- further impairing the oxygen-delivering capabilties of the body.  Clearly, by limiting oxygen delivery, cigarette smoking impairs the ability to generate energy through the oxidative energy system. However, literature also suggests that smoking impairs anaerobic energy provision by altering contractile proteins, creatine kinase, and other glycolytic enzymes. With this in mind, therapists should be weary of setting unrealistic goals for patients who are smokers. 

Smoking is a huge risk factor coronary artery disease and many other complications such as myocardial infarction and sudden death. Smoking is one of the biggest cause of death in the world. Smoking is also associated with marked, acute, and increase in blood pressure, systemic vascular resistance, and heart rate.  Nicotine is one factor that stimulates epinephrine and norepinephrine release from the sympathetic nerve terminals and adrenal glands, which explains that acute cardiovascular effects may be due to adrenergic stimulation at the peripheral levels. Acute cigarette smoking is associated with a significant decrease in vagal cardiac modulations which may increase the risk of complications during daily exercise or intense physical activity. Acute smoking affects the cardiorespiratory responses to both submaximal and maximal exercise, which can result in an increase of sympathetic dominance at lower levels of submaimal work. Clinicians should be considerate of all options and treatment plans for patients who are avid smokers.

References

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