Medication Choice

Athletes are often assumed to be healthy, and yet medication use among athletes is very common. As with any patient, the medical history of the athlete must be considered when deciding whether to prescribe a medication, but additional considerations can affect the care of this population. For instance, the use of medications that can affect performance by causing fatigue, gastrointestinal symptoms, or dehydration must be taken into account. Awareness of an athlete’s supplement and over-the-counter medication use has a role in their care as well. There is significant potential for interactions between these products and prescription medications, which can lead to adverse effects. There is also a tendency toward aggressive management of “in-season” athletes that must be recognized by the team physician and taken into account when assessing the pros and cons of various treatment options. Alongside treatment decisions comes a needed familiarity with drug-testing policies and banned substances. Relatively common medications that are appropriately prescribed can be deemed unallowable by a sporting body and cause the athlete to be ineligible. These factors make medication selection a crucial topic within sports medicine.

Nonsteroidal Antiinflammatory Drugs

The topic of medication use in sports often starts and ends with pain control, primarily nonsteroidal antiinflammatory drugs (NSAIDs). Athletes have become familiar with NSAIDs such as ibuprofen and naproxen, which poses a unique issue: As athletes become more comfortable taking these medications, the pills come to be perceived as benign rather than as medications with potentially severe adverse effects that should be used cautiously. An evaluation of adolescent football players and their use of NSAIDs showed that 75% used NSAIDs in the past 3 months and 15% use them daily. The majority of players (63%) did not acknowledge the risk of any adverse effects, and 76% did not consult an adult before taking the medication. Olympians have demonstrated similar dispositions; they regularly use these medications at both incorrect doses and for inappropriate indications and sometimes overlap the use of multiple NSAIDs. NSAIDs should be used judiciously, and efforts must be made to teach athletes about the proper use and risks of these drugs.

NSAIDs have both analgesic and antiinflammatory properties, and both of these attributes lead to their regular use in the practice of sports medicine. Pain and inflammation are common results of muscle, tendon, and ligament injuries. As these injuries occur, there is an influx of inflammatory cells, and cytokines and growth factors are recruited to the site of tissue damage. Subsequently, cascades of cell-mediated responses to the injury and inflammation start the process of healing and rebuilding tissue. NSAIDs are useful for reducing edema and soreness after activities that call for quicker recovery of motion and short-term muscle function recovery. NSAIDs also have benefits in persons with arthritis; a metaanalysis of hip and knee arthritis studies showed improved pain and function with NSAID use compared with placebo. An additional benefit may be seen in muscle contusions, which can be complicated by heterotopic calcification if they are not properly treated. At least 2 weeks of scheduled NSAID use may decrease the rate of heterotopic calcification.

NSAIDs function by blocking the enzyme cyclooxygenase, which converts arachidonic acid into prostaglandins and thromboxane. Prostaglandins are involved in pain sensation, inflammation, and fever. They also play a role in gastric mucosa protection, which leads to the common adverse effect of gastritis, ulcer disease, and gastrointestinal bleeding. The severity and frequency of these issues can be reduced with the use of proton pump inhibitors. Thromboxane promotes platelet aggregation, and therefore its inhibition leads to an increased risk of bleeding.

Other considerable risks are associated with use of NSAIDs. Stroke, myocardial infarction, and thrombotic events are potential outcomes of NSAID use. Renal toxicity is another complication; analgesic nephropathy with reversible renal toxicity has been documented in persons of all ages, including adolescents. Acute use of NSAIDs in the event setting may lead to decreased renal perfusion, thus exacerbating the renal insufficiency caused by dehydration. Endurance athletes are at risk of exacerbating exercise-associated hyponatremia during long races and during training, which is thought to be secondary to a reduced glomerular filtration rate.

Ketorolac has been a mainstay in sports medicine for years. The function of ketorolac is similar to that of all the other NSAIDs, but it is often used as an intramuscular injection. The medication is commonly used by professional and collegiate teams for analgesia before a game begins. It has a rapid onset of as early as 10 minutes, reaching peak serum concentration in 30 to 60 minutes. Effects last from 4 to 8 hours. Arguments against the use of intramuscular ketorolac include the potential to achieve similar effects with oral medications; masking of symptoms, which can lead to further injury; and the usual risks associated with NSAID use. As with all medications, the decision to administer it should be reserved for patients with the proper indications, and all risks and benefits should be discussed.

Topical formulations of NSAIDs have become popular in sports medicine. This delivery method can decrease the risks of gastric, renal, and vascular adverse effects. Less systemic effect occurs as a result of the decreased serum concentration, which leads to fewer complications and a lower risk of drug interactions. Topical NSAIDs have been shown to be as effective in the treatment of certain musculoskeletal pathologies as the oral form. The most common adverse effects with the topical formula are rash and pruritus. Used appropriately, topical NSAIDs can be a safe and effective substitute for oral NSAIDs, but they are often cost prohibitive.

Asthma Medications

Asthma is a pulmonary condition attributed to inflammation of the airways that is associated with increased pulmonary responsiveness to intrinsic or extrinsic stimuli. Asthma manifests clinically as cough, dyspnea, and wheezing. Asthma can affect athletes primarily by limiting their performance as a result of coughing and the inability to take deep, effective respirations. This effect is seen in athletes with either chronic asthma or exercise-induced bronchospasm (EIB), which are more prevalent in competitive and elite athletes than in the general population. It is unclear if this increased prevalence is a true increase or is due to other causes, such as a heightened awareness of asthma in sports or the belief that taking asthma medications may result in performance enhancement. Surveys have demonstrated that 10% of athletes have EIB, with the highest estimate of 45% among cyclists specifically. Overall, 22% of American and Italian athletes experienced asthma during the previous three Olympic Games. As noted, EIB is most prominent in athletes who participate in cycling, cross-country skiing, cold-weather sports, summer endurance sports, and swimming.

Athletes with chronic asthma should be treated the same way as persons with chronic asthma in the general population, with control of exacerbations and maintenance of lung function being the guiding treatment goals. EIB involves a slightly different management philosophy because treatment focuses on allowing performance through short-term symptom control. Short-acting β-agonists are used 30 minutes prior to exercise in athletes with EIB. Limited data show a role for long-acting β-agonists in persons with EIB, with formoterol demonstrating a decreased number of exacerbations in some cases. Leukotriene receptor antagonists (e.g., montelukast and zafirlukast) can attenuate EIB in 50% of patients. Cromolyn sodium, a mast cell stabilizer, has been shown to be beneficial if it is taken prior to exercise, but it is less effective than albuterol.

β-Agonists are the most commonly used medication for EIB and chronic asthma treatment in athletes. They do pose risks and can have adverse effects, including tachycardia, muscle tremor, headache, and irritability. Conversely, the potential performance-enhancing effects of β-agonists have been researched and discussed. Performance improvements were documented in two small studies that initially brought this idea to light, but the results have not been replicated. A recent metaanalysis by Pluim et al. reinforces this idea. Twenty-six randomized controlled trials involving 403 participants were reviewed and showed no significant effect on maximum oxygen uptake (VO ₂ max), anaerobic threshold, endurance time, peak power, or strength performance with the use of inhaled β-agonists. A significant effect was found in 13 studies that tested systemic β-agonist use versus placebo in endurance time to exhaustion and peak power, although the evidence base was deemed to be weak. Signorile et al. observed an increase in peak performance after inhaled short-acting β-agonist use in recreational athletes, but it is unclear whether this finding was due to any ergogenic effects or simply improved asthma control. Ergogenic effects with resultant improvement in strength, performance, and anaerobic power have been seen with oral (but not inhaled) administration of salbutamol. The overall evidence points toward no ergogenic effect from inhaled β-agonists at therapeutic doses. β-Agonists are prohibited by the World Anti-Doping Agency (WADA) except for salbutamol, formoterol, and salmeterol when used via inhalation at recommended doses, and therefore a therapeutic use exemption (TUE) is no longer required. All athletes with asthma who require use of inhaled β-agonists other than salbutamol, formoterol, and salmeterol require a TUE and documented proof of a diagnosis of asthma, including results of pulmonary function tests. Athletes with only EIB must undergo exercise challenge testing per WADA guidelines. Close monitoring of asthma symptoms and control is important for performance despite the regulatory issues that can arise.

Allergic Rhinitis

Allergic rhinitis is a common and relatively benign condition, but it can have a profound effect on athletic performance. Significant congestion of the nasal passages inhibits optimal oxygen intake, which alters breathing patterns during high exertion. Limiting allergen exposure is the first-line treatment for allergic rhinitis but is difficult in sports settings because many events are outdoors, in extremes of weather, or at indoor pools that can worsen symptoms. Chronic nasal swelling also predisposes to poor sleep and fatigue from snoring, nighttime cough, and postnasal drip, causing a sore throat. With the widespread availability of over-the-counter allergy medications, it is important to ask the athlete what he or she is taking to treat the symptoms, because athletes often try self-treatment before they present to the sports medicine physician. Antihistamines such as loratadine, fexofenadine, and cetirizine are easily available and are often tried by athletes who attempt to treat themselves. Optimally, the avoidance of allergens and the subsequent use of intranasal glucocorticoids are first-line treatments. Use of oral or topical decongestants can also be tried. If allergies are severe enough, allergy testing and subsequent desensitization can be pursued.

Antibiotics

Antibiotics are often well tolerated, and their use is not limited by any governing bodies. Nevertheless, special considerations need to be taken into account when treating athletes with antibiotics. When treating skin, respiratory, or urinary infections, the athlete’s expectations, the dosing frequency, and adverse effects should be evaluated. Like every patient, athletes have expectations of treatment, and the culture of athletics tends toward aggressive care, particularly with in-season athletes. Sports medicine physicians have the important duty of maintaining appropriate, evidence-based care despite pressures for antibiotic use at the first sign of a possible infection. Deciding when to prescribe an antibiotic can be difficult because the value of one extra day missed is much higher for in-season athletes than for the general population. Busy training and practice schedules create an added value to limiting medication dosing because athletes often do not have the opportunity to take many breaks in their schedule. To improve compliance, it is important to limit the number of pills that need to be taken on a daily basis.

The issue of adverse effects plays a profound role when the decision is made to treat an infection. Aside from possible allergies, the penicillin and cephalosporin classes do not have any specific limitations. On the other hand, fluoroquinolones have a multitude of indications, but caution should be taken when prescribing them for active patients. The major concern is the increased overall risk of tendon injury. This risk has been shown to have an odds ratio of 1.4, with the highest risk being Achilles tendon injury. The mechanism of tendon injury from fluoroquinolones is not well understood, but increased risk was seen with concomitant steroid use. QT prolongation, photosensitivity, and poor glycemic control have also been observed in persons who use fluoroquinolones. Photosensitivity reactions are also seen with tetracyclines and sulfamethoxazole. Azithromycin use has also been associated with QT prolongation, which has changed many providers’ prescribing habits. Comprehensive knowledge of these adverse effects and a thorough discussion of the risks of these usually benign medications need to be a part of treatment discussions with athletes.

Community-acquired methicillin-resistant Staphylococcus aureus has become more prevalent in the past several years, primarily in athletic populations. S. aureus is found commonly as part of normal skin flora. Athletes can be at risk because skin disruptions are common as a result of abrasions, turf burns, shaving, and chafing. Exposures from the training room, workout equipment, and shared towels are considered vectors of contamination for athletes. These infections should be treated aggressively because of the risk that they will spread through soft tissue structures, and because of the risk of infecting teammates. First-line treatments include trimethoprim-sulfamethoxazole, doxycycline, or clindamycin. Resulting abscesses should be drained and cultures obtained to confirm sensitivity as appropriate. Clindamycin is associated with diarrhea and the risk of Clostridium difficile colitis and needs to be considered, although this risk is seen with other antibiotics as well. Definitive evidence does not exist for decolonization with soap baths or nasally applied mupirocin. In addition, no validated role exists for methicillin-resistant S. aureus screening in athletes at this time.

Acne

Acne and other skin conditions can worsen during participation in athletics. Skin irritation from prolonged sweating, wet clothing, and equipment are the usual culprits for exacerbation of symptoms. Acne itself does not have much effect on performance because it is primarily a social and cosmetic concern, but medications used in its treatment should be assessed for their effects. Topical antibiotics and benzoyl peroxide are often used in combination to treat acne. Topical clindamycin and erythromycin are commonly used antibiotics because they have both antiinflammatory and antimicrobial effects. They are generally well tolerated with adverse effects of local irritation, erythema, itching, peeling, and burning. Combination therapy with benzoyl peroxide is needed to prevent the resistance to treatment that can occur with monotherapy. Benzoyl peroxide is a powerful antimicrobial agent, but it can cause skin dryness, irritation, and bleaching of hair and clothes. Overall, these topical therapies are well tolerated.

Retinoid drugs are used for treatment of severe or nodulocystic acne. These medications have known concerns, particularly for women of reproductive age, because they are known teratogens. Women of reproductive age who take retinoid drugs must undergo monthly pregnancy tests that are monitored through a federally mandated registry. Retinoid drugs also have a known association with photosensitivity reactions. Joint pain, back pain, and elevation of creatine kinase levels have been observed as well. These medications should be used with caution, especially with young, healthy female athletes.

Oral antibiotics are also used as a regular treatment for acne. Tetracyclines are well known for being associated with phototoxic cutaneous reactions, with an incidence as high as 5%. Minocycline has been shown to cause lupuslike illness, joint pain, myalgia, and fever.