For the Temporary Relief of Minor Aches …

… there are a plethora of choices. Here’s how to steer your athletes in the right direction when they have questions about pain medications.

By Dr. Stan Reents

Stan Reents, PharmD, is President and CEO of AthleteInMe, LLC. He is the author of Sport and Exercise Pharmacology, published by Human Kinetics, and the former Editor-in-Chief of Clinical Pharmacology, at www.cp.gsm.com.

Training & Conditioning, 14.7, October 2004, http://www.momentummedia.com/articles/tc/tc1407/reliefofaches.htm

Sometimes it’s to help ease the pain of an injury. Other times it’s for delayed-onset muscle soreness. Or maybe it’s just for a headache. Whatever the reason, pain medications are often needed by athletes.

While athletic trainers are neither physicians nor pharmacists, they are often the first source that athletes turn to for advice on pain medications. Thus, as new drugs continue to be introduced, it’s imperative that athletic trainers keep up with the changes in the field.

In this article, I’ll update athletic trainers on the types of oral medications they should know about (including the newer "selective COX-2 inhibitors"), contraindications, and how to choose among products. I’ll also answer some of the most-asked questions about dosing.

Different Types
Although pain medications can be dispensed in many different forms, this article will be limited to pain medications taken orally, which can be grouped as follows:

• NSAIDs
• aspirin
• acetaminophen
• opiate agonists

NSAID stands for non-steroidal anti-inflammatory drug, and they are used most often when an athlete has pain and/or inflammation. They also help reduce fever. The first NSAID to be marketed was Motrin® (ibuprofen) in 1974, and thus some people refer to NSAIDs as Motrin-like drugs.

Aspirin is a salicylate, and it works similarly to NSAIDs in that it can be used to reduce pain, fever, and inflammation. Acetaminophen, while treating pain and lowering fever, has no anti-inflammatory properties. Opiates are used only for reducing pain and require a physician’s prescription.

Aspirin and NSAIDs are effective in treating joint injuries, overuse injuries (such as tendinitis and bursitis), and muscle or soft-tissue injuries, including strains and delayed-onset muscle soreness (DOMS). They are also used for headache and fever.

The main differences between types of NSAIDs are their duration of action and their availability as over-the-counter (OTC) or prescription-only drugs. (See Table One, below, for a list of first-generation NSAIDs.) They all have similar potency, although OTC forms of a particular drug are always lower strength than their prescription-only equivalents. Most clinicians consider indomethacin and piroxicam to be the most potent of the group, but determining the relative potency of these drugs is very difficult.

Athletic trainers should be most familiar with the three NSAIDs that are available without a prescription: ibuprofen (sold under the brand names Advil®, Motrin®, and Nuprin®), ketoprofen (Orudis-KT®), and naproxen (Aleve®). Of these three, naproxen is slightly longer-acting, thus it can be dosed less frequently. Other than that difference, these three NSAIDs are essentially interchangeable.

Aspirin and NSAIDs suppress the inflammatory response by inhibiting cyclooxygenase (COX), the enzyme responsible for prostaglandin synthesis. Because prostaglandins are also involved in fever and sensitizing nerves, these drugs also reduce fever and have analgesic properties.

In the 1990s, two forms of cyclooxygenase, COX-1 and COX-2, were identified. In 1999, drugs that inhibited COX-2 to a greater degree than COX-1 began to be marketed in the United States. These "selective COX-2 inhibitors" appear to produce fewer adverse reactions than the older, first-generation NSAIDs. However, within both groups, there is substantial variation in the degree to which COX-2 is affected relative to COX-1, making generalizations difficult.

Currently, all of the COX-2 inhibitor drugs can be identified by the ending "-coxib" in the generic name. Celecoxib (Celebrex®) and rofecoxib (Vioxx®) are two being used to treat pain in athletes, while another, valdecoxib (Bextra®) is not yet FDA-approved for the treatment of pain or other uses that may pertain to athletes.

Choices
Because of their convenience and widespread use, OTC NSAIDs are the likely first choice for an analgesic or anti-inflammatory drug by an athlete or athletic trainer. Aspirin is also very effective for most of the minor conditions described here, though it is short-acting and may cause more gastrointestinal (GI) upset than an NSAID.

Choices abound in the NSAID group. If one of the OTC NSAIDs (ibuprofen, ketoprofen, naproxen) doesn’t help, ask the athlete’s physician to prescribe a more potent NSAID. Or if the athlete has GI upset with one of the traditional NSAIDs, discuss one of the new COX-2 inhibitors (celecoxib, rofecoxib).

If NSAIDs cannot be used, acetaminophen can be considered, though it is not very effective for joint-related inflammatory pain. Thus, it is not a good choice when you need to treat swelling caused by a twisted ankle, for example.

Finally, when a pure analgesic is needed, a physician may prescribe opiates. Morphine is a superb analgesic, when dosed correctly. Codeine, hydrocodone, and oxycodone are other examples of opiates that can be administered orally. Meperidene is not recommended as it is not a very good analgesic, despite how frequently it is used. Opiates can cause side effects such as dizziness, however, which the athlete should be made aware of.

For a football player who just broke his leg, or a gymnast who just broke her wrist, a physician will often prescribe morphine, which is highly effective for bone-related pain. However, like acetaminophen, opiates do not offer any anti-inflammatory effects. Thus, combining an opiate with an NSAID is logical and effective. In fact, some pharmaceutical manufacturers offer products with these two components—one example is Vicoprofen®, which combines the opiate hydrocodone with the NSAID ibuprofen.

Physicians may also prescribe other combination drugs. There are far too many multi-ingredient analgesics on the market to discuss here. However, the following are prescribed frequently:

• Acetaminophen with codeine (Tylenol® No. 3): This drug product combines 300 mg of acetaminophen with 30 mg of codeine. It is strictly an analgesic and thus has no anti-inflammatory effects.

• Acetaminophen with oxycodone (Percocet®, Tylox®): These two ingredients are available in several different strength combinations. OxyContin®, which is a single-entity oxycodone product, has been well publicized because of its addictive property. Combination oxycodone products, however, are much safer.

• Hydrocodone with ibuprofen (Vicoprofen®): This drug product combines 7.5 mg of hydrocodone with 200 mg of ibuprofen. It is an excellent choice for moderate to severe pain when an oral medication is needed, for example, in the management of pain associated with a broken bone.

Contraindications
Along with knowing what works well, it’s just as important to know what drugs are contraindicated. Aspirin and NSAIDs should NOT be used in the following situations:

Undiagnosed abdominal pain or a history of blood in the stool: Anyone, even perfectly healthy athletes, can develop gastritis by taking too much aspirin or NSAIDs. Some evidence shows that strenuous exercise itself, such as marathon running, can cause GI bleeding, so adding one of these drugs only increases that risk. Most often, this is not a serious problem and recovery is prompt if the offending agent is discontinued. For athletes who have had epigastric pain after taking aspirin or an NSAID and who need an occasional dose of a mild analgesic, acetaminophen (such as Tylenol®) is safer. Alcohol should be avoided while taking aspirin or NSAIDs since the combination may have additive erosive effects on the stomach lining.

Any kind of bleeding problem: This warning always applies to drugs like aspirin and NSAIDs because of their effects on platelet function, but generally, the medical conditions that generate this kind of warning are highly uncommon in athletes. If, however, an athlete develops easy bruising while taking aspirin, discontinue use and consult a physician. Athletes in this situation who need an occasional dose of a mild analgesic should use acetaminophen instead. In addition, if an athlete is bleeding from a laceration, aspirin or NSAIDs should not be administered due to their effects on platelet function.

Liver disease: All types of analgesics discussed here (aspirin, NSAIDs, acetaminophen) have the potential for causing liver damage. Fortunately, this is not very common with occasional use of any of these drugs. Acetaminophen, however, is slightly different. Athletes should not use this drug in high doses (more than 2,400 mg/day) or take it chronically as this increases the risk of liver toxicity. Regular consumption of alcohol and acetaminophen together also increases the risk of liver damage.

Asthma, history of aspirin sensitivity, or allergy to tartrazine dye: This warning is one that always appears in the literature, but fortunately, problems are very rare. Nevertheless, if your athlete is asthmatic, you should question him or her about shortness of breath and any allergies to aspirin, NSAIDs, or any other drugs before administering medications.

Concussion or altered mental status: If an athlete has just sustained a concussion or is exhibiting anything other than a clear mental state, drugs should not be administered. If the athlete loses consciousness after taking a dose of medication, making an accurate diagnosis is more difficult.

Dosing
With the dozens of available drug products that include an NSAID component, specific dosing information is well beyond the scope of this article. Instead, I will address general questions about dosing these drugs.

What are the short-term limits of taking NSAIDs? When managing DOMS or simple joint aches not related to a specific injury, NSAIDs can be used for several days, up to a week or two. If the problem does not resolve, the athlete should rest the affected area—using a higher dose or switching to a more potent drug will just cover up the problem.

For management of fever or headache, NSAIDs should not be continued for more than three days. If the fever or headache doesn’t go away quickly, the athlete should be referred to a physician.

What are the long-term limits? Considering that patients with rheumatoid arthritis take NSAIDs for years and years, these drugs are relatively safe. However, possible long-term effects should not be ignored.

The risk of toxicity and side effects is determined somewhat by frequency of use. If an otherwise healthy athlete takes one or two ibuprofen tablets once a week for an entire season, it is highly unlikely that he or she will develop any long-term toxicities. However, anyone who takes any of the drugs discussed here daily for months could, and probably will, develop problems. Generally, problems stemming from the chronic use of aspirin and NSAIDs will be seen in the GI tract: epigastric pain, GI bleeding, or liver damage. Chronic use of acetaminophen raises the possibility of liver toxicity, and chronic use of opiates can lead to dependence.

More recently, a condition known as "medication overuse headache" has been attributed to the chronic use of NSAIDs. This situation can be explained as a drug withdrawal phenomenon: When each dose of the drug wears off, the headache returns, and the patient takes another dose, thereby perpetuating a never-ending cycle. Some patients who have chronically taken NSAIDs for migraine headaches find that their headaches stop after they discontinue regular use of NSAIDs for several days. If you have an athlete who takes NSAIDs regularly for headaches, this situation should be considered.

When using NSAIDs in sports-medicine situations, the duration of time that an athlete should take one of these drugs is usually determined more by the injury than by the drug. If a tennis player cannot serve or a football player cannot run without first consuming anti-inflammatory drugs or analgesics, this suggests that rest and rehabilitation are needed. It would be illogical to let an athlete go through an entire season dependent on drug therapy to dull the pain of movement.

Should athletes be concerned about developing kidney ailments from taking pain medications? Aspirin and any of the NSAIDs certainly affect the normal physiology of the kidney. For 98 percent of people, however, it never causes any problems and is quickly reversible when the drug is eliminated. Following the suggestions mentioned above should ensure no long-term problems arise.

It is possible, however, that these drugs could contribute to hyponatremia and other electrolyte disturbances because of their effects on kidney function. Hyponatremia (also called reverse dehydration) occurs when athletes participating in endurance events or prolonged strenuous exercise ingest a large volume of water but no salt. NSAIDs have a very real, though low, potential to add to this problem by causing dysregulation of fluid and electrolyte control within the nephron (the filtering unit of the kidney). To avoid the possibility of hyponatremia, athletes should drink fluid containing salt and other electrolytes if they exercise for a prolonged period of time while using NSAIDs.


Effects on Performance
Do any of these pain medications affect performance? In cases of toxic overdoses, aspirin can disrupt oxidative phosphorylation, leading to life-threatening metabolic disturbances. This raises an interesting question: What is the effect of high doses, or chronic use, of aspirin during prolonged physical exertion? Unfortunately, such a study has never been done.

In 1988, De Meersman studied the acute effects of a single dose of aspirin during 60 minutes of treadmill exercise at 50 percent VO2 max and found no effect on glucose, insulin, or free fatty acid utilization. He concluded that single doses of aspirin should not affect glucoregulatory and counterregulatory metabolism during exercise.

In 1994, Roi and colleagues evaluated healthy, active subjects 30 minutes after a single, 1,000-mg dose of aspirin, and no significant effects on cycle ergometer performance were observed. Lisse and colleagues, in 1991, looked at the effects of a single, 650-mg dose on a two-mile run 30 minutes after runners ingested the aspirin and also found no effect.

Thus, it appears that single doses of aspirin do not affect aerobic performance. But whether daily, continuous ingestion or higher doses produce different results is uncertain. More clinical research is needed to determine the effects of chronic aspirin ingestion on energy metabolism during sustained aerobic exercise.

The effects of NSAIDs on athletic performance may be different. NSAIDs have been shown to increase the production of adenosine, which, in turn, stimulates capillary growth. This pharmacologic action raises the possibility that repeated use of an NSAID over a period of several weeks might boost an athlete’s VO2 max, but this has never been demonstrated.

Opiates may have performance-enhancing qualities for some athletes and thus are banned substances. They also have unwanted side effects, as they adversely affect psychomotor performance and actions that require speed.

The ATC’s Role
Pain medication is a necessity in athletics, and athletic trainers will be well served to know the implications of the different choices. Controlled substances should never be administered without a physician’s prescription, but athletes need guidance on making OTC choices and will have questions about their prescriptions.

Most important is looking for contraindications and making sure athletes are not taking any pain medications for prolonged periods. Discuss any problems with the prescribing physician and ask to be kept in the loop about any out-of-the-ordinary prescriptions. Finally, take the time to read about new types of medications and their application to competitive athletes.


Sidebar:
TAKE-HOME POINTS
Before giving a pain medication to an athlete, consider the following questions:

What is the specific injury?
If the injury is severe, acetaminophen, aspirin, or a low dose of an OTC NSAID may not be very effective. If there is substantial bleeding, aspirin should be avoided due to its more pronounced effects on platelet function. If there is any possibility that the athlete might lose consciousness, never administer anything orally.

Is the athlete allergic?
If an athlete has ever had an allergic reaction to aspirin or other drugs, be careful about administering aspirin or NSAIDs. Acetaminophen and the opiates are safe, as long as the specific product does not also contain an NSAID.

Does the athlete drink alcohol?
Tell athletes that drinking alcohol while taking aspirin or an NSAID greatly increases the risk of gastritis and GI bleeding. Combining alcohol and acetaminophen increases the risk of liver damage. Combining alcohol with an opiate should never be allowed.

What is an appropriate stopping point?
Talk to your athletes about when to stop medicating. One week should be considered the maximum time frame to self-medicate with an NSAID for musculoskeletal injuries, less for headache or fever. Chronic use of NSAIDs should be discouraged, not only to reduce the risk of ADRs but also because the condition may require medical attention if it does not resolve within this time period.


Table One: First Generation NSAIDs

GENERIC NAME -- DURATION OF ACTION -- RX or OTC
(TRADE NAME)

diclofenac (Cataflam®, Voltaren®) ......short ............Rx
etodolac (Lodine®) ............................short ............Rx
fenoprofen (Nalfon®) ..........................short ............Rx
flurbiprofen (Ansaid®) ........................short ............Rx
ibuprofen (Advil®, Motrin®, Nuprin®)..short ......Rx and OTC
indomethacin (Indocin®) ..............intermediate .......Rx
ketoprofen (Orudis-KT®) ....................short ......Rx and OTC
ketorolac (Toradol®) ...........................short ............Rx
nabumetone (Relafen®) ........................long .............Rx
naproxen (Aleve®, Naprosyn®) .....intermediate ...Rx and OTC
oxaprozin (Daypro®) ...........................long .............Rx
piroxicam (Feldene®) .......................very long ........Rx
sulindac (Clinoril®) .......................intermediate ......Rx
tolmetin (Tolectin®) ...........................short ............Rx