Study on Asthma: Can Asthma Inhalers Cause Muscle Damage?

Perhaps the most commonly prescribed asthma drug in the United States is albuteral, available by prescription under the trade names Ventolin and Proventil. Albuterol is classified as a beta-2 receptor agonist. In simple terms, beta-2 cell receptors are adrenergic receptors (i.e., epinephrine or adrenaline interact with them) that, among other functions, rapidly dilate the breathing passages in the lungs. This explains why these drugs are so often a doctor's first choice to treat a sudden asthma attack. Albuterol has advantages aver its predecessors because if specifically targets beta-2 receptors in the lungs. In contrast, older drugs, including forms of epinephrine, which are still available over-the- counter (e.g., Primatene Mist), and ephedrine were often associated with potentially serious side effects, such as over stimulation of the heart. This adverse reaction occurred because the early asthma drugs locked onto both beta-2 and beta-i receptors in the heart. The interaction with the latter is what produces cardiac side effects.

Anyone who has taken too many ephedrine tablets has felt this beta-I adrenergic effect. Ephedrine is favored by many bodybuilders as part of a fat- burning combination that also includes caffeine and aspirin. But the truth is that even so- called beta-2 agonist drugs, such as albuterol and the newer long-acting albuterol, have some beta-I overlap. This means that in certain dosages, such drugs could produce cardiac effects ranging from palpitations to heart- rhythm disturbances. Versions of beta-2 agonists not available in the United Slates, such as clenbuterol, appear to have potent properties not usually seen in similar drugs approved for use in this country.

For example, many studies show that administering large doses of clenbuterol to animals leads to muscle enlargement due to a thickening of type II muscle fibers. Another effect observed with clenbuterol is thermogenesis, or the conversion of fat calories into heat. This in turn leads to a "repartitioning" effect, evident by the replacement of body fat with muscle. This feature has made clenbuterol popular among athletes, including bodybuilders, who use the drug prior to contests. On the downside, the beta cell receptors that clenbuterol interacts with are extremely sensitive: They begin to downgrade in as little as two weeks.

Many athletes wonder if other beta-2 agonists can produce beneficial changes in body composition similar to those produced by clenbuterol. While clenbuterol is potent in this regard, several other drugs in the same class, such as fenoterol and Cimaterol, have also shown similar effects. Like clenbuterol, neither is approved for use in the United States. The studies on these drugs that are available in the United States are equivocal: Some have shown minor strength increases, while other studies have documented few or no effects. Those that have shown some effectiveness usually involve use of the tablet form, rather than the more common metered-dose inhalers.

The mixed results of beta-2 agonists have convinced athletic organizations, such as the International Olympic Committee, that these commonly available drugs have no intrinsic ergogenic effects capable of giving athletes a competitive edge. The most common side effects of using beta-2 agonists such as albuterol are often related to the overlap effect seen when they spill over and lock onto beta-I cell receptors. However, beta-2 receptors also exist in muscle cells, which partially explains the anabolic effects noted with clenbuterol. Taking an overdose of beta-2 drugs, including those provided by inhalers, may produce symptoms such as muscle tremors and cramps. The oral versions of the drugs may lead to serious heart effects evidenced by the release of a cardiac-specific enzyme.

One pressing question is whether beta- 2 agonist Inhalers are directly associated with skeletal-muscle damage. In a published study in the Annals of Allergy and Immunology (17:488-90, 1996), a 47-year- old man who regularly lifted weights showed increased muscle damage linked to his use of an albuterol inhaler to treat asthma. The man had developed unusual myalgia (muscle pain) and cramps after using his inhaler. The cramps became particularly severe after exercise, and he had difficulty sleeping due to his extensive muscle pain and cramps. He also noted decreased strength while lifting weights, although his day-to-day activities and movements weren't compromised. Blood tests performed on the man revealed that he had an increase in an enzyme - (IC (MM) - associated with damage specific to skeletal muscle - creatine kinase (CK) with a subunit known as (MM). When doctors substituted two other drugs (neither a beta-2 agonist) for his albuterol inhal the man's myalgia abated.

Did this man's muscle symptoms occur because of his use of the asthma inhaler, or was it a preexisting condition? The examining physicians suspect that he had a previously dormant myopathy (muscle disease) that was worsened by his use of the asthma inhales It is evident that his muscle pain and cramps were increased by his use of the inhaler. Does this mean that bodybuilders who suffer from recurrent asthma should immediately toss out their inhalers? No: The above case is considered rare. However, if you do have to use such an inhaler, be careful not to decrease your potassium level. Some evidence shows that beta-2 agonist drugs - including inhaler versions - may somehow interact with serum-potassium levels, lowering them or perhaps promoting potassium excretion. This could be relevant to those who either consume a low-potassium diet or take drugs, such as diuretics, that promote potassium excretion.

A story tangentially related to this subject was recently published in the Italian newspaper La Repcthlka. It involves a 41- year-old Italian man sentenced to 17 years in prison for murdering his wife. The newspaper reported that the man is appealing his sentence on the grounds that his violent act was caused by a temporary imbalance in CX enzyme. (IC is found in the heart, brain and muscles, where it facilitates the transfer of phosphate to reform adenosine triphosphate (ATP) and creatine within cells for energy usage. Creatine kinase is released after normal physical activity. However, after a head attack, which often causes the death of local cardiac tissue, extra amounts of the enzyme specific to the head - (IC (MB) - are released into the blood.

This is one indication that a heart attack, or myocardial infarction, has indeed occurred. Another isoenzyme, (IC (MM), is found in skeletal muscle, as described in the Allergy end Immunology case, and is also released into the blood after muscle damage - including that caused by exercise - has occurred. The Italian man claims that he shot his wife because he had experienced a sudden increase in the level of CX in his blood. According to his lowyer "(IC could be the trigger for a transitory psychiatric illness, determined in this case by the pressure the victim applied against [the killer] Ortolina's desire to end their relationship."

The charge that elevated (IC favors violent impulses is viewed skeptically by Italian psychiatrist Dr. Enrico Smeroldi, whom the newspaper quotes as saying: "Creatine kinase is released by the organism each time there is intense muscular activity. It is present in great quantities in the organism of athletes who have undergone particularly tiring training, but that does not mean that they become dangerously aggressive."