Inhibition of exercise-induced bronchoconstriction by MK-571, a potent leukotriene D4-receptor antagonist

Article Abstract:

Leukotrienes are small peptide molecules which play an important role in many processes involved with immunological reactions and inflammation. In particular, the sulfidopeptide leukotrienes C4, D4, and E4 play key roles in anaphylaxis and may be important mediators of the bronchoconstriction (narrowing of the airways) occurring in asthma. Unfortunately, a lack of suitable antagonists for leukotriene receptors has prevented the exploration of the importance of these molecules in the asthmatic attack. This situation is changing with the development of new pharmacologic agents. Using one such new compound, MK-571, researchers are now exploring the role of leukotrienes in asthma. MK-571 is a potent and specific inhibitor of the receptor for the leukotriene, D4 (LKD4). In a crossover trial involving 12 volunteers with stable asthma, investigators determined if MK-571 was effective in ameliorating the effects of exercise. Exercise stimulates asthma in many patients, by cooling the airways, changing the concentration of the fluid lining the airways, or both. The investigators not only measured the time required to recover normal breathing after exercise-induced asthma, but also measured the FEV1, which is the amount of air which can be forcibly expelled from the lungs in one second (FEV stands for forced expiratory volume). The results showed that pretreatment with MK-571 reduced the bronchoconstriction which followed exercise in all subjects. After being given placebo, subjects experienced a reduction in FEV1 of 25 percent, but after MK-571 they experienced a reduction of only 9 percent. Likewise, after placebo subjects took about 33 minutes to recover normal breathing, while only eight minutes were required for recovery after MK-571. The results demonstrate that MK-571 is a potent inhibitor of the bronchoconstriction which results from exercise among asthmatic patients. Since MK-571 is an antagonist of the receptor for the leukotriene D4, the results also suggest that LKD4 is an important mediator of bronchoconstriction in asthmatics. (Consumer Summary produced by Reliance Medical Information, Inc.)

Inflammation, Inflammation mediators

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Treatment of asthma with drugs modifying the leukotriene pathway

Article Abstract:

Leukotriene inhibitors can be used in addition to inhaled corticosteroids in the treatment of asthma. Leukotrienes are naturally occurring chemicals in the body that constrict lung passages, among other actions. The drugs that block the action of leukotrienes include zafirlukast, montelukast, pranlukast, and zileuton. These drugs can be taken orally and although they are not as effective alone as inhaled corticosteroids, they can allow patients to take reduced doses of corticosteroids. This would protect patients from the severe side effects of corticosteroids. The drugs can also reduce the need for beta agonists, another group of drugs used to treat asthma.

Evaluation, Antiasthmatic agents

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Inhaled beta2-agonists in the treatment of asthma

Article Abstract:

People with mild asthma and few symptoms can probably manage their disease by using beta-agonists as needed rather than regularly. This was demonstrated in a 1996 study which found no significant differences in symptoms or disease control among people who inhaled albuterol regularly or only when needed. However, this may not be true for people with more severe disease who are using other beta-agonists such as salmeterol. Since 1968, researchers have reported increased mortality rates in asthma patients who use beta-agonists. However, frequent drug use could be a marker of more severe disease.

Editorial, Dosage and administration, Adrenergic beta agonists, Adrenergic beta-agonists, Albuterol

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