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May 1997
Focus on Zafirlukast: a leukotriene receptor antagonist for the prophylaxis and chronic treatment of asthma.
Baldinger SL, PharmD, Shore ET; Formulary 1996; 31:1029-52
[ see abstract below ]
This article reviews the pharmacology and clinical trials of the first agent of a new therapeutic class of drugs approved by the FDA to treat asthma by antagonism of the cysteinyl leukotriene receptor. Approximately 10 million individuals in the United States are known to have asthma, a disease which has only relatively recently been recognized to be comprised in part of a significant inflammatory component. This is in part the basis for the increased use of anti-inflammatory agents such as inhaled corticosteriods to treat the underlying pathophysiology.
Zafirlukast was approved by the FDA on September 26, 1996, for the prophylaxis and chronic treatment of asthma in adults. It represents the first new class of asthma medications to be introduced in the United States in twenty years. Its actions are based on antagonism of the leukotriene receptor. Leukotrienes, prostaglandins, and thromboxanes are endogenously synthesized products of arachidonic acid metabolism. The cysteinyl leukotrienes have been closely linked to bronchoconstriction, vascular permeability and mucus production associated with asthma. Additionally, leukotriene concentrations are significantly increased in inflammatory cells and biological fluids of patients with asthma. This drug is administered twice daily, orally in 20-mg doses. Its onset of action ranges from 3-14 days after treatment is begun.
Extensive clinical trials have been performed with this drug and several points are important for the anesthesia practitioner. In all cases, Albuterol served as the rescue medication with the experimental drugs failed to adequately treat asthma. This is probably important for the practitioner to remember when treating patients who come to surgery and anesthesia on a regimen of steroids, Cromolyn or Zafirlukast.
Clinical trials suggest that Zafirlukast is an appropriate therapy for patients whose asthma is not controlled by beta antagonists alone, but how this new drug compares with other treatment modalities such as inhaled corticosteroids in patients with moderate to severe asthma has not been thoroughly addressed. Additionally, it is important to appreciate that there exists considerable variance in efficacy of Zafirlukast among patients with asthma, ranging from no response to dramatic response. This drug appears to have a relatively favorable safety profile, the most prevalent side effect being headache, infection, nausea, and diarrhea in percentages just slightly greater than observed in patients receiving placebo.
A final point in the early evaluation of Zafirlukast is that it is not indicated in the treatment of acute bronchospasm. It appears that it is appropriate to continue the administration of this drug along with other asthma treatments during exacerbations of asthma.
These points will be useful to the perioperative assessment and treatment of the asthmatic patient.
Return to the Current Literature Review Front Page, or read the abstract:
ABSTRACT
Zafirlukast (Accolate) is a potent and specific leukotriene receptor antagonist recently approved by the FDA for the treatment of asthma in patients 12 years of age and older. The drug binds specifically to the cysteinyl leukotriene receptor. Zafirlukast has a half-life of approximately 10 hours, is highly protein bound, and extensively metabolized. Results of available clinical trials in patients with mild-to-moderate asthma have shown 20-mg, twice-daily oral doses of zafirlukast improve lung function and reduce daytime and nighttime asthma symptoms. The most frequently occurring adverse side effects associated with the drug's use are headache, infection, and nausea. The precise role of zafirlukast in asthma therapy remains to be determined.
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