Leukotriene inhibitors and antagonists in asthma

Abstract

Objective: This article reviews the literature on the effects of leukotrienes in asthma. In particular, the ability of recently developed receptor antagonists and synthesis inhibitors to attenuate the asthma-causing effects of leukotrienes is examined.

Design: Published literature on the role of leukotrienes in asthma was reviewed. Reports of research on agents that inhibit the synthesis of leukotrienes or block leukotriene receptors were also studied.

Results: Leukotrienes are endogenous molecules formed by the breakdown of a membrane constituent, arachidonic acid, via the 5-lipoxygenase enzyme pathway. This pathway ultimately produces several species of leukotrienes with various biologic activities, including generalized inflammatory effects associated with asthma: increased vascular permeability, enhanced mucous production, and decreased mucociliary transport. Particularly important in asthma, leukotriene receptors on the airways mediate a potent bronchoconstriction. Two general types of drugs have been developed with the goal of attenuating the leukotrienes' effects in inflammation and asthma: the leukotriene receptor blockers and the leukotriene synthesis inhibitors (eg, 5-lipoxygenase inhibitors).

Conclusions: The antileukotriene drugs attenuated the responses to inhaled leukotrienes and allergen challenges. These agents produced beneficial effects in cold-, exercise-, and aspirin-induced asthma, as well as clinical asthma. Many of these medications appear to be effective in the treatment of asthma; however, further clinical research is needed to determine which patients would benefit most from their use.