LEUKOTRIENE INHIBITORS AND ANTAGONISTS IN ASTHMA

Objective: This article reviews the literature on the effects of leuko trienes in asthma. In particular, the ability of recently developed re ceptor antagonists and synthesis inhibitors to attenuate the asthma-ca using effects of leukotrienes is examined. Design: Published literatur e on the role of leukotrienes in asthma was reviewed. Reports of resea rch on agents that inhibit the synthesis of leukotriene or block leuko triene receptors were also studied. Results: Leukotrienes are endogeno us molecules formed by the breakdown of a membrane constituent, arachi donic acid, via the 5-lipoxygenase enzyme pathway. This pathway ultima tely produces several species of leukotrienes with various biologic ac tivities, including generalized inflammatory effects associated with a sthma: increased vascular permeability, enhanced mucous production, an d decreased mucociliary transport. Particularly important in asthma, l eukotriene receptors on the airways mediate a patent bronchoconstricti on. Two general types of drugs have been developed with the goal of at tenuating the leukotrienes' effects in inflammation and asthma: the le ukotriene receptor blockers and the leukotriene synthesis inhibitors l eg, 5-lipoxygenase inhibitors). Conclusions: The antileukotriene drugs attenuated the responses to inhaled leukotrienes and allergen challen ges. These agents produced beneficial effects in cold-, exercise-, and aspirin-induced asthma, as well as clinical asthma. Many of these med ications appear to be effective in the treatment of asthma; however, f urther clinical research is needed to determine which patients would b enefit most from their use.