Pharmacology of leukotriene receptor antagonists and 5-lipoxygenase inhibitors in the management of asthma.

Abstract

The leukotrienes (LTs), a family of inflammatory mediators arising from the metabolism of arachidonic acid via the 5-lipoxygenase pathway, are prominently implicated in the pathobiology of asthma. Two classes of LTs, the cysteinyl LTs (LTC4, LTD4, and LTE4) and the dihydroxy-LT (LTB4) have been identified, with each class acting via distinct receptors. Inhibition of LT-mediated inflammation can be achieved by either interruption of 5-lipoxygenase action, thereby preventing formation of the LTs, or inhibition at specific LT receptor sites in the airway. Both the 5-lipoxygenase inhibitors and the cysLT receptor antagonists have thus far demonstrated the capacity to improve pulmonary function and reduce symptoms in clinical models of asthma, such as exercise-, aspirin-, or antigen-induced bronchoconstriction, and to improve pulmonary function in patients with mild-to-moderate, chronic stable asthma. The LTs are therefore critical effector molecules in some patients with asthma and important targets in the pharmacologic management of this disease.