Elspeth

FIG. 27.2  Synthesis and effects of leukotrienes and sites of drug action. Asthmatic stimuli (antigens, cold air, exercise, cytokines, and others) activate phospholipase A2 (PLA 2), leading to formation of leukotriene A4 (LTA 4) by 5-lipoxygenase, which is inhibited by zileuton. LTA4 is converted to leukotriene B4, which activates B leukotriene receptors, such as BLT1. LTA4 is also converted to the cysteinyl leukotrienes C4, D4, and E4, which activate cysteinyl leukotriene receptors, such as CysLT1. These receptors are blocked by montelukast and zafirlukast. Leukotriene receptors are coupled with Gq and Gi, leading to increased intracellular calcium, decreased cAMP, activation of protein kinases, and biologic effects.