Cysteinyl leukotrienes (cys-LTs); B4 (LTB4), C4 (LTC4), D4 (LTD4), and E4 (LTE4), are potent
bronchial smooth muscle constrictors, and mediators of inflammation
They exert their action through receptors cys-LT1 and cys-LT2
Zafirlukast and Montelukast are competitive antagonists for the cys-LT1 receptor
Zileuton has the potential advantage of blocking synthesis of leukotrienes from arachidonic acid via the 5-lipoxygenase pathway, by inhibiting 5-lipoxygenase activity. This would prevent other effects of cys-LTs that occur via cys-LT2 receptors (not substantiated in practice)
Zileuton: hepatotoxicity, must monitor liver function tests q4-6wks, Headaches.
Montelukast: eosinophilia and Churg-Strauss syndrome very rare.
Zafirlukast: hepatotoxicity (much lower than Zileuton), eosinophilia and Churg-Strauss syndrome very rare, and increased incidence of infections, rare.
Zileuton: elevated liver enzymes 3 times normal.
Zafirlukast: elevated liver enzymes 3 times normal,eosinophilia and vasculitis symptoms.
Montelukast: eosinophilia and vasculitis symptoms
Zileuton: increases levels of coumadin, theophylline, and propanolol.
Zafirlukast: aspirin increases levels of zafirlukast, erythromycin and theophylline reduce levels of zafirlukast, effect of coumadin increased. Drugs that effect CYP2C9.