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- Zileuton(synthesis inhibitor) – still available
- 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.
- Montelukast: drugs that effect CYP2C9.
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