Tolerability of leukotriene modifiers in asthma: a review of clinical experience.
The so called leukotriene antagonists or, more accurately, the leukotriene modifiers are a rather heterogeneous set of drugs that work by several mechanisms. Such mechanisms include: (i) 5-lipoxygenase enzyme inhibition (e.g. zileuton); (ii) 5-lipoxygenase-activating-protein inhibition (e.g. quiflapon, BAYx 1005); (iii) LTD4-receptor antagonism (e.g. zafirlukast, montelukast, MK-571, pranlukast). The first leukotriene modifiers tested (L-649,923 and tomelukast) had adverse gastrointestinal effects. Since then, several leukotriene modifiers have been marketed, including zafirlukast, zileuton and montelukast. Zafirlukast has been associated with 8 cases of Churg-Strauss syndrome, although these were probably not caused by zafirlukast. It is more likely that this syndrome is related to the underlying illness, which was masked by corticosteroids, and revealed after zafirlukast-mediated asthma treatment allowed steroid withdrawal and unmasking of underlying vasculitis. The main adverse effects of zileuton include liver function test abnormalities, while montelukast, the most recently marketed, has so far shown minimal adverse effects. Zafirlukast causes a decrease in warfarin clearance and a clinically significant increase in prothrombin time, probably by cytochrome P450 isoenzyme interactions. Moreover, terfenadine decreases zafirlukast maximum serum concentrations. Calcium antagonists, cyclosporin, cisapride and astemizole are metabolised via the cytochrome P450 system, and interactions with leukotriene modifiers can be expected.
Reques
F G
FG
Sección de Alergología, Hospital de León, Leon, Spain. 24001@medscape.com
Rodriguez
J L
JL