Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0042384 (vasculitis)
 20,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Zafirlukast, montelukast and pranlukast are all cysteinyl leukotriene receptor antagonists that have recently been approved for the treatment of asthma. Within 6 months of zafirlukast being made available on the market, 8 patients who received the agent for moderate to severe asthma developed eosinophilia, pulmonary infiltrates, cardiomyopathy and other signs of vasculitis; the syndrome that these patients developed was characteristic of the Churg-Strauss syndrome. All of the patients had discontinued systemic corticosteroid use within 3 months of presentation and all developed the syndrome within 4 months of zafirlukast initiation. The syndrome dramatically improved in each patient upon reinitiation of corticosteroid therapy. Since the initial report, there have been multiple similar cases reported to the relevant pharmaceutical companies and to federal drug regulatory agencies in association with zafirlukast as well as with pranlukast, montelukast, and with use of high doses of inhaled corticosteroids, thus leading to an increased incidence rate of the Churg-Strauss syndrome. Many potential mechanisms for the association between these drugs and the Churg-Strauss syndrome have been postulated including: increased syndrome reporting due to bias; potential for allergic drug reaction; and leukotriene imbalance resulting from leukotriene receptor blockade. However, careful analysis of all reported cases suggests that the Churg-Strauss syndrome develops primarily in those patients taking these asthma medications who had an underlying eosinophilic disorder that was being masked by corticosteroid treatment and unmasked by novel asthma medication-mediated corticosteroid withdrawal, similar to the forme fruste of the Churg-Strauss syndrome. It remains unclear what the exact mechanism for this syndrome is and whether this represents an absolute increase in cases of vasculitis, but it appears that none of the asthma medications implicated in leading to the development of Churg-Strauss syndrome was directly causative of the syndrome. These agents remain well tolerated and effective medications for the treatment of asthma, although physicians must be wary for the signs and symptoms of the Churg-Strauss syndrome, particularly in patients with moderate to severe asthma in whom corticosteroids are tapered.
 ...
PMID:Leukotriene modifiers and Churg-Strauss syndrome: adverse effect or response to corticosteroid withdrawal? 1051 17

Zafirlukast is a leukotriene inhibitor that has recently been approved for the prophylaxis of asthma. Although this new product has been well accepted because of its convenient dosing and relatively few side effects, several cases of Churg-Strauss syndrome have been reported to be associated with its use. In this paper we describe the case of a 54-year-old white man with no history of corticosteroid therapy in whom leukocytoclastic vasculitis, hepatitis and eosinophilia developed while he was on zafirlukast therapy for mild asthma.
 ...
PMID:Vasculitis induced by zafirlukast therapy. 1218 65

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.
 ...
PMID:Tolerability of leukotriene modifiers in asthma: a review of clinical experience. 1803 Nov 50