Antileukotriene Drugs: Clinical Application, Effectiveness and Safety

Abstract

Cysteinyl leukotrienes (Cys-LTs) are potent proinflammatory mediators derived from arachidonic acid through the 5-lypoxigenase (5-LO) pathway. They exert important pharmacological effects by interaction with at least two different receptors: Cys-LT(1) and Cys-LT(2). By competitive binding to the Cys-LT(1) receptor, leukotriene receptor antagonist drugs such as montelukast, zafirlukast, and pranlukast, block the effects of Cys-LTs and alleviate the symptoms of many chronic diseases, especially bronchial asthma and allergic rhinitis. Evidence obtained by randomized clinical trials as also by direct experience derived from patients suffering from asthma and allergic rhinitis justifies a broader role for leukotrienes receptor antagonists (LTRAs). Recently published studies and case reports have demonstrated beneficial effects of LTRAs on other diseases commonly associated with asthma (exercise induced asthma, rhinitis, chronic obstructive pulmonary disease, interstitial lung disease, chronic urticaria, atopic dermatitis, allergic fungal disease, nasal polyposis, and paranasal sinus disease) as well as other diseases not connected to asthma (migraine, respiratory syncytial virus postbronchiolitis, systemic mastocytosis, cystic fibrosis, pancreatitis, vulvovaginal candidiasis, cancer, atherosclerosis, eosinophils cystitis, otitis media, capsular contracture, and eosinophilic gastrointestinal disorders). The aim of this review is to show the most recent applications and effectiveness in clinical practice of the LTRAs.

Montelukast: Pharmacology, Safety, Tolerability and Efficacy

“…28 Isolated reports of Churg-Strauss syndrome (CSS), a rare systemic vasculitis asssociated with asthma, have been described in asthma patients treated with montelukast. 29,30 CSS is a rare necrotizing vasculitis with an annual prevalence of approximately 60 per million in asthma patients and 2-7 per million in the general population. 16,31 Its precise etiology is not known, yet its clinical onset is most often preceded by discontinuation or tapering of corticosteroid therapy 26,32 and consists of eosinophilia, pulmonary infiltrates, cardiomyopathy and other signs of vasculitis.…”

“…16,31 Its precise etiology is not known, yet its clinical onset is most often preceded by discontinuation or tapering of corticosteroid therapy 26,32 and consists of eosinophilia, pulmonary infiltrates, cardiomyopathy and other signs of vasculitis. 29 A likely explanation is that inhaled or oral corticosteroid treatment in these patients may mask the underlying vasculitis that develops as the glucocorticosteroid doses are reduced in patients with severe asthma being treated with leukotriene receptor antagonists (LTRAs). Physicians should be aware of signs and symptoms of CSS in patients with moderate to severe asthma with tapering doses of corticosteroids.…”

“…Physicians should be aware of signs and symptoms of CSS in patients with moderate to severe asthma with tapering doses of corticosteroids. 29 Although they are well tolerated, particular attention should be given to the consideration of periodically monitoring liver function tests during treatment with LTRA. There have been reported cases of liver dysfunction going from mild to severe in patients treated with these medications.…”

Treatment of Chronic Urticaria

“…They exert important pharmacological effects by interaction with at least two different receptors, CysLT1 and CysLT2 (1,81). By competitive binding to the CysLT1 receptor, leukotriene receptor antagonist drugs such as montelukast, zafirlukast and pranlukast block the effects of cysteinyl leukotrienes.…”

“…By competitive binding to the CysLT1 receptor, leukotriene receptor antagonist drugs such as montelukast, zafirlukast and pranlukast block the effects of cysteinyl leukotrienes. Recently published studies and case reports have demonstrated beneficial effects of leukotriene receptor antagonist (LTRAs) on other diseases commonly associated with asthma, e.g., exercise induced asthma, rhinitis, chronic obstructive pulmonary disease, interstitial lung disease, chronic urticaria, atopic dermatitis, allergic fungal disease, nasal polyposis, and paranasal sinus disease (81). LTRAs are not licensed for urticaria.…”