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.
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ABSTRACT: Previous studies suggested that leukotrienes (LTs) were involved in the pathogenesis of Henoch-Schönlein purpura (HSP). This study investigates the efficacy of an add-on therapy with Montelukast in treatment of HSP. In this four-centers, double-blind, placebo-controlled, parallel paired comparative study, 130 children with HSP were divided into two large groups, 84 patients without nephritis and 46 patients with nephritis. Every pair of patients with same severity of disease in each large group was randomly allocated to two subgroups, and one subgroup received routine treatment plus placebo treatment, another subgroup received routine treatment plus Montelukast treatment for 3 months. The efficacy was determined by using Severity Scale Score (SSS). Blood eosinophil counts, eosinophil cationic protein (ECP), IgE, interleukin (IL)-4, IL-5, IL-6, IL-8, IL-17, LTB4 , and urinary LTE4 were measured. Add-on therapy with Montelukast alleviated the manifestation of HSP including purpura, abdominal pain, stool occult blood, arthritis, proteinuria and hematuria, and accordingly, shortened the length of hospital stay, and inhibited the blood eosinophil counts, ECP, IgE, IL-4, IL-5, IL-6, IL-8, IL-17, LTB4 , and urinary LTE4 productions, and also inhibited the relapse of HSP during the first three months after treatment, but did not alter the outcome of nephritis at the end of the follow-up. Add-on therapy with Montelukast alleviated the manifestation of HSP. The present studies provided a disease, i.e. HSP which may be improved by add-on therapy with a leukotriene receptor antagonist.Pediatrics International 12/2013; · 0.88 Impact Factor
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ABSTRACT: Metabolic syndrome (MetS) is a global health problem. Elucidation of the role of 5- lipooxygenase/leukotriene pathway and renin angiotensin system in the pathogenesis of MetS suggests a variety of potential therapies worthy of testing. The present work investigated the effect of montelukast, a leukotriene antagonist and/or irbesartan, an angiotensin II-receptor blocker, in the prevention of fructose-induced MetS in rats. Rats were allocated into 9 groups and treated for 6 weeks as follow: normal control; MetS group (received 20% fructose); MetS+montelukast groups (treated with montelukast, 5, 10, and 20mg/kg/day, respectively); MetS+irbesartan groups (treated withirbesartan 15, 30, and 45mg/kg/day, respectively); and MetS+montelukast+irbesartan group (co treated with montelukast 5mg/kg plus irbesartan 15mg/g). Metabolic parameters (visceral fat index, liver index, insulin resistance, and serum lipid profile), oxidative stress markers (malondialdehyde, reduced glutathione, and catalase), and inflammatory mediators (tumor necrosis factor-α, and uric acid) were measured. Expression of caspase-3 in hepatic tissues was detected by immunohistochemistry. Liver injury was evaluated by histopathological examination and serum alanine aminotransferase (ALT). Montelukast, irbesartan, and their combination caused significant attenuation in metabolic and hepatic disorders. Their effect was associated with attenuation of oxidative stress markers, inflammatory mediators, and caspase-3 expression. This study highlighted the protective effects of montelukast and irbesartan against fructose-induced metabolic and hepatic disorders. The protective effect of either drug relies, at least in part, on their antioxidant and antiinflammatory effect, as well as on the reduction of caspase-3 expression in hepatic tissue.European journal of pharmacology 12/2013; · 2.59 Impact Factor
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ABSTRACT: A significant proportion of patients with chronic urticaria respond inadequately to first line treatment with antihistamines. Leukotreine receptor antagonists (LTRA) are also used for chronic urticaria, although firm recommendations on their use are lacking. We performed a systematic review of randomised trials to determine the role of LTRA in treatment of chronic urticaria. A search of PUBMED, EMBASE, SCOPUS, LILACS, the Cochrane Central Register of Controlled Trials, and the Web of Science for relevant randomized control trials or cross over studies yielded 10 eligible studies. The heterogeneity of trials were high, preventing valid meta-analysis of data. Most trials indicated that LTRA are not superior to placebo or antihistamine therapy, while combination therapy of LTRA and antihistamines appear to be more efficacious compared to antihistamine alone. The side effect profile and tolerability of this group of drugs is acceptable. The use of LTRA as monotherapy cannot be recommended. LTRA are effective add-on therapy to anti-histamines, and their use in patients responding poorly to antihistamines is justifiable. Further well designed randomized controlled trials with clear and standardized outcome measures are needed to determine the role of LTRA in chronic urticaria.Allergy Asthma and Clinical Immunology 01/2014; 10(1):24.