Antileukotriene Drugs: Clinical Application, Effectiveness and Safety

Department of Biomedical Science, Faculty of Medicine and Surgery, University G. D'Annunzio, Chieti, Italy.
Current Medicinal Chemistry (Impact Factor: 3.85). 02/2007; 14(18):1966-77. DOI: 10.2174/092986707781368522
Source: PubMed


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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    • "CysLTR1 antagonists have a significant role to play in airway disorders, in particular allergic rhinitis (AR) and/or asthma [48, 49]. Studies have also suggested that they may have potential benefit in other disorders that are often associated with asthma, as well as in a number of conditions that are not linked to asthma [49]. This section will review the role of cysLTR1 antagonists in allergic rhinitis (AR) and asthma, including pediatric, adult, and elderly patients, as well as the various subsets of asthmatic patients, such as those with AR, those with aspirin-sensitive asthma and those with exercise-induced asthma [50]. "
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    ABSTRACT: Cysteinyl leukotrienes (cysLTs) are produced predominantly by cells of the innate immune system, especially basophils, eosinophils, mast cells, and monocytes/macrophages. Notwithstanding potent bronchoconstrictor activity, cysLTs are also proinflammatory consequent to their autocrine and paracrine interactions with G-protein-coupled receptors expressed not only on the aforementioned cell types, but also on Th2 lymphocytes, as well as structural cells, and to a lesser extent neutrophils and CD8(+) cells. Recognition of the involvement of cysLTs in the immunopathogenesis of various types of acute and chronic inflammatory disorders, especially bronchial asthma, prompted the development of selective cysLT receptor-1 (cysLTR1) antagonists, specifically montelukast, pranlukast, and zafirlukast. More recently these agents have also been reported to possess secondary anti-inflammatory activities, distinct from cysLTR1 antagonism, which appear to be particularly effective in targeting neutrophils and monocytes/macrophages. Underlying mechanisms include interference with cyclic nucleotide phosphodiesterases, 5'-lipoxygenase, and the proinflammatory transcription factor, nuclear factor kappa B. These and other secondary anti-inflammatory mechanisms of the commonly used cysLTR1 antagonists are the major focus of the current review, which also includes a comparison of the anti-inflammatory effects of montelukast, pranlukast, and zafirlukast on human neutrophils in vitro, as well as an overview of both the current clinical applications of these agents and potential future applications based on preclinical and early clinical studies.
    Full-text · Article · May 2014 · Research Journal of Immunology
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    • "Cysteinyl leukotrienes are potent pro-inflammatory mediators whose effect can be blocked by LTRA such as montelukast, zafirlukast and pranlukast. The benefit of these drugs in patients suffering from asthma and allergic rhinitis is well established, and current evidence clearly justifies their use in those conditions [9]. Several recent studies have addressed the use of these agents, as monotherapy as well as in combination with other first line therapies, for chronic urticaria. "
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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.
    Full-text · Article · May 2014 · Allergy Asthma and Clinical Immunology
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    • "Cysteinyl leukotrienes (Cys-LTs) are proinflammatory mediators derived from arachidonic acid through the 5-lypoxigenase (5-LO) pathway (3). These products cause bronchial smooth muscle contraction, stimulation of mucous production, enhancement of vascular permeability, and recruitment of eosinophils (4–6). "
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    ABSTRACT: There is little evidence about the role of Zafirlukast (a highly selective LTD4 antagonist) in Chronic Obstructive Pulmonary Disease (COPD). The Zafirlukast can reduce the need for short-acting rescue β2 agonists, produce fewer exacerbations of asthma and increased quality of life as possible benefits treatment for asthma. The aim of our study was to evaluate the effects of Zafirlukast improvement of lung function in patients with COPD. Twenty five patients with moderate to severe COPD, in stable phase of the disease, participated in this interventional, quasi-experimental study. All patients were received 40mg oral Zafirlukast per day for 2 weeks. Pulmonary function Test was performed both at the baseline and at the end of the study. Data were analyzed with paired t-test using SPSS v.16. The mean age of the patients was 67.29 (SD=5.56) years with the mean baseline for forced expiratory volume in first second (FEV1) equal to 41.79% (SD=14.96) of predicted value. After 2 weeks, the mean improvements in forced vital capacity (FVC), FEV1 and FEV1/FVC were 4.75% (SD=13.18), 3.71% (SD=9.19) and 9.33(SD=27.08), respectively. Zafirlukast produced a non-significant (p>0.05) bronchodilation, with maximum mean increase in FEV1 of 0.04 lit (3%) above baseline. Results showed that Zafirlukast has no considerable bronchodilatory effect in COPD. Present study consisted of a very short treatment period and it is possible that the extension of this period could possibly have more effects. Additional larger studies are needed to verify the impact of leukoterien receptor antagonists on improving the lung function in COPD patients.
    Full-text · Article · May 2013 · Medical journal of the Islamic Republic of Iran
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