17 March 2011

MONTELUKAST: New perspective for the treatment of asthma?

Introduction : Asthma remains one of the problems of global public health, epidemiological data as its prevalence has increased in recent decades, affecting nearly one hundred million people around the world. For this reason the interest in this disease is increasing.
    Has recently been recognized to inflammation and airway hyperresponsiveness as the primary pathophysiologic mechanisms. The cells involved are presumably mast cells, eosinophils, macrophages, neutrophils and lymphocytes. Mediators released, histamine, bradykinin, leukotrienes C, D and E, platelet activating factor and prostaglandin E 2 , F 2 a and D 2 , induce immediate and intense inflammatory reaction consisting of bronchospasm, vascular congestion and edema. Apart from causing a permanent contraction of smooth muscle and mucosal edema in the airway, leukotrienes could justify other pathophysiological manifestations of asthma such as increased production of mucus and impaired mucociliary transport. 1 In this sense, the combined use corticosteroids and B 2 agonists in the traditional treatment of this disease has proven effective. However, the long-term use of steroids causes local adverse effects such as cough, dysphonia, oropharyngeal candidiasis, and systemic, adrenal suppression, osteoporosis, thinning skin, easy bruising, and cataracts that can limit their use. 2
    The recent development of antagonists of leukotriene receptor as a complementary drug to conventional therapy, especially the last to appear, Montelukast, offers a potential benefit for the treatment of asthma, mainly due to the low incidence of adverse effects.
    The aim of this literature review is to evaluate the advantages and disadvantages of Montelukast in the treatment of asthma.
Materials and methods: For the preparation of this review classical literature has been used in clinical medicine and randomized controlled trials, double-blind multicenter studies, these were extracted from search engines (PubMed and Google) using key words and asthma Montelukast . The search was restricted to articles published in 1999-2002.
Development: The cysteinyl leukotrienes are released by mast cells in the airway, a product of arachidonic acid metabolism, and increased eosinophil migration, mucus production, edema of the airway wall, bronchoconstriction and decreased ciliary motility. Leukotriene modifiers are the newest medications for controlling asthma in the long term. Zileuton, first to appear, is an inhibitor of 5 - lipoxygenase which reduces leukotriene production but may cause reversible elevations of aminotransferases; zafirlukast and montelukast are antagonists of cysteinyl leukotriene receptors, but a small number of patients treated with the first, has been diagnosed with Churg-Strauss syndrome. 2
    Montelukast (Singulair) blocks selectively the binding of LT E4 (the cysteinyl leukotriene predominant in the air) to its receptor provide significant protection against bronchoconstriction and other changes induced by AMP in patients with asthma, including eosinophilic inflammation ( % reduction in sputum eosinophils from 24.6 to 15.1% and decreased to 314.1 eosinophilia + / - 237.6 ml). 3.4
    Montelukast is administered orally at a dose of one tablet of 10 mg. a day. It is rapidly absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 3 to 4 hours. post ingestion. Its half-life is 2 to 5 hours, metabolised in the liver and excreted mainly at the bile.
    Several clinical trials comparing the efficacy of montelukast (M) vs. corticosteroids (GCC) have been published. One of them (n = 395), prospective, multicenter, utilizing patients with persistent asthma refractory to treatment with B 2 agonists of short duration. The GCC used was fluticasone propionate, which was more effective as maintenance therapy in first line. Significantly improved lung function, the percentage of days free of symptoms, nighttime awakenings and the use of albuterol as compared with M rescuer, plus a greater number of patients were satisfied with therapy (85% vs with GCC. 56% M) and the quality of life improved substantially compared to GCC M (p £ 0.01). The incidence of exacerbations was similar with both treatments. 5
    In another study (n = 533) dose decreased the need for rescue albuterol, asthma symptoms, nighttime awakenings and the percentage of symptom-free days in a more pronounced with the GCC with M; exacerbations were similar in the number of episodes, as well as adverse effects. 6
    Malmstrom et al., In a clinical trial, double-blind, placebo over a period of 12 weeks (n = 895), which compared M 10 mg once a day with beclomethasone 200ug twice daily and placebo , found an average increase in FEV 1 with beclomethasone 13.1%, with M of 7.4% and 0.7% with placebo. Both M Beclomethasone as PEF improved quality of life and increasing the number of days with asthma control and the consequent reduction of exacerbations. They also found that although the average Beclomethasone has greater clinical benefits, the M has a faster onset and higher initial effects. 7
    With regard to treatment of acute asthma, a study in an emergency department (n = 20) included patients who seemed to need systemic GCC for their crisis, were randomized to receive M or placebo. As a result, those who received M had a shorter stay in the service (M = 2.5 hours, placebo = 2.9 hours) and better development of the PEF (55% average increase from baseline vs. 44% placebo) no significant difference. However, supplementary administration of GCC or aminophylline was significantly less necessary with M (p = 0.03). These data and the safety profile of M indicate that there may be a useful additional therapy should be considered in emergency rooms as an alternative in the management of acute asthma. 8
    As for exercise-induced asthma in one study (n = 10) compared with salmeterol demonstrated to be equally effective considering the immediate onset of action (within the first hour) and the maintenance of the same (12 hours), with an increase in FEV 1 by 9 ± 4%. 9
Conclusion: As the disease asthma, not controlled, diminishes the quality of life for those who suffer and who has been increasing its prevalence (about 100 million people), the wider knowledge of this proposal that increases drug effects of conventional drugs will be beneficial. Based on these findings it has been concluded that montelukast has a complementary action to the classic treatment by reducing the need for medications used to present and promote their actions, thus maintaining control of the disease, highlighting which itself does not replace the 1st line therapy (corticosteroids and B 2 agonists).
    Benefits of using Montelukast associated to conventional therapy:
  1. Controlled clinical trials suggest that this new drug can improve lung function and reduce the requirement for inhaled or oral corticosteroids and B 2 agonists.
  2. It has proved effective as maintenance therapy in patients with asthma by decreasing the adverse effects compared with long-term therapy with corticosteroids (GCC).
  3. Comfortable and easy administration (single daily oral dose).
  4. Useful in exercise-induced asthma.
  5. Faster onset and higher initial effects.
  1. It is noticeably more expensive than conventional treatments.
  2. Have less clinical experience compared with traditional alternatives.

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