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.

Disadvantages:

1. It is noticeably more expensive than conventional treatments.
2. Have less clinical experience compared with traditional alternatives.

What parents should do and avoid if you have an asthmatic child

• Allow your child to participate as much as possible in the regular school work, sports and other leisure activities, and encourage them to explore new areas of interest.
• Report to your child about your condition, how to control with medications and what factors may trigger a crisis.
• Allow your child to have more responsibility in their daily activities to grow, including the treatment of asthma.
• Do not treat differently because they have asthma.
• Do not consent to unacceptable behaviors.
• Do not worry if you have breathing problems while your child's asthma / to be controlled, he / she knows what to do.

  Important:

  Do not panic!

  • Do not be panic if your child has a crisis. Your reaction may put even more nervous and worsen the crisis.
  • Do not hesitate to contact your doctor in case of emergency

Recognition and avoidance of asthma triggers

The good news is you can do many things to minimize the effects of asthma. Here are instructions for initiating an action plan for asthma.
You can help protect your child from identifying and avoiding asthma symptoms, or controlling, the things that trigger an asthma attack.
Ask your doctor to help you identify the factors triggers in your child and recommend measures to help reduce the symptoms of your child's asthma. Their efforts should focus on eliminating the sources and circumstances of the triggers in your child and / or own triggers

Indicative list to avoid or reduce exposure to common triggers: 

Caspian animal

• Do not have pets at home.
• If you must have a pet, do not let the bedroom ever.
• Bathe your pet weekly.
• Avoid visiting homes with pets or carry your reliever medication when visiting homes with pets.
• Avoid products containing feathers, such as pillows and cushions. 
• Cover mattresses, cushions and pillows in airtight plastic bags.
• Wash all bedding and blankets once a week in hot water (> 55 ° C). 
• Remove all rugs, if possible

Environmental pollens and molds

• Keep windows closed at stations with high pollen counts.
• Avoid sources of molds, such as wet leaves and debris from the garden. 
• Avoid going outside at noon and afternoon when pollen and mold is higher.

Snuff Smoke

• If you have asthma, do not smoke
• Do not allow smoking in your home.
• Encourage family members to leave the snuff or avoid smoking around you or your child.

Asthma Symptoms

During asthma attacks the bronchial mucosa lining the airways swells and produces thick mucus that clogs the ducts of the airways. As a result, the muscles around these tubes tighten and constrict reducing its diameter, prevent the passage of air and complicate breathing. The basic features of the disease are: Inflammation: Increased sensitivity and bronchial obstruction. Sometimes your home is allergic. Produces an increase in secretions and bronchial muscle contraction.
Increased bronchial responsiveness : After exposure to various stimuli (fumes, gases, odors, cold air or exercise), the bronchi of asthmatics are contracted to produce the narrowing of the airway.
Bronchial obstruction : It is variable and reversible spontaneously or with treatment. During the crisis the air circulates with difficulty producing beeps and feeling of fatigue or breathlessness. At the time when the crisis is resolved normally air can move through the bronchial tubes and symptoms disappear.