Montelukast, asthma

Leukotrienes are rapidly produced and released during a Type I reaction (Fig. 3). They are responsible for a massive bronchoconstriction in allergic bronchial asthma and attract leukocytes, thus being proinflamma-tory. Consequently, antagonists of the LTC recqDtor have been proven useful in the therapy of bronchial asthma, often in combination with bronchodilators (example montelukast). 

Zafirlukast and zileuton are used in the prophylaxis and treatment of chronic asthma in adults and children older than 12 years. Montelukast is used in the prophylaxis and treatment of chronic asthma in adults and in children older than 2 years. 

These dru are contraindicated in patients with a known hypersensitivity to the dragp. Montelukast, zaflrlukast, and zileuton are not used in the reversal of bronchospasm in acute asthma attacks. Zileuton is con-... 

Montelukast—Take once daily in the evening, even when free of symptoms. Contact physician if the asthma is not well controlled. This drug is not for the treatment of an acute attack. Avoid taking aspirin and the NSAIDs while taking montelukast. 

Discuss what to include in a teaching plan for a patient taking montelukast for asthma. 

Leukotriene modifiers either inhibit 5-lipoxygenase (zileuton) or competitively antagonize the effects of leukotriene D4 (montelukast and zafirlukast). These agents improve FEV, and decrease asthma symptoms, rescue drug use, and exacerbations due to asthma. Although these agents offer the convenience of oral therapy for asthma, they are significantly less effective than low doses of inhaled corticosteroids.2,33... 

Malmstrom K, Rodriguez-Gomez G, Guerra J et al. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclometha-sone Study Group. Ann Intern Med 1999 130 487-495. 

Baena-Cagnani CE, Berger WE, Du-Buske LM Comparative effects of desloratadine versus montelukast on asthma symptoms and use of (Jj agonists in patients with seasonal allergic rhinitis and asthma. Int Arch Allergy Immunol 2003 130 307-313. 

Shafiee, A., Motamedi, H. and King, A., Purification, characterization and immobilization of an NADPH-dependent enzyme involved in the chiral specific reduction of the keto ester M, an intermediate in the s3mthesis of an anti-asthma drug, montelukast, from Microbacterium campoquemadoensis (MB5614). App/. Microbiol. Biotechnol., 1998, 49, 709-717. 

Reiss, T. L., Altman, L. C., Chervinsky, P., et al. (1996) Effects of montelukast (MK-0476), a new potent cysteinyl leukotriene (LDT(4)) receptor antagonist, in patients with chronic asthma. J. Allergy Clin. Immunol. 98, 528-534. 

Jarvis, B., and Markham, A. (2000) Montelukast—a review of its therapeutic potential in persistent asthma. Drugs. 59, 891-928. 

Williams, B., Noonan, G., Reiss, T. F., et al. (2001) Long-term asthma control with oral montelukast and inhaled beclomethasone for adults and children 6 years and older. Clin. Exp. Allergy. 31, 845-854. 

Noonan, M. J., Chervinsky, P., Brandon, M., et al. (1998) Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Eur. Respir. J. 11, 1232-1239. 

Lima JJ, Zhang S, Grant A, et al. (2006) Influence of leukotriene pathway polymorphisms on response to montelukast in asthma. Am J Respir Crit Care Med. 173, 379-385. 

LTB4 is a potent bronchoconstrictor, as are several other leukotrienes. A 5-lip-oxygenase inhibitor, Zileuton, is approved for therapy of asthma (though it is not much used for this purpose) as is a leukotriene blocker, montelukast, marketed as Singulair. Singulair is widely used by asthmatics as a preventive for asthma attacks. Certain corticosteroids are employed for the same purpose. Neither montelukast nor the steroids are effective in terminating an established asthmatic attack. Beta agonists are employed for that purpose (see chapter 17). 

Montelukast Leukotriene modi- Tab 5.10 mg 10 mg qd at bedtime for chronic asthma. Headache, abdominal pain no... 

Acute asthma attacks Montelukast is not indicated for use in acute asthma attacks, including status asthmaticus. Advise patients to have appropriate rescue medication available. Montelukast therapy can be continued during acute exacerbations of asthma. 

Children Safety and efficacy of montelukast have been established in adequate and well-controlled studies in children with asthma 6 to 14 years of age. Safety and efficacy profiles in this age group are similar to those seen in adults. 

Montelukast, zafirlukast, and zileuton are indicated for the prophylaxis and chronic treatment of asthma. They should not be used to treat acute asthmatic episodes. All three agents are administered orally. 

Montelukast is not intended to treat acute asthma attacks... 

Zileuton (8.81) is an inhibitor of 5-lipoxygenase montelukast (8.82) and zafirlukast (8.83) are inhibitors of the leukotriene LTD4 receptor. All of these agents have demonstrated efficacy in the treatment of asthma, a common chronic inflammatory disease of the airways. 

It is a cysteinyl leukotriene receptor antagonist indicated for the management of persistent asthma. It has been shown to have substantial blockade of airway leukotriene receptors 24 hours after oral dosing. Montelukast appears to be a useful alternative or adjunct to inhaled corticosteroid therapy in adults and an alternative to sodium cro-moglycate in children. 

Montelukast Granules For prophylaxis and chronic treatment of asthma in adult and pediatric patients of 12 months age and older... 

Although they remain less effective than inhaled corticosteroids, a 5-LOX inhibitor (zileuton) and selective antagonists of the CysLTl receptor for leukotrienes (zafirlukast, montelukast, and pranlukast see Chapter 20) are used clinically in mild to moderate asthma. Growing evidence for a role of the leukotrienes in cardiovascular disease has expanded the potential clinical applications of leukotriene modifiers. Conflicting data have been reported in animal studies depending on the disease model used and the molecular target (5-LOX versus FLAP). Human genetic studies have demonstrated a link between cardiovascular disease and polymorphisms in the leukotriene biosynthetic enzymes, in particular FLAP, in some populations. 

Of these agents, zileuton is the least prescribed because of reports of occasional liver toxicity. The receptor antagonists appear to have little toxicity. Reports of Churg-Strauss syndrome (a systemic vasculitis accompanied by worsening asthma, pulmonary infiltrates, and eosinophilia) appear to have been coincidental, with the syndrome unmasked by the reduction in prednisone dosage made possible by the addition of zafirlukast or montelukast. Of these two, montelukast is the most prescribed, probably because it can be taken without regard to meals and because of the convenience of once-daily treatment. 

Montelukast, zafirlukast Block leukotriene D4 receptors Block airway response to exercise and antigen challenge Prophylaxis of asthma, especially in children and in aspirin-induced asthma Oral duration hours Toxicity Minimal... 

There is also continuous interaction throughout the review process. For example, over roughly six years, the sponsor, Merck Research Laboratories of West Point, Pa., and the FDA had several face-to-face meetings and about 28 teleconferences regarding the asthma drug Singulair (montelukast sodium). 

In a probable pharmacodynamic interaction, severe peripheral edema followed treatment with montelukast and prednisone for asthma (494). 

A 23-year-old man, with a history of asthma, house dust mite allergy, and rhinoconjunctivitis, presented with acute respiratory symptoms. He was given oral cetirizine, inhaled salmeterol, and fluticasone propionate, and oral prednisone 40 mg/day for 1 week and 20 mg/day for 1 week. His asthma recurred when prednisone was withdrawn and he took oral prednisone 60 mg/day for 1 week and 40 mg/day for 1 week. He also took montelukast 10 mg/day. He then developed severe peripheral edema with a gain in weight of 13 kg. Prednisone was withdrawn and his edema resolved. Montelukast was continued. 

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