Montelukast Corticosteroids

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... 

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). 

Concurrent corticosteroids While the dose of inhaled corticosteroid may be reduced gradually under medical supervision, montelukast should not be abruptly substituted for inhaled or oral corticosteroids. 

Eosinophilia Physicians should be alert to eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, or neuropathy in their patients. In rare cases, patients on therapy with montelukast may present with systemic eosinophilia. These events usually, but not always, have been associated with the reduction of oral corticosteroid therapy. 

Zafirlukast and montelukast are well tolerated. Zafirlukast increases plasma concentrations of warfarin and decreases the concentrations of theophylline and erythromycin. In rare cases, treatment of patients with CysLT receptor antagonists is associated with the development of Churg-Strauss syndrome, a condition marked by acute vasculitis, eosinophilia, and a worsening of pulmonary symptoms. Because these symptoms often appear when patients are given the leukotriene receptor antagonists when they are being weaned from oral corticosteroid therapy, it is not clear whether they are related to the action of the antagonists or are due to a sudden reduction in corticosteroid therapy. 

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. 

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. 

Treatment with a leukotriene-receptor antagonist, particularly montelukast, is widely prescribed, especially by primary care providers. Taken orally, leukotriene-receptor antagonists are easy to use and appear to be used more regularly than inhaled corticosteroids. They are rarely associated with troublesome side effects. Maintenance therapy with a leukotriene antagonist or with cromolyn or nedocromil appears to be roughly as effective as maintenance therapy with theophylline. Because of concerns over the possible long-term toxicity of systemic absorption of inhaled corticosteroids, this maintenance therapy is widely used for treating children in the USA. 

Theophylline [the OFF i lin] is a bronchodilator that relieves airflow obstruction in chronic asthma, and decreases the symptoms of the chronic disease. Previously the main-stay of asthma therapy, theophylline has been largely replaced with (3-agonists and corticosteroids. Theophylline is well absorbed by the gastrointestinal tract, and several sustained-release preparations are available. The drug has a narrow therapeutic window, and an overdose of the drug may cause seizures or potentially fatal arrhythmias. Further, theophylline interacts adversely with many drugs. See pp. 450-451 for a description of newly approved drugs, zileuton, zafirlukast, and montelukast. 

Other, recent additions to prophylaxis in asthma therapy include the leukotriene receptor antagonist montelukast. This drug is taken as a tablet and blocks the actions of cysteinyl leukotrienes in the airways. The latter are products of the lipoxygenase pathway which cause bronchoconstriction and inflammation. It is no more effective than standard corticosteroids in the prophylaxis of asthma, but there is some evidence that when given together with a steroid there maybe a beneficial additive effect. 

Stempel DA, O Donnell JC, Meyer JW. Inhaled corticosteroids plus salmeterol or montelukast Effects on resource utiUzation and costs. J Allergy ain Immunol 2002 109 433-439. 

Current examples are montelukast and zaflrlukast, both of which are given orally, either alone or in combination with corticosteroids. They are not recommended for use in chronic bronchitis. 

Zalirlukast, a cysteinyl leukotriene antagonist, has shown therapeutic efficacy in cough-variant asthma, even in patients unresponsive to inhaled bronchodilators and corticosteroids (Dicpinigaitis et al. 2002), whist a similar drug, montelukast has also... 

A study in patients with moderately severe asthma found no adverse inter-aetions when salbutamol (albuterol) was given with montelukast 100 mg or 250 mg, with or without inhaled corticosteroids. The British Thoracic Society guidelines recommend that a leukotriene antagonist is used as an add-on therapy in patients using short-acting inhaled beta2 agonists. ... 

A study in healthy subjects (55 taking montelukast and 36 taking a placebo) found that the plasma profiles of oral prednisone 20 mg and of intravenous prednisolone 250 mg were unaffected by montelukast 200 mg daily for 6 weeks. The manufacturers also report that licensed doses of montelukast do not have any clinically significant effect on the pharmacokinetics of prednisone and prednisolone. Other studies in patients using inhaled and/or oral corticosteroids have found that concurrent use is beneficial and well tolerated. 

Phipatanakul W, Greene C, Downes SJ, Cronin B, Eller TJ, Schneider LC, Irani A-M. Montelukast improves asthma control in asthmatic children maintained on inhaled corticosteroids. Arm Allergy Asthma Immunol QDOy) 91,49-54. 

Nelsen LM, Shields KE, Cunningham ML, Staler JM, Bamshad MJ, Eng PM, et al. Congenital malformations among infants bom to women receiving montelukast, inhaled corticosteroids, and other asthma medications. J AKergy CKn Immunol January 2012 129(l) 251-4. el-6. 

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