Leukotriene receptor antagonist

FIGURE 9.20 Design of multiple ligancl activity, (a) Dual histamine HI receptor and leukotriene receptor antagonist incorporating known antihistaminic properties of cyproheptadine and LTD4. (b) Joint ACE/NEP inhibitor formed from incorporating similarities in substrate structures for both enzymes. From [57],... 

Antiasthma Drugs Leukotriene Receptor Antagonists and Leukotriene Formation Inhibitors... 

Leukotriene receptor antagonists include montelukast sodium (Sngulair) and zafirlukast (Accolate). Zileuton (Zyflo) is classified as a leukotriene formation inhibitor. Additional information concerning these drags is found in the Summary Drag Table Antiasthma Drugs. 

Leuko trienes are bronchoconstrictive substances released by the body during the inflammatory process. When leukotriene production is inhibited, bronchodilation is facilitated. Zileuton acts by decreasing tire formation of leukotrienes. Although the result is tire same, montelukast and zafirlukast work in a manner slightly differently from that of zileuton. Montelukast and zafirlukast are considered leukotriene receptor antagonists because they inhibit leukotriene receptor sites in the respiratory tract, preventing airway edema and facilitating bronchodilation. 

Affect activity occur greater than or OR leukotriene receptor antagonist or theo-... 

Oral pseudoephedrine should not be used in children under 1 year of age due to safety concerns. Intranasal ipratropium can be used as intermittent therapy for mild rhinitis or as add-on therapy in more severe cases. AIT is recommended for persistent rhinitis, particularly severe disease, because studies have shown that children respond better than adults. Montelukast is indicated for children 2 years of age and older with SAR and for infants 6 months of age and older with PAR. Studies evaluating leukotriene receptor antagonists as monotherapy or in combination with antihistamines have contradictory results.33... 

Sorkness CA. Leukotriene receptor antagonists in the treatment of asthma. Pharmacotherapy 2001 21 34S-37S. 

Cromolyn, leukotriene receptor antagonists, and theophylline are considered alternative agents, but they are not preferred. 

Montelukast (Singulair) is a leukotriene receptor antagonist approved for treatment of seasonal allergic rhinitis. It is effective alone or in combination with an antihistamine. 

Leukotriene receptor antagonists also are successful as additive therapy in patients inadequately controlled on inhaled corticosteroids alone and as corticosteroid-sparing therapy. However, the magnitude of these benefits is less than that reported with the addition of long-acting fi2-agonists. 

Spinozzi, F. et al., Biological effects of montelukast, a cysteinyl-leukotriene receptor-antagonist, on T lymphocytes, Clin. Exp. Allergy, 34, 1876, 2004. 

Marked species differences in hydrolytic cleavage were also observed for pranlukast (4.160), a leukotriene receptor antagonist. In rats, amide hydrolysis represented a major metabolic pathway, whereas, in humans, it was apparently absent. Investigations with purified enzymes showed that pranlukast... 

Grossman, J., Laiferman, I., Dubb, J. W., et al. (1997) Results of the first U.S. double-bUnd, placebo-controUed, multicenter clinical study in asthma with pranlukast, a novel leukotriene receptor antagonist. J. Asthma. 34, 321-328. 

Suissa, S., Dennis, R., Ernst, P., Sheehy, O., and WoodDauphinee, S. (1997) Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to-moderate asthma—a randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 126, 177-183. 

Yoshida, S., Sakamoto, H., Ishizaki, Y., et al. (2000) Efficacy of leukotriene receptor antagonist in bronchial hyperresponsiveness and hypersensitivity to analgesic in aspirin-intolerant asthma. Clin. Exp. Allergy. 30, 64-70. 

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. 

Q88 Zafirlukast is a leukotriene-receptor antagonist. Zafirlukast is used in the treatment of an acute severe asthma attack. 

Acetazolamide is a carbonic anhydrase inhibitor that reduces aqueous humour production and is therefore indicated in glaucoma to reduce the intraocular pressure. Salbutamol is a selective, short-acting beta2-agonist used as a bronchodilator in asthma. Tolbutamide is a short-acting sulphonylurea used in type 2 (non-insulin dependent) diabetes mellitus. Chlorpromazine is an aliphatic neuroleptic antipsychotic drug used in schizophrenia. Zafirlukast is a leukotriene-receptor antagonist that is indicated in the prophylaxis of asthma but should not be used to relieve acute severe asthma. 

Pharmacology Montelukast is a selective and orally active leukotriene receptor antagonist that inhibits the cysteinyl leukotrine (CysLTi) receptor. 

Zileuton Mechanisms 5-Upogenase inhibition or leukotrien receptor antagonist Elevation of liver enzymes... 

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. 

Leukotriene receptor antagonists (to prevent leukotriene binding)... 

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 sodium Antiasthmatic (leukotriene receptor antagonist)... 

The structure of the leukotrienes receptor antagonist cinalukast (58-9) bears only the vaguest resemblance to its predecessor, or, for that matter, to a leukotriene. Reaction of the cyanomethylphosphonate (58-1) with hydrogen sulfide converts the nitrile to a thioamide (58-2). Treatment of that intermediate with the bromoketone... 

---