Asthma leukotriene receptor antagonists

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

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. 

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. 

LTC4 and LTD4 are potent bronchoconstrictors and are recognized as the primary components of the slow-reacting substance of anaphylaxis (SRS-A) that is secreted in asthma and anaphylaxis. There are four current approaches to antileukotriene drug development 5-LOX enzyme inhibitors, leukotriene-receptor antagonists, inhibitors of FLAP, and phospholipase A2 inhibitors. 

Cromolyn or nedocromil by inhalation, or a leukotriene-receptor antagonist as an oral tablet, may be considered as alternatives to inhaled corticosteroid treatment in patients with symptoms occurring more than twice a week or who are wakened from sleep by asthma more than twice a month. Neither treatment is as effective as even a low dose of an inhaled corticosteroid, but both avoid... 

Bisgaard H. Pathophysiology of the cysteinyl leukotri-enes and effects of leukotriene receptor antagonists in asthma. Allergy. 2001 56 (suppl 66) 7—11. 

Spahr JE, Krawiec ME. Leukotriene receptor antagonists—risks and benefits for use in paediatric asthma. Expert Opin Drug Saf. 2004 3 173-185. 

Aside from 11, -receptor antagonists, the symptoms of seasonal allergies may also be treated with leukotriene receptor antagonists. The lone successful drug from this class is montelukast (Singulair, A.16) (Figure A.4). Montelukast is most often prescribed to treat asthma but can be used for allergic rhinitis as well. 

Several commercial products have been produced via Heck reactions on a scale in excess of one ton year"1 [43]. The sunscreen agent 2-ethylhexyl-p-methoxycinna-mate has been synthesized on a pilot scale by using Pd/C as the catalyst [44]. Albermarle produces Naproxen via a Heck reaction of 2-bromo-6-methoxy-naphthalene with ethylene, followed by carbonylation of the product [45]. A key step in the production of Singulair (montelukast sodium), a leukotriene receptor antagonist for treatment of asthma, is Heck reaction of methyl 2-iodobenzoate with an allylic alcohol to give a ketone [43]. 

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. 

Arachidonic acid is also metabolised by lipoxygenase to straight-chain hydroperoxy acids and then to leukotrienes which cause increased vascular permeability, vasoconstriction, bronchoconstriction, as well as chemotactic activity for leucocytes (whence their name). Inhibitors of lipoxygenase, e.g. zileuton, and leukotriene receptor antagonists, e.g. montelukast, zafirlukast, have found a place in the therapy of asthma (see p. 559). 

Anaphylaxis after ibuprofen was reported in a patient with asthma who was also taking zafirlukast, a leukotriene receptor antagonist (SEDA-22,116). 

Reicin A, White R, Weinstein SF, Finn AF Jr, Nguyen H, Peszek I, Geissler L, Seidenberg BC. Montelukast, a leukotriene receptor antagonist, in combination with loratadine, a histamine receptor antagonist, in the treatment of chronic asthma. Arch Intern Med 2000 160(16) 2481-8. 

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