Leukotrienes receptors

Most of the drugs such as epinephrine and albuterol used to treat asthma attacks are bronchodilators—substances that expand the bronchial passages Newer drugs are designed to either inhibit the enzyme 5 lipoxygenase which acts on arachidomc acid m the first stage of leukotriene biosynthesis or to block leukotriene receptors... 

Table 14. Prostanoid and Leukotriene Receptor Agonists and Antagonists...

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],... 

Along with the bronchodilators, several types of dragp are effective in Hie treatment of asthma. These include corticosteroids, leukotriene formation inhibitors, leukotriene receptor agonists, and mast cell stabilizers. 

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-... 

Lung Function concentration of 5-15 mcg/mL holding chamber) OR leukotriene receptor... 

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... 

Cysteinyl leukotriene receptor M201V, SNPs Tristan da Cunha, Caucasian, Loss of function (167,287-292) ... 

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. 

Fukai, H., Ogasawara, Y., Migita, O., et al. (2004) Association between a polymorphism in cysteinyl leukotriene receptor 2 on chromosome 13ql4 and atopic asthma. Pharmacogenetics. 14,683-690. 

Leukotrienes (LTA, LTB LTC, LTD, and LTE ) are synthesized from arachi-donic acid by a cascade of enzymes that include 5-lipoxygenase (5-LOX), 5-lipoxy-genase-activating protein (FLAP), and leukotriene C4 synthase (LTC synthase) (79,80). The leukotriene LTA is synthesized by 5-LOX in the first step and is an unstable precursor that is then enzymatically converted to LTB or LTC (80,81), which can subsequently be metabolized to LTD and LTE. LTC, LTD, and LTE are the components of the slow-reacting substance of anaphylaxis. These moieties, particularly LTC and LTD, are active forms of CysLTs that interact with the G protein-coupled cysteinyl leukotriene receptors (CysLtrl and CysLtr2) (70,81,82). Once engaged, the activated CysLtrs receptors stimulate the secretion of mucus and induce edema and bronchoconstriction (81). 

Hui Y, Funk CD. (2002) Cysteinyl leukotriene receptors. Biochem Pharmacol. 64, 1549-1557. 

Corrigan C, Mallett K, Ying S, et al. (2005) Expression of the cysteinyl leukotriene receptors cysLT(l) and cysLT(2) in aspirin-sensitive and aspirin-tolerant chronic rhinosinusitis. J Allergy Clin Immunol. 115, 316-322. 

Kim SH, Oh JM, Kim YS, et al. (2006) Cysteinyl leukotriene receptor 1 promoter polymorphism is associated with aspirin-intolerant asthma in males. Clin Exp Allergy. 36, 433-439. 

Park JS, Chang HS, Park CS, et al. (2005) Association analysis of cysteinyl-leukotriene receptor 2 (CY SLTR2) polymorphisms with aspirin intolerance in asthmatics. Pharmacogenet Genomics. 15, 483 92. 

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

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