Leukotriene in asthma

Coffey M, Peters-Golden M. (2003) Extending the understanding of leukotrienes in asthma. Curr Opin Allergy Clin Immunol. 3, 57-63. 

Wenzel SE. The role of leukotrienes in asthma. Prostaglandins Leukot Essent Fatty Acids. 2003 69 145-155. 

Stechschulte, D. J., Leukotrienes in Asthma and Allergic Rhinitis [editorial], New Eng-land Journal of Medicine 323(25) 1769-1770, 1990. 

Hay DWP, Torphy TJ, Undem BJ. Cysteinyl leukotrienes in asthma old mediators up to new tricks. Trends Pharmacol Sci 1995 16 304-309. 

Henderson WR. Role of leukotrienes in asthma. Ann Allergy 1994 72 272—278. Wasserman SI. Mast cells and airway inflammation in asthma. Am J Respir Crit Care Med 1994 150 S39-S41. 

Leff AR (2001) Regulation of leukotrienes in the management of asthma biology and clinical therapy. Annu Rev Med 52 1-14... 

Fisher AR, Drazen JM (1997) Leukotrienes. In Barnes P, Grunstein MM, Leff AR, Wool cock A (eds) Asthma, vol 1. Lrppincott-Raven, Philadelphia, pp 547-558... 

Finnerty, J.P., Wood-Baker, R., Thompson, H. and Holgate, S.T. (1992). Role of leukotrienes in exercise-induced asthma. Inhibitory effect of ICI 204,219, a potent leukotriene D4 receptor antagonist. Am. Rev. Resp. Dis. 145, 746-749. 

Holgate ST, Bradding P, Sampson AP. Leukotriene antagonists and synthesis inhibitors new directions in asthma therapy. J Allergy Clin Immunol 1996 98 1-13. 

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. 

Drazen JM. (1995) Leukotrienes. In Busse W.W., Holgate ST, eds. Asthma and rhinitis. Boston Blackwell Scientific 838-850. 

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. 

Currie GP, Lima JJ, Sylvester JE, Lee DK, Cockburn WJ, Lipworth BJ. (2003) Leukotriene C4 synthase polymorphisms and responsiveness to leukotriene antagonists in asthma. Br J Clin Pharmacol. 56, 422-426. 

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. 

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. 

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. 

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