Leukotriene pathway

Aspirin sensitive asthma, affecting about 10% of all asthmatics, is a nonallergic response to aspirin and other agents that inhibit cyclooxygenase-1. Mechanistically, the most likely reasons are lack of bronchoprotective prostaglandin E2 and shunting of arachidonic acid into the leukotriene pathway. 

Although there are data on the variability of the treatment response for each of these classes of agents, there are no systematic studies on the reasons for variance in the treatment response to steroids or theophylline. Therefore, this chapter will focus on the specific pharmacogenomics of /1-agonists and inhibitors of the cysteinyl-leukotriene pathway [18, 30] and on general considerations related to pharmacogenomic mechanisms. 

Drazen JM, Israel E, O Byrne PM. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med 1999 340 197-206. 

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. 

Like the other eicosanoids, the leukotrienes are also involved in inflammatory diseases. Accordingly, leukotriene pathway inhibitors are emerging as important agents. Two fundamental approaches to the design of leukotriene pathway inhibitors have been pursued ... 

This chapter presents the basic pharmacology of the methylxanthines, cromolyn, leukotriene pathway inhibitors, and monoclonal anti-IgE antibody—agents whose medical use is almost exclusively for pulmonary disease. The other classes of drugs previously... 

Szczeklik A, Sanak M, Nizankowska-Mogilnicka E, Kielbasa B. Aspirin intolerance and the cyclooxygenase-leukotriene pathways. Curr Opin Pulm Med. 2004 10 51-56. 

Two approaches to interrupting the leukotriene pathway have been pursued inhibition of 5-... 

In this context it may be helpful to mention the finding of another isomer of LTB4. This is 5(S),12(S)-dihydroxy-6-rra s,8-cw,10-traMs,14-cw-eicosatetraenoic acid, that is not formed via the leukotriene-pathway. It will therefore be discussed in Section 4. 

Vanderhoek, J. Y., Bailey, J. M., 1984 Activation of a 15-lipoxy-genase/leukotriene pathway in human polymorphonuclear leukocytes by the anti-inflammatory agent Ibuprofen. J. Biolog. Chem. 259, 6752-6756. 

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