Asthma treatment: antileukotriene drugs.
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Leukotrienes are derived from the cell membrane phospholipid arachidonic acid and are members of a larger group of molecules known as eicosanoids. It is possible to inhibit the production of leukotrienes by inhibiting their synthesis or antagonizing their receptor (the cysteinyl leukotrine 1 [CysLT1] receptor). Several drugs have been investigated extensively in clinical trials of asthmatic patients and are now available for prescription use in the management of asthma in several countries. These drugs include one enzyme inhibitor, zileuton, and three chemically distinct CysLT1 receptor antagonists, zafirlukast, pranlukast and montelukast. Antileukotrienes have been shown to inhibit effectively allergen- induced early and late responses, airway hyper-responsiveness and allergen-induced airway inflammation. They are also effective in attenuating exercise-induced bronchoconstriction and acetylsalicylic acid-induced asthmatic responses. In clinical trials, antileukotrienes improve spontaneous bronchoconstriction, reduce symptoms, reduce rescue beta2-agonist use and may reduce severe asthma exacerbations. Antileukotrienes are a new class of drugs; therefore, the total patient exposure, which needs to be known to evaluate safety fully, is limited. Antileukotrienes are the first new class of novel and effective therapy for asthma in more than 20 years. They have been shown to have a beneficial effect in the treatment of both induced and spontaneously occurring asthma. The results from these studies provide evidence that the cysteinyl leukotrienes are important mediators in the pathogenesis of asthma. While encouraging results have been obtained from clinical trials of antileukotrienes, there are no guidelines for the optimal clinical use of antileukotrienes in asthma treatment.
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