Zileuton Corticosteroids

Leukotriene modifiers either inhibit 5-lipoxygenase (zileuton) or competitively antagonize the effects of leukotriene D4 (montelukast and zafirlukast). These agents improve FEV, and decrease asthma symptoms, rescue drug use, and exacerbations due to asthma. Although these agents offer the convenience of oral therapy for asthma, they are significantly less effective than low doses of inhaled corticosteroids.2,33... 

LTB4 is a potent bronchoconstrictor, as are several other leukotrienes. A 5-lip-oxygenase inhibitor, Zileuton, is approved for therapy of asthma (though it is not much used for this purpose) as is a leukotriene blocker, montelukast, marketed as Singulair. Singulair is widely used by asthmatics as a preventive for asthma attacks. Certain corticosteroids are employed for the same purpose. Neither montelukast nor the steroids are effective in terminating an established asthmatic attack. Beta agonists are employed for that purpose (see chapter 17). 

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. 

Theophylline [the OFF i lin] is a bronchodilator that relieves airflow obstruction in chronic asthma, and decreases the symptoms of the chronic disease. Previously the main-stay of asthma therapy, theophylline has been largely replaced with (3-agonists and corticosteroids. Theophylline is well absorbed by the gastrointestinal tract, and several sustained-release preparations are available. The drug has a narrow therapeutic window, and an overdose of the drug may cause seizures or potentially fatal arrhythmias. Further, theophylline interacts adversely with many drugs. See pp. 450-451 for a description of newly approved drugs, zileuton, zafirlukast, and montelukast. 

Coadministration of inhaled corticosteroids increases risk of UTI. Hepatotoxicity may result from the use of zileuton. 

Figure VI-1-3 presents the pathways for the synthesis of PGe, PGE]( PGE2, PGF2a, IX Aj, and the i leukotrienes from the membrane phospholipids. It also shows the sites of action of the corticosteroids, i NSAIDS, COX 2 inhibitors, zileuton and zafirlukast, and other "-lukasts."...

Beta-blockers (eg, timolol), corticosteroids, and zileuton do not cause diarrhea. LTB is a chemotactic factor. The answer is (C). 

Hydrocortisone and other corticosteroids inhibit phospholipase. Ibuprofen and indoineihacin inhibit cyclooxygenase reversibly, while zileuton inhibits lipoxygena.se. The answer is (A), a.s-pirin. 

The most important anti-inflammatory drugs in the treatment of asthma are the corticosteroids and dmgs such as cromolyn and nedocromil that inhibit release of mediators from mast cells and other inflammatory cells. The lipoxygenase inhibitor zileuton probably also exerts an anti-inflammatory effect in asthma. 

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