Zileuton

The effects of leukotrienes can be blocked at several levels. Inhibitors of FLAP or 5-LO inhibit LT synthesis at all levels. However, FLAP antagonists developed to date have been too hepatotoxic for human use. Zileuton, a 5-LO synthase inhibiting drug, also demonstrated some hepatotoxicity in a small percentage of patients, which was nonetheless entirely reversible. However, the short half-life of this compound requires four times daily... 

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. 

Zafirlukast and zileuton are used in the prophylaxis and treatment of chronic asthma in adults and children older than 12 years. Montelukast is used in the prophylaxis and treatment of chronic asthma in adults and in children older than 2 years. 

These dru are contraindicated in patients with a known hypersensitivity to the dragp. Montelukast, zaflrlukast, and zileuton are not used in the reversal of bronchospasm in acute asthma attacks. Zileuton is con-... 

Administration of zafirlukast and aspirin increases plasma levels of zafirlukast, When zafirlukast is administered with warfarin, there is an increased effect of the anti coagulant. Administration of zafirlukast and theophylline or erythromycin may result in a decreased level of zafirlukast. Administration of montelukast with other drugs has not revealed any adverse responses. Administration of montelukast with aspirin and NSAIDs is avoided in patients with known aspirin sensitivity. Administration of zileuton with propranolol increases the activity or the propranolol with theophylline increases serum theophylline levels and with warfarin may increase prothrombin time (PT). A prothrombin blood test should be done regularly in the event dosages of warfarin need to be decreased. 

These drugs are administered orally. Montehikast is administered once daily in the evening, zafirlukast is administered twice daily 1 hour before meals or 2 hours after meals. Zileuton is administered four times daily. 

When zileuton is prescribed, the nurse expects which laboratory test to be checked periodically ... 

Benzothiophenes have always been of interest for medicinal chemistry and can be found in a number of marketed drugs such as Sertaconazole (Gineder-mofix), Zileuton (Leutrol) and Raloxifene (Evista). The classical synthesis of benzo thiophenes starts from thiophenols, reacting with bromoacetaldehyde dimethyl acetal, followed by cycUzation using strong acid. An alternative and more convenient route was also described starting from benzaldehydes which... 

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... 

Use of zileuton is uncommon due to the need for dosing four times a day, potential drug interactions, and the potential for hepatotoxicity with the resulting need for frequent monitoring of liver enzymes. In patients started on zileuton, serum alanine aminotransferase concentrations should be monitored before treatment begins, monthly for the first 3 months, every 2 to 3 months for the remainder of the first year, and then periodically thereafter for as long as the patient continues to receive the medication. Zileuton also inhibits the cytochrome P-450 (CYP) mixed function enzyme system and has been shown to decrease the clearance of theophylline, R-warfarin and propranolol.34... 

This hypothesis was investigated in a retrospective analysis of the response to an ALOX5 inhibitor, ABT-761, which is clinically similar to zileuton. In 221 patients with asthma who received either high-dose ABT-761 (n= 114) or placebo (n= 107] treatment, approximately 6% of asthmatic patients had no wild-type allele... 

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