Leukotriene antagonists Zafirlukast

ANTICOAGULANTS - ORAL LEUKOTRIENE ANTAGONISTS Zafirlukast t anticoagulant effect Zafirlukast inhibits CYP2C9-mediated metabolism of warfarin Monitor INR at least weekly until stable... 

Suissa, S., Dennis, R., Ernst, P., Sheehy, O., and WoodDauphinee, S. (1997) Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to-moderate asthma—a randomized, double-blind, placebo-controlled trial. Ann. Intern. Med. 126, 177-183. 

Q88 Zafirlukast is a leukotriene-receptor antagonist. Zafirlukast is used in the treatment of an acute severe asthma attack. 

ASPIRIN LEUKOTRIENE ANTAGONISTS t levels of zafirlukast Uncertain Watch for early features of zafirlukast toxicity. Monitor FBC and liver function closely... 

MACROLIDES LEUKOTRIENE RECEPTOR ANTAGONISTS-ZAFIRLUKAST i zafirlukast levels Induction of metabolism Watch for poor response to zafirlukast... 

THEOPHYLLINE LEUKOTRIENE RECEPTOR ANTAGONISTS -ZAFIRLUKAST Possibly t theophylline levels. Also possibly 4 zafirlukast levels Mutual alteration of metabolism Be aware watch for features of theophylline toxicity and measure levels... 

Reinus JF, Persky S, Burkiewicz JS, Quan D, Bass NM, Davern TJ. Severe liver injury after treatment with the leukotriene receptor antagonist zafirlukast. Ann Intern Med 2000 133(12) 964-8. 

Two clinically distinct cysteinyl leukotriene receptor antagonists (zafirlukast and montelukast) and one inhihitor of leukotriene synthesis (zUeuton) have been available in the United States since 1996 for both children and adults with persistent asthma. In challenge studies, they reduce allergen-, exercise-, cold-air hyperventilation-, irritant-, and aspirin-induced asthma. Chnical use of zileuton is limited owing to the need for four-times-daily dosing, the potential for elevated liver enzymes (especially in the first 3 months of therapy), and the potential inhibition of drugs metabolized by the CYP3A4 isoenzymes. ... 

Leukotriene Antagonists As noted above, an inhibitor of lipoxygenase (zileuton) and LTD (and LTE ) receptor antagonists (zafirlukast, montelukast) have become available for clinical use. At present, these agents are approved only for use in asthma. 

Leukotriene antagonists and inhibitors Oral Amlexanox, Ibudilast, Montelukast, Pemirolast, Pranlukast, Zafirlukast... 

Asthma Leukotriene D antagonists Zafirlukast (ICI 204 2I9) Sulukast (LY170680)... 

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. 

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. 

The biological actions of the cysteinyl leukotrienes are mediated via stimulation of CysLTi receptors. Montelukast and zafirlukast are competitive antagonists of these receptors. In contrast, zileuton suppresses synthesis of the leukotrienes by inhibiting 5-lipoxygenase, a key enzyme in the bioconversion of arachidonic acid to the leukotrienes. Zileuton also blocks the production of leukotriene B4, another arachidonic acid metabolite with proinfiammatory activity. The CysLTi-receptor antagonists alter neither the production nor the actions of leukotriene B4. 

Zafirlukast and montelukast are well tolerated. Zafirlukast increases plasma concentrations of warfarin and decreases the concentrations of theophylline and erythromycin. In rare cases, treatment of patients with CysLT receptor antagonists is associated with the development of Churg-Strauss syndrome, a condition marked by acute vasculitis, eosinophilia, and a worsening of pulmonary symptoms. Because these symptoms often appear when patients are given the leukotriene receptor antagonists when they are being weaned from oral corticosteroid therapy, it is not clear whether they are related to the action of the antagonists or are due to a sudden reduction in corticosteroid therapy. 

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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