Pharmacological Management: Leukotriene Receptor Antagonists

Amarachi Uzosike, PharmD, and Bindu George, MD

Mechanism of Action

•Antileukotriene agents are also referred to as leukotriene modifiers.

•Airflow obstruction in asthma is the result of numerous pathologic processes.

•Inflammatory infiltrates and exudates distinguished by eosinophils, but also including other inflammatory cell types (neutrophils, monocytes, lymphocytes, mast cells, basophils), can fill and obstruct the airways and induce epithelial damage and desquamation into the airway lumen.

•Leukotrienes are potent proinflammatory mediators that can induce bronchospasm, mucus secretion, altered cellular activity, and airway edema.

•Two classes of leukotriene modifiers exist: inhibitors of leukotriene synthesis (5-lipoxygenase inhibitor [5-LOX]) and leukotriene receptor antagonists (LTRAs).

—Zileuton is the 5-LOX inhibitor used in the management of asthma.

—Montelukast and zafirlukast are LTRAs used in the management of asthma.

•LTRAs reduce the proinflammatory (increased microvascular permeability and airway edema) and bronchoconstriction effects of leukotriene D4_, especially in exercise, aspirin, and allergen-induced bronchoconstriction.

Indications, Administration, and Dosing

•LTRAs are suggested as alternative therapy for mild persistent asthma and as add-on medication with inhaled corticosteroids (ICS) for moderate or severe persistent asthma.

•