Pulmonology · USMLE Step 1 and Step 2

Leukotriene Inhibitors song

Leukotriene Inhibitors: Montelukast - Mechanism & Uses, as a song. Hear the short teaser here. The full song is on YouTube and Spotify.

Leukotriene Inhibitors

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Key points in this song10

Montelukast is a cysteinyl leukotriene receptor antagonist (CysLT1 blocker) that prevents leukotriene D4 (LTD4)-mediated bronchoconstriction, mucus secretion, and airway inflammation.
Leukotrienes are derived from arachidonic acid via the 5-lipoxygenase (5-LOX) pathway; montelukast blocks the receptor downstream, while zileuton inhibits 5-LOX itself.
Classic USMLE trigger: aspirin-exacerbated respiratory disease (Samter's triad = asthma + nasal polyps + aspirin sensitivity) is a preferred indication for montelukast because COX inhibition shunts arachidonic acid toward the leukotriene pathway.
Montelukast is FDA-approved for mild persistent asthma, exercise-induced bronchoconstriction, and allergic rhinitis; it is not a rescue inhaler and cannot abort an acute attack.
Unlike beta-2 agonists and corticosteroids, montelukast is orally administered, making it useful for patients with poor inhaler technique, especially pediatric patients.
Montelukast carries an FDA black box warning for neuropsychiatric events including depression, suicidal ideation, and behavioral changes; this limits its use as a first-line agent.
Montelukast does not cause bronchospasm or adrenal suppression, distinguishing it from inhaled corticosteroids and making it safe in patients with HPA-axis concerns.
Zileuton (5-LOX inhibitor), unlike montelukast, requires monitoring of liver function tests due to hepatotoxicity risk and has significant drug interactions via CYP1A2 inhibition.
In the asthma stepwise management framework, leukotriene receptor antagonists are an alternative (not preferred) controller for Step 2 mild persistent asthma, with inhaled corticosteroids remaining first-line.
Key distinction: montelukast blocks CysLT1 receptors on bronchial smooth muscle and eosinophils, reducing both early and late-phase allergic responses, explaining its dual efficacy in asthma and allergic rhinitis.