Montelukast is used in asthma prophylaxis. It blocks leukotriene receptors (CysLT1). Which mechanism best explains why montelukast is particularly useful as an add-on therapy in aspirin-exacerbated respiratory disease (AERD)?

• A Montelukast inhibits aspirin absorption from the GI tract preventing COX-1 inhibition
• B Montelukast upregulates COX-2 to compensate for aspirin's COX-1 inhibition
• C Montelukast directly inhibits 5-lipoxygenase preventing leukotriene synthesis
• D Aspirin-induced COX-1 blockade shunts arachidonic acid through the 5-lipoxygenase pathway generating excess cysteinyl leukotrienes; montelukast blocks their CysLT1 receptors ✓

Explanation

In AERD (Samter's triad: asthma, nasal polyps, aspirin sensitivity), aspirin inhibits COX-1, blocking the conversion of arachidonic acid to prostaglandins. This diverts excess arachidonic acid into the 5-lipoxygenase (5-LOX) pathway, producing large amounts of cysteinyl leukotrienes (LTC4, LTD4, LTE4), which cause bronchoconstriction, mucosal oedema and nasal symptoms. Montelukast selectively blocks CysLT1 receptors, mitigating these effects. Zileuton inhibits 5-LOX directly (the other pharmacological target in AERD). Montelukast does not affect COX-2.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.