In a patient with aspirin-exacerbated respiratory disease, ingestion of aspirin precipitates bronchospasm. The underlying mechanism is inhibition of cyclooxygenase with shunting of arachidonic acid metabolism toward which pathway?
- A 5-lipoxygenase pathway generating cysteinyl leukotrienes ✓
- B 12-lipoxygenase pathway generating 12-HETE
- C Cyclooxygenase-2 pathway generating prostacyclin
- D Cytochrome P450 epoxygenase pathway generating EETs
Correct answer: A. 5-lipoxygenase pathway generating cysteinyl leukotrienes
Explanation
Aspirin irreversibly inhibits COX-1, reducing bronchodilatory and bronchoprotective prostaglandin E2 and diverting free arachidonic acid into the 5-lipoxygenase pathway. The resulting surge of LTC4, LTD4, and LTE4 produces intense bronchoconstriction and mucus secretion in susceptible asthmatics. Leukotriene receptor antagonists such as montelukast mitigate these reactions. The other pathways do not generate the cysteinyl leukotrienes responsible for the attack.
Reference: Katzung Basic and Clinical Pharmacology, 15th ed.
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