Pharmacology · NSAIDs and Autocoids (Histamine, Serotonin, Eicosanoids, Gout Drugs)

Montelukast, a cysteinyl leukotriene receptor antagonist, is most effective in which asthma phenotype?

  • A Aspirin-exacerbated respiratory disease (AERD) / Samter's triad, where shunting of arachidonic acid to 5-lipoxygenase pathway produces excess leukotrienes
  • B Eosinophilic asthma with blood eosinophils >300 cells/μL requiring biologic therapy
  • C Neutrophilic asthma triggered by occupational sensitizers
  • D Allergic bronchopulmonary aspergillosis with central bronchiectasis
Correct answer: A. Aspirin-exacerbated respiratory disease (AERD) / Samter's triad, where shunting of arachidonic acid to 5-lipoxygenase pathway produces excess leukotrienes

Explanation

In AERD (aspirin-exacerbated respiratory disease), COX-1 inhibition by aspirin or NSAIDs blocks prostaglandin E2 synthesis, which normally suppresses the 5-lipoxygenase (5-LOX) pathway. With PGE2 inhibited, arachidonic acid is shunted toward 5-LOX, producing massive cysteinyl leukotriene (CysLT: LTC4, LTD4, LTE4) excess. These potent bronchoconstrictors trigger bronchoconstriction, nasal polyposis, and urticaria in susceptible patients. Montelukast (CysLT1 receptor antagonist) is highly effective in this phenotype and also allows aspirin desensitization. Option B describes an indication for mepolizumab/benralizumab, not primarily montelukast.

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

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