A patient with mast cell activation syndrome is poorly controlled on H1 and H2 antihistamines. The rationale for adding montelukast (a leukotriene receptor antagonist) to the regimen is that:

• A Montelukast antagonizes H3 receptors in the CNS, reducing neuroimmune-mediated mast cell degranulation
• B Mast cells also release cysteinyl leukotrienes (LTC4, LTD4, LTE4) via 5-lipoxygenase/FLAP pathway, which are not blocked by antihistamines and contribute to bronchospasm, urticaria, and abdominal cramps ✓
• C LTB4 is the primary neutrophil chemoattractant in mast cell disease; montelukast blocks BLT1 receptors reducing tissue inflammation
• D Montelukast stabilizes mast cell membranes by blocking calcium entry through CRAC channels

Explanation

Activated mast cells degranulate releasing histamine (blocked by H1/H2 antagonists) but also synthesize and release cysteinyl leukotrienes (LTC4 → LTD4 → LTE4) via the 5-lipoxygenase/FLAP (5-LOX activating protein) pathway from arachidonic acid. These cysteinyl leukotrienes act on CysLT1 and CysLT2 receptors, producing bronchoconstriction, mucosal edema, urticaria, and GI cramps — symptoms that persist despite antihistamines. Montelukast blocks CysLT1 receptors, complementing antihistamine therapy. LTB4 acts on BLT1/BLT2 receptors but montelukast is selective for CysLT1, not BLT receptors.

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

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Written and medically reviewed by the StethoPrep medical team.