A 46-year-old woman started on lisinopril for newly diagnosed hypertension returns after two weeks complaining of a persistent dry, tickling cough that is worse at night. There is no wheeze, fever, or postnasal drip. The mediator most responsible for this adverse effect is:

• A Prostaglandin E2 release from airway epithelium
• B Increased angiotensin II acting on bronchial AT1 receptors
• C Accumulated bradykinin and substance P in the respiratory tract ✓
• D Histamine release from bronchial mast cells

Explanation

ACE degrades bradykinin and substance P in the lung. When ACE is inhibited, these peptides accumulate in the respiratory tract and irritate vagal afferent endings, producing the classic dry cough seen in up to 20 percent of patients. Angiotensin II levels actually fall with ACE inhibitors, so option B contradicts the pharmacology, and the cough is not histamine mediated like bronchial asthma. Switching to an ARB, which does not affect kinin metabolism, resolves it.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

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Written and medically reviewed by the StethoPrep medical team.