A 58-year-old woman from Mumbai with a 5-year history of hypertension on amlodipine 10 mg daily presents with BP 156/98 mmHg. She has a dry, persistent cough that started 2 weeks after her doctor added enalapril 10 mg daily to her regimen. Chest X-ray is normal. Serum creatinine is 0.9 mg/dL (baseline 0.8 mg/dL), K+ is 5.2 mEq/L (normal 3.5–5.0). She denies orthopnea or dyspnea on exertion. What is the most appropriate next step?

Explanation

## Clinical Diagnosis This patient has developed **ACE inhibitor-induced cough**, a well-recognized and common adverse effect occurring in 5–10% of patients on ACE inhibitors. ## Mechanism of ACE Inhibitor Cough **Key Point:** ACE inhibitors block the degradation of bradykinin in the lungs. Accumulation of bradykinin stimulates cough receptors in the airways, causing a dry, persistent cough typically within 2–4 weeks of initiation. **High-Yield:** This cough: - Is dry and non-productive - Occurs in 5–10% of ACE inhibitor users - Resolves within 1–4 weeks of drug discontinuation - Is NOT a sign of heart failure or pulmonary edema (CXR is normal here) - Does NOT respond to cough suppressants **Clinical Pearl:** The normal chest X-ray and absence of dyspnea/orthopnea rule out pulmonary edema or heart failure. The temporal relationship (cough started 2 weeks after enalapril initiation) is pathognomonic for ACE inhibitor-induced cough. ## Why Losartan Is Correct **Mnemonic: ARB = Alternative to ACE inhibitor** Angiotensin II receptor blockers (ARBs) are the ideal replacement for ACE inhibitors in patients who develop intolerable side effects. ARBs: - Block angiotensin II at the AT1 receptor (downstream of ACE) - Do NOT inhibit bradykinin degradation - Cause cough in <2% of patients (much lower than ACE inhibitors) - Provide equivalent BP control and cardiovascular protection - Are especially useful in combination with calcium channel blockers (amlodipine) **Dosing:** Losartan 50 mg daily is appropriate for this patient; can be titrated to 100 mg if needed. ## Comparison of Management Options | Approach | Rationale | Outcome | |----------|-----------|----------| | Continue enalapril + cough suppressant | Cough suppressants do not address bradykinin accumulation; ineffective | Cough persists | | Switch to losartan | Eliminates bradykinin pathway; maintains RAS blockade | **Cough resolves, BP controlled** | | Reduce enalapril dose | Dose reduction rarely eliminates cough; patient still symptomatic | Suboptimal | | Add spironolactone | Addresses neither the cough nor the underlying ACE inhibitor problem | Cough persists; K+ already borderline elevated | **Warning:** Spironolactone is contraindicated here—the patient's K+ is already 5.2 mEq/L (upper normal range), and ACE inhibitors increase potassium retention. Adding a potassium-sparing agent risks hyperkalemia.