HCTZ Does Not Cause Cough
Hydrochlorothiazide (HCTZ) does not cause the dry, persistent cough that is characteristic of ACE inhibitors. If a patient on HCTZ presents with cough, you should look for other causes rather than attributing it to the thiazide diuretic.
Key Distinction: ACE Inhibitors vs. Thiazide Diuretics
The evidence clearly differentiates between these drug classes:
- ACE inhibitors cause cough in 5-35% of patients through accumulation of bradykinin and substance P when ACE is inhibited 1, 2
- HCTZ does not share this mechanism and has a cough incidence similar to placebo 3
In a direct comparison study, patients with confirmed ACE inhibitor-induced cough were randomized to valsartan, lisinopril, or HCTZ. The cough recurrence rate was 68.9% with lisinopril but only 19.0% with HCTZ—statistically indistinguishable from the angiotensin receptor blocker (19.5%) 3. This demonstrates that HCTZ does not trigger the cough reflex in the same manner as ACE inhibitors.
Clinical Implications
When evaluating a patient on HCTZ who develops cough:
- Do not discontinue HCTZ based on cough alone 3
- Investigate alternative causes including:
Rare HCTZ Pulmonary Reactions
While HCTZ does not cause the typical dry ACE inhibitor cough, be aware of two rare but serious pulmonary complications:
- Acute pulmonary edema from allergic reaction (presents with dyspnea, not isolated dry cough) 5
- Interstitial pneumonitis (extremely rare) 6
These reactions present with dyspnea and systemic symptoms, not the isolated dry, tickling throat cough characteristic of ACE inhibitors 6, 5.
Common Pitfall to Avoid
Do not confuse HCTZ with ACE inhibitors when counseling patients about cough risk. The American College of Chest Physicians guidelines specifically address ACE inhibitor-induced cough but make no mention of thiazide diuretics causing this side effect 1. HCTZ's common side effects include dizziness, weakness, fatigue, cramps, and electrolyte abnormalities—not cough 6, 7.