Which of the following diuretics causes hyperkalemia as a characteristic adverse effect due to its mechanism of action?

Explanation

## Potassium-Sparing Diuretics and Hyperkalemia **Key Point:** Amiloride is an epithelial sodium channel (ENaC) blocker that prevents sodium reabsorption in the collecting duct, thereby reducing the driving force for potassium secretion. This leads to **hyperkalemia** as a cardinal adverse effect. ### Mechanism of Hyperkalemia In the collecting duct, the normal process is: 1. Aldosterone upregulates ENaC and Na⁺/K⁺-ATPase 2. Sodium enters the cell via ENaC, creating a negative lumen potential 3. This negative potential drives K⁺ secretion into the lumen When amiloride blocks ENaC: - Sodium reabsorption is blocked - The driving force for K⁺ secretion is abolished - Potassium accumulates in the blood → **hyperkalemia** **Mnemonic:** **KASP** — **K**⁺-sparing diuretics: **A**miloride, **S**pironolactone, **P**erfessor (potassium-retaining). All three cause hyperkalemia. ### Potassium-Sparing Diuretics Classification | Agent | Mechanism | Hyperkalemia Risk | Clinical Use | |---|---|---|---| | **Amiloride** | ENaC blocker | High | Hypertension + hypokalemia | | **Triamterene** | ENaC blocker | High | Hypertension + hypokalemia | | **Spironolactone** | Aldosterone antagonist | High | Heart failure, ascites | | **Eplerenone** | Selective aldosterone antagonist | Moderate | Heart failure post-MI | **High-Yield:** Hyperkalemia is the most serious adverse effect of K⁺-sparing diuretics; contraindicated in renal impairment, diabetes, and ACE inhibitor/ARB use. **Clinical Pearl:** K⁺-sparing diuretics are weak diuretics (cause <2% natriuresis) but are valuable when combined with loop or thiazide diuretics to prevent hypokalemia. **Warning:** Do NOT combine K⁺-sparing diuretics with ACE inhibitors or ARBs without close monitoring — risk of life-threatening hyperkalemia. [cite:Harrison 21e Ch 297]