Potassium-Wasting Diuretics
Loop diuretics (furosemide, bumetanide, torsemide) and thiazide/thiazide-like diuretics (hydrochlorothiazide, chlorthalidone, metolazone, chlorothiazide, indapamide) are potassium-wasting diuretics that increase urinary potassium excretion and can cause hypokalemia. 1
Loop Diuretics
Loop diuretics inhibit sodium and chloride reabsorption at the loop of Henle, resulting in significant potassium losses through increased delivery of sodium to the distal tubule where sodium-potassium exchange occurs 1. The loop diuretics include:
- Furosemide (20-600 mg daily, duration 6-8 hours) 1
- Bumetanide (0.5-10 mg daily, duration 4-6 hours) 1
- Torsemide (10-200 mg daily, duration 12-16 hours) 1
Loop diuretics cause a rebound in sodium retention after their initial natriuretic effect wears off, which paradoxically makes many oral formulations less potent natriuretics than thiazide-type diuretics over 24 hours 2. However, they produce more pronounced potassium wasting during their active phase 3, 2.
Thiazide and Thiazide-Like Diuretics
Thiazide diuretics act in the distal convoluted tubule to block sodium and chloride reabsorption 1. This increases sodium delivery to the collecting duct where sodium-potassium exchange occurs, leading to potassium loss 4. With continued use and sodium depletion, compensatory mechanisms increase this exchange and may produce excessive loss of potassium, hydrogen, and chloride ions 4.
The thiazide and thiazide-like diuretics include:
- Hydrochlorothiazide (25-200 mg daily, duration 6-12 hours) 1
- Chlorthalidone (12.5-100 mg daily, duration 24-72 hours) 1
- Metolazone (2.5-20 mg daily, duration 12-24 hours) 1
- Chlorothiazide (250-1000 mg daily, duration 6-12 hours) 1
- Indapamide (2.5-5 mg daily, duration 36 hours) 1
Metabolic toxicities associated with excessive electrolyte changes caused by hydrochlorothiazide, including hypokalemia, have been shown to be dose-related 4. During once-daily administration of high-dose thiazide formulations, plasma aldosterone increases, accounting for elevated potassium excretion 2.
Clinical Implications
For patients on loop or thiazide diuretics with persistent hypokalemia despite supplementation, adding potassium-sparing diuretics (spironolactone, triamterene, or amiloride) is more effective than chronic oral potassium supplements 5. The combination of thiazide or loop diuretics with potassium-sparing agents reduces the risk of hypokalemia and hypomagnesemia 3.
Addition of a thiazide (e.g., metolazone) to treatment with a loop diuretic should be reserved for patients who do not respond to moderate- or high-dose loop diuretics to minimize electrolyte abnormalities 1. This combination produces synergistic diuresis but dramatically increases potassium wasting 1.
Monitoring Requirements
Monitor for hypokalemia with thiazide and loop diuretics 1. Target serum potassium should be maintained at 4.0-5.0 mEq/L, as both hypokalemia and hyperkalemia increase mortality risk, particularly in patients with heart failure or cardiac disease 5.