Is chlorothalidone a potassium-sparing diuretic?

Chlorthalidone is Not a Potassium-Sparing Diuretic

Chlorthalidone is not a potassium-sparing diuretic; it is a thiazide-like diuretic that can cause hypokalemia and requires monitoring of serum potassium levels. 1

Mechanism of Action and Classification

• Chlorthalidone is an oral diuretic with prolonged action (48-72 hours) that works at the cortical diluting segment of the ascending limb of Henle's loop of the nephron 1
• It belongs to the thiazide-like diuretic class, which is distinct from potassium-sparing diuretics such as spironolactone, triamterene, and amiloride 2
• Unlike potassium-sparing diuretics, chlorthalidone increases potassium excretion, which can lead to hypokalemia, especially with brisk diuresis 1

Risk of Hypokalemia with Chlorthalidone

• Chlorthalidone has a higher risk of causing hypokalemia compared to hydrochlorothiazide, with an adjusted hazard ratio of 3.06 3
• Hypokalemia may develop especially with brisk diuresis, severe cirrhosis, or concomitant use of corticosteroids or ACTH 1
• Warning signs of hypokalemia include: dry mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances 1

Potassium Monitoring and Management

• All patients receiving chlorthalidone should be observed for clinical signs of fluid or electrolyte imbalance, particularly hypokalemia 1
• Periodic determination of serum electrolytes should be performed at appropriate intervals to detect possible electrolyte imbalance 1
• Serum potassium and creatinine should be monitored every 5-7 days after initiation of treatment until values are stable, then every 3-6 months 3

Dosing Considerations to Minimize Hypokalemia

• Lower doses of chlorthalidone (25 mg daily) can provide similar antihypertensive efficacy as higher doses (50-75 mg) with less potassium depletion 4, 5
• In one study, hypokalaemia was rarely seen in patients who took 25 mg per day of chlorthalidone, but was common with 100 mg per day 5
• Potassium-sparing diuretics (triamterene, amiloride, spironolactone) may be considered if hypokalaemia persists despite potassium supplementation 3

Clinical Implications

• Digitalis therapy may exaggerate metabolic effects of hypokalemia, especially with reference to myocardial activity 1
• Thiazide-induced hypokalemia is associated with increased blood glucose, and treatment of thiazide-induced hypokalemia may reverse glucose intolerance 6
• Dietary sodium restriction may increase diuretic-induced potassium loss, presumably by increased activity of the renin-angiotensin-aldosterone system 7

Potassium Supplementation Efficacy

• Potassium chloride supplements may not be fully effective in treating chlorthalidone-induced hypokalemia; in one study, 39 mEq potassium chloride supplements daily for 4 weeks caused only a small, non-significant rise in serum potassium from 3.23 mEq/L to 3.38 mEq/L 8
• Potassium-sparing diuretics may be more effective than supplements for managing persistent hypokalemia 3

In summary, chlorthalidone is definitively not a potassium-sparing diuretic but rather a thiazide-like diuretic that increases potassium excretion and requires careful monitoring of serum potassium levels to prevent hypokalemia.