Hydrochlorothiazide and Hypokalemia

Yes, hydrochlorothiazide (HCTZ) can definitely cause hypokalemia in patients, with approximately 12.6% of users developing this condition. 1

Mechanism and Risk Factors

Hypokalemia may develop with HCTZ use, especially in cases of brisk diuresis, severe cirrhosis, concomitant use of corticosteroids or ACTH, or after prolonged therapy. 2
Thiazide diuretics cause potassium wasting through increased urinary excretion, leading to reduced serum potassium levels. 3
Women have a significantly higher risk of developing hypokalemia (adjusted OR 2.22) compared to men when taking hydrochlorothiazide. 1
Non-Hispanic Black patients have a 65% higher risk (adjusted OR 1.65) of developing hypokalemia on HCTZ therapy. 1
Underweight individuals and those taking HCTZ for five years or more have increased risk of hypokalemia. 1
Higher doses of HCTZ are associated with greater risk of hypokalemia - doses of 50-200 mg daily show a dose-dependent decrease in serum potassium levels. 4

Warning signs of electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances. 2
Hypokalemia can provoke ventricular arrhythmias or sensitize the heart to toxic effects of digitalis. 2
Studies show a significant correlation between the fall in serum potassium and the occurrence of premature ventricular contractions (PVCs), especially during exercise. 4
Patients with serum potassium levels ≤3.0 mmol/L have a twofold increase in ventricular arrhythmias compared to those with normal levels. 5

The FDA recommends periodic determination of serum electrolytes in patients who may be at risk for hypokalemia. 2
Hypokalemia may be avoided or treated by potassium supplementation or increased intake of potassium-rich foods. 2
Fixed-dose combination therapy with potassium-sparing agents significantly reduces the risk of hypokalemia (adjusted OR 0.32) compared to HCTZ monotherapy. 1
Even among patients taking potassium supplements, hypokalemia was found in 27.2% of those on HCTZ monotherapy, indicating that supplements alone may not be sufficient. 1
Combining HCTZ with potassium-sparing diuretics or blockers of the renin-angiotensin system helps reduce the risk of hypokalemia. 3
Lowering salt intake and increasing consumption of vegetables and fruits can help prevent hypokalemia in patients on HCTZ. 3

Chlorthalidone (another thiazide-type diuretic) has been shown to cause a higher incidence of hypokalemia compared to HCTZ. 6
Concomitant use of other medications like corticosteroids, ACTH, or digitalis can exacerbate hypokalemia risk or its consequences. 2
Regular monitoring of serum potassium is essential, particularly in high-risk groups such as women, ethnic minorities, underweight individuals, and those on long-term therapy. 1
In overdose situations, hypokalemia may be severe and can accentuate cardiac arrhythmias, especially if digitalis has also been administered. 2