Is HCTZ a Diuretic?
Yes, hydrochlorothiazide (HCTZ) is definitively a thiazide diuretic that acts in the distal convoluted tubule of the kidney to inhibit sodium and chloride reabsorption, thereby promoting diuresis and lowering blood pressure. 1, 2
Classification and Mechanism
HCTZ is classified as a thiazide-type diuretic, specifically containing the benzothiadiazine ring structure that distinguishes it from thiazide-like agents (such as chlorthalidone and indapamide). 3
The drug works by inhibiting sodium and chloride reabsorption in the distal convoluted tubule, which is distinct from loop diuretics that act at the loop of Henle and potassium-sparing diuretics that act in the collecting duct. 1
HCTZ promotes urinary sodium excretion and decreases physical signs of fluid retention, with a duration of action of 6-12 hours. 1
Clinical Indications
HCTZ is FDA-approved for the management of hypertension either as monotherapy or in combination with other antihypertensives. 2
The drug is indicated for patients with hypertension and heart failure with mild fluid retention, though loop diuretics are preferred for most heart failure patients with significant congestion. 1
HCTZ becomes ineffective in patients with eGFR <30 mL/min/m², at which point loop diuretics should be used instead. 4
Dosing and Pharmacokinetics
Standard dosing ranges from 25 mg once or twice daily up to a maximum of 200 mg daily, with typical starting doses of 12.5-25 mg in elderly patients. 1, 2
HCTZ has a renal clearance of approximately 18.3 L/h in patients with normal kidney function (creatinine clearance 120 mL/min), but this decreases significantly with renal impairment. 5
The drug has a terminal half-life of approximately 14.8 hours and is primarily eliminated renally via organic anion transporters OAT1 and OAT3. 5, 6
Important Clinical Considerations
HCTZ is less potent than thiazide-like diuretics (chlorthalidone and indapamide) by approximately 4.2-6.2 mm Hg systolic blood pressure on 24-hour measurements. 7
Major guidelines recommend thiazide or thiazide-type diuretics as first-line agents for hypertension, though some expert statements prefer thiazide-like agents (chlorthalidone or indapamide) over HCTZ due to longer duration of action and more robust cardiovascular outcomes data. 1
Common adverse effects include hypokalemia, hypomagnesemia, hyperuricemia, and dilutional hyponatremia, requiring electrolyte monitoring particularly for potassium, sodium, and magnesium levels. 4, 2
Renal function should be carefully monitored, as HCTZ therapy is typically associated with mild increases in blood urea nitrogen and creatinine levels. 4