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Hydrochlorothiazide

Hydrochlorothiazide

Microzide Esidrix Hydrodiuril Oretic Aquazide H

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Updated: December 06, 2025

Overview

Hydrochlorothiazide is a widely prescribed thiazide diuretic that has been used clinically since the 1950s. It is primarily utilized for the management of hypertension and edema associated with various conditions. As a first-line antihypertensive agent, it is often combined with other medications like ACE inhibitors or ARBs for enhanced therapeutic effects. This sulfonamide-derived drug promotes diuresis by inhibiting renal tubular reabsorption of sodium and chloride. Beyond its diuretic effects, hydrochlorothiazide demonstrates antihypertensive properties through vasodilatory mechanisms. Its well-established safety profile and low cost make it a cornerstone in cardiovascular pharmacotherapy.

Drug Class

Thiazide diuretic Antihypertensive agent Sulfonamide derivative

Mechanism of Action

Inhibits sodium-chloride symporter (NCC) in the distal convoluted tubule of nephrons • Blocks reabsorption of approximately 5% of filtered sodium • Promotes excretion of sodium, chloride, and water • Secondary effects include: - Vasodilation through calcium channel effects - Reduced peripheral vascular resistance - Activation of potassium channels

Pharmacokinetics

Absorption: Rapid but variable absorption (60-70% bioavailability) Distribution: Extracellular fluid distribution, protein binding 40-70% Metabolism: Minimal hepatic metabolism Excretion: Primarily renal excretion (95% unchanged) Half-life: 6-15 hours (dose-dependent)

Pharmacodynamics

• Onset of diuresis: 2 hours • Peak effect: 4-6 hours • Duration: 6-12 hours • Reduces systolic BP by 10-15 mmHg and diastolic BP by 5-10 mmHg • Increases urinary excretion of sodium, potassium, magnesium, and bicarbonate • Decreases calcium excretion

Indications

• Hypertension: First-line therapy alone or in combination with other antihypertensives • Edema: Management of fluid retention in heart failure, cirrhosis, and nephrotic syndrome • Nephrolithiasis: Prevention of calcium-containing kidney stones in hypercalciuric patients

Contraindications

Absolute: • Anuria • Hypersensitivity to sulfonamides or thiazides Relative: • Severe renal impairment (eGFR <30 mL/min) • Refractory hypokalemia • Hypercalcemia • Gout • Systemic lupus erythematosus

Dosage & Administration

Hypertension: 12.5-50 mg once daily (max 100 mg/day) Edema: 25-100 mg daily in single or divided doses Nephrolithiasis: 25-50 mg daily Note: Administer in morning to avoid nocturia

Special Populations

Pediatric: Not recommended <6 years; 1-2 mg/kg/day in children ≥6 years Geriatric: Start with lower doses (12.5 mg) Renal impairment: Avoid in severe impairment (eGFR <30) Hepatic impairment: Use cautiously due to electrolyte disturbances

Adverse Effects

Common (>10%): • Hypokalemia (may require supplementation) • Hyperuricemia (may precipitate gout) • Orthostatic hypotension • Hyperglycemia Serious (<1%): • Stevens-Johnson syndrome • Acute pancreatitis • Photosensitivity reactions • Severe hyponatremia • Aplastic anemia

Drug Interactions

• NSAIDs: Reduced antihypertensive effect • Lithium: Increased lithium toxicity risk • Digoxin: Hypokalemia potentiates digitalis toxicity • Corticosteroids: Enhanced potassium wasting • Antidiabetic agents: Reduced glucose control • Cholestyramine: Reduced absorption

Warnings & Precautions

• Risk of severe electrolyte imbalances (monitor potassium) • Sulfa allergy cross-reactivity possible • May exacerbate systemic lupus erythematosus • Increased risk of hyperglycemia in diabetics • Photosensitivity reactions reported • Gout exacerbation in susceptible patients

Pregnancy & Lactation

Pregnancy: FDA Category B (generally safe but may cause fetal electrolyte disturbances) Lactation: Excreted in breast milk (not recommended)

Monitoring Parameters

• Serum electrolytes (potassium, sodium, magnesium) • Renal function tests (BUN, creatinine) • Blood pressure • Uric acid levels • Blood glucose in diabetics • Body weight in heart failure patients

Patient Counseling

• Take in morning to avoid nighttime urination • Report muscle cramps, weakness, or irregular heartbeat • Maintain adequate hydration • Avoid excessive sun exposure • Dietary potassium recommendations based on serum levels • Regular blood pressure monitoring • Watch for signs of dehydration

Storage & Stability

Store at 20-25°C (68-77°F) Protect from light and moisture Keep in original container Discard expired medication

Clinical Pearls

• More effective with low-sodium diet • Consider potassium-sparing agent when used long-term • Monitor electrolytes more frequently in elderly • Less effective in advanced renal disease • May cause false-negative results in phentolamine tests • Can unmask diabetes insipidus

References

• UpToDate: Hydrochlorothiazide Drug Information • Goodman & Gilman's: The Pharmacological Basis of Therapeutics • FDA Prescribing Information for Microzide • Chobanian AV et al. JNC 7: Complete Report. Hypertension 2003 • Ellison DH, Loffing J. Thiazide Effects and Adverse Effects. Kidney Int 2009