Hydrochlorothiazide (Microzide®)
| Hydrochlorothiazide |  |
|---|---|
| Brand Names | Microzide®, HydroDIURIL® |
| Drug Class | Thiazide Diuretic |
| Primary Indication | Hypertension |
| Site of Action | Distal Convoluted Tubule |
| Mechanism | Na⁺/Cl⁻ Cotransporter Inhibition |
| Potassium Effect | ↓ (Hypokalemia risk) |
| Calcium Effect | ↑ Reabsorption |
| Half-Life | ~6–15 hours |
| FDA Approval | 1959 |
Overview
Hydrochlorothiazide (HCTZ) is a thiazide diuretic used primarily for the treatment of hypertension and mild edema.
It lowers blood pressure by promoting natriuresis and reducing plasma volume, followed by long-term reduction in systemic vascular resistance.
Thiazides remain first-line therapy for uncomplicated hypertension in many patients.
Mechanism of Action
Site of Action
- Distal convoluted tubule
Transporter Blocked
- Na⁺/Cl⁻ cotransporter (NCC)
Physiologic Effects
- ↑ Sodium and water excretion
- ↑ Potassium excretion
- ↑ Calcium reabsorption
- ↓ Plasma volume
- ↓ Peripheral vascular resistance (long term)
Net effect:
- Reduction in blood pressure
Indications
- Primary hypertension
- Mild edema
- Nephrolithiasis (calcium stone prevention)
- Adjunct in heart failure (mild cases)
Often combined with:
Contraindications
Absolute:
- Anuria
- Sulfonamide allergy (relative; cross-reactivity low)
Relative / Caution:
- Severe renal impairment (ineffective at low GFR)
- Gout
- Diabetes mellitus
- Hyponatremia
- Hypokalemia
Dosing
Hypertension:
- 12.5–25 mg once daily
Edema:
- 25–100 mg daily
Higher doses increase metabolic side effects without significant additional BP benefit.
Pharmacokinetics
Absorption:
- Oral
Bioavailability:
- ~65–75%
Half-life:
- ~6–15 hours
Elimination:
- Renal
Effectiveness decreases when eGFR < 30 mL/min/1.73 m².
Adverse Effects
Electrolyte:
- Hypokalemia
- Hyponatremia
- Hypomagnesemia
- Hypercalcemia
Metabolic:
- Hyperglycemia
- Hyperuricemia (gout)
- Hyperlipidemia (mild)
Other:
- Photosensitivity
Drug Interactions
Increased lithium levels Additive hypokalemia with:
- Loop diuretics
- Corticosteroids
RAAS inhibitors:
- May mitigate potassium loss
Monitoring
- Blood pressure
- Electrolytes (Na⁺, K⁺)
- Renal function
- Uric acid (if history of gout)
- Glucose (diabetics)
Clinical Pearls
- First-line therapy for uncomplicated hypertension.
- Lower doses (12.5–25 mg) preferred.
- Causes hypokalemia and metabolic alkalosis.
- Increases calcium reabsorption — useful in kidney stones.
- Less effective when eGFR < 30.
Comparison Within Class
Compared to Chlorthalidone:
- Shorter half-life
- Less potent
- Less outcome data
Compared to Indapamide:
- More metabolic effects
- Shorter duration
Compared to Furosemide:
- Less potent diuretic
- Ineffective in severe renal failure