hydrochlorothiazide
Brand: Microzide, HydroDIURIL
Prototype Drug
Drug Class: thiazide diuretic
Drug Family: diuretic
Subclass: benzothiadiazine diuretic
Organ Systems: cardiovascularrenal
Mechanism of Action
Inhibits NCC in the distal convoluted tubule reducing sodium and water reabsorption; increased calcium reabsorption (useful in hypercalciuria); activates RAAS secondarily.
Na-Cl cotransporter (NCC) in distal convoluted tubule
Indications
- hypertension
- edema
- nephrogenic diabetes insipidus (paradoxical)
- nephrolithiasis (calcium oxalate, hypercalciuria)
Contraindications
- anuria
- sulfonamide allergy
- hypokalemia (severe)
- severe renal impairment (CrCl <30, ineffective)
Adverse Effects
Common
- hypokalemia
- hyponatremia
- hyperuricemia
- hyperglycemia
- hypercholesterolemia
- photosensitivity
Serious
- electrolyte disturbances
- acute pancreatitis (rare)
- SJS (rare)
Pharmacokinetics (ADME)
| Absorption | 65-75% oral |
| Distribution | distributed widely |
| Metabolism | minimal hepatic |
| Excretion | renal unchanged |
| Half-life | 6-15 hours |
| Onset | 2 hours |
| Peak | 4 hours |
| Duration | 6-12 hours |
| Protein Binding | 40-68% |
| Vd | 3-4 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| digoxin | hypokalemia increases digoxin toxicity | major |
| lithium | reduces lithium clearance | major |
| NSAIDs | reduced antihypertensive and diuretic effect | moderate |
Nursing Considerations
- Monitor K+, Na+, uric acid, glucose
- Thiazides lose efficacy in CKD (CrCl <30) — switch to loop diuretic
- Effective synergy with ACE inhibitors/ARBs (counters RAAS activation)
- Good osteoporosis adjunct: increases calcium reabsorption reducing urinary calcium loss
Clinical Pearls
- First-line for hypertension in JNC/AHA guidelines
- ALLHAT: chlorthalidone superior to other classes for CV event prevention
- Reduces urinary calcium — protective against kidney stones and osteoporosis
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.