chlorthalidone
Brand: Thalitone, Hygroton
Prototype: hydrochlorothiazide
Drug Class: thiazide-like diuretic
Drug Family: diuretic
Subclass: phthalimidine thiazide-like diuretic
Organ Systems: cardiovascular
Mechanism of Action
Inhibits NCC with longer duration of action than HCTZ; also inhibits carbonic anhydrase.
NCC cotransporter (distal tubule)
Indications
- hypertension
- edema
- heart failure
Contraindications
- anuria
- sulfonamide allergy
- severe hypokalemia
Adverse Effects
Common
- hypokalemia
- hyponatremia
- hyperuricemia
- hyperglycemia
Serious
- severe electrolyte disturbances
Pharmacokinetics (ADME)
| Absorption | 65% oral |
| Distribution | large Vd — RBC distribution |
| Metabolism | minimal |
| Excretion | renal |
| Half-life | 40-55 hours (much longer than HCTZ) |
| Onset | 2-6 hours |
| Peak | 8-12 hours |
| Duration | 24-72 hours |
| Protein Binding | 75-85% |
| Vd | 3.9 L/kg |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| digoxin | hypokalemia → toxicity | major |
| lithium | increased lithium levels | major |
Nursing Considerations
- ALLHAT preferred agent
- Once-daily dosing due to very long half-life
- More effective BP lowering than HCTZ at equivalent doses per meta-analyses
- Preferred in JNC guidelines over HCTZ for hypertension
Clinical Pearls
- ALLHAT: best CV outcomes vs other antihypertensive classes including CCBs, ACE inhibitors
- 40-55h half-life provides smoother, more sustained BP control than HCTZ
Safety Profile
Pregnancy use-with-caution
Lactation use-with-caution
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Guideline Update pending
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.