Chlorthalidone (Thalitone®)
| Chlorthalidone |  |
|---|---|
| Brand Name | Thalitone® |
| Drug Class | Thiazide-like Diuretic |
| Primary Indication | Hypertension |
| Site of Action | Distal Convoluted Tubule |
| Mechanism | Na⁺/Cl⁻ Cotransporter Inhibition |
| Potassium Effect | ↓ (Hypokalemia risk) |
| Calcium Effect | ↑ Reabsorption |
| Half-Life | ~40–60 hours |
| Landmark Trial | ALLHAT |
| FDA Approval | 1960 |
Overview
Chlorthalidone is a thiazide-like diuretic used primarily for the treatment of hypertension.
Although often grouped with thiazides, chlorthalidone has a significantly longer half-life and stronger outcome data compared to Hydrochlorothiazide.
It is frequently preferred in hypertension guidelines due to its durable 24-hour blood pressure control and cardiovascular outcome benefit.
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 effect)
Net effect:
- Sustained blood pressure reduction
Indications
- Primary hypertension
- Edema (less commonly)
Supported by:
- ALLHAT trial — reduction in cardiovascular events
Often combined with:
Contraindications
Absolute:
- Anuria
Relative / Caution:
- Severe renal impairment (reduced efficacy when eGFR < 30)
- Gout
- Hyponatremia
- Hypokalemia
- Diabetes mellitus
Dosing
Hypertension:
- 12.5–25 mg once daily
Higher doses:
- Increase metabolic side effects
- Provide minimal additional BP reduction
Long half-life supports once-daily dosing with sustained effect.
Pharmacokinetics
Absorption:
- Oral
Half-life:
- ~40–60 hours
Duration:
- >24-hour BP control
Elimination:
- Renal
Longer duration compared to hydrochlorothiazide.
Adverse Effects
Electrolyte:
- Hypokalemia
- Hyponatremia
- Hypomagnesemia
- Hypercalcemia
Metabolic:
- Hyperglycemia
- Hyperuricemia (gout)
- Mild dyslipidemia
Other:
- Photosensitivity
Electrolyte abnormalities may be more pronounced than with HCTZ.
Drug Interactions
Lithium:
- Increased lithium levels
RAAS inhibitors:
- May blunt potassium loss
Loop diuretics:
- Additive electrolyte depletion
Monitoring
- Blood pressure
- Electrolytes (Na⁺, K⁺)
- Renal function
- Uric acid (if gout risk)
- Glucose (diabetics)
Clinical Pearls
- Longer half-life than hydrochlorothiazide.
- Strong cardiovascular outcome data (ALLHAT).
- Often preferred thiazide for hypertension.
- More sustained 24-hour BP control.
- Greater risk of electrolyte abnormalities than HCTZ.
Comparison Within Class
Compared to Hydrochlorothiazide:
- Longer half-life
- Better cardiovascular outcome data
- More potent
Compared to Indapamide:
- Similar mechanism
- Slightly different metabolic profile
Compared to Furosemide:
- Less potent diuretic
- Not effective in severe renal failure