Onset of Action for Diuril (Chlorothiazide)
Diuril (chlorothiazide) has an onset of action within 1-2 hours after oral administration, with peak diuretic effect occurring at approximately 4 hours and duration lasting 6-12 hours. 1, 2
Pharmacokinetic Profile
The FDA drug label provides definitive timing for chlorothiazide's clinical effects 2:
- Oral administration: Diuresis begins within 2 hours, peaks at approximately 4 hours, and lasts 6-12 hours 2
- Intravenous administration: Onset occurs within 15 minutes with maximal action at 30 minutes 2
The American Thoracic Society confirms that thiazide absorption from the gastrointestinal tract is efficient, with onset of action within 1-2 hours and drug clearance within 3-6 hours 1.
Mechanism and Site of Action
Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption, increasing excretion of sodium and chloride in approximately equivalent amounts 2. This distal tubule action distinguishes it from loop diuretics like furosemide, which acts on the ascending limb of Henle's loop 1.
Clinical Considerations
The drug is not metabolized but is eliminated rapidly by the kidney, with 96% of an intravenous dose excreted unchanged in urine within 23 hours 2. The plasma half-life ranges from 45 to 120 minutes 2.
When combined with spironolactone (a potassium-sparing diuretic), chlorothiazide has been shown to improve pulmonary function in infants with chronic lung disease by increasing dynamic pulmonary compliance and decreasing airway resistance 1.
Important Caveats
- Periodic monitoring of serum electrolytes is essential during chronic therapy, as thiazide diuretics can cause hypokalemia and metabolic alkalosis 1
- Clinical toxicity of chlorothiazide is rare compared to loop diuretics 1
- The drug crosses the placental barrier but not the blood-brain barrier and is excreted in breast milk 2