CLINICAL PHARMACOLOGY
The mechanism of the antihypertensive effect of thiazides is unknown. Chlorothiazide does not usually affect normal blood pressure.
Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy.
Chlorothiazide increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.
After oral use diuresis begins within 2 hours, peaks in about 4 hours, and lasts about 6 to 12 hours.
Pharmacokinetics and Metabolism
Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. The plasma half-life of chlorothiazide is 45 to 120 minutes. After oral doses, 10 to 15 percent of the dose is excreted unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
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