Chlorthalidone inhibits reabsorption of sodium and chloride in the distal renal tubule thus promoting water loss. The higher urine volume increases potassium loss, therefore restricting salt intake decreases potassium loss.
Little information is available on the extent of absorption of the drug.
This may not be important clinically because the biological effects of thiazides particularly as antihypertensives may be prolonged compared to their elimination rate. The longer acting agents appear to cause increased potassium loss. Although a mild diuretic, its combination with a loop diuretic is particularly potent because the latter presents much more sodium chloride to the distal tubule. The blood pressure lowering effects are initially due to volume reduction but the persisting effect includes other undetermined mechanisms that reduce peripheral resistance. A high salt intake reverses its antihypertensive effect.