Clinical pharmacology of chlorothiazide compounds.

Abstract

The chlorothiazide compounds are effective, safe diuretics. They are as potent when administered by mouth as when given parenterally. They augment the excretion of water, salt, and to a lesser extent K+ and HCO3‐ ions. They combine the saluretic action of the organic mercurials with the carbonic anhydrase inhibitory action of sulfonamyl compounds. In the former activity, they might like the mercurials cause alkalosis and refractoriness to diuretic therapy. Because of their latter activity, they minimize alkalosis by limiting H+ ion excretion. Alkalinization of the urine by chlorothiazide is accompanied by K+ ion loss which in itself may cause disease. With recognition of this danger, K+ loss can be minimized by dietary supplementation. Another danger inherent in chlorothiazide is elevation of plasma urate concentration. Depending on dosage, urinary urate excretion may be increased or decreased. In either event, the plasma concentration of urate increases and can be neither prevented nor corrected during chlorothiazide therapy. The chlorothiazide compounds are secreted by the cells of the prOXimal segment of the nephron. They share this transport system with p‐aminohippuric acid, phenol red, penicillin, and analogous compounds. By this route, they are rapidly removed from body fluids, chemically unchanged.