Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients

Dose-response curves for amiloride and spironolactone were defined in 15 hypertensive patients treated with bendroflumethiazide (bendrofluazide). The relative potency amiloride:spironolactone in correcting hypokalemia was 2.8:1, an estimate significantly lower than the 5:1 potency currently accepted. The relative potency for reduction of plasma sodium was 3.9:1 (amiloride:spironolactone). Amiloride was disproportionately potent in lowering serum bicarbonate, and the data do not suggest that these drugs elevate plasma potassium simply by correcting metabolic alkalosis. Changes in blood pressure were confounded by the presence of carryover effect between treatment phases. Both drugs increased plasma angiotension II and aldosterone, but the rise in aldosterone with spironolactone was smaller than expected from concurrent plasma angiotension II and potassium concentrations. This was consistent with a partial block of aldosterone biosynthesis by spironolactone. The activity of spironolactone did not require the presence of hyperaldosteronism. In a smaller study potassium chloride induced a significant log dose-response on plasma potassium, but the effect was small in absolute terms. At least 64 mmole potassium chloride was needed to match the effect of 20 mg amiloride or 56 mg spironolactone.