Amiloride

Abstract

Amiloride, a new, well-tolerated oral natriuretic and mild diuretic agent, was evaluated alone and in combination with other diuretics. Its remarkable ability to promote retention rather than loss of K makes it a useful adjunct in the management of even the most severe edematous states. It also retards the alkalosis produced by certain of the stronger diuretics by blocking H secretion and promoting HCO3- loss. In addition to being a valuable adjunctive agent, the compound may be useful alone because of the advantages inherent in steady, sustained natriuretic therapy with a mild diuresis as opposed to incurring precipitous alterations in fluid and electrolyte balance with the intermittent use of more potent agents. In certain patients it was mildly antihypertensive. Amiloride produced marked increases in aldosterone secretion with lesser rises in plasma renin. The adrenal stimulation therefore appeared to result from both K retention and renin activation consequent to natriuresis. The compound appears to act primarily in the distal nephron, blocking both Na-H exchange and Na-K exchange. Like triamterene, but unlike spirolactone, amiloride has the characteristics of a noncompetitive inhibitor of aldosterone-directed Na and K transport. Because of this, it may be expected to produce more predictable effects than spirolactone and at least in certain instances to be more powerful. It may also be preferable to spirolactone for the acute control of derangements in K balance because of its more rapid onset and disappearance of action. No significant toxicity was encountered; serum K values should be carefully monitored, especially in situations involving impaired renal function.