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(Circulation. 1968;37:45.)
© 1968 American Heart Association, Inc.

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Amiloride

A Potassium-Sparing Natriuretic Agent

MARCIA B. BULL M.D.¹ JOHN H. LARAGH M.D.¹

¹ From the Department of Medicine, Columbia University, College of Physicians and Surgeons, and the Presbyterian Hospital, New York, New York.

Amiloride, a new, well-tolerated oral natriuretic and mild diuretic agent, has been evaluated alone and in combination with other diuretics. Its remarkable ability to promote retention rather than loss of potassium 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 hydrogen secretion and promoting bicarbonate 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 potassium retention and renin activation consequent to natriuresis.

The compound appears to act primarily in the distal nephron, blocking both sodium-hydrogen exchange and sodium-potassium exchange. Like triamterene, but unlike spirolactone, amiloride has the characteristics of a noncompetitive inhibitor of aldosteronedirected sodium and potassium 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 potassium balance because of its more rapid onset and disappearance of action.

No significant toxicity was encountered; however, serum potassium values should be carefully monitored, especially in situations involving impaired renal function.

Key Words: Spirolactone • Plasma renin activity • Diuretic agents • Potassium retention • Acid-base balance • Electrolyte excretion • Aldosterone excretion

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