Which medications in the drug class Potassium-Sparing Diuretics are used in the treatment of Primary Aldosteronism?

Updated: Mar 24, 2020
  • Author: Gabriel I Uwaifo, MD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Potassium-Sparing Diuretics

These agents are used as second-line medication for the treatment of primary aldosteronism due to nonlateralizing disease and/or lateralizing disease for which surgery is otherwise contraindicated or refused. They often must be used with other antihypertensives to achieve the best blood pressure control, because they are not potent antihypertensives.

Triamterene (Dyrenium)

Triamterene is a potassium-sparing diuretic with relatively weak natriuretic properties. It exerts a diuretic effect on the distal renal tubule to inhibit reabsorption of sodium in exchange for potassium and hydrogen. Triamterene increases sodium excretion and reduces the excessive loss of potassium and hydrogen associated with hydrochlorothiazide. It is not a competitive antagonist of mineralocorticoids; its potassium-conserving effect is observed in patients with Addison disease (ie, without aldosterone).

The onset and duration of activity with triamterene are similar to those of hydrochlorothiazide. No predictable antihypertensive effect is demonstrated. It is rapidly absorbed following oral administration, and peak plasma levels are achieved within 1 hour of dosing. Triamterene is primarily metabolized to a sulfate conjugate of hydroxytriamterene. Plasma and urine levels of this metabolite greatly exceed triamterene levels.


Amiloride is a pyrazine-carbonyl-guanidine unrelated chemically to other known antikaliuretic or diuretic agents. It is a potassium-conserving (antikaliuretic) drug that, compared with thiazide diuretics, possesses weak natriuretic, diuretic, and antihypertensive activity. Amiloride's effects have been partially additive to the effects of thiazide diuretics in some clinical studies. When it is administered with a thiazide or loop diuretic, it has been shown to decrease the enhanced urinary excretion of magnesium that occurs when a thiazide or loop diuretic is used alone.

Amiloride has potassium-conserving activity in patients receiving kaliuretic-diuretic agents. Amiloride is not an aldosterone antagonist, and its effects are observed in the absence of aldosterone. It exerts its potassium-sparing effect through the inhibition of sodium reabsorption at the distal convoluted tubule, cortical collecting tubule, and collecting duct. This decreases the net negative potential of the tubular lumen and reduces potassium and hydrogen secretion and their subsequent excretions.

Amiloride usually begins to act within 2 hours after an oral dose. Its effect on electrolyte excretion reaches a peak between 6-10 hours and lasts about 24 hours. Peak plasma levels are obtained in 3-4 hours, and the drug's plasma half-life varies between 6 and 9 hours.

Amiloride is not metabolized by the liver; it is instead excreted unchanged by the kidneys. Within 72 hours, about 50% of a dose of amiloride is excreted in urine and 40% in stool. The drug has little effect on the glomerular filtration rate or on renal blood flow. Because the liver does not metabolize amiloride hydrochloride, drug accumulation is not anticipated in patients with hepatic dysfunction; however, accumulation can occur if hepatorenal syndrome develops.

Amiloride should rarely be used alone. Used as single agents, potassium-sparing diuretics, including amiloride, result in an increased risk of hyperkalemia (approximately 10% with amiloride). Amiloride should be used alone only when persistent hypokalemia has been documented and only with careful titration of the dose and close monitoring of serum electrolyte levels.

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