indication

For use as adjunctive treatment with thiazide diuretics or other kaliuretic-diuretic agents in congestive heart failure or hypertension.

pharmacology

Amiloride, an antikaliuretic-diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. It is an antihypertensive, potassium-sparing diuretic that was first approved for use in 1967 and helps to treat hypertension and congestive heart failure. The drug is often used in conjunction with thiazide or loop diuretics. Due to its potassium-sparing capacities, hyperkalemia (high blood potassium levels) are occasionally observed in patients taking amiloride. The risk is high in concurrent use of ACE inhibitors or spironolactone. Patients are also advised not to use potassium-containing salt replacements.

mechanism of action

Amiloride works by inhibiting sodium reabsorption in the distal convoluted tubules and collecting ducts in the kidneys by binding to the amiloride-sensitive sodium channels. This promotes the loss of sodium and water from the body, but without depleting potassium. Amiloride 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 both potassium and hydrogen secretion and their subsequent excretion. Amiloride is not an aldosterone antagonist and its effects are seen even in the absence of aldosterone.

toxicity

No data are available in regard to overdosage in humans. The oral LD₅₀ of amiloride hydrochloride (calculated as the base) is 56 mg/kg in mice and 36 to 85 mg/kg in rats, depending on the strain. The most likely signs and symptoms to be expected with overdosage are dehydration and electrolyte imbalance.

biotransformation

Amiloride is not metabolized by the liver but is excreted unchanged by the kidneys.

absorption

Readily absorbed following oral administration.

half life

Plasma half-life varies from 6 to 9 hours.

route of elimination

Amiloride HCl is not metabolized by the liver but is excreted unchanged by the kidneys. About 50 percent of a 20 mg dose of amiloride HCl is excreted in the urine and 40 percent in the stool within 72 hours.

drug interactions

Benazepril: Increased risk of hyperkalemia

Candesartan: Increased risk of hyperkalemia

Captopril: Increased risk of hyperkalemia

Cilazapril: Increased risk of hyperkalemia

Dihydroquinidine barbiturate: Decreases the antiarrhythmic effect of quinidine

Enalapril: Increased risk of hyperkalemia

Eplerenone: Increased risk of hyperkalemia. Monitor serum potassium levels during concomitant threapy.

Eprosartan: Increased risk of hyperkalemia

Forasartan: Increased risk of hyperkalemia

Fosinopril: Increased risk of hyperkalemia

Irbesartan: Increased risk of hyperkalemia

Lisinopril: Increased risk of hyperkalemia

Losartan: Increased risk of hyperkalemia

Moexipril: Increased risk of hyperkalemia

Perindopril: Increased risk of hyperkalemia

Polystyrene sulfonate: Risk of alkalosis in renal impairment

Potassium: Increased risk of hyperkalemia

Quinapril: Increased risk of hyperkalemia

Quinidine: Amiloride may decrease the therapeutic effect of quinidine. Monitor for changes in the therapeutic and adverse effects of quinidine if amiloride if initiated, discontinued or dose changed.

Quinidine barbiturate: Decreases the antiarrhythmic effect of quinidine

Ramipril: Increased risk of hyperkalemia

Saprisartan: Increased risk of hyperkalemia

Spirapril: Increased risk of hyperkalemia

Tasosartan: Increased risk of hyperkalemia

Telmisartan: Telmisartan may increase the hyperkalemic effect of Amiloride. Monitor for increased serum potassium concentrations during concomitant therapy.

Trandolapril: Increased risk of hyperkalemia. Monitor serum potassium levels.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Valsartan: Increased risk of hyperkalemia