indication

For the treatment of edema associated with congestive heart failure, cirrhosis of the liver, and the nephrotic syndrome; also in steroid-induced edema, idiopathic edema, and edema due to secondary hyperaldosteronism.

pharmacology

Triamterene, a relatively weak, potassium-sparing diuretic and antihypertensive, is used in the management of hypokalemia. Triamterene is similar in action to amiloride but, unlike amiloride, increases the urinary excretion of magnesium.

mechanism of action

Triamterene inhibits the epithelial sodium channels on principal cells in the late distal convoluted tubule and collecting tubule, which are responsible for 1-2% of total sodium reabsorption. As sodium reabsorption is inhibited, this increases the osmolarity in the nephron lumen and decreases the osmolarity of the interstitium. Since sodium concentration is the main driving force for water reabsorption, triamterene can achieve a modest amount of diuresis by decreasing the osmotic gradient necessary for water reabsorption from lumen to interstitium. Triamterene also has a potassium-sparing effect. Normally, the process of potassium excretion is driven by the electrochemical gradient produced by sodium reabsorption. As sodium is reabsorbed, it leaves a negative potential in the lumen, while producing a positive potential in the principal cell. This potential promotes potassium excretion through apical potassium channels. By inhibiting sodium reabsorption, triamterene also inhibits potassium excretion.

toxicity

In the event of overdosage it can be theorized that electrolyte imbalance would be the major concern, with particular attention to possible hyperkalemia. Other symptoms that might be seen would be nausea and vomiting, other G.I. disturbances, and weakness. It is conceivable that some hypotension could occur. The oral LD₅₀ in mice is 380 mg/kg.

biotransformation

Triamterene is primarily metabolized to the sulfate conjugate of hydroxytriamterene. Both the plasma and urine levels of this metabolite greatly exceed triamterene levels.

absorption

Rapidly absorbed, with somewhat less than 50% of the oral dose reaching the urine.

half life

255 minutes (188 minutes for OH-TA-ester metabolite) after IV administration.

drug interactions

Benazepril: Increased risk of hyperkalemia

Candesartan: Increased risk of hyperkalemia

Captopril: Increased risk of hyperkalemia

Cilazapril: Increased risk of hyperkalemia

Drospirenone: Increased risk of hyperkalemia

Enalapril: Increased risk of hyperkalemia

Eplerenone: This association presents an increased risk of hyperkalemia

Eprosartan: Increased risk of hyperkalemia

Forasartan: Increased risk of hyperkalemia

Fosinopril: Increased risk of hyperkalemia

Indomethacin: Risk of acute renal impairment with this combination

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: Antagonism of action

Potassium: Increased risk of hyperkalemia

Quinapril: Increased risk of hyperkalemia

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 Triamterene. 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