| 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. |
| Pharmacodynamics |
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. |
| Absorption |
Rapidly absorbed, with somewhat less than 50% of the oral dose reaching the urine. |
| Volume of distribution |
Not Available |
| Protein binding |
55-67% (93% for the OH-TA-ester metabolite) |
| Metabolism |
Triamterene is primarily metabolized to the sulfate conjugate of
hydroxytriamterene. Both the plasma and urine levels of this metabolite
greatly exceed triamterene levels. |
| Route of elimination |
Not Available |
| Half life |
255 minutes (188 minutes for OH-TA-ester metabolite) after IV administration. |
| Clearance |
- 4.5 l/min [total plasma clearance]
- 0.22 l/kg [renal plasma clearance]
|
| 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. |
