Potassium sparing diuretic
POTASSIUM SPARING DIURETIC
|
-
There are 2 groups of drugs in this category.
-
The only thing, they have in common is their site of action (late distal tubule and collecting duct).
-
However their mechanism of action is quite different.
-
Inhibition of aldosterone - Spiranolactone
-
Inhibition of the Na+ K+ exchange in the collecting duct - Triamterene, Amiloride
Aldosterone antagonists
-
Aldosterone (a steroid hormone) enters tubular cells and binds to a mineralocorticoid receptor in the cytoplasm.
-
This hormone receptor complex binds to a response element on the DNA.
-
Binding results in the expression of aldosterone induced proteins leading to activation of silent Na+ channels/pumps, alteration of the cycling of the channels and pumps, increased expression of channels and pumps and altered permeability of the tight junction (zonula occludens).
-
All the above effects result in an increase in Na+ conductance (reabsorption) and secretion of K+ (One of the complications of excess aldosterone secretion is hypokalemia).
-
Spiranolactone binds to the mineralocorticoid receptor and prevents aldosterone from binding.
-
Spiranolactone a true competitive antagonist of aldosterone enhances direct reabsorption of sodium in more proximal areas of the distal tubules.
-
This drug has a very slow onset of action, which is not dose dependent.
-
It may exert oestrogen like activity
-
It is used in combination with thiazide diuretics.
-
Spiranolactone is not effective in the presence of low levels of aldosterone.
-
-
If hyperkalemia occurs as a result of spiranolactone toxicity, thiazide diuretics can be administered.
Triamterene and amiloride
-
These drugs have a limited diuretic efficacy.
-
They act on the collecting tubules and collecting ducts, inhibiting sodium reabsorption and decreasing potassium excretion.
-
Triamterene inhibits aldosterone specific ATPase.
-
But, is not dependent on aldosterone levels.
-
Amiloride blocks Na+ channels in the luminal membrane affecting Na+ permeability.
-
Both the drugs promote excretion of uric acid.
-
The main importance of these drugs lies in their potassium-sparing ability.
-
They can be given with potassium-losing diuretics like thiazides to maintain potassium balance.
-
They are useful in conditions where K+ loss cannot be tolerated (often used in conjunction with thiazides)
-
In hypertension and congestive heart failure - If a person is being treated with digoxin for their heart failure, loss of K+ can enhance the toxicity of digoxin (cardiac glycoside).
-
If K+ is reduced, the actions of digoxin are enhanced because normally, digoxin must compete with K+ for the Na+ K+ ATPase.
-
By using the drugs in combination, there is an enhanced diuretic effect and the added benefit of not losing K+.
-
Spironolactone is used in primary hyperaldosteronism (tumor of the adrenals) or secondary hyperaldosteronism (cardiac failure, hepatic cirrhosis).
Side effects
-
Hyperkalemia,
-
Metabolic acidosis,
-
Gynaecomastia,
-
Impotence,
-
Decreased libido,
-
Hirsuitism and
-
Gastric upsets.
|
Last modified: Wednesday, 25 April 2012, 12:16 PM