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Potassium Sparing Diuretics

Potassium sparing diuretics act on the collecting tubule.


Eplerenone is more selective for aldosterone receptors.

Canrenone is an active metabolite of aldosterone.

Triamterene and amiloride act independent of aldosterone. They are basic in nature, which are secreted in PCT by base secretory mechanism. All others are secreted by acid secretory methods.

Spironolactone is a synthetic compound which competitively blocks aldosterone receptors.


Spironolactone is 65% absorbed and metabolized in liver.

Canrenone has half life of 16.5 hours, and undergoes enterohepatic circulation.

Amiloride is basic in nature, secreted by base secretory mechanism.

Triamterene and hydroxyl triamterene are actively eliminated by kidneys. Toxicity might occur if liver or kidney failure occurs (metabolized in liver, excreted by kidneys)

Mechanism of Action

1. Site of action is collecting tubule.
2. Reach the site of mechanism by two mechanisms:

Aldosterone antagonists differ from others as they have intracellular receptors and diffuse though blood. No tubular secretion occurs.

3. Normal Physiology

Sodium moves in while potassium moves out, a gradiant is established which pumps in chloride ions by transcellular pathway.

4. Ionic Changes

Aldosterone is a steroid having intracytoplasmic receptors. The receptor drug complex enters the nucleus, leading to protein synthesis and increased activity of certain silent Na+ channels and pumps (aldosterone induced proteins). They cause greater reabsorptive capacity of Na+. More Na+ present in cells is pumped into interstitium. More potassium is present in lumen. Which is titrated by hydrogen.

Aldosterone antagonists competitively antagonize the effects of aldosterone. This leads to decreased reabsorption of Na+ and decreased excretion of K+. So called K+ sparing diuretics.

Minimal NaCl is reabsorbed at this site but is the final site which determines Na+ excretion.

Non aldosterone antagonists physically block the channels. No sodium moves in and no potassium is lost, having K+ sparing effect. Decreased Na+ reabsorption leads to increased excretion of Na+, H+ and water.

These diuretics are weak. Only 2-5% NaCl reabsorption occurs.

5. No hemodynamic changes occur.


  1. Primary –due to adenoma secreting aldosterone (Conn’s syndrome), tumor, ectopic
  2. Secondary –due to CCF, cirrhosis, nephritic syndrome

The body senses hypovolemia and increases renin secretion.

Diuretics are used to mobilize the fluid (spironolactone like drugs)


In combination with thiazide diuretics. Moduretic (Amiloride and Hydrochlorothiazide) is an example.


To guard the development of hypokalemia, K+ sparing diuretics can be combined to counter alkalosis.

 Side Effects


Decreased K+ excretion occurs if given with beta blockers, ACE inhibitors, renin antagonists, angiotensin receptor blockers.

Electrolytes levels must be checked.

Metabolic Acidosis

Due to blockage of H+ excretion.

Hormonal Effects

Spironolactone has steroid nature, due to which it might lead to:

  1. impotence
  2. menstrual abnormalities
  3. hirsuitism
  4. gynecomastia

Due to interference with androgens and progesterone receptors.

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