Introduction

Potassium sparing diuretics inhibit the reabsorption of sodium (and water) from the distal tubule by antagonising aldosterone. They have only a relatively weak diuretic effect. They reduce potassium excretion (hence the name “potassium sparing”).

  • Aldosterone causes the synthesis of more sodium channels. Spironolactone and eplerenone competitively bind to the receptors that cause this action.
  • Amiloride and triamterene have a different mechanism of action, and they directly block the sodium channels at the luminal surface of the renal tubule – and hence reduce the reabsorption of sodium. 

Aldosterone is thought to contribute to the pathophysiology of heart failure, and as such, potassium sparing diuretics are frequently used to treat heart failure. In fact, they are one of the only medical treatments for heart filature that improve long term outcome.

Spironolactone is the most commonly used potassium sparing diuretic.

When used in conjunction with loop diuretics or thiazide diuretics, potassium sparing diuretics can reduce the loss of potassium in the urine.

The kidney is complicated, you might want to read about renal physiology to help understand how diuretics work.

Examples

Potassium sparing diuretics e.g. spironolactone, eplerenone, amiloride, triamterene

Mechanism

These act at the distal DCT and the cortical collecting ducts. They competitively bind with aldosterone binding sites but do not activate the binding site as aldosterone would – thus they inhibit the action of aldosterone. Thus, these only work in the presence of aldosterone.
These are the only diuretics that do not act on the luminal membrane of the nephron lumen.
Amiloride and triamterene have a different mechanism of action – blocking the sodium channel at the lumen.
These drugs reduce sodium reabsoprtion by 2-3% and thus are the least effective of the diuretics, however, the effect of spironolactone is increased in the presence of hyperadrenalism
These drugs are useful because they prevent loss of K+, because they act on this exchange mechanism. Thus, these drugs are often used in conjunction with other diuretics to prevent the hypokalaemia that they cause.
Spironolactone is metabolised quickly, but its metabolite, canrenone is probably responsible for most of its action. This has a long half-life, but this is not necessarily important, as it is the mechanism of the drug that determines the lasting effect. It may take a day before effects are seen, and maximal effects occur after 3-4 days.
The onset of amiloride and triamterene is much quicker.
You might want to red more about renal physiology and aldosterone, as well as a summary of effects of diuretics.

Unwanted effects

  • Hyperkalaemia is more common in those with pre-existing renal disease or who are also taking ACE-inhibitors. Magnesium retention occurs, in contrast to the other diuretics. It also occurs in pre-existing renal disease, and their use should be avoided in severe renal impairment (see below).
  • Spironolactone is able to bind to oestrogen receptors. This can cause gynecomastia and impotence in men, and menstrual problems in women. Eplerenone has greater steroid receptor specificity and does not cause these problems.

Uses and indications

  • Heart failure
  • Causes of hyperaldosteronism (potassium sparing diuretics help to reduce oedema in these circumstances)
    • Liver Failure
  • Resistant hypertension

Contraindications and Cautions

  • Contraindicated Renal failure – typically contra-indicated if Creatinine clearance <30
    • Increases risk of hyperkalaemia
  • Pregnancy
    • Can cause feminisation of the male fetus
  • Breastfeeding – safe to use

References

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