Diuretics, potassium-sparing

Key examples

• Amiloride (as co-amilofruse, co-amilozide)

 

Common indications

• As part of combination therapy, for the treatment of hypokalaemia arising from loop- or thiazide-diuretic therapy. Aldosterone antagonists (e.g. spironolactone) also have a potassium-sparing effect, and may be used as an alternative.

 

Mechanisms of action

• Potassium-sparing diuretics such as amiloride are relatively weak diuretics alone. However, in combination with another diuretic, they can counteract potassium loss and enhance diuresis. 
• Amiloride acts on the distal convoluted tubules in the kidney. It inhibits the reabsorption of sodium (and therefore water) by epithelial sodium channels (ENaC), leading to sodium and water excretion, and retention of potassium. This counteracts the potassium losses associated with loop- or thiazide-diuretic therapy. 
• Amiloride is available as a medicine in its own right, but tends more often to be used as part of a combination tablet with furosemide (a loop diuretic) as co-amilofruse, or with hydrochlorothiazide (a thiazide diuretic) as co-amilozide. 
• The ratio of the two drugs in the combination tablets is designed to have a neutral effect on potassium balance, although in practice this may not always be the case.

 

Important adverse effects

• Side effects are uncommon at low doses, but gastrointestinal upset may occur. When used in combination with other diuretics, dizziness, hypotension and urinary symptoms may be problematic. As combined preparations, electrolyte disturbances should cancel each other out, but the risk of hypokalaemia, hyperkalaemia and hyponatraemia should not be ignored.

 

Warnings

• Avoid in severe renal impairment and hyperkalaemia. 
• Combination therapy should not be started in the context of hypokalaemia, as the effect on potassium may be unpredictable. 
• As with all diuretics, they should be avoided in states of volume depletion.

 

Important interactions

• Do not use in combination with other potassium-elevating drugs, including potassium supplements (oral or IV) and aldosterone antagonists, due to the risk of hyperkalaemia. 
• As with other diuretics, renal clearance of drugs including digoxin and lithium may be altered, requiring dose adjustment.