CV - Diuretics, potassium-sparing

Question 1

Diuretics, potassium-sparing: amiloride (as co-amilofruse, co-amilozide)

Clinical pharmacology

Common indications

Answer 1

• 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.

Question 2

Mechanisms of action?

Answer 2

• 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.

Question 3

Warnings?

Answer 3

• 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.

Question 4

Important interactions?

Answer 4

• 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.

Question 5

Practical prescribing

Prescription?

Answer 5

• The most commonly used product is co-amilofruse, a tablet containing furosemide and amiloride in a ratio of 1 : 8.
• It is important to state the ‘strength’ of the tablet (i.e. their drug content) on the prescription.
• This is specified as, for example, ‘co-amilofruse 2.5/20’, meaning that the tablet contains 2.5 mg of amiloride and 20 mg of furosemide.
• You then state the dose as the number of tablets to be taken daily.
• The strength and dose are usually selected to match the dose of the existing loop or thiazide diuretic.
• So, for example, if you have a patient currently taking furosemide 40 mg daily (which is controlling their symptoms but causing hypokalaemia), you might replace this with co-amilofruse 5/40, 1 tablet daily.

Question 6

Monitoring?

Answer 6

• The best form of monitoring for efficacy is the patient’s symptoms of fluid overload (in the case of co-amilofruse) or their blood pressure (for co-amilozide).
• You should monitor their serum potassium concentration to ensure this returns to normal.
• The intensity of biochemical monitoring will depend on the severity of the hypokalaemia.