Potassium saving diuretics

Potassium-sparing diuretics are an (inhomogeneous) group of drugs that affect the Na+ channel in the luminal membrane of the late distal tubule and collecting duct at the nephron, increasing Na+ ions and water and decreasing K+ ^ions excreted in the urine. Although pharmacologically different in structure, they share a common functional site and that is the mineral corticoid receptors.

The so-called potassium-saving diuretics include the organic cations

• Amiloride
• triamterene

and the aldosterone antagonists

• Spironolactone (active metabolite=canrenone)
• Eplerenone

The orally available drugs amiloride and triamterene are only available in Germany as combination preparations with hydrochlorothiazide (e.g. Dytide®, Moduretik®). In cases of severe hepatic or nephrotic edema, they are used together with loop diuretics.

The aldosterone antagonists spironolactone and eplerenone are not primarily used as antidiuretics but for the treatment of chronic heart failure. Their diuretic effect is not in the foreground here.

In the late distal tubule and collecting duct, an epithelial Na+ channel provides electrogenic Na+ uptake into the principal cells of this tubular segment. Amiloride and triamterene block this Na+ channel, with amiloride acting 10xpotently than triamterene. Blockade of this channel leads to an increase in Na+ excretion to 2-4% of filtered Na+. This process leads to hyperpolarization of the luminal cell membrane with the consequence that the luminal negative transepithelial potential is reduced. As a result, tubular K+ secretion decreases markedly. The reduction of the luminal trnasepithelial potential is also responsible for the decreased renal excretion of H+, Ca2+ and Mg2+.

Potassium-sparing diuretics are usually used in combination with a thiazide diuretic for the treatment of arterial hypertension. This is to prevent hypokalemia under thiazides. Unlike a thiazide diuretic and a loop diuretic, a potassium-sparing diuretic can also be combined with a cardiac glycoside.

Other indications:

Oedema of cardiac, renal and hepatic origin (when reduced potassium excretion is desired).

Adverse reactions: see below the individual substances.

ADRs mainly concern the electrolyte balance, in this case hyperkalaemia with bradycardic cardiac arrhythmias. Use together with ACE inhibitors, sartans and potassium preparations should be avoided. Occasionally, therapy with potassium-sparing diuretics may lead to non-specific gastrointestinal side effects (nausea, vomiting, diarrhoea).

Other potential side effects include:

• metabolic acidosis
• fatigue, dizziness
• Muscle cramps
• skin exanthema
• Phototoxicity
• Triamterene may also impair glucose tolerance; furthermore, the drug is contraindicated in diseases with possible folic acid deficiency (liver cirrhosis, alcoholism) (Graefe KH 2016).

See below the individual preparations

severe hepatic impairment

Hypovolemia

Hyponatremia

Hyperkalemia

Folic acid deficiency