Potassium-sparing diuretics

Abstract

The hemodynamic and the endocrine disturbances in congestive heart failure (CHF) impose major changes in electrolyte balance with a retention of sodium and concomitant losses of potassium and magnesium from the body. These changes are of great importance for the development of cardiac dysrhythmias, a diminished glucose tolerance and for the well-being of the patient. The use of conventional diuretics imposes further burdens on the already deranged electrolyte balance. On long-term therapy with conventional diuretics in CHF we observed that approximately 50% of the 297 patients studied had potassium and magnesium deficiencies and an increased sodium content as judged by skeletal muscle biopsies. The magnesium deficiency is especially dangerous since it prevents the cells from keeping their high intracellular potassium concentration unchanged. Potassium substitution is without effect in a magnesium deficiency since magnesium is necessary for the transportation of potassium over the cell membrane against the concentration gradient. In case of magnesium depletion, potassium substitution may even have negative effects on the body potassium content. The reason for this is probably the increase of p-potassium concentration induced by the substitution, leading to an increase of aldosterone secretion. An increase of p-potassium levels by 0.2-0.4 mmol/l may thus result in a 50-100% rise in p-aldosterone concentration. These changes promote further urinary losses of potassium and magnesium. Several studies have demonstrated the positive effects of the potassium-sparing diuretics amiloride, spironolactone and triamterene on p-potassium concentration, but also on the body potassium content. There are theoretical indications that these diuretics may also save magnesium. This would mean a further protection against the electrolyte disturbances induced by the combination of CHF and conventional diuretic therapy. In three different studies we have confirmed the potassium-sparing properties of amiloride, spironolactone and triamterene. Furthermore, these diuretics had the ability to restitute the magnesium balance that had been deranged prior to the investigation by CHF and conventional diuretic therapy. On using these potassium- and magnesium-sparing diuretics-amiloride, spironolactone and triamterene-sizeable increases of p-aldosterone levels have been observed, probably induced by the raised p-potassium concentration and by volume changes induced by the additional diuresis. Prior investigations on the body potassium content have been performed on a short-term basis. It has been speculated that the duration of the effects of amiloride and triamterene on the body content of potassium would not be lasting in the long-term prospect in the face of a persistently raised p-aldosterone level. In the above three investigations, however, we observed that all three agents were capable of even restituting the skeletal muscle content of both potassium and magnesium on a long-term basis (6 months).