Systolic time intervals during spironolactone treatment of digitalized and non-digitalized patients with ischaemic heart disease

Abstract

The effect of spironolactone on cardiac contractility indices was studied by externally recording systolic time intervals in four digitalized and four non-digitalized patients with ischaemic heart disease. A negative inotropic effect was found after spironolactone 100mg b.i.d. in all eight patients, as measured by an increase in pre-ejection period index PEPI (p less than 0.01), and the ratio between pre-ejection period and left ventricular ejection time PEP/LVET (p less than 0.001), while pre- and afterload remained constant. As expected, digoxin exerted a positive inotropic effect, as a decrease was observed in PEPI (p less than 0.01), and PEP/LVET (p less than 0.001). It was not possible to ascertain whether the observed effect was caused by a pharmacological interaction at receptor level between spironolactone and digoxin, or indirectly to changes in endogenous substances e.g. aldosterone. The results suggest that spironolactone may have unintended side effects in patients with severe heart failure and that its use be reevaluated.

Amiloride improves hemodynamics in patients with chronic congestive heart failure treated with chronic digoxin and diuretics

“…Because of the potassium-sparing characteristics of amiloride, triamterene, and spironolactone, these drugs are frequently used to prevent hypokalemia, which can occur with the thiazide diuretics. Recently there have been reports of an interaction between potassium-sparing diuretics and digoxin, which have been interpreted to show a reversal of the positive inotropic activity of digoxin [1][2][3].…”

“…Waldorff et al [2] in 14 patients with ischemic heart disease and cardiac "decompensation," reported a negative inotropic effect of spironolactone alone or with diogoxin, compared to the effect of digoxin alone, based upon systolic time interval measurements. They defined cardiac decompensation by evidence of cardiac enlargement by chest x-ray, peripheral edema, and abnormal electrocardiogram.…”

“…In the past, interactions between the potassium-sparing diuretics amiloride and spironolactone and digoxin have been shown to decrease the positive inotropic effect of digoxin [1][2][3]. In view of these studies and the widespread concomitant use of digoxin with potassiumsparing diuretics, we studied the hemodynamic effects of amiloride in patients taking digoxin for chronic congestive heart failure.…”

Cardiac Glycosides Drug Interactions of Clinical Significance

“…l42 ] The clinical implication of this interaction is, however, not fully established. As spironolactone appeared in one study to decrease the inotropic effect of digoxin, as measured by systolic time intervals, [44] it is possible that the resulting increase in SOC may have no clinical significance. The drug appears to increase the renal elimination of digitoxin, thus decreasing its plasma half-life, but the clinical consequences are not defined.…”

Drug Interactions Involving Digitalis Glycosides

“…Quinine, an optical isomer of quinidine, was found by Wandell et al (1980) to increase digoxin elimination half-life by 32% via a decrease in non-renal clearance of 55% and a decreased total body clearance of 26%; no change in distribution volume or renal clearance was noted. Quinine, an optical isomer of quinidine, was found by Wandell et al (1980) to increase digoxin elimination half-life by 32% via a decrease in non-renal clearance of 55% and a decreased total body clearance of 26%; no change in distribution volume or renal clearance was noted.…”