Digoxin Toxicity Compared With Myocardial Digoxin and Potassium Concentration

Abstract

1 Twenty-nine dogs were given digoxin (0.25 mg) by mouth twice daily for eight days. Some of them (group 1) also received diuretics and others (group 2) a mineralocorticoid. The dogs were then given an intravenous bolus injection of digoxin and plasma and cardiac muscle were analysed for digoxin and potassium. 2 In the digitalized dogs, myocardial potassium concentration decreased following the intravenous injection of either 0.05 or 0.15 mg/kg digoxin; in contrast, in those dogs given diuretics or mineralocorticoid the potassium concentration increased. 3 Ventricular arrhythmias occurred after digoxin injection (0.05 mg/kg) in the hypokalemic dogs, in those given a mineralocortocoid and in those dogs which received a toxic digoxin dose (0.15 mg/kg). No arrhythmias where seen in the control (digitalized) group. 4 Myocardial digoxin concentrations were similar in the control digitalized group and in the mineralocorticoid-treated dogs after the intravenous administration of the lower digoxin dose (0.05 mg/kg). The myocardial digoxin concentration was significantly higher in the hypokalemic group and in the group receiving the higher digoxin dose (0.15 mg/kg). 5 There was no obvious relationship between the occurrence of arrhythmias and the myocardial concentration of digoxin or potassium.

The influence of reduced serum potassium level on the toxicity of some cardenolides in guinea pigs

“…With digoxin, digitoxin and the aglycone k-strophanthidin in hypokalemia the expected decrease of the lethal doses (that means increase in toxicity) was observed. A similar change in toxicity by variation of the extracellular potassium concentration has already been reported in the intact animal (Marcus et al, 1969 andHall et al, 1977;Steiness, 1978) On the contrary, reports on the influence of extracellular potassiumvariations on the ouabain-induced toxicity are rather divergent and support in part the (unexpected) missing effect of the altered serum-potassium concentration in the present study. Whereas some findings in the dog as well as in the rabbit indicate the well-known potassium-digitalis antagonism for ouabain (Baker, 1947;Williams et al, 1966; Lown and Wittenberg, 1968), contradictory results have been reported in the guinea pig by Greeff and Knippers (1964) and Schaumann and Chatoor (1966).…”

Time Course of Ouabain Uptake in Isolated Myocardial Cells: Dependence on Extracellular Potassium and Calcium Concentration

“…The same relationship between extracellular potassium and digitalis content in the myocardial tissue has been found by Cohn, Kleiger & Harrison (1967) and Steiness (1978). It seems that a pharmacodynamic effect of digitalis is influenced by potassium so that the lower potassium concentration increases the positive inotropic response considerably (Prindle et al, 1969).…”

“…The characteristics of the binding of the cardiac glycosides to this enzyme have been investigated both in fragments from cell membrane and in homogenates obtained from different tissues (Akera, Larsen & Brody, 1969). The binding of digitalis to the isolated (Na+ + K+) ATPase preparations and also the total amount of digitalis bound to intact myocardium are markedly influenced by the extracellular potassium concentration (Prindle, Skelton, Epstein & Marcus, 1969;Akera, Temma, Wiest & Brody, 1978;Steiness, 1978).…”

Risk of digoxin intoxication in heart failure patients exposed to digoxin–diuretic interactions: a population‐based study

“…Their analyses also indicated that different thiazides could result in variation in the reduction of the serum potassium concentration. In addition, tubular secretion of digoxin is reduced when serum potassium concentrations are below 3 mmol l –1 [41]; i.e. hypokalaemia not only increases the serum digoxin concentration but also potentiates its toxicity [42].…”