Dose response in vivo to digoxin in normo- and hyperkalaemia: associated biochemical changes

Abstract

The effect of digoxin, at two different inotropic levels, was examined in normo- and hyperkalaemic dogs. For similar inotropic responses, normo- and hyperkalaemic dogs had similar levels of (Na+, K+)-ATPase inhibition and microsomal-bound digoxin.

SATURABLE ADENOSINE 5′‐TRIPHOSPHATE‐INDEPENDENT BINDING OF [3H]‐OUABAIN TO BRAIN AND CARDIAC TISSUE in vitro

“…This binding and that observed in vivo or in isolated hearts closely parallels the positive inotropic action of these agents (Akera, Larsen & Brody, 1969;Besch, Allen, Glick & Schwartz, 1970;Prindle, Skelton, Epstein & Marcus, 1971;Akera, Baskin, Tobin & Brody, 1973;Ku, Akera, Pew & Brody, 1974;Schwartz, Allen, Van Winkle & Munson, 1974; Goldman, Coltart, Schweizer, Snidow & Harrison, 1975;Hall, Gilbart, Silverman & Goldman, 1977). Nevertheless, the concept that Na+, K+-ATPase is the receptor for the positive inotropic action of digitalis is not universally accepted (Okita, 1977).…”

Inhibition of the sodium pump in guinea‐pig ventricular muscle by dihydro‐ouabain: effects of external potassium and sodium.

“…An antagonism between K ions and the therapeutic and toxic effects of cardioactive steroids has been observed in vivo (Marcus, Nimmo, Kapadia & Goldsmith, 1971;Goldman, Coltart, Schweizer, Snidow & Harrison, 1975) and in vitro (Miller, 1963;Reiter, etal. 1966;Reiter, 1981).…”

Drug Interactions Involving Digitalis Glycosides

“…There is good experimental evidence that hyperkalemia inhibits the inotropic response to digitalis (Goldman et al, 1972;Lee et al, 1977), probably by potassium competing for specific myocardial binding sites (Marcus et al, 1969;Goldman et al, 1975). This mechanism may contribute to the inhibition of digoxin-induced inotropy and reversal of digoxin electrocardiographic effects reported for amiloride (Horn, 1982;Waldorff et al, 1981).…”