Digoxin Toxicity
Digoxin's inhibition of the myocyte Na/K-ATPase pump raises intracellular calcium to boost contractility, but the same mechanism becomes arrhythmogenic in excess, and hypokalaemia potentiates toxicity because potassium and digoxin compete for the same binding site.
First principles
Na/K-ATPase inhibition is both the therapeutic effect and the toxic mechanism
Digoxin inhibits the myocyte Na/K-ATPase pump, so intracellular sodium rises. This reduces the gradient that normally drives the Na/Ca exchanger to expel calcium, so intracellular calcium rises instead: the basis of digoxin's positive inotropic effect in heart failure. At toxic concentrations, the same excess intracellular calcium drives abnormal automaticity and delayed afterdepolarisations, producing ectopic and re-entrant arrhythmias: the beneficial and toxic effects are two points on the same dose-response curve.
Educational content pending clinical review. Not medical advice.