Digoxin toxicity is worsened in states of hypokalemia (low potassium) since digoxin normally binds to the ATPase pump on the same site as potassium. When potassium levels are low, digoxin can more easily bind to the ATPase pump exerting the inhibitory effects.

The end-point of digoxin’s effect is to increase calcium influx into cells by opening calcium channels. Hypercalcemia in the setting of digoxin toxicity results in exaggeration of calcium influx and enhanced toxicity. The treatment for hyperkalemia causing ECG changes is usually intravenous calcium administration, however this can be pro-arrhythmic and fatal in the setting of digoxin toxicity.

Recall that digoxin toxicity actually causes hyperkalemia (high potassium). The sodium/potassium ATPase pump normally results in sodium effluxing out of cells and potassium influxing into cells. Blocking this mechanism results in higher serum potassium levels.