Which electrolyte abnormality increases the risk of digoxin toxicity?

• A. Hyperkalemia
• B. Hyponatremia
• C. Hypokalemia
• D. Hypercalcemia

Answer: (C)

Digoxin works by inhibiting the Na+/K+-ATPase pump in heart muscle. Potassium competes with digoxin for the same binding site on this pump. When potassium is low, there’s less competition, so more digoxin can bind and inhibit the pump. That stronger inhibition raises intracellular calcium via the Na+/Ca2+ exchanger, which enhances both the drug’s effect and the risk of toxic effects such as arrhythmias, nausea, and vision changes. So the electrolyte abnormality that most increases the risk of digoxin toxicity is low potassium. Hyperkalemia, by contrast, reduces digoxin binding to the pump and thus lowers the toxicity risk (though toxicity can still occur if levels are very high). Hyponatremia isn’t the primary determinant, and hypercalcemia can contribute to toxicity but isn’t the main factor influencing digoxin binding in the same way potassium is.