Digoxin and Hypokalemia

Question 1

Why is hypokalemia a risk factor for digoxin toxicity?

Answer 1

Digoxin binds to the Na-K-ATPase pump at the same site as potassium. When potassium is decreased, Digoxin has more readily available binding sites. This results in inhibition of the Na-K-ATPase pump which leads to increased intracellular sodium. Increased intracellular sodium causes the Na-Ca exchanger to move calcium into the cell in order to decrease intracellular sodium. Increased intracellular calcium results in increased contractility of the heart. This is the mechanism for why digoxin works; however, when there is less potassium we see a larger effect for the same amount of drug decreasing the therapeutic window (which is narrow to begin with).

Question 2

Why is hypokalemia a risk factor for digoxin toxicity?

Answer 2

Increased extracellular potassium