What is the MOA of digoxin?
Digoxin (a cardiac glycoside) works mainly by inhibiting the Na⁺/K⁺-ATPase pump on the surface of heart cells. This inhibition increases intracellular sodium (Na⁺), which reduces the activity of the Na⁺/Ca²⁺ exchanger. As a result, intracellular calcium (Ca²⁺) rises. The increased Ca²⁺ availability enhances calcium-dependent contraction in cardiac muscle (positive inotropy) [1].
How does digoxin affect heart rate (its vagal effects)?
Beyond its direct effects on contraction, digoxin also increases vagal (parasympathetic) tone. This slows conduction through the AV node, which can reduce ventricular rate in atrial fibrillation or atrial flutter [1].
What does that mean clinically?
Because digoxin increases the force of heart contraction and slows AV-node conduction, it has been used to:
- Improve systolic heart failure symptoms (in selected patients), largely via its inotropic effect [1]
- Control ventricular rate in atrial fibrillation/atrial flutter by slowing AV nodal conduction [1]
What are the key risks tied to its MOA?
Digoxin’s effects on intracellular calcium help explain why it has a narrow safety margin. Excessive levels can cause arrhythmias and other toxicity, since elevated intracellular Ca²⁺ can disturb cardiac electrical activity. Risk increases with electrolyte abnormalities like low potassium or low magnesium [1].
What happens if Na⁺/K⁺-ATPase is inhibited too much?
More Na⁺/K⁺-ATPase inhibition leads to higher intracellular Na⁺ and Ca²⁺, making the heart more prone to abnormal rhythms and digoxin toxicity. This is one reason clinicians monitor drug levels and electrolytes in patients taking digoxin [1].
Sources:
[1] https://en.wikipedia.org/wiki/Digoxin