Digoxin MOA?

• A. Inhibits Na+/K+-ATPase pump
• B. Inhibits Na+/Ca2+ exchanger
• C. Blocks potassium channels
• D. Activates beta-adrenergic receptors

Answer: (A)

The key effect of digoxin is inhibition of the Na+/K+-ATPase pump on cardiac myocytes. This pump normally pumps Na+ out and K+ in; blocking it raises intracellular Na+. That higher Na+ reduces the driving force for the Na+/Ca2+ exchanger, which normally uses Na+ gradient to remove Ca2+ from the cell. With less Ca2+ being extruded, intracellular Ca2+ rises, enhancing contractility (positive inotropy). At the same time, digoxin increases vagal (parasympathetic) tone, which slows conduction through the AV node and helps control ventricular rate in atrial fibrillation.

The other mechanisms listed don’t describe digoxin’s action. Blocking potassium channels would affect repolarization in a different way (and is typical of certain antiarrhythmics), activating beta-adrenergic receptors would raise cAMP and increase heart rate and contractility via a different pathway, and digoxin does not directly inhibit Na+/Ca2+ exchange.