Digoxin moa?

What is digoxin’s mechanism of action (MOA)?

Digoxin is a cardiac glycoside that works mainly by inhibiting the Na⁺/K⁺-ATPase pump in heart cells. This inhibition increases intracellular sodium (Na⁺), which reduces the activity of the Na⁺/Ca²⁺ exchanger. As a result, intracellular calcium (Ca²⁺) rises. Higher Ca²⁺ increases contractile force (positive inotropy) in the myocardium.[1]

Digoxin also increases vagal (parasympathetic) tone, which slows conduction through the atrioventricular (AV) node (negative dromotropy). This is why it can help control heart rate in some arrhythmias, particularly atrial fibrillation or atrial flutter.[1]

How does Na⁺/K⁺-ATPase inhibition translate into stronger heart contractions?

By blocking Na⁺/K⁺-ATPase, digoxin leads to:
- Higher intracellular Na⁺ in cardiomyocytes
- Less Na⁺ being exchanged for Ca²⁺ via the Na⁺/Ca²⁺ exchanger
- Net increase in intracellular Ca²⁺
- More Ca²⁺ available for excitation-contraction coupling, boosting systolic contraction strength.[1]

Why does digoxin slow the AV node?

Digoxin enhances parasympathetic (vagal) influence on the heart, which reduces AV nodal conduction velocity. Slower AV nodal conduction helps lower ventricular rate in patients with atrial arrhythmias where the atria drive the ventricles through the AV node.[1]

What drugs or conditions can be especially risky with digoxin’s MOA?

Digoxin’s therapeutic effect depends on cardiac ion handling and it has a narrow therapeutic window. Changes that alter potassium levels can affect digoxin’s binding/function on Na⁺/K⁺-ATPase, and drug–drug interactions can raise digoxin levels. Those risks are tightly connected to its Na⁺/K⁺-ATPase mechanism.[1]

Sources

1. https://www.drugs.com/digoxin.html