Direct inhibition of Na⁺/K⁺ ATPase → indirect inhibition of Na⁺/Ca²⁺ exchanger.↑ [Ca²⁺]_i → positive inotropy. Stimulates vagus nerve → ↓ HR.

Clinical use:- Heart failure (↑ contractility)- Atrial fibrillation (↓ conduction at AV node and depression of SA node)

Adverse effects:- Nausea, vomiting, diarrhea, anorexia, blurry yellow vision, arrhythmias, AV block.- Can lead to hyperkalemia, which indicates poor prognosis.- Factors predisposing to toxicity: renal failure (↓ excretion), hypokalemia (permissive for digoxin binding at K⁺-binding site on Na⁺/K⁺ ATPase), drugs that displace digoxin from tissue-binding sites, and ↓ clearance (eg, verapamil, amiodarone, quinidine).

Antidote: Slowly normalize K⁺, cardiac pacer, anti-digoxin Fab fragments, Mg²⁺.