What is digoxin used for and how does it work?

Digoxin: Mechanism of Action and Clinical Applications

Digoxin is primarily used for heart failure management and ventricular rate control in atrial fibrillation, working by inhibiting the sodium-potassium ATPase pump which increases intracellular calcium and improves cardiac contractility. 1, 2

Mechanism of Action

Digoxin works through several key mechanisms:

• Inhibits the sodium-potassium ATPase pump in cardiac myocytes, leading to increased intracellular sodium 1
• The elevated sodium concentration reduces the sodium-calcium exchange, resulting in increased intracellular calcium 3
• Higher intracellular calcium enhances cardiac contractility (positive inotropic effect) 1
• Exerts vagotonic effects on the atrioventricular (AV) node, slowing conduction and ventricular response in atrial fibrillation 4, 2

Clinical Applications

Heart Failure Management

Digoxin is indicated for:

• Persistent heart failure symptoms (NYHA class II-IV) despite conventional therapy with diuretics, ACE inhibitors, and beta-blockers 1
• Improving symptoms, quality of life, and exercise tolerance in patients with mild, moderate, or severe heart failure 1
• Reducing heart failure hospitalizations, though it has a neutral effect on total mortality 3, 5
• Benefits are evident regardless of underlying rhythm (normal sinus rhythm or atrial fibrillation) or heart failure etiology 1

Atrial Fibrillation Rate Control

Digoxin is used for:

• Ventricular rate control in patients with atrial fibrillation, particularly those with heart failure or sedentary lifestyle 4, 2
• Combination therapy with beta-blockers or non-dihydropyridine calcium channel blockers for more effective rate control both at rest and during exercise 4
• Note: Digoxin monotherapy is ineffective for controlling ventricular rate during exercise or high adrenergic states 4, 2

Dosing Considerations

• Standard dosage: 0.125-0.25 mg daily for most patients 1
• Lower doses (0.125 mg daily) recommended for:
  • Patients over 70 years of age 1, 2
  • Those with impaired renal function 1, 2
  • Patients with low lean body mass 1
• Higher doses (0.375-0.50 mg daily) are rarely needed 1
• Loading doses are not necessary for chronic heart failure management 1
• Elderly patients have significantly increased half-life (approximately 69 hours vs. 37 hours in younger patients) and decreased clearance 2

Important Precautions and Monitoring

• Avoid in patients with significant sinus or atrioventricular block unless treated with a permanent pacemaker 1
• Use cautiously with medications that depress sinus or AV nodal function (amiodarone, beta-blockers) 1
• Monitor for drug interactions with agents that can increase serum digoxin levels:
  • Quinidine, verapamil, spironolactone, flecainide, and amiodarone 1
• Toxicity risk increases with:
  • Serum levels >2 ng/mL 1
  • Hypokalemia, hypomagnesemia, or hypothyroidism 1
• Not indicated as primary treatment for acutely decompensated heart failure 1
• Routine monitoring of serum digoxin levels is unnecessary in most patients 1

Special Considerations in Elderly Patients

• Elderly patients show comparable benefits to younger populations for heart failure management 2
• Conservative dosing strategy and therapeutic monitoring recommended due to reduced elimination 2
• Particularly useful in elderly patients with atrial fibrillation who have heart failure or sedentary lifestyle 2