Onset of Action of Intravenous Digoxin
Intravenous digoxin begins to exert its therapeutic effect within 1-3 hours after administration, with peak effects not developing for up to 6 hours. 1
Pharmacokinetics and Mechanism of Action
Digoxin works through the following mechanism:
- Inhibits the sodium-potassium ATPase pump in myocardial cells
- Produces a transient increase in intracellular calcium
- Results in increased myocardial contractility
- In atrial fibrillation, suppresses AV node conduction to increase effective refractory period and decrease conduction velocity 1
After IV administration:
- Initial 6-8 hour tissue distribution phase occurs 2
- Early high serum concentrations do not reflect concentration at site of action 2
- With chronic use, steady-state post-distribution serum concentrations correlate with pharmacologic effects 2
- Elimination half-life is 36-48 hours in patients with normal renal function 1
- 50-70% of the drug is excreted unchanged in the urine 1, 2
Clinical Considerations
Rate Control in Atrial Fibrillation
While digoxin can effectively slow ventricular rate at rest, there are important limitations:
- Delay of at least 60 minutes before onset of therapeutic effect 1
- Peak effect may not develop for up to 6 hours 1
- Efficacy is reduced in states of high sympathetic tone 1
- Not first-line therapy for management of acute AF except in patients with heart failure or LV dysfunction 1
Dosing Considerations
- Standard IV loading dose: 0.25-0.5 mg IV bolus 1
- Can repeat 0.25 mg IV bolus up to maximum dose of 1.0 mg over 24 hours 1
- Maintenance dosing should be based on patient's age, lean body weight, renal function, and concomitant drugs 1
Special Populations
- Renal impairment: Patients demonstrate prolonged elimination half-life and greater exposure to digoxin 2
- Elderly: May eliminate digoxin more slowly due to age-related decline in renal function 2
- Dialysis-dependent patients: Reduced apparent volume of distribution (by about one-third) 3
Potential Pitfalls and Monitoring
Drug Interactions
- P-glycoprotein inhibitors (e.g., amiodarone, macrolides) can increase digoxin levels 4
- High-dose atorvastatin (80 mg) can increase digoxin peak concentration by 20% 1
- Drugs causing hypercalcemia or hypokalemia can potentiate cardiac adverse effects 4
Monitoring
- Monitor for early warning signs of toxicity:
- Bradycardia
- Gastrointestinal disorders
- Neuropsychological disorders 4
- Serum digoxin concentration monitoring alone is not always sufficient 4
- Close clinical monitoring is necessary, especially in patients with renal failure, elderly patients, or those on potentially interacting drugs 4
Combination Therapy
For rapid rate control in atrial fibrillation, combining digoxin with other agents may be more effective: