Introduction
- Primary agent: Digoxin
- Oldest cardiac medication still in clinical use
- Narrow therapeutic window
- Available in oral and parenteral forms
- Requires careful monitoring and dose adjustment
Clinical Pharmacology
Mechanism of Action
- Inhibition of Na+/K+-ATPase pump
- Increased intracellular calcium
- Enhanced contractility (positive inotropic effect)
- Decreased conduction through AV node
- Reduced sympathetic activation
- Enhanced parasympathetic tone
Pharmacokinetics
- Bioavailability: 60-80%
- Distribution: Large volume of distribution
- Protein binding: 20-30%
- Half-life: 36-48 hours
- Elimination: Primarily renal
- Time to peak effect: 4-6 hours oral, 1-4 hours IV
Physiologic Effects
- Increased myocardial contractility
- Reduced heart rate
- Decreased AV conduction velocity
- Increased vagal tone
- Reduced sympathetic activity
- Improved baroreceptor sensitivity
Clinical Indications
Primary Indications
- Supraventricular tachycardia (chronic management)
- Atrial fibrillation with rapid ventricular response
- Heart failure with reduced ejection fraction
- Post-operative junctional tachycardia
Specific Clinical Scenarios
- Chronic heart failure in infants
- Rate control in chronic atrial arrhythmias
- Bridge to heart transplantation
- Selected cases of dilated cardiomyopathy
Role in Modern Therapy
- Second-line agent for most indications
- Still valuable in specific populations
- Important in resource-limited settings
- Useful in combination therapy
Dosing Guidelines
Loading Dose (when needed)
- Total digitalizing dose (TDD):
- Premature: 15-25 mcg/kg
- Full-term neonates: 20-30 mcg/kg
- Children 1 month-2 years: 30-50 mcg/kg
- Children 2-5 years: 25-35 mcg/kg
- Children 5-10 years: 15-30 mcg/kg
- Children >10 years: 8-12 mcg/kg
Maintenance Dose
- Premature: 4-6 mcg/kg/day
- Full-term neonates: 8-10 mcg/kg/day
- Infants 1-24 months: 10-12 mcg/kg/day
- Children 2-5 years: 8-10 mcg/kg/day
- Children 5-10 years: 5-8 mcg/kg/day
- Children >10 years: 2-5 mcg/kg/day
Dosing Adjustments
- Renal dysfunction: Reduce dose by 25-75%
- Prematurity: Extended dosing interval
- Concurrent medications: Consider interactions
- Body composition: Lean body mass basis
Monitoring & Toxicity
Required Monitoring
- Serum digoxin levels
- Therapeutic range: 0.5-2.0 ng/mL
- ECG monitoring
- Electrolytes (K+, Mg2+, Ca2+)
- Renal function
- Clinical symptoms
Signs of Toxicity
- Cardiac manifestations:
- Bradycardia
- Heart block
- Ventricular arrhythmias
- Bidirectional ventricular tachycardia
- Gastrointestinal symptoms:
- Anorexia
- Nausea and vomiting
- Abdominal pain
- Neurologic symptoms:
- Visual disturbances
- Confusion
- Weakness
- Seizures
Risk Factors for Toxicity
- Electrolyte imbalances:
- Hypokalemia
- Hypomagnesemia
- Hypercalcemia
- Renal dysfunction
- Drug interactions
- Hypothyroidism
- Acute illness
Management of Toxicity
- Immediate discontinuation of drug
- ECG monitoring
- Correction of electrolyte abnormalities
- Digoxin-specific antibody fragments (Digibind)
- Supportive care
- Treatment of arrhythmias
Drug Interactions
- Increased digoxin levels:
- Amiodarone
- Verapamil
- Macrolide antibiotics
- Spironolactone
- Increased risk of toxicity:
- Diuretics (via electrolyte depletion)
- Beta-blockers
- Calcium channel blockers
Further Reading
