Example of a Cardiac Glycoside
Digoxin is the most commonly used cardiac glycoside and is the only glycoside that has been evaluated in placebo-controlled trials for heart failure management. 1
Pharmacology and Clinical Use
Digoxin is a cardiac glycoside extracted from the leaves of Digitalis lanata. It consists of a sugar portion and a cardenolide (hence "glycoside") 2. As a cardiac glycoside, digoxin has specific effects on the myocardium and is primarily used for:
- Rate control in atrial fibrillation
- Symptomatic heart failure with reduced ejection fraction
- Certain cardiac arrhythmias
Mechanism of Action
Digoxin works through:
- Inhibition of Na-K ATPase in cardiac tissue (positive inotropic effect)
- Inhibition of Na-K ATPase in vagal afferent fibers (sensitizes cardiac baroreceptors)
- Reduction of sympathetic outflow from the central nervous system
- Inhibition of Na-K ATPase in the kidney (affects sodium reabsorption and renin secretion) 1
Dosing and Administration
Digoxin is typically administered at the following doses:
- Initial daily dose: 0.125-0.25 mg daily
- Maximum maintenance dose: 0.25 mg daily 1
- Loading dose (when needed): 0.5 mg, with additional 0.125-0.25 mg doses at 6-8 hour intervals until adequate effect (maximum 8-12 mcg/kg over 24 hours) 1
Special Dosing Considerations:
- Lower doses (0.125 mg daily or every other day) should be used in:
- Patients over 70 years old
- Patients with impaired renal function
- Patients with low lean body mass 1
- Target serum concentration: 0.5-1.0 ng/mL 1
Potential Adverse Effects
Common adverse effects include:
- Cardiac arrhythmias (ectopic and re-entrant cardiac rhythms, heart block)
- Gastrointestinal symptoms (anorexia, nausea, vomiting)
- Neurological complaints (visual disturbances, disorientation, confusion) 1
Digoxin toxicity is commonly associated with serum levels above 2 ng/mL, but can occur at lower levels with:
- Hypokalemia
- Hypomagnesemia
- Hypothyroidism 1
Precautions and Contraindications
Digoxin should be used with caution or avoided in:
- Renal dysfunction (primary route of elimination) 1
- Wolff-Parkinson-White syndrome with AF/atrial flutter
- AV block greater than first degree or SA node dysfunction (without pacemaker)
- Patients taking drugs with SA and/or AV nodal-blocking properties 1
Drug Interactions
Dose adjustments are needed when co-administered with:
- Amiodarone (reduce digoxin dose by 30-50%)
- Dronedarone (reduce digoxin dose by 50%)
- Verapamil, clarithromycin, erythromycin, itraconazole, cyclosporine, propafenone, flecainide (monitor digoxin concentrations) 1
Clinical Pearls
- Digoxin has a narrow therapeutic window, making therapeutic drug monitoring essential 3
- In older adults (≥65 years), lower target concentrations (0.5-0.9 ng/mL) are recommended to prevent toxicity 3
- Digoxin is not indicated as primary therapy for acute heart failure exacerbations 1
- For heart failure, digoxin should be considered in patients with persistent symptoms despite therapy with diuretics, ACE inhibitors/ARBs, and beta-blockers 1
- For atrial fibrillation, beta-blockers are usually more effective when added to digoxin for rate control, particularly during exercise 1
Digoxin remains the most clinically relevant cardiac glycoside with extensive evidence supporting its use in specific cardiovascular conditions when properly dosed and monitored.