Cardiac glycosides are drugs that inhibit the Na+/K+- ATPase found on the outer cell surface. Digoxin is the only drug of this class that is commonly used in clinical settings. The main indications for digoxin treatment are atrial fibrillation and heart failure in treatment-resistant cases. Because cardiac glycosides have a narrow therapeutic index, close monitoring of serum concentrations is necessary. Typical symptoms of cardiac glycoside poisoning are nausea, vomiting, blurry vision, and cardiac arrhythmias. Overdose can quickly become life-threatening and swift treatment is vital. The first-line treatment for cardiac glycoside poisoning is administration of digoxin-specific antibodies.
Inhibition of Na+/K+-ATPase → higher intracellular Na+ concentration → reduced efficacy of Na+/Ca2+ exchangers → higher intracellular Ca2+ concentration
- In cardiomyocytes, this leads to increased contractility (positive inotropic effect), reduced velocity of electric conduction (negative dromotropic effect) via AV node depression,; and a reduction of the heart rate (negative chronotropic effect) via SA node depression.
- In neurons of the vagal nerve, this leads to increased velocity of electric conduction, which causes reduced heart rate (via increased vagal tone and a reflexive reduction of sympathetic transmission).
- Digoxin overdose (iatrogenic, by nonadherence to prescribed dosages or by ingestion of plants containing cardiac glycosides)
- Ouabain poisoning
- Hypokalemia, because digitalis compounds compete with K+ for binding of Na+/K+-ATPase
- Renal failure → ↓ digoxin excretion
- Treatment with verapamil, diltiazem, amiodarone, and/or quinidine → removal of digoxin from binding site in body tissues and ↓ renal elimination
- Volume depletion (e.g., treatment with diuretics)
- Via cholinergic agonism: nausea, vomiting, diarrhea, abdominal pain, and anorexia
- Visual disturbances
- Disorientation, weakness
- Palpitations (due to arrhythmias or AV block)
- ECG: potentially severe cardiac arrhythmias
- Laboratory studies
- Digoxin-specific antibody (œ) fragments (anti-digoxin Fab fragments)
- Atropine for symptomatic bradycardia
- Slowly normalize serum potassium levels
- Class IB antiarrhythmics
- Temporary cardiac pacing
Digoxin has a narrow therapeutic index! Serum concentrations of cardiac glycosides must be monitored closely because overdoses can have severe consequences!
“You better visit a hospital directly!”: Yellow blurry vision and halos are the signs of digoxin poisoning.
- Ventricular fibrillation
Use with caution in pregnant women and in patients with:
- Electrolyte and fluid disorders (e.g., volume depletion, hypokalemia, hypomagnesemia, and/or hypercalcemia )
- Cardiovascular disorders (e.g., acute coronary syndrome, AV blocks, Wolff-Parkinson-White syndrome, hypertrophic obstructive cardiomyopathy, sick sinus syndrome)
- Renal failure (can lead to digoxin overdose and, vice versa, digoxin can also cause/worsen renal failure)
- Certain medications (see “Interactions” below)
We list the most important contraindications. The selection is not exhaustive.