- Clinical science
Cardiac glycosides are drugs that inhibit the Na+/K+- ATPases 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-resistent 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+-ATPases → higher intracellular Na+ concentration → reduced efficacy of Na+/Ca2+ exchangers → higher intracellular Ca2+ concentration → increased vagal tone
- → In cardiomyocytes, this leads to increased contractility; (positive inotropic effect), reduced velocity of electric conduction; (negative dromotropic effect), and a reduction of the heart rate (negative chronotropic effect).
- → In neurons (of the vagal nerve), this leads to reduced velocity of electric conduction and reduction of the heart rate (via a reflexive reduction of sympathetic transmission).
Cardiac glycosides inhibit Na+/K+-ATPase, increasing cardiac contractility and decreasing AV conduction and heart rate!
- Nausea/vomiting, diarrhea, gastrointestinal pain, and anorexia
- Blurry vision with a yellow tint and halos, disorientation, weakness
- ECG: potentially severe cardiac arrhythmias
- Serum digoxin concentration (ideally, measure 6 hours after ingestion)
- Serum electrolyte levels: hyperkalemia
- Creatinine and blood urea nitrogen to evaluate renal function
Digoxin has a narrow therapeutic index! Serum concentrations of cardiac glycosides must be monitored closely because overdoses can have severe consequences!
- 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.