Cardiac glycosides

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.

See also “Digoxin poisoning.”

• Drugs: digoxin, ouabain
• Mechanism: inhibition of the cardiac and neuronal Na⁺/K⁺- ATPase
• Onset of effect
  • Oral: 0.5–2 h
  • IV: 15–30 min
• Half-life: 36–40 hours
• Protein binding: 20–40%
• Elimination: renal

References:^[1][2][3][4]

• 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).

Cardiac glycosides inhibit Na⁺/K⁺-ATPase, increasing cardiac contractility and decreasing AV conduction and heart rate!

• Poisoning can occur from the ingestion of medications and/or plants containing cardiac glycosides.
• Medications primarily consist of digoxin and its derivatives.
• Naturally occurring cardiac glycosides can be found in:
  • Plants of the genus Digitalis (also known as foxglove), lily of the valley, oleander, and pheasant's eye (Adonis vernalis)
  • Plants that cause ouabain poisoning
• Patients can present with life-threatening bradyarrhythmias or tachyarrhythmias; and electrolyte disturbances (e.g., hyperkalemia).
• Other symptoms include disorientation, nausea, vomiting, abdominal pain,; and visual disturbances (e.g., blurry vision with a yellow tint and halos).
• ECG most often shows premature ventricular beats; the digitalis effect (e.g., ↑ PR interval, T-wave inversion or flattening) may be present even at therapeutic levels. ^[5][6][7]
• Treatment typically consists of immediate hemodynamic support, Digoxin immune fab administration, and correction of electrolyte abnormalities.
• See “Digoxin poisoning” for details on the diagnosis and management of all forms of cardiac glycoside poisoning.

• Congestive heart failure (symptomatic patients with NYHA ≥ II despite pharmacotherapy)
• Atrial fibrillation
• Supraventricular tachycardia

References:^[3][8]

• 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)

References:^[8]

We list the most important contraindications. The selection is not exhaustive.

• K⁺-depleting diuretics → hypokalemia → arrhythmias
• Verapamil, diltiazem, amiodarone, quinidine → possible overdose (reduce digoxin dose to avoid overdose)