Cardiac Glycosides (FETT)

Positive inotropic agents

DIGOXIN

• 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

• 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!

• Congestive heart failure (symptomatic patients with NYHA ≥ II despite pharmacotherapy)

• Atrial fibrillation

• Supraventricular tachycardia

• 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)

• K+-depleting diuretics → hypokalemia → arrhythmias

• Verapamil, diltiazem, amiodarone, quinidine → possible overdose (reduce digoxin dose to avoid overdose)

Cardiac glycoside poisoning.

• Via cholinergic agonism: nausea, vomiting, diarrhea, abdominal pain, and anorexia

• Visual disturbances

  • Xanthopsia (yellow-tinted vision)

  • Photophobia

  • Blurry vision with a yellow tint and halos

• Disorientation, weakness

• Palpitations (due to arrhythmias or AV block)

• ECG: potentially severe cardiac arrhythmias

  • Premature ventricular beats

  • T-wave inversion or flattening

  • Deformed ST segment (“scooped” or “sagging” ST segments)

  • ↓ QT interval

  • ↑ PR interval

  • Atrial tachycardia with AV block

• Laboratory studies

  • Serum digoxin concentration (ideally, measure 6 hours after ingestion)

  • Serum electrolyte levels: hyperkalemia (associated with poor prognosis) resulting from inhibition of the Na+/K+-ATPase

  • Creatinine and blood urea nitrogen to evaluate renal function

• Digoxin-specific antibody (œ) fragments (anti-digoxin Fab fragments)

• Atropine for symptomatic bradycardia

• Slowly normalize serum potassium levels

• Magnesium

• 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.