CARDIAC GLYCOSIDES
- Digoxin
- Digitoxin
- Cardiac glycoside containing plants (e.g. Yellow oleander)
- Bufadienolides from toad venom (cha’n su)
- Toxic Level – >2 ng/ml
- Mechanism of toxicity
Digoxin inhibits the sodium/potassium ATPase transport mechanism in myocardial and cardiac conducting tissue. It binds to the ‘ouabain binding site’ and prevents potassium being transported into the cell which leads to intracellular increases in sodium and subsequently calcium ions.
These effects lead to increased automaticity and excitability with both early and late after-depolarizations. Digoxin also causes AV nodal block and decreased conduction velocity throughout the His-Purkinje system.
The binding of digoxin to the sodium/potassium ATPase transport system is inhibited by high concentrations of potassium and the activity of this enzyme is increased by the presence of magnesium.
Thus both hypokalaemia and hypomagnesaemia increase digoxin toxicity and hyperkalaemia and hypermagnesaemia are protective.
Drug and disease interactions
Various other drugs may have effects on slowing the AV node (e.g. Verapamil and beta blockers) or may lead to hypokalaemia and hypomagnesaemia (e.g. diuretics) or alter renal clearance of Digoxin (e.g. Quinidine, Verapamil, Diltiazem, Amiodarone, Indomethacin, Spironolactone). Patients with myocardial disease, respiratory disease or hypothyroidism have increased sensitivity to digoxin.
- Clinical effects
Patients initially complain of nausea, vomiting and diarrhoea. In chronic toxicity, confusion and visual changes may develop. The most serious manifestations are in the cardiovascular system: - ECG changes (Extrasystoles and minor degrees of AV nodal block. In addition, there may be ST depression.)
- Bradyarrhythmia (2nd and 3rd degree heart block and slow atrial fibrillation)
- Supraventricular tachycardia
- Ventricular tachycardia
Investigations
- Urgent ECG, Electrolytes (especially potassium and magnesium), Digoxin concentrations.
- Urgent measurement of potassium, sodium, magnesium, calcium and bicarbonate is necessary. (Hypokalaemia, hypomagnesaemia may present)
Treatment
- Supportive
- GI Decontamination
Gastric lavage, if presenting within 1-2 hours, patients should be given activated charcoal and repeated dose of activated charcoal can be given. - Treatment for electrolytes imbalances.
- Antidotes
i. Digoxin Fab fragments, these digoxin specific antibodies bind rapidly to digoxin and removed it from the Na+-K+-ATPase pump.)
Indications - Life threatening dysrhythmias
(Ventricular tachycardia/ventricular fibrillation, Third degree heart block.) - Cardiac compromise – in patients with underlying cardiac diseases.
- Serum potassium > 6 mmol/L
- Digoxin concentration > 20 nmol/L (15.6 microgram/L}) 6 hours after an acute overdose.
- Digoxin concentration > 10 nmol/L (7.8 microgram/L) in chronic toxicity.
Dose - Fab fragments bind to digoxin in a one to one ratio. Thus the dose of digoxin Fab fragments depends on the dose of digoxin that is to be neutralized. The dose may be calculated from the known dose ingested or from the digoxin concentration if digoxin has equilibrated.
- Dose calculation from dose ingested, 1× 40 mg vial of digoxin Fab fragments binds to 0.6 mg} of digoxin. Thus an ingestion of 3 mg of digoxin requires 5 vials.
- ii. Magnesium – contra indicated in bradycardia/ AV block.
- iii. Atropine