Introduction
This topic covers acute poisoning with cardiac glycosides such as digoxin and digitoxin, obtained from the foxglove plant (Digitalis species) and used for heart failure and atrial fibrillation. The key exam points are the mechanism of toxicity, the characteristic arrhythmias, the role of potassium and digoxin levels, and the specific antidote.
Pharmacology and mechanism of toxicity
Digitalis glycosides inhibit the membrane Na+/K+-ATPase pump in cardiac myocytes. Intracellular sodium rises, the sodium-calcium exchanger then removes less calcium, and intracellular calcium accumulates. This gives the therapeutic positive inotropic effect. Toxicity follows when the inhibition becomes excessive, and the drug also increases vagal (parasympathetic) tone and depresses conduction through the AV node.
- Narrow therapeutic index: the difference between effective and toxic concentrations is small.
- Excessive calcium accumulation causes delayed afterdepolarisations and ectopic beats.
- Potassium loss out of the cell, which the pump normally takes up, raises serum potassium in acute poisoning.
Causes and risk situations
Acute intoxication usually results from a large single ingestion, most often a suicide attempt, or from accidental ingestion by children or confused elderly patients. Plant poisoning by foxglove or other cardiac glycoside-containing plants (for example oleander or lily of the valley) must be considered when the history is unclear. Iatrogenic overdose occurs mainly in patients with reduced renal function, and chronic toxicity is favoured by hypokalaemia, hypomagnesaemia, hypothyroidism and interacting drugs such as amiodarone, verapamil and quinidine.