Digoxin Poisoning
Foxglove
Digoxin, also known as Digitalis, is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. Digoxin is widely used in the treatment of various heart conditions, namely atrial fibrillation, atrial flutter and sometimes heart failure that cannot be controlled by other medication.
Common adverse effects include: loss of appetite, nausea, vomiting, diarrhea, blurred vision, visual disturbances (yellow-green halos), confusion, drowsiness, dizziness, nightmares, agitation, and/or depression, as well as a higher acute sense of sensual activities.
Mechanism of Action
Digoxin binds to a site on the extracellular aspect of the ?-subunit of the Na+/K+ ATPase pump in the membranes of heart cells (myocytes) and decreases its function. This causes an increase in the level of sodium ions in the myocytes and corresponding decreased extracellular Na+ levels, which in turn slows down the extrusion of Ca2+ by the Sodium-calcium exchanger that relies on the high Na+ gradient.
This effect causes an increase in the length of Phase 4 and Phase 0 of the cardiac action potential, which when combined with the effects of Digoxin on the parasympathetic nervous system, lead to a decrease in heart rate.
Increased amounts of Ca2+ are then stored in the sarcoplasmic reticulum and released by each action potential, which is unchanged by digoxin. This leads to increased contractility of the heart.
Digoxin also increases vagal activity via its action on the central nervous system, thus decreasing the conduction of electrical impulses through the AV node. This is important for its clinical use in different arrhythmias
Adverse Effects
The occurrence of adverse drug reactions is common, owing to its narrow therapeutic index (the margin between effectiveness and toxicity). Adverse effects are concentration-dependent, and are rare when plasma digoxin concentration is <0.8 ?g/L. They are also more common in patients with low potassium levels (hypokalemia), since digoxin normally competes with K+ ions for the same binding site on the Na+/K+ ATPase pump.
Common adverse effects include: loss of appetite, nausea, vomiting, diarrhea, blurred vision, visual disturbances (yellow-green halos), confusion, drowsiness, dizziness, nightmares, agitation, and/or depression, as well as a higher acute sense of sensual activities. Less frequent adverse effects include: acute psychosis, delirium, amnesia, shortened QRS complex, atrial or ventricular extrasystoles, paroxysmal atrial tachycardia with AV block, ventricular tachycardia or fibrillation, heart block but when systematically sought, the evidence for this is equivocal. The pharmacological actions of digoxin usually results in electrocardiogram (ECG) changes, including ST depression or T wave inversion, which do not indicate toxicity. PR interval prolongation, however, may be a sign of digoxin toxicity. Additionally, increased intracellular Ca2+ may cause a type of arrhythmia called bigeminy (coupled beats), eventually ventricular tachycardia or fibrillation. The combination of increased (atrial) arrhythmogenesis and inhibited atrio-ventricular conduction (for example paroxysmal atrial tachycardia with A-V block – so-called “PAT with block”) is said to be pathognomonic (i.e. diagnostic) of digoxin toxicity.
An often described but rarely seen adverse effect of digoxin is a disturbance of colour vision (mostly yellow and green colour) called xanthopsia. It has been proposed that the painter Vincent Van Gogh’s “Yellow Period” may have somehow been influenced by concurrent digitalis therapy.
