Digitoxin and Digoxin

Digoxin is a cardiac glycoside and extracted from the foxglove plant, Digitalis lanata.  The natural toxin is called digitoxin. It is more helpful to treat them together for the purpose of this section.
 
The main pharmacological effects of digoxin and digitoxin are on the heart. Extracardiac effects are responsible for some of the therapeutic and many of the adverse effects.

The mechanism of action is not completely understood; however the current hypothesis is that “Digoxin binds to a site on the extracellular aspect of the α-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, which leads to a rise in the level of intracellular calcium ions. Digoxin decreases sodium concentration gradient and the subsequent calcium outflow, thus raising the calcium concentration in myocardiocytes and pacemaker cells”.

Overall, the heart rate is decreased, while blood pressure increases as the stroke volume is increased.  So in a way the heart beats more forcefully, but less often.  It may cause ventricular tachycardia and fibrillation.

Slight vasodilation is seen in heart failure. This effect is contrary to effects that should be seen as a result of increased intracellular calcium levels, but this occurs since digoxin improves hemodynamics, which leads to restored angiotensin levels and decreased sympathetic discharge, causing indirect vasodilation.

Digoxin also affects the kidney by increased renal blood flow. A mild diuretic effect is seen only in heart failure.

Common adverse effects (≥1% of patients) include: loss of appetite, nausea, vomiting and diarrhea as the gastrointestinal motility increase. Other common effects are blurred vision, confusion, drowsiness, dizziness, insomnia, nightmares, agitation, and depression, as well as a higher acute sense of sensual activities

Less frequent adverse effects (0.1%–1%) include: acute psychosis, delirium, amnesia, convulsions, atrial tachycardia, ventricular tachycardia or fibrillation, and heart block

It ‘works’ via Poisoning.  As you up the dose, digitoxin becomes a deliriant – in other words a drug capable of giving you delirium and killing you.