Digoxin also known as Digitalis, is a purified cardiac glycoside extracted from the foxglove plant, Digitalis lanata. Its corresponding aglycone is digoxigenin. 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. Digoxin preparations are commonly marketed under the trade names Lanoxin, Digitek, and Lanoxicaps. It is also available as a 0.05 mg/mL oral solution and 0.25 mg/mL or 0.5 mg/mL injectible solution.
The main pharmacological effect of digoxin are on the heart. Extracardiac effects are responsible for many of the adverse effects (see below).
Its main cardiac effects are
- A decrease of conduction of electrical impulses through the AV node, making it a commonly used antiarrhythmic agent in controlling the heart rate during atrial fibrillation or atrial flutter.
- An increase of force of contraction via inhibition of the Na+/K+ ATPase pump (see below).
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). This causes an increase in the level of sodium ions in the myocytes, which then leads to a rise in the level of calcium ions. The proposed mechanism is the following: inhibition of the Na+/K+ pump leads to increased intracellular Na+ levels, which in turn slows down the extrusion of Ca2+ by the Na+/Ca2+ exchange pump 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. This is a different mechanism from that of catecholamines.
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 (see below).
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