| Class | Antiarrhythmic |
|---|---|
| Chemistry |
Cardiac glycoside |
| Routes of administration |
Oral and IV; theoretically also IM |
| Absorption |
Oral bioavailability 80% (some is secreted back into the gut lumen by P-glycoprotein, an enterocyte efflux pump) |
| Solubility |
pKa = 7.15; basically insoluble in water. |
| Distribution |
VOD=5.1–7.4 L/kg; 25% protein-bound |
| Metabolism |
Hepatic metabolism accounts for only abut 16% of clearance |
| Elimination |
Elimination is renal, as unchanged drug, and slow because of the large VOD. Half-life is about 36-44 hrs |
| Time course of action |
Onset of effect is relatively rapid with IV infusion, or delayed by 2-3 hrs following oral loading. |
| Target receptor |
Digoxin inhibits Na+/K+ ATPase. |
| Mechanism of action |
By inhibiting Na+/K+ ATPase, digoxin increases intracellular sodium, which increases sodium-calcium exchange by the Na+/Ca2+ exchanger (INCX) during Phase 1 of the cardiac action potential. The resulting increase in intracellular calcium promotes inotropy. It also acts as a vagotonic agent, which slows conduction through the AV node, and decreases the duration of the action potential mainly by reducing the duration of Phase 2. The slope of Phase 4 is increased, promoting automaticity, but then automaticity is overall suppressed by the vagotonic effects. |
| Clinical effects |
Bradycadia, AV block, prolonged PR interval, shortened QT interval, tachyarrhythmias (including VF and Vt which can be bidirectional), nausea, anorexia, depressed level of consciousness, and arterial vasoconstriction. Toxicity is exacerbated by hypokalemia |
| Literature reference |
FDA data sheet |
| CICM details of understanding | Level 3 |
| Mentioned around Deranged Physiology | |
| Related SAQs |