This negative chronotropic effect is synergistic with the direct effect on cardiac pacemaker cells. The arrhythmia itself is not affected, but the pumping function of the heart improves, owing to improved filling. Overall, the heart rate is decreased while stroke volume is increased, resulting in a net increase in blood pressure, leading to increased tissue perfusion. This causes the myocardium to work more efficiently, with optimized hemodynamics and an improved ventricular function curve. Other electrical effects include a brief initial increase in action potential, followed by a decrease as the K+ conductance increases due to increased intracellular amounts of Ca2+ ions. The refractory period of the atria and ventricles is decreased, while it increases in the sinoatrial and AV nodes. A less negative resting membrane potential is made, leading to increased irritability. The conduction velocity increases in the atria, but decreases in the AV node. The effect upon Purkinje fibers and ventricles is negligible. Automaticity is also increased in the atria, AV node, Purkinje fibers, and ventricles.ECG changes seen in people taking digoxin include increased PR interval (due to decreased AV conduction) and a shortened QT interval. Also, the T wave may be inverted and accompanied by ST depression. It may cause AV junctional rhythm and ectopic beats (bigeminy) resulting in ventricular tachycardia and fibrillation. Pharmacokinetics
Digoxin is usually given orally, but can also be given by IV injection in urgent situations (the IV injection should be slow, and heart rhythm should be monitored).
Quinidine, verapamil, and amiodarone increase plasma levels of digoxin (by displacing tissue binding sites and depressing renal digoxin clearance), so plasma digoxin must be monitored carefully when coadministered.A study which looked to see if digoxin affected men and women differently found that digoxin did not reduce deaths overall, but did result in less hospitalization. Women who took digoxin died "more frequently" (33%) than women who took placebo (29%). Digoxin increased the risk of death in women by 23%. There was no difference in the death rate for men in the study.Digoxin is also used as a standard control substance to test for P-glycoprotein inhibition.Digoxin appears to be a peripherally selective drug due to limited brain uptake caused by binding to P-glycoprotein. Pharmacomicrobiomics
The bacteria Eggerthella lenta has been linked to a decrease in the toxicity of Digoxin. These effects have been studied through comparisons of North Americans and Southern Indians, in which a reduced digoxin metabolite profile correlates with E. lentum abundance. Further studies have also revealed an increase in digoxin toxicity when used alongside erythromycin or tetracycline, the researches attributed this to the decrease in the E. lentum population.Overall, bacterial inactivation of Digoxin, as in Digoxin being inactivated by bacteria in the gut microbiome occurs often. This is why Digoxin is given as a capsule or as a solution in capsule. History
Derivatives of plants of the genus Digitalis have a long history of medical use.