This inhibition causes an increase in intracellular sodium levels, resulting in decreased activity of the sodium-calcium exchanger, which normally imports three extracellular sodium ions into the cell and transports one intracellular calcium ion out of the cell. The reversal of this exchanger, triggered by the increase in intracellular sodium, results in  an increase in the intracellular calcium concentration that is available to the contractile proteins. The increased calcium concentrations lead to the binding of more calcium to troponin C, which results in increased inotropy. Increased intracellular calcium lengthens phase 4 and phase 0 of the cardiac action potential, which leads to a decrease in heart rate. Increased amounts of Ca2+ also leads to increased storage of calcium in the sarcoplasmic reticulum, causing a corresponding increase in the release of calcium during each action potential. This leads to increased contractility (the force of contraction) of the heart without increasing heart energy expenditure.The inhibition of the sodium pump may also improve baroreceptor sensitivity in heart failure and may explain some of the neurohormonal effects of digoxin.Digoxin also has important parasympathetic effects, particularly on the atrioventricular node. While it does increase the magnitude of myocardial contractility, the duration of the contraction is only slightly increased. Its use as an antiarrhythmic drug, then, comes from its direct and indirect parasympathetic stimulating properties. Vagus nerve stimulation slows down conduction at the AV node by increasing the refractory period of cardiac myocytes. The slowed AV node gives the ventricles more time to fill before contracting.
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.