Digox Mechanism of Action

Pharmacologic Category: Digitalis Glycoside.
Pharmacology: Pharmacodynamics: Digoxin directly increases contractility of the myocardium and primarily acts by inhibiting the action of adenosine triphosphatase, and Na⁺/K⁺ exchange activity. It augments calcium ion influx and increases calcium availability at the excitation-contraction coupling. The potency of digoxin may be enhanced when extracellular potassium concentration is low, with hyperkalaemia having opposite effect. Digoxin inhibits the Na⁺-K⁺ exchange mechanism on cells of the autonomic nervous system, stimulating them to exert indirect cardiac activity. Increases in efferent vagal impulses result in reduced sympathetic tone and diminished impulse conduction rate through the atria and atrio-ventricular node and reduces ventricular rate.
Pharmacokinetics: The absorption of Digoxin from the gastrointestinal tract is variable depending upon the formulation used. About 70% of a dose is absorbed from the tablets which comply with BP or USP specifications, 80% is absorbed from elixir, and over 90% is absorbed from the liquid-filled soft gelatin capsules. The generally accepted therapeutic plasma concentration range is 0.5 to 2.0 nanograms/mL but there is considerable interindividual variation. Digoxin has a large volume of distribution and is widely distributed in tissues, including the heart, brain, erythrocytes, and skeletal muscle. The concentration of Digoxin in the myocardium is considerably higher than in plasma. From 20% to 30% is bound to plasma proteins. Digoxin has been detected in cerebrospinal fluid and breast milk; it also crosses the placenta. It has an elimination half-life of 1.5 to 2 days.
Digoxin is mainly excreted unchanged in the urine by glomerular filtration and tubular secretion; reabsorption also occurs. Extensive metabolism has been reported in a minority of patients. Excretion of Digoxin is proportional to the glomerular filtration rate. After intravenous injection 50% to 70% of the dose is excreted unchanged. Digoxin is not removed from the body by dialysis, and only small amounts are removed by exchange transfusion and during cardiopulmonary by-pass.