Ref: KD Tripathi, 7th ed. pg. 496* Digitalis increases force of cardiac contraction by a direct action independent of innervation. It selectively binds to extracellular face of the membrane associated Na+K+ ATPase of myocardial fibers and inhibits this enzyme.* Inhibition of this cation pump results in progressive accumulation of Na+ intracellularly. Phis indirectly results in intracellular Ca2+ accumulation by reversing the direction of Na-Ca+ exchanger channel, which causes ionotropic action.* Note: in normal situation, Na-Ca+ exchanger pumps out Ca+- in exchange of Na+. But after bloking action of Digoxin, the direction of exchanger channel is reversed causing Pumping out Na+ in exchange with Ca+ from outside.# This accumulated Ca+ intracellular acts at sarcoplasmic reticulum and causes release of more calcium - Ionotropic action* Higher serum potassium concentration inhibits digitalis binding to Na-K+ATPase. Therefore, hyperkalemia can reduce digitalis toxicity and Hypokalemia can cause digitalis toxicity.* Note: Hypokalemia and hypercalcemia precipitate digoxin toxicity.* Action:# Digitalis increases the force of contraction and decreases the heart rate due to its vagomimetic action# It also decreases the AV conduction, hence contraindication in WPW syndrome.# Causes diuresis in CHF patients# Causes decrease in peripheral resistance in CHF patients (because of withdrawal of reflex sympathetic overactivity)1. Inhibition of NA+/K ATPase pump by digitalis2. Increased NA+concentration inside the cell3. Increased exchange of Na+for Ca++4. Increased intracellular Ca++5. Increased influx of Ca++from sarcoplasmic reticulum6. Increased contractility of cardiac muscle