<prompt> Which of the following condition precipitate Digoxin toxicity?HypokalemiaHyperkalemiaHypernatremiaHyperphosphatemia  <response>: 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 NaK 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-KATPase. 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 overactivity1. Inhibition of NAK ATPase pump by digitalis2. Increased NAconcentration inside the cell3. Increased exchange of Nafor Ca4. Increased intracellular Ca5. Increased influx of Cafrom sarcoplasmic reticulum6. Increased contractility of cardiac muscle 