Digoxin Pharmacology and Pathophysiology 1) Na/K ATPase Pump - Digoxin works by directly binding to and inhibiting the action of the Na+/K+ ATPase pump. By blocking this pump, those sodium ions are NO longer pumped outside the cell and sodium increase. 2) The Na/Ca Exchanger - When digoxin blocks the Na+/K+ ATPase pump and intracellular sodium concentrations increase, the Na+2/Ca+2 exchanger compensates by becoming inhibited so it won't increase the intracellular sodium concentrations further. As a result, calcium ions are no longer exchanged for sodium and intracellular calcium concentration increases. This increase of intracellular calcium causes: - Increased contractility (force of contraction) of the heart - Decreased heart rate (lengthens phase 4 and phase O of the cardiac action potential) Watch the Potassium! - Hyperkalemia (high potassium levels) is a side effect of digoxin toxicity. Since digoxin blocks the action of the Na+/K+ ATPase pump and prevents potassium from entering the cell, serum potassium levels can be elevated with toxic digoxin levels. - Because digoxin binds to the same site as potassium on the ATPase pump, in states of hypokalemia (or low potassium levels), digoxin can more easily bind to the Na+/K+ ATPase pump (since there's less competition!) - because of this, it's important to make sure potassium levels stay within normal limits so digoxin toxicity isn't worsened. by Cait E. Kulig, PharmD @CaitEKulig #Digoxin #Pharmacology #Pathophysiology #cardiology
