Digoxin toxicity is worsened by hypokalemia. The mechanism linking hypokalemia to increased digoxin toxicity is:
- A Potassium normally binds the same extracellular site on Na+/K+ ATPase as digoxin; hypokalemia reduces competition, enhancing digoxin binding and inhibition ✓
- B Low extracellular K+ increases the rate of digoxin renal excretion, causing accumulation in cardiac tissue
- C Hypokalemia causes hyperpolarization of cardiac cells, making them more sensitive to digoxin-mediated conduction slowing
- D Low K+ impairs the ATP synthesis needed to activate Na+/K+ ATPase, synergizing with digoxin's inhibition
Correct answer: A. Potassium normally binds the same extracellular site on Na+/K+ ATPase as digoxin; hypokalemia reduces competition, enhancing digoxin binding and inhibition
Explanation
Digoxin binds to the extracellular K+-binding site of the alpha-subunit of Na+/K+ ATPase, inhibiting it. Extracellular potassium (K+e) competes with digoxin for this binding site — higher K+e reduces digoxin binding, while lower K+e (hypokalemia) decreases competition, increasing digoxin's occupancy of and inhibition of the pump. Hypokalemia also predisposes to cardiac arrhythmias independently. This is why digoxin toxicity is treated partly by restoring serum K+ to normal levels.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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