Digoxin toxicity is worsened by hypokalaemia because:

• A Hypokalaemia increases digoxin absorption from the gut by upregulating intestinal P-glycoprotein
• B Hypokalaemia stimulates CYP3A4 metabolism of digoxin, producing a more cardiotoxic metabolite
• C K+ deficit reduces renal clearance of digoxin by impairing proximal tubular secretion
• D K+ and digoxin compete for binding at the extracellular face of the Na+/K+-ATPase; low extracellular K+ increases digoxin binding affinity to the pump, enhancing inhibition ✓

Explanation

Digoxin inhibits Na+/K+-ATPase by binding to its extracellular K+-binding site. Potassium and digoxin compete for the same binding site on the alpha-subunit of the pump. When extracellular K+ is low (hypokalaemia), less K+ competes with digoxin for this site, resulting in increased digoxin binding affinity and greater pump inhibition at any given digoxin concentration. This is why hypokalaemia (caused by diuretics, vomiting) dramatically increases digoxin toxicity.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.