Digoxin toxicity manifests with bradyarrhythmias and ventricular ectopics. At the cellular level, digoxin toxicity arises from:

• A Excessive vagal stimulation via muscarinic M2 receptors causing complete AV block
• B Complete inhibition of cardiac Na+/K+-ATPase causing intracellular sodium overload, reversed Na+/Ca2+ exchange and calcium overload ✓
• C Upregulation of cardiac L-type calcium channels increasing calcium influx
• D Inhibition of ryanodine receptors causing abnormal spontaneous calcium release from SR

Explanation

Therapeutic digoxin partially inhibits Na+/K+-ATPase, modestly raising intracellular Na+, which reduces the Na+ gradient driving forward Na+/Ca2+ exchange, and thus modestly raises intracellular Ca2+ (positive inotropy). In toxicity, more complete Na+/K+-ATPase inhibition causes gross intracellular Na+ overload, forcing the Na+/Ca2+ exchanger to operate in reverse mode, massively loading cardiomyocytes with Ca2+. This calcium overload generates delayed afterdepolarisations (DADs) and triggered arrhythmias (ventricular ectopics, VT). Bradycardia/AV block is due to enhanced vagal tone.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.