Pharmacodynamics

• Inhibition of Na⁺/K⁺-ATPase → higher intracellular Na⁺ concentration → reduced efficacy of Na⁺/Ca²⁺ exchangers → higher intracellular Ca²⁺ concentration
  • In cardiomyocytes, this leads to increased contractility (positive inotropic effect), reduced velocity of electric conduction (negative dromotropic effect) via AV node depression, and a reduction of the heart rate (negative chronotropic effect) via SA node depression.
  • In neurons of the vagal nerve, this leads to increased velocity of electric conduction, which causes reduced heart rate (via increased vagal tone and a reflexive reduction of sympathetic transmission).

Digoxin poisoning

Risk factors

• Electrolyte imbalances
  • Hypokalemia: digoxin competes with K⁺ for binding to Na⁺/K⁺-ATPase
• Medical conditions
  • Renal failure (reduced digoxin excretion)
  • Volume depletion (e.g., treatment with diuretics)
• Drug interactions
  • Treatment with verapamil, diltiazem, amiodarone, and/or quinidine: These drugs may displace digoxin from tissue binding sites and decrease renal elimination.
    • Both mechanisms of action lead to increased digoxin serum levels.

Clinical features

• Acute and chronic poisoning: Symptoms are less obvious in chronic poisoning.
  • Vagal symptoms: nausea, vomiting, diarrhea, abdominal pain, anorexia
  • Arrhythmia symptoms: palpitations, syncope, and presyncope
• Chronic poisoning
  • Confusion, fatigue, lethargy, weakness, and disorientation
  • Visual disturbances
    • Blurred vision, halos, scotomas, diplopia
    • Photophobia
    • Xanthopsia (yellow-tinted vision)