Digoxin toxicity

• Digoxin:

  • Cardiac glycoside - originating from the Digitalis lanata genus of the foxglove plant family
  • Indications - heart failure with reduced EF, rate control in supraventricular tachyarrhythmias e.g. AF
  • Requires initial loading doses followed by daily maintenance dose
  • Dose reduction required in the elderly and in renal impairment - primarily renally excreted
• Pharmacodynamics:

  • Reversibly inhibits the Na+/K+/ATPase enzyme = increased sodium in cardiac myocytes = decreased calcium expulsion = increased myocardial contractility
  • At lower doses it exerts parasympathomimetic effects via the vagus nerve - slows conduction through AV node
• Monitoring:

  • Has narrow therapeutic window
  • Excretion is primarily renal so renal function so renal function must be monitored
  • Electrolytes should also be closely monitored as imbalances can precipitate toxicity
  • Regular monitoring of serum digoxin during maintenance treatment is not required unless clinically indicated
• Therapeutic range:

  • Safe range is -.5-0.9 mg/L
  • Toxicity may develop when levels reach 1.5-3.0mg/L
  • Illness severity does not necessarily correlate with serum levels
  • Acute toxicity - serum levels rise sharply within a short timeframe - most commonly secondary to overdose
  • Chronic toxicity arises over a longer period
• Causes of chronic digoxin toxicity:

  • Chronic overmedication
  • CKD - decreased renal clearance
  • Electrolyte abnormalities - hypokalaemia, hypomagnesaemia, hypercalcaemia
  • Drug interactions
  • Displacement of digoxin from protein binding sites - drug interactions
• Digoxin toxicity can CAUSE hyperkalaemia - is common and is a predictor of mortality

  • Inhibition of Na+/K+/ATPase prevents potassium influx
  • Results in higher serum levels and increased risk of fatal cardiac arrhythmias
• Electrolyte abnormalities that can potentiate toxicity:

  • Hypokalaemia - potassium and digoxin bind to same ATPase pump at the same site. Lower potassium enables increased binding of digoxin
  • Hypomagnesaemia - normal ATPase pump function is magnesium dependent
  • Hypercalcaemia - excessive calcium + digoxin increases calcium - overloaded intracellular calcium stores
• Clinical features:

  • Constitutional - fatigue, headache, weakness
  • Cardiac - palpitations, syncope, chest pain, bradycardia, hypotension
  • GI - anorexia, nausea and vomiting, diarrhoea, abdo pain
  • Neuro - confusion, delirium, weakness
  • Ocular - xanthopsia, blurred vision, diplopia, photophobia, flashing lights
• Xanthopsia:

  • Yellow/green discolouration of vision
  • Yellow halo around lights
• Most common ECG changes:

  • Premature ventricular complexes
  • Significant bradycardia
  • Prolongation of the PR interval and QRS complex
• Serum digoxin level:

  • Take immediately in chronic toxicity
  • Take 6 hours post acute overdose
• Initial management:

  • Activated charcoal if within 2 hours of acute ingestion
  • Withhold digoxin and potentiating medications
  • Cardiac telemetry
  • Anti-emetics
  • IV fluids
  • Correction of electrolyte disturbance
  • Digoxin binding therapy
• Digoxin binding therapy:

  • digoxin-specific antibody (Fab) fragments
  • Fab fragments bind free digoxin in the plasma
  • May precipitate severe hypokalaemia
  • Called DIGIFab, Digibind