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DIGOXIN

CLASS

Antiarrhythmic, inotrope

PRESENTATION

Clear colourless solution, tablets, elixir.

Formulations

  • IV; 2ml vial, 500mcg, 250mcg/ml
  • Tablets; 250mcg, 62.5mcg
  • Elixir; 50mcg/ml

INDICATIONS & DOSING

Rate control in atrial flutter/fibrillation tachycardia
Congestive cardiac failure

  • Adult; loading dose 250-500mcg IV, subsequent doses 100-300mcg IV Q6H until adequate response, maintenance 62.5-250mcg PO Q6H, max daily dose 1.5mg
  • Paediatric; specific age-based dosing schedule, refer to literature

PRACTICALITIES

Administration

  • Slow IV bolus over 5 minutes to avoid hypertension

Practice tips

  • Less efficacious for management of arrhythmias perioperatively as commonly driven by increased sympathetic tone
  • Ineffective at chemical cardioversion of AF or preventing recurrence of AF post cardioversion
  • Dose reduction by ~50% recommended in the elderly and renal impairment (CrCl <60ml/min)
  • Not removed by dialysis
  • Requires dose monitoring to prevent toxicity; therapeutic range 1-2μg/L, toxic range >2.5μg/L (significant >10μg/L)
  • The ECG signs of the digoxin effect are not indicative of toxicity; prolonged PR, characteristic ST segment depression, T-wave flattening, shortened QT (Salvador Dali’s moustache)

PHARMACOKINETICS

Onset

  • IV; 5-30 minutes, peak effect ~2-3 hours
  • PO; 0.5-2 hours, peak effect ~3-5 hours

Duration of action

  • 3-4 days upon cessation of maintenance dosing

Metabolism

<10% undergoes hepatic metabolism

Elimination

50-70% excreted unchanged in urine, clearance largely dependent on renal function

MECHANISM

Dual mechanism of action; positive isotropy due to increased intracellular calcium concentration (via inhibition of cardiac Na/K/ATPase and subsequent Ca-exchange), and negative dromotropy due to relative intracellular hypokalaemia and indirectly via increased parasympathetic tone.

DESIRED CLINICAL EFFECTS

Cardiovascular

  • Depression of SA node automaticity, depression of AV node conduction, increase in AV refractory period; rate control of atrial arrhythmias
  • Increased cardiac contractility, cardiac output

OTHER CLINICAL EFFECTS, ADVERSE EFFECTS & TOXICITIES

Cardiovascular

  • Increased atrial and ventricular automaticity with potential for dysrhythmias; atrial tachycardia, ventricular ectopy/bigemini/tachycardia
  • Depression of AV node conduction, increase in AV refractory period with potential for dysrhythmias; 1st/2nd/3rd degree heart block, junctional bradycardia
  • In toxicity atrial tachycardias with high-grade conduction deficit a common presentation
  • Rapid IV dosing: peripheral vasoconstriction, hypertension 

Neurological

  • Headache, lethargy, confusion
  • Reduced GCS in toxicity
  • Visual disturbance; deranged red/green vision 

Renal & electrolytes

  • Hyperkalaemia
  • Mild diuretic action 

Gastrointestinal

  • Anorexia, nausea/vomiting, diarrhoea
  • Abdominal pain 

Other

  • Muscle weakness 
  • Rash
  • Gynaecomastia  

Antidote

  • Digoxin-specific antibody (IgG fragments, renally excreted)

CONSIDERATIONS

Precautions

  • Sinus dysfunction, high-grade AV conduction block; worsening of conduction block
  • Ventricular extrasystoles, ventricular tachycardia; increased risk of ventricular fibrillation
  • Wolff-Parkinson-White with atrial fibrillation, atrial flutter, antidromic AVRT; may facilitate conduction via accessory tract, leading to rapid ventricular response and degeneration to ventricular tachycardia/fibrillation
  • Renal impairment, hyperthyroidism, hypokalaemia, hypercalcaemia, hypomagnesaemia, hypernatraemia, pH disturbances, hypoxaemia; increased risk of digoxin toxicity
  • Myocardial ischaemia/failure/myocarditis, severe pulmonary disease; increased risk of digoxin-induced arrhythmias
  • Myocardial ischaemia; increased oxygen demand, worsening of ischaemia
  • Diuretics; increased risk of electrolyte disturbances
  • Hypertrophic obstructive cardiomyopathy; worsening of outflow obstruction
  • Carotid sinus hypersensitivity; worsening of vagal tone

Obstetric

ADEC category A

Drug interactions

  • Suxamethonium, pancuronium; increased risk of dysrhythmias 
  • Beta-adrenergic agonists; increased risk of dysrhythmias
  • Verapamil (and to a lesser extent diltiazem, nifedipine), amiodarone, diazepam, erythromycin; increased digoxin plasma concentration
  • Antacids, metoclopramide, phenytoin; reduced digoxin plasma concentration
  • Adenosine; risk of ventricular fibrillation

REFERENCES

Drug information has been compiled from multiple sources including

  • Drugs in Anaesthesia and Intensive Care (Scarth & Smith)
  • Micromedex (IBM)
  • BJA Education (Oxford Academic)
  • Pharmacology for Anaesthesia and Intensive Care (Cambridge)
  • Australian Prescriber (NPS MedicineWise)

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