Digoxin

Mechanism of Action

• Inhibits the Na-K-ATPase membrane pump, causing increased intracellular sodium.  This increases the activity of the NCX, causing increased influx of calcium
  • This promotes contraction of filament (increased strength of contraction)
  • It also increased the slope of phase 4 cardiac depolarisation, shortening the action potential duration and decreasing the maximal diastolic potential
  • It also reduces the conductivity of the AV node
• NB Digoxin has a very long half life of 3.5-5 days.  Therefore, should not be used to rapidly reverse/treat any heart condition and the dose should be changed (particularly if increasing) very slowly when necessary

Indications

• Main indication os for patients with heart failure and supraventricular arrhythmia e.g. atrial fibrillation
  • More suitable for patients with a sedentary life style (long-half life and not effective at rate controle during exercise/exertion)
• MEASURE U&Es PRIOR to treatment

Contraindications/Cautions

• Use with caution in the elderly who may be particularly sensitive and susceptible to toxicity (a reduced dose may be indicated).  Also in patients who have suffered recent MI; patients with sick sinus syndrome; thyroid disease; severe respiratory disease; hypokalaemia (ideally correct prior to treatment)
• Contraindicated in 2nd and 3rd degree heart block; SVTs associated with accessory pathways; VT/VF; hypertrophic cardiomayopathy; myocarditis/pericarditis;
• In renal failure, reduce the dose and monitor digoxin levels

Side effects

• Digoxin toxicity is dependent on plasma levels and individual sensitivity to the drug (may be increased in heart disease)
  • Between 1.5-3μg/l (plasma)- there is increasing toxicity; hypokalaemia predisposes to toxicity (increased effect of action)
    • may require potassium supplementation
  • May be difficult to differentiate toxicity and worsening heart failure
  • NB MONITORING DIGOXIN LEVELS are NOT required unless suspected toxicity
  • Features of toxicity can be
    • Extracardiac (CNS)
      • Drowsiness
      • Lethargy
      • Fatigue
      • Neuralgia
      • Headache
      • Dizziness
      • Confusion or giddiness
      • Hallucinations
      • Seizures
      • Paraesthesia/neuropathic pain
    • Visual Problems (often the earliest signs)
      • ‘Snowy’ vision
      • Photophobia
      • Photopsia (flashes)
      • Decreased visual acuity
      • Yellow vision/haloes (xanthopsia)
    • GI symptoms
      • Anorexia; weight loss
      • Nausea/vomiting; abdominal pain; diarrhoea
    • Kidney failure (AKI)
      • hyperkalaemia
    • Cardiac symptoms
      • Palpitations
      • Shortness of breath
      • Syncope/pre-syncope
      • Peripheral oedema
      • Bradycardia
      • Hypotension
  • Investigations include ECG- which may show classical ‘reverse tick’ traces (SVT with slow ventricular response), sinus bradycardia with periods of atrioventricular block and with ventricular ectopics (may also cause VT or Torsades de Pointes)
  • If digoxin toxicity is suspected, stop drug and measure plasma levels (if high, consider stopping or reducing dose long-term)
    • Give digibind/digifrag if features are severe/life-threatening
• DO MONITOR U&Es/KIDNEY FUNCTION
• Regular side effects include:
  • Nausea/vomiting/diarrhoea
  • Arrhythmias; conduction disturbances
  • Dizziness; blurred vision; Yellow vision 
  • Rash
  • Gynaecomastia with long term use; thrombocytopenia

Interactions

• Several drugs may increase the plasma levels of digoxin and thus increase likelihood of toxicity e.g.
  • Amiodarone; hydroxychloroquine; ciclosporin; most calcium channel blockers; spironolactone
• Also increased cardiac toxicity with diuretics