Digoxin

CLASS

  • anti-arrhythmic (cardiac glycoside)

MECHANISM OF ACTION

  • inotropic effect
  • increased automaticity
  • negative dromotropy (slowing of AV conduction)
  • increased vagal tone

DIRECT:
inhibition of Na/K ATPase on the cell surface
-> increased intracellular Na+ and increased extracellular K+
-> increased intracellular Ca2+ due to Na+/Ca2+ antiporter
-> calcium-medated  inotropy and increased automaticity, as well as negative dromotropy due to decreased intracellular K+

INDIRECT EFFECT:
increased vagal tone (vagomimetic effect)

PHARMACEUTICS

  • IV
  • tablets

DOSE

  • loading = 1mg in divided doses over 24 hrs
  • maintenance = 10-20mcg/kg/day
  • take level 12-24 hours post administration (take long time to distribute to heart)
  • therapeutic range = 0.6-1.2nmol/L
  • if started in ICU only measure level @ 5-7 days

INDICATIONS

  • SVT (AF): 1-3ng/mL
  • Heart failure: 0.5-0.8ng/mL
  • Prevention of supraventricular dysrrhythmias

ADVERSE EFFECTS

  • digoxin toxicity
  • ST depression (reverse tick appearance)
  • tachycardias (flutter with block, VT, VF)
  • bradycardia -> complete heart block
  • headache
  • GI symptoms

Drug interactions

  • increased digoxin levels (e.g. P glycoprotein inhibitors (efflux pump in distal renal tubules and intestine), and increased bioavailability)
    -> amiodarone, verapamil, quinidine, spirinolactone, clarithromycin, itraconazole, captopril
  • decreased digoxin levels
    -> cholestyramine, oral antacids, metoclopramide, neomycin, sulfasalazine, rifampicin

PHARMACOKINETICS

  • Absorption – bioavailability = 80%
  • Distribution – 30% protein bound, Vd 10L/kg
  • Metabolism – minimal hepatic metabolism
  • Elimination – 60% renal, t ½ = 48 hrs, longer in renal failure

EVIDENCE

-> Treat toxicity with digibind (and Mg)
-> CCF + AF: rate control AF, improve mortality, exercise tolerance and symptoms
-> CCF: improved symptoms (not change in mortality and hospital admission rate)


References and Links



CCC 700 6

Critical Care

Compendium

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