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

Chris is an Intensivist and ECMO specialist at the Alfred ICU in Melbourne. He is also the Innovation Lead for the Australian Centre for Health Innovation at Alfred Health and Clinical Adjunct Associate Professor at Monash University. He is a co-founder of the Australia and New Zealand Clinician Educator Network (ANZCEN) and is the Lead for the ANZCEN Clinician Educator Incubator programme. He is on the Board of Directors for the Intensive Care Foundation and is a First Part Examiner for the College of Intensive Care Medicine. He is an internationally recognised Clinician Educator with a passion for helping clinicians learn and for improving the clinical performance of individuals and collectives.

After finishing his medical degree at the University of Auckland, he continued post-graduate training in New Zealand as well as Australia’s Northern Territory, Perth and Melbourne. He has completed fellowship training in both intensive care medicine and emergency medicine, as well as post-graduate training in biochemistry, clinical toxicology, clinical epidemiology, and health professional education.

He is actively involved in in using translational simulation to improve patient care and the design of processes and systems at Alfred Health. He coordinates the Alfred ICU’s education and simulation programmes and runs the unit’s education website, INTENSIVE.  He created the ‘Critically Ill Airway’ course and teaches on numerous courses around the world. He is one of the founders of the FOAM movement (Free Open-Access Medical education) and is co-creator of litfl.com, the RAGE podcast, the Resuscitology course, and the SMACC conference.

His one great achievement is being the father of two amazing children.

On Twitter, he is @precordialthump.

| INTENSIVE | RAGE | Resuscitology | SMACC

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