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 – Digoxin
• CCC – Digoxin Toxicity
• ECG library – Digoxin Effect
• ECG library – Digoxin Toxicity
• CCC – Digibind / Digoxin-specific Fab Fragments
• CCC – Calcium, Digoxin Toxicity and ‘Stone Heart’ Theory