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)