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
Critical Care
Compendium
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