Digoxin
‘it has a power over the motion of the heart to a degree yet unobserved in any other medicine…’
Withering, 1775
Topics of Discussion Introduction Pharmacokinetics Mechanism of Action Effects Clinical Uses Interactions Toxicity The Future
Introduction Digoxin is a naturally occuring drug
and comes from the foxglove plant (Digitalis spp.)
Classified as a Cardiac Glycoside All cardiac glycosides have a steroid
nucleus and a lactone ring and most also have one or more sugar residues.
Other examples are Digitoxin and Oubain (short-acting drug)
Pharmacokinetics Oral bioavailability: 60-85% Volume of distribution: 6-8 litres/kg Elimination: Predominantly kidneys Elimination half-life, t1/2: 36-40 hours Clearance (ml/min/kg): 0.88 X
creatinine clearance (ml/min/kg) + 0.33
Therapeutic range: 0.8-2 g/L
Mechanical Effects
ventricular ejection cardiac output end-systolic and end-diastolic
cardiac size renal perfusion
Overall: sympathetic tone and renin-angiotensin system stimulation
Electrical Effects
Atrial Muscle AV Node Purkinje,Ventricles
EffectiveRefactory Period
(Para) (Para) (Direct)
Conductionvelocity
(Para) (Para) Negligible
Automaticity (Direct) (Direct) (Direct)
ECG Early Negligible PR int. QT intv, T inv,
ST dep Arrhythmias AT, AF AVN tachy
AV blockadePVBs, VT, VF
Clinical Uses Congestive Heart Failure
Positive inotropic agent Other drugs used are diuretics,
vasodilators and ACE inhibitors Need careful monitoring
Atrial Fibrillation Decreases conduction velocity and
effective refactory period of AVN
Interactions Absorption is dependant on intestinal
motility, therefore with metoclopramide and with propantheline
Various drugs e.g. quinidine, amiodarone increase levels
Inhibited by extracellular K+ , Mg2+ and facilitated by extracelluar Ca2+ . Therefore can loop and thiazide diuretics may cause toxicity
Toxicity
Non-cardiac signs are nausea, vomiting, diarrhoea, anorexia, fatigue and less commonly neurological symptoms.
Cardiac signs are arrhythmias secondary to increased intracellular calcium.
Toxicity - Management
Correction of electrolyte disturbances e.g. hypokalaemia, hypomagnesaemia.
Antiarrhythmics Digoxin antibodies
Note: In severe acute intoxication, potassium and antiarrythmics may worsen condition.
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