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

Mechanism of Action

Effects

1.Mechanical

2.Electrical

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.

The Future...

Digoxin is a very cheap and effective drug and therefore useful clinically in heart failure however, it does not reduce mortality, unlike ACE inhibitors.

It does reduce hospitalisation when added to diuretics and ACE inhibitors in patients with chronic heart failure.