Digoxin

1
Digoxin

• it has a power over the motion of the heart to a
  degree yet unobserved in any other medicine
• Withering, 1775

2
Topics of Discussion

• Introduction
• Pharmacokinetics
• Mechanism of Action
• Effects
• Clinical Uses
• Interactions
• Toxicity
• The Future

3
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)

4
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

5
Mechanism of Action
6
Effects

• 1. Mechanical
• 2. Electrical

7
Mechanical Effects

• ? ventricular ejection
• ? cardiac output
• ? end-systolic and end-diastolic cardiac size
• ? renal perfusion
• Overall ? sympathetic tone and ?
  renin-angiotensin system stimulation

8
Electrical Effects
9
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

10
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

11
Toxicity

• Non-cardiac signs are nausea, vomiting,
  diarrhoea, anorexia, fatigue and less commonly
  neurological symptoms.
• Cardiac signs are arrhythmias secondary to
  increased intracellular calcium.

12
Toxicity - Management

• Correction of electrolyte disturbances e.g.
  hypokalaemia, hypomagnesaemia.
• Antiarrhythmics
• Digoxin antibodies
• Note In severe acute intoxication, potassium and
  antiarrythmics may worsen condition.

13
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.