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

3. Introduction n Digoxin is a naturally occuring drug and comes from the foxglove plant (Digitalis spp.) n Classified as a Cardiac Glycoside n All cardiac glycosides have a steroid nucleus and a lactone ring and most also have one or more sugar residues. n Other examples are Digitoxin and Oubain (short-acting drug)

4. Pharmacokinetics n Oral bioavailability: 60-85% n Volume of distribution: 6-8 litres/kg n Elimination: Predominantly kidneys n Elimination half-life, t 1/2 : 36-40 hours n Clearance (ml/min/kg): 0.88 X creatinine clearance (ml/min/kg) + 0.33 n Therapeutic range: 0.8-2  g/L

5. Mechanism of Action

6. Effects 1.Mechanical 2.Electrical

7. Mechanical Effects n  ventricular ejection n  cardiac output n  end-systolic and end-diastolic cardiac size n  renal perfusion Overall:  sympathetic tone and  renin-angiotensin system stimulation

8. Electrical Effects

9. Clinical Uses n Congestive Heart Failure u Positive inotropic agent u Other drugs used are diuretics, vasodilators and ACE inhibitors u Need careful monitoring n Atrial Fibrillation u Decreases conduction velocity and effective refactory period of AVN

10. Interactions n Absorption is dependant on intestinal motility, therefore  with metoclopramide and  with propantheline n Various drugs e.g. quinidine, amiodarone increase levels n Inhibited by extracellular K +, Mg 2+ and facilitated by extracelluar Ca 2+. Therefore can loop and thiazide diuretics may cause toxicity

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

12. Toxicity - Management n Correction of electrolyte disturbances e.g. hypokalaemia, hypomagnesaemia. n Antiarrhythmics n Digoxin antibodies Note: In severe acute intoxication, potassium and antiarrythmics may worsen condition.

13. The Future... n Digoxin is a very cheap and effective drug and therefore useful clinically in heart failure however, it does not reduce mortality, unlike ACE inhibitors. n It does reduce hospitalisation when added to diuretics and ACE inhibitors in patients with chronic heart failure.