Cardiac Glycosides
Examples
Digoxin
Indications
- Atrial fibrillation and flutter - rapid digitalisation, maintenance and emergency management
- Heart failure
Contraindications
Contraindications
- Complete heart block and 2nd degree AV block
- Wolff-Parkinson-White syndrome
- Hypertrophic cardiomyopathy
- Ventricular tachycardia/fibrillation
- Electrolyte disturbance (particularly hypokalaemia, hypercalcaemia and hypomagnesaemia) - the risk of toxicity is greatly increased
- Renal failure
- Elderly
- Thyroid disease
Mechanism
The main action of Digoxin is to slow the heart rate and increase the force of cardiac contraction.
Digoxin acts by inhibiting the Na/K-ATPase within the myocardial cell membrane, so that less sodium is excreted from the cell. The resulting change in concentration gradient means that less calcium is exchanged for sodium by the Na/Ca exchanger. The result is an increase in calcium ions which cause a small positive inotropic effect (i.e. an increase in the force of contraction).
Digoxin has a secondary action as a modifier of autonomic activity causing an increase in vagal activity and muscarinic transmission. This slows the heart rate and reduces conduction across the AV node.
Digoxin acts by inhibiting the Na/K-ATPase within the myocardial cell membrane, so that less sodium is excreted from the cell. The resulting change in concentration gradient means that less calcium is exchanged for sodium by the Na/Ca exchanger. The result is an increase in calcium ions which cause a small positive inotropic effect (i.e. an increase in the force of contraction).
Digoxin has a secondary action as a modifier of autonomic activity causing an increase in vagal activity and muscarinic transmission. This slows the heart rate and reduces conduction across the AV node.
Administration
Oral.
IV - intravenous injection must be slow.
For the control of atrial fibrillation, a loading dose is required (which may need adjustment in the elderly or in renal impairment). This is not needed in heart failure.
Therapy should be adjusted according to response and guided by serum levels of Digoxin.
IV - intravenous injection must be slow.
For the control of atrial fibrillation, a loading dose is required (which may need adjustment in the elderly or in renal impairment). This is not needed in heart failure.
Therapy should be adjusted according to response and guided by serum levels of Digoxin.
Adverse Reactions
- Gastrointestinal disturbance - nausea, anorexia, abdominal pain, vomiting and diarrhoea
- Neurological / psychological disturbances - visual disturbance (blurred/yellow vision), drowsiness, confusion, delirium (especially in the elderly)
- Heart Block
- Arrhythmias (ventricular tachycardia)
- Toxicity is more likely to develop in the elderly, in renal impairment and in hypokalaemia
Interactions
Digoxin concentrations are increased by:
Any drug which causes electrolyte disturbance (i.e. diuretics) can increase the risk of toxicity.
- Amiodarone
- Diltiazem
- Verapamil
- Quinidine
- Quinine
- Itraconazole
- Clarithromycin
Any drug which causes electrolyte disturbance (i.e. diuretics) can increase the risk of toxicity.
Education
Patients will need to have blood taken for U&E's and in some circumstances Digoxin levels.
Pharmacokinetics
Digoxin has a narrow therapeutic index.
Toxicity is common. In the case of severe toxicity, Digoxin specific antibody fragment can be administered which will bind to Digoxin and inactivate it.
Digoxin is renally excreted. Check electrolytes and renal function before starting therapy and reduced the dose in the elderly and in renal impairment.
Digoxin has a half-life of approximately 36 hours, increasing the time needed to reach a steady state concentration and necessitating a loading dose.
Toxicity is common. In the case of severe toxicity, Digoxin specific antibody fragment can be administered which will bind to Digoxin and inactivate it.
Digoxin is renally excreted. Check electrolytes and renal function before starting therapy and reduced the dose in the elderly and in renal impairment.
Digoxin has a half-life of approximately 36 hours, increasing the time needed to reach a steady state concentration and necessitating a loading dose.
