Pharm 101: Digoxin
Class
Antiarrhythmic
Pharmacodynamics
- Inhibits Na/K ATPase
- At therapeutic doses digoxin is a positive inotrope, shortens AP duration, and at low doses has predominately parasympathomimetic effects
- Multiple direct and indirect cardiovascular effects with both therapeutic and toxic consequences (see below)
- In addition, it has undesirable effects on CNS and gut
Cardiac effects
- Mechanical effects cause positive inotropy via a two-step process:
- Na/K ATPase inhibition increases intracellular Na
- This increase consequently reduces Ca expulsion by the Na/Ca exchanger
- The net result is increased intracellular Ca, which:
- Increases contractility
- Increases stroke volume/CO per beat
- Electrical effects are a mixture of direct and autonomic actions
- Direct effects cause a shortened AP duration, likely due to increased K conductance caused by increased intracellular Ca
- Autonomic effects are a mixture of parasympathetic and sympathetic systems
- At low therapeutic doses, cardioselective parasympathomimetic effects predominate
- This involves baroreceptor sensitisation, central vagal stimulation, facilitation of muscarinic transmission at nerve ending-myocyte synapse. Cholinergic innervation is greater in the atria, therefore these actions affect atria and AV node more than ventricular/purkinje fibres
- Slow HR allows greater stroke volume
Other organ system effects
- Effects on other organs: smooth muscle and CNS
- GIT: anorexia, nausea/vomiting/diarrhoea
- CNS: vagal and chemoreceptor trigger zone stimulation
- Interactions with K, Ca, Mg
- K and digoxin inhibit each other’s binding to Na/K ATPase, therefore:
- Hyperkalaemia reduces enzyme-inhibiting actions of digoxin
- Hypokalaemia facilitates these actions
- Ca facilitates toxic actions of digoxin by accelerating overloading of intracellular Ca stores that appear to be responsible for digitalis-induced abnormal automaticity:
- Hypercalcaemia therefore increases risk of digitalis-induced arrhythmia
- Effects of Mg are opposite to those of calcium
- K and digoxin inhibit each other’s binding to Na/K ATPase, therefore:
Pharmacokinetics
- Bioavailability 65-80%
- Large volume of distribution, widely distributed to all tissues including CNS
- 25% plasma protein bound
- Half-life 36-40 hours in normal renal function
- 2/3 excreted unchanged in urine
- Renal clearance is proportional to creatinine clearance
Clinical uses
- Heart failure
Adverse effects
Digoxin can cause virtually any arrhythmia, due to a combination of enhanced automaticity and decreased AV nodal conduction.
Most common cardiac manifestations of toxicity:
- AV junctional rhythm
- PVCs
- Bigeminy
- VT
- 2nd degree AV block
- Bradycardia, R on T
Other adverse effects include:
- Hyperkalaemia
- GIT:
- Anorexia
- Nausea/vomiting/diarrhoea
- CNS:
- Disorientation
- Hallucinations
- Yellow/green vision
- CTZ
Precautions/contraindications
- Drugs that increase effect of digoxin:
- Amiodarone
- Macrolide antibiotics (due to increased bioavailability)
- Quinidine
- K depleting drugs (increases likelihood of digitalis toxicity)
- Ca channel blockers
- Drugs that decrease effect of digoxin:
- Acid-reducing agents
- Patients in heart failure are more prone to digoxin toxicity:
- Poor renal function from low cardiac output
- Potential dehydration and other drug interactions (e.g. ACE-I, diuretics, Ca channel blockers)
- Hypokalaemia from other heart failure medications especially diuretics
- Poor cardiac reserve/output
Further Reading
- Long N. Digoxin poisoning
- Burns E. ECG library: Digoxin toxicity
- Long N. Digoxin Immune Fab
References
- Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 217-219, 1044-1045 p.
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Adult/Paediatric Emergency Medicine Advanced Trainee in Melbourne, Australia. Special interests in diagnostic and procedural ultrasound, medical education, and ECG interpretation. Co-creator of the LITFL ECG Library. Twitter: @rob_buttner