Compare and contrast the mechanism of action, pharmacokinetics and adverse effects of digoxin and sotalol.
Good answers listed class and the multiple mechanisms of action for both these antiarrhythmics, briefly outlining relevant downstream physiological effects and contrasting effects on inotropy. Knowledge of specific pharmacokinetic parameters of these agents was generally lacking. Clinically relevant adverse effects were frequently omitted (e.g. prolonged QT/Torsades for sotalol, hypokalaemia potentiating toxicity of digoxin).
|Class||Antiarrhythmic||Class II antiarrhythmic|
|Chemistry||Cardiac glycoside||Ethanolamine derivative|
|Routes of administration||Oral and IV; theoretically also IM||Oral and IV|
|Absorption||Oral bioavailability 80% (some is secreted back into the gut lumen by P-glycoprotein, an enterocyte efflux pump)||Well absorbed from the GI tract; bioavalaility 90-100%|
|Solubility||pKa = 7.15; basically insoluble in water.||pKa = - 8.3; highly water-soluble|
|VOD = 1.6 to 2.4 L/kg;
no protein binding whatsoever
|Target receptor||Digoxin inhibits Na+/K+ ATPase.||Sotalol is a non-selective beta-blocker without sympathomimetic activity or
membrane stabilising activity. It is also a Class III antiarrhythmic, as it blocks potassium current during cardiac myocyte repolarisation
|Metabolism||Hepatic metabolism accounts for only abut 16% of clearance||Sotalol is not metabolised|
|Elimination||Elimination is renal, as unchanged drug, and slow because of the large VOD. Half-life is about 36-44 hrs||Eliminated by the kidneys; mean elimination half-life of sotalol is 12.7hrs|
|Time course of action||Onset of effect is relatively rapid with IV infusion, or delayed by 2-3 hrs following oral loading.||Rapid onset with IV and oral administration; duration of action is closely related to half-life|
|Mechanism of action||By inhibiting Na+/K+ ATPase, digoxin increases intracellular sodium, which increases sodium-calcium exchange by the Na+/Ca2+ exchanger (INCX) during Phase 1 of the cardiac action potential. The resulting increase in intracellular calcium promotes inotropy. It also acts as a vagotonic agent, which slows conduction through the AV node, and decreases the duration of the action potential mainly by reducing the duration of Phase 2. The slope of Phase 4 is increased, promoting automaticity, but then automaticity is overall suppressed by the vagotonic effects.||Blocks repolarising potassium currents in Phase 3 of the cardiac action potential prolonging the repolarisation, which prolongs the QT interval. Also decreases the velocity of AV nodal conduction by its beta blocker effect.|
|Clinical effects||Bradycadia, AV block, shortened QT interval, tachyarrhythmias (including VF and Vt which can be bidirectional), nausea, anorexia, depressed level of consciousness, and arterial vasoconstriction. Toxicity is exacerbated by hypokalemia||Bradycardia, hypotension, AV nodal block, prolonged QT. Acts as a negative inotrope.|
|Single best reference for further information||FDA data sheet||TGA PI document|
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