Question 14

Compare and contrast the mechanism of action, pharmacokinetics and adverse effects of digoxin and sotalol.

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College Answer

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).


Name Digoxin Sotalol
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
Distribution VOD=5.1–7.4 L/kg;
25% protein-bound
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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