Pharmacology for Anaesthesia and Intensive Care

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Section IIICardiovascular drugs

Kinetics

Absorption from the gut is nearly complete and initially oral bioavailability is 50%.

However, this increases disproportionately to nearly 100% as the enzymes involved in

first-pass metabolism become saturated. It is more than 95% protein bound. Hepatic

metabolism ensures that only tiny amounts are excreted unchanged. However, the

enzyme responsible for its metabolism demonstrates genetic polymorphism so that

affected patients may have an increased response.

Sotalol

Sotalol is aβ-blocker but also has class I and III anti-arrhythmic activity.

Presentation

Itis available as tablets and as a solution containing 40 mg in 4 ml. It is a racemic

mixture, thed-isomer conferring the class III activity while thel-isomer has both

class III andβ-blocking actions.

Uses

Sotalol is used to treat ventricular tachyarrhythmias and in the prophylaxis of parox-

ysmal SVT. The oral dose is 80–160 mg bd and the intravenous dose is 50–100 mg

over 20 minutes.

Mechanism of action

Sotalol prolongs the duration of the action potential so that the effective refractory

period is prolonged in the conducting tissue. It is also a non-selectiveβ-blocker and

is more effective at maintaining sinus rhythm following DC cardioversion for atrial

fibrillation than otherβ-blockers. The ventricular rate is also well controlled if the

rhythm degenerates back into atrial fibrillation.

Side effects


Cardiac – the most serious side effect is precipitation of torsades de pointes, which

occurs in less than 2% of those being treated for sustained VT or VF. It is more

common with higher doses, a prolonged QT interval and electrolyte imbalance. It

may precipitate heart failure.


Non-cardiac – bronchospasm, masking of symptoms of hypoglycaemia, visual dis-

turbances and sexual dysfunction are all rare.

Kinetics

Sotalol is completely absorbed from the gut and its oral bioavailability is greater

than 90%. It is not plasma protein-bound and is not metabolized. Approximately

90% is excreted unchanged in the urine while the remainder is excreted in bile. Renal

impairment significantly reduces clearance.