Pharmacology for Anaesthesia and Intensive Care

P1: PSB Printer: Yet To Come
9780521704632c13 CUFX213A/Peck 9780521618168 December 28, 2007 12:27

Section IIICardiovascular drugs

Kinetics

Owing to its high lipid solubility it is well absorbed from the gut but a high first-pass

metabolism reduces its oral bioavailability to 30%. It is highly protein bound although

this may be reduced by heparin. Hepatic metabolism of the R-isomer is more rapid

than the S-isomer and one of their metabolites, 4-hydroxypropranolol, retains some

activity. Its elimination is dependent on hepatic metabolism but is impaired in renal

failure by an unknown mechanism. The duration of action is longer than its half-life

of 4 hours would suggest.

Sotalol

Sotalol is a non-selectiveβ-blocker with no intrinsic sympathomimetic properties.

It also has class III anti-arrhythmic properties (see Chapter 14 ).

Itis a racemic mixture, thed-isomer conferring the class III activity while the

l-isomer has both class III and class II (β-blocking) actions.

Uses

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

ysmal supraventricular tachycardias following direct current (DC) cardioversion. The

ventricular rate is also well controlled if sinus rhythm degenerates back into atrial

fibrillation. The CSM states that sotalol should not be used for angina, hypertension,

thyrotoxicosis or peri-myocardial infarction. The oral dose is 80–160 mg bd and the

intravenous dose is 50–100 mg over 20 minutes.

Other effects

The most serious side effect is precipitation of torsades de pointes, which is rare,

occurring in less than 2% of those being treated for sustained ventricular tachycardia

or fibrillation. It is more common with higher doses, a prolonged QT interval and

electrolyte imbalance. It may precipitate heart failure.

Kinetics

Sotalol is completely absorbed from the gut and its oral bioavailability exceeds 90%.

It is not protein bound or metabolized. Approximately 90% is excreted unchanged in

urine while the remainder is excreted in bile. Renal impairment significantly reduces

clearance.

Combinedα- andβ-adrenoceptor antagonists

Labetalol

Labetalol, as its name indicates, is anα- andβ-adrenoceptor antagonist;α-blockade

is specific toα 1 -receptors whileβ-blockade is non-specific. It contains two asym-

metric centres and exists as a mixture of four stereoisomers present in equal propor-

tions. The (SR)-stereoisomer is probably responsible for theα 1 effects while the