Pharmacology for Anaesthesia and Intensive Care

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Section IIICardiovascular drugs

metabolized in the liver. They have a shorter half-life and consequently need more

frequent administration. In addition, they cross the blood–brain barrier resulting in

sedation and nightmares. Protein binding is variable.

Individualβ-blockers

Acebutolol

Acebutolol is a relatively cardioselectiveβ-blocker that is only available orally. It has

limited intrinsic sympathomimetic activity and some membrane stabilizing prop-

erties. The adult dose is 400 mg bd but may be increased to 1.2 g.day−^1 if required.

Kinetics

Acebutolol is well absorbed from the gut due to its moderately high lipid solubility, but

due to a high first-pass metabolism its oral bioavailability is only 40%. Despite its lipid

solubility it does not cross the BBB to any great extent. Hepatic metabolism produces

the active metabolite diacetol, which has a longer half-life, and is less cardioselective

than acebutolol. Both are excreted in bile and may undergo enterohepatic recycling.

They are also excreted in urine and the dose should be reduced in the presence of

renal impairment.

Atenolol

Atenolol is a relatively cardioselectiveβ-blocker that is available as 25–100 mg tablets,

asyrup containing 5 mg.ml−^1 and as a colourless solution for intravenous use con-

taining 5 mg in 10 ml. The oral dose is 50–100 mg.day−^1 while the intravenous dose

is 2.5 mg slowly, repeated up to a maximum of 10 mg, which may then be followed

byan infusion.

Kinetics

Atenolol is incompletely absorbed from the gut. It is not significantly metabolized

and has an oral bioavailability of 45%. Only 5% is protein bound. It is excreted

unchanged in the urine and, therefore, the dose should be reduced in patients with

renal impairment. It has an elimination half-life of 7 hours but its actions appear to

persist for longer than this would suggest.

Esmolol

Esmolol is a highly lipophilic, cardioselectiveβ-blocker with a rapid onset and offset.

Itis presented as a clear liquid with either 2.5 g or 100 mg in 10 ml. The former should

be diluted before administration as an infusion (dose range 50–200μg.kg−^1 .min−^1 ),

while the latter is titrated in 10 mg boluses to effect. It is used in the short-term

management of tachycardia and hypertension in the peri-operative period, and for

acute supraventricular tachycardia. It has no intrinsic sympathomimetic activity or

membrane stabilizing properties.