Pharmacology for Anaesthesia and Intensive Care

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13 Adrenoceptor antagonists

Table 13.2.Comparison between receptor selectivity, intrinsic sympathomimetic

activity and membrane stabilizing activity of variousβ-blockers.

β 1 -receptor

selectivity-

cardioselectivity

Intrinsic

sympathomimetic

activity

Membrane

stabilizing

activity

Acebutolol +++

Atenolol ++ − −

Esmolol ++ − −

Metoprolol ++ − +

Pindolol −+++

Propranolol −−++

Sotalol −−−

Timolol −++

Labetalol −±+

effects. Atenolol, esmolol and metoprolol demonstrateβ 1 -adrenoceptor selectivity

(cardioselectivity) although when given in high doseβ 2 -antagonism may also be

seen. Allβ-blockers should be used with extreme caution in patients with poor

ventricular function as they may precipitate serious cardiac failure.

Intrinsic sympathomimetic activity – partial agonist activity

Partial agonists are drugs that are unable to elicit the same maximum response as

afull agonist despite adequate receptor affinity. In theory,β-blockers with partial

agonist activity will produce sympathomimetic effects when circulating levels of

catecholamines are low, while producing antagonist effects when sympathetic tone

is high. In patients with mild cardiac failure they should be less likely to induce

bradycardia and heart failure. However, they should not be used in those with more

severe heart failure asβ-blockade will further reduce cardiac output.

Membrane stabilizing activity

These effects are probably of little clinical significance as the doses required to elicit

them are higher than those seen in vivo.

Effects


Cardiac –β-blockers have negative inotropic and chronotropic properties on car-

diac muscle; sino-atrial (SA) node automaticity is decreased and atrioventricular

(AV) node conduction time is prolonged leading to a bradycardia, while contrac-

tility is also reduced. The bradycardia lengthens the coronary artery perfusion

time (during diastole) thereby increasing oxygen supply while reduced contractility

diminishes oxygen demand. These effects are more important than those that tend

to compromise the supply/demand equation, that is, prolonged systolic ejection