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13 Adrenoceptor antagoniststime, dilation of the ventricles and increased coronary vascular resistance (due
to antagonism of the vasodilatoryβ 2 coronary receptors). The improvement in
the balance of oxygen supply/demand forms the basis for their use in angina
and peri-myocardial infarction. However, in patients with poor left ventric-
ular functionβ-blockade may lead to cardiac failure.β-blockers are class II
anti-arrhythmic agents and are mainly used to treat arrhythmias associated with
high levels of catecholamines (see Chapter 14 ).
Circulatory – the mechanism by whichβ-blockers control blood pressure is not
yet fully elucidated but probably includes a reduced heart rate and cardiac output,
and inhibition of the renin-angiotensin system. Inhibition ofβ 1 -receptors at the
juxtaglomerular apparatus reduces renin release leading ultimately to a reduction
in angiotensin II and its effects (vasoconstriction and augmenting aldosterone
production). In addition, the baroreceptors may be set at a lower level, presynaptic
β 2 -receptors may inhibit noradrenaline release and someβ-blockers may have
central effects. However, due to antagonism of peripheralβ 2 -receptors there will
be an element of vasoconstriction, which appears to have little hypertensive effect
but may result in poor peripheral circulation and cold hands.
Respiratory – allβ-blockers given in sufficient dose will precipitate bronchospasm
viaβ 2 -antagonism. The relatively cardioselective drugs (atenolol, esmolol and
metoprolol) are preferred but should still be used with extreme caution in patients
with asthma.
Metabolic – the control of blood sugar is complicated involving different tissue
types (liver, pancreas, adipose), receptors (α-,β-adrenoceptors) and hormones
(insulin, glucagon, catecholamines). Non-selectiveβ-blockade may obtund the
normal blood sugar response to exercise and hypoglycaemia although it may
also increase the resting blood sugar levels in diabetics with hypertension. There-
fore, non-selectiveβ-blockers should not be used with hypoglycaemic agents. In
addition,β-blockade may mask the normal symptoms of hypoglycaemia. Lipid
metabolism may be altered resulting in increased triglycerides and reduced high
density lipoproteins.
Central nervous system – the more lipid-solubleβ-blockers (metoprolol, propra-
nolol) are more likely to produce CNS side effects. These include depression, hal-
lucination, nightmares, paranoia and fatigue.
Occular – intra-occular pressure is reduced, probably as a result of decreased pro-
duction of aqueous humour.
Gut–drymouth and gastrointestinal disturbances.Kinetics
Var ying lipid solubility confers the main differences seen in the kinetics ofβ-blockers.
Those with low lipid solubility (atenolol) are poorly absorbed from the gut, undergo
little hepatic metabolism and are excreted largely unchanged in the urine. However,
those with high lipid solubility are well absorbed from the gut and are extensively