page118
dioselective
, but they are not
cardiospecific
. They have
a lesser effect on airways resistance but are not free of
this side-effect.
Beta-blockers are also associated with fatigue, coldness
of the extremities (may be less common with those with
ISA, see above), and sleep disturbances with nightmares
(may be less
common with the water-soluble beta-
blockers,
see above).
Beta-blockers
can
affect
carbohydrate
metabolism,
causing hypoglycaemia or hyperglycaemia in patients
with or without
diabetes;
they can also interfere with
metabolic and autonomic responses to hypoglycaemia,
thereby masking symptoms such as tachycardia.
How-
ever, beta-blockers are not contra-indicated in diabetes,
although the cardioselective beta-blockers (see above)
may be preferred.
Beta-blockers
should be avoided
altogether in those with frequent episodes of hypoglyc-
aemia. Beta-blockers, especially when combined with a
thiazide diuretic,
should be avoided for
the routine
treatment
of
uncomplicated hypertension in patients
with diabetes or
in those at
high risk of
developing
diabetes.
Pregnancy
Beta-blockers
may cause intra-uterine
growth restriction, neonatal hypoglycaemia, and brady-
cardia;
the risk is greater in severe hypertension.
The
use of
labetalol
in maternal
hypertension is not known
to be harmful,
except
possibly in the first
trimester.
Information
on
the
safety
of
carvedilol
during
pregnancy is lacking.
If beta-blockers are used close to
delivery,
infants should be monitored for signs of beta-
blockade (and alpha-blockade with labetalol
or carve-
dilol).
For the treatment of hypertension in pregnancy,
see section 2.5.
Breast-feeding
Infants should be monitored as there
is a risk of possible toxicity due to beta-blockade (and
alpha-blockade with labetalol
or
carvedilol),
but
the
amount
of
most
beta-blockers present
in milk is too
small to affect infants. Acebutolol, atenolol, nadolol, and
sotalol are present in milk in greater amounts than other
beta-blockers. The manufacturers of celiprolol, esmolol,
and nebivolol advise avoidance if breast-feeding.
Hypertension
The mode of action of beta-blockers in
hypertension is not understood, but they reduce cardiac
output,
alter
baroceptor
reflex sensitivity,
and block
peripheral
adrenoceptors.
Some beta-blockers depress
plasma renin secretion. It is possible that a central effect
may also partly explain their mode of action.
Beta-blockers are effective for reducing blood pressure
but
other
antihypertensives
(section 2.5)
are usually
more effective for
reducing the incidence of
stroke,
myocardial
infarction,
and
cardiovascular
mortality,
especially in the elderly.
Other
antihypertensives are
therefore
preferred
for
routine
initial
treatment
of
uncomplicated hypertension.
In general,
the dose of a beta-blocker does not have to
be high;
for example,
atenolol is given in a dose of 25–
50 mg daily and it
is rarely necessary to increase the
dose to 100 mg.
Beta-blockers can be used to control
the pulse rate in
patients
with
phaeochromocytoma
(section
2.5.4).
However,
they should never
be used alone as beta-
blockade without concurrent alpha-blockade may lead
to a hypertensive crisis.
For this reason phenoxybenz-
amine should always be used together with the beta-
blocker.
Angina
By
reducing
cardiac
work
beta-blockers
improve exercise tolerance and relieve symptoms in
patients with
angina
(for further details on the manage-
ment of
stable angina and acute coronary syndromes,
see section 2.10.1).
As with hypertension there is no
good evidence of
the superiority of
any one drug,
although occasionally a patient
will
respond better to
one beta-blocker than to another.
There is some evi-
dence that sudden withdrawal may cause an exacerba-
tion of angina and therefore gradual reduction of dose is
preferable when beta-blockers are to be stopped. There
is a risk of precipitating heart failure when beta-blockers
and
verapamil
are
used
together
in
established
ischaemic heart disease (important:
see p.
133).
Myocardial
infarction
For
advice on the manage-
ment of ST-segment elevation myocardial infarction and
non-ST-segment
elevation myocardial
infarction,
see
section 2.10.1.
Several
studies have shown that
some
beta-blockers can reduce the recurrence rate of
myo-
cardial infarction
.
However,
uncontrolled heart failure,
hypotension,
bradyarrhythmias,
and obstructive
air-
ways disease render beta-blockers unsuitable in some
patients following a myocardial infarction. Atenolol and
metoprolol
may reduce early mortality after
intra-
venous
and
subsequent
oral
administration
in
the
acute phase,
while acebutolol,
metoprolol,
proprano-
lol,
and timolol have protective value when started in
the early convalescent phase.
The evidence relating to
other beta-blockers is less convincing;
some have not
been tested in trials of
secondary prevention.
Sudden
cessation of
a beta-blocker can cause a rebound wor-
sening of myocardial ischaemia.
Arrhythmias
Beta-blockers
act
as
anti-arrhythmic
drugs
principally by attenuating the effects of the sym-
pathetic system on automaticity and conductivity within
the heart. They can be used in conjunction with digoxin
to control
the ventricular response in atrial
fibrillation,
especially in patients with thyrotoxicosis. Beta-blockers
are also useful
in the management of
supraventricular
tachycardias,
and are used to control
those following
myocardial infarction (see above).
Esmolol is a relatively cardioselective beta-blocker with
a very short duration of
action,
used intravenously for
the short-term treatment
of
supraventricular
arrhyth-
mias, sinus tachycardia, or hypertension, particularly in
the peri-operative period.
It may also be used in other
situations,
such as acute myocardial
infarction,
when
sustained beta-blockade might be hazardous.
Sotalol,
a non-cardioselective beta-blocker with addi-
tional
class
III
anti-arrhythmic
activity,
is
used for
prophylaxis
in paroxysmal
supraventricular
arrhyth-
mias.
It
also suppresses ventricular ectopic beats and
non-sustained
ventricular
tachycardia.
It
has
been
shown to be more effective than lidocaine in the termi-
nation of spontaneous sustained ventricular tachycardia
due to coronary disease or cardiomyopathy. However, it
may induce torsade de pointes in susceptible patients.
Heart failure
Beta-blockers may produce benefit
in
heart
failure
by
blocking
sympathetic
activity.
Bisoprolol
and carvedilol
reduce mortality in any
grade of
stable heart
failure;
nebivolol
is licensed for
stable mild to moderate heart failure in patients over 70
98
2.4 Beta-adrenoceptor blocking drugs
BNF 61
2
Cardiovascular system