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P A R T 5
Drugs acting on the autonomic nervous system
reaction
; and women who are breastfeeding
because of
the potential adverse effects on the neonate.
These drugs should be used with caution in indi-
viduals with diabetes
because the disorder could be
aggravated by the blocked sympathetic response and
because the usual signs and symptoms of hypogly
caemia and hyperglycaemia are masked with the SNS
blockade.
Caution also should be used in people with
bronchospasm,
which could progress to respiratory
distress due to the loss of noradrenaline’s broncho
dilating actions
; and in pregnancy
because there are no
well-defined studies to evaluate the potential risk to the
fetus.
The drugs should only be used if the benefit to the
mother clearly outweighs the potential risk to the fetus
.
Adverse effects
The adverse effects associated with the use of non-
selective adrenergic blocking agents are usually associ-
ated with the drug’s effects on the SNS. These effects
can include dizziness, paraesthesias, insomnia, depres-
sion, fatigue and vertigo,
which are related to the
blocking of noradrenaline’s effect in the CNS
. Nausea,
vomiting, diarrhoea, anorexia and flatulence are
associ
ated with the loss of the balancing sympathetic effect on
the gastrointestinal (GI) tract and increased parasym
pathetic dominance.
Cardiac arrhythmias, hypotension,
HF, pulmonary oedema and cerebrovascular accident
or stroke, are
related to the lack of stimulatory effects
and loss of vascular tone in the cardiovascular (CV)
system.
Bronchospasm, cough, rhinitis and bronchial
obstruction are
related to loss of bronchodilation of the
respiratory tract and vasodilation of mucous membrane
vessels.
Other effects reported include decreased exercise
tolerance, hypoglycaemia and rash
related to the sym
pathetic blocking effects.
Abruptly stopping these drugs
after long-term therapy can result in MI, stroke and
arrhythmias
related to an increased hypersensitivity to
catecholamines that develops when the receptor sites
have been blocked.
Carvedilol has been associated with
hepatic failure
related to its effects on the liver.
Clinically important drug–drug interactions
There is increased risk of excessive hypotension if any
of these drugs is combined with general anaesthet-
ics in volatile liquid form such as enflurane, halothane
or isoflurane. The effectiveness of diabetic agents is
increased, leading to hypoglycaemia when such agents
are used with these drugs; individuals should be moni
tored closely and dose adjustments made as needed. In
addition, carvedilol has been associated with poten-
tially dangerous conduction system disturbances when
combined with verapamil or diltiazem; if this combina-
tion is used, the person requires continuous monitoring.
TABLE 31.1
DRUGS IN FOCUS Non-selective adrenergic blocking agents
Drug name
Dosage/route
Usual indications
amiodarone (Cordarone X )
200 mg PO t.d.s. initially, reduced for
maintenance to 200 mg/day; 5 mg/
kg IV diluted in 5% glucose over
20 minutes–2 hours to maximum
1200 mg/24 hours
Treatment of life-threatening ventricular
arrhythmias
carvedilol (Dilatrend,
Vedilol)
6.25–12.5 mg PO b.d. for hypertension;
3.125–6.25 mg PO b.d. for heart failure
Treatment of hypertension and heart failure
in adults, alone or as part of combination
therapy
labetalol (Presolol,
Trandate)
100 mg PO b.d. initially, maintenance
200–400 mg PO b.d.; 20 mg IV, slowly with
additional doses given at 10-minute intervals
to a maximum dose of 300 mg for severe
hypertension
Treatment of hypertension, hypertension
associated with phaeochromocytoma,
and clonidine withdrawal
Prototype summary: Labetalol
Indications:
Hypertension, alone or in combination
with other drugs; off-label uses—control of blood
pressure in phaeochromocytoma, clonidine-
withdrawal hypertension.
Actions:
Competitively blocks alpha- and beta-
receptor sites in the SNS, leading to lower blood
pressure without reflex tachycardia and decreased
renin levels.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
Varies
1–2 hours
8–12 hours
IV Immediate 5 mins
5.5 hours
T
1/2
:
6 to 8 hours, with hepatic metabolism and
excretion in the urine.
Adverse effects:
Dizziness, vertigo, fatigue, gastric
pain, flatulence, impotence, bronchospasm,
dyspnoea, cough, decreased exercise tolerance.
