C H A P T E R 4 5
Antiarrhythmic agents
705
decrease in heart rate, cardiac excitability and cardiac
output, a slowing of conduction through the AV node
and a decrease in the release of renin. These effects
stabilise excitable cardiac tissue and decrease blood
pressure, which decreases the heart’s workload and may
further stabilise hypoxic cardiac tissue. These drugs are
indicated for the treatment of supraventricular tachy
cardias and PVCs. See Table 45.1 for usual indications
for each drug.
Pharmacokinetics
Esmolol is administered intravenously. Propranolol may
be administered orally or intravenously. These drugs
are absorbed from the GI tract or have an immediate
effect when given intravenously and undergo hepatic
metabolism. They are excreted in the urine. Food has
been found to increase the bioavailability of proprano-
lol, although this effect has not been found with other
beta-adrenergic blocking agents.
Contraindications and cautions
The use of these drugs is contraindicated in the presence
of sinus bradycardia (rate less than 45 beats/minute) and
AV block,
which could be exacerbated by the effects of
these drugs
; with cardiogenic shock, HF, asthma or res-
piratory depression,
which could worsen due to blockage
of beta receptors
; and with pregnancy and breastfeeding
because of the potential for adverse effects on the fetus
or neonate.
Caution should be used in people with diabetes
and thyroid dysfunction,
which could be altered by the
blockade of the beta-receptors
, and in people with renal
and hepatic dysfunction,
which could alter the metabo
lism and excretion of these drugs.
Adverse effects
The adverse effects associated with class II antiarrhyth-
mics are related to the effects of blocking beta-receptors
in the sympathetic nervous system. CNS effects include
dizziness, insomnia, nightmares and fatigue. Cardiovas-
cular symptoms can include hypotension, bradycardia,
AV block, arrhythmias and alterations in peripheral per-
fusion. Respiratory effects can include bronchospasm
and dyspnoea. GI problems frequently include nausea,
vomiting, anorexia, constipation and diarrhoea. Other
effects to anticipate include a loss of libido, decreased
exercise tolerance and alterations in blood glucose levels.
Clinically important drug–drug interactions
The risk of adverse effects increases if these drugs are
taken with verapamil; if this combination is used, dose
adjustment will be needed.
There is a possibility of increased hypoglycaemia
if these drugs are combined with insulin; individuals
should be monitored closely.
Other specific drug interactions may occur with
each drug; check a drug reference before combining
these drugs with any others.
phase
4
0
phase
1
Effects of Class III
antiarrhythmics:
K
+
channel blocker,
prolongs repolarisation
Effects of Class II
antiarrhythmic blockers
of beta-adrenergic receptors:
diminish phase 4, cell less
excitable, slower conducting
Effects of Class IV
calcium channel
blockers:
slow phase 4,
spontaneous depolarisation,
slow conduction
phase
2
phase
3
0
0
+20
–80
–100
–40
–60
–20
FIGURE 45.7
The cardiac action potentials, showing the effects of
class II, III and IV antiarrhythmics.
Prototype summary: Propranolol
Indications:
Treatment of cardiac arrhythmias,
especially supraventricular tachycardia; treatment
of ventricular tachycardia induced by digitalis or
catecholamines.
Actions:
Competitively blocks beta-adrenergic
receptors in the heart and kidney, has a membrane-
stabilising effect, and decreases the influence of the
sympathetic nervous system.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
20–30 mins 60–90 mins 6–12 hours
IV Immediate 1 min
4–6 hours
T
1/2
:
3 to 5 hours; metabolised in the liver and
excreted in urine.
Adverse effects:
Bradycardia, HF, cardiac
arrhythmias, heart blocks, cerebrovascular accident
(CVA), pulmonary oedema, gastric pain, flatulence,
nausea, vomiting, diarrhoea, impotence, decreased
exercise tolerance, antinuclear antibody (ANA)
development.
■■
Class II antiarrhythmics are beta-adrenergic receptor
blockers that prevent sympathetic stimulation.
■■
Adverse effects related to class II antiarrhythmics are
associated with blocking of the sympathetic response.
KEY POINTS
