C H A P T E R 4 5
Antiarrhythmic agents
707
Pharmacokinetics
Diltiazem is administered intravenously. When used
as an antiarrhythmic, verapamil is used intravenously.
These drugs are well absorbed after intravenous admini
stration. They are highly protein bound, metabolised
in the liver and excreted in the urine. They cross the
placenta and enter breast milk.
Contraindications and cautions
These drugs are contraindicated with known allergy
to any calcium channel blocker
to avoid hypersensitiv
ity reactions
; with sick sinus syndrome or heart block
(unless an artificial pacemaker is in place)
because the
block could be exacerbated by these drugs
; with preg-
nancy or breastfeeding
because of the potential for
adverse effects on the fetus or neonate
; and with HF or
hypotension
because of the hypotensive effects of these
drugs.
Caution should be used in cases of idiopathic
hypertrophic subaortic stenosis (IHSS),
which could be
exacerbated
, or impaired renal or liver function,
which
could affect the metabolism or excretion of these
drugs.
Adverse effects
The adverse effects associated with these drugs are
related to their vasodilation of blood vessels through-
out the body. CNS effects include dizziness, weakness,
fatigue, depression and headache. GI upset, nausea and
vomiting can occur. Hypotension, HF, shock, arrhyth-
mias and oedema have also been reported.
Clinically important drug–drug interactions
Verapamil has been associated with many drug–drug
interactions, including increased risk of cardiac depres-
sion with beta blockers; additive AV slowing with
digoxin; increased serum levels and toxicity of digoxin,
carbamazepine, prazosin and quinidine; increased res-
piratory depression with atracurium, pancuronium and
vecuronium; and decreased effects if combined with
calcium products or rifampicin.
There is a risk of severe cardiac effects if these drugs
are given IV within 48 hours of IV beta-adrenergic
drugs. The combination should be avoided.
Diltiazem can increase the serum levels and toxicity
of cyclosporin if the drugs are taken concurrently.
■■
Class IV antiarrhythmics are calcium channel
blockers that shorten the action potential, disrupting
ineffective rhythms and rates.
■■
Whichever type of antiarrhythmic is used, the
person receiving an antiarrhythmic drug needs
to be constantly monitored while being stabilised
and throughout the course of therapy to detect the
development of arrhythmias or other adverse effects
associated with alteration of the action potentials of
other muscles or nerves.
O
ther antiarrhythmics
Drugs other than those classified as class I, II, III or IV
may be used to treat arrhythmias. Table 45.2 provides a
summary of types of arrhythmias and the specific drugs
used to treat each type. Additional antiarrhythmics
include adenosine (
Adenocor
,
Adenoscan
) and digoxin
(
Lanoxin
). For dosages and usual indications see also
Table 45.1.
Adenosine is another antiarrhythmic agent that is
used to convert supraventricular tachycardia to sinus
rhythm if vagal manoeuvres have been ineffective. It is
often the drug of choice for terminating supraventricu-
lar tachycardias, including those associated with the
use of alternative conduction pathways around the AV
node (e.g. Wolff–Parkinson–White syndrome), for two
reasons: (1) it has a very short duration of action (about
15 seconds), after which it is picked up by circulating
red blood cells and cleared through the liver; and (2) it
is associated with very few adverse effects (headache,
flushing and dyspnoea of short duration). This drug
slows conduction through the AV node, prolongs the
refractory period and decreases automaticity in the
AV node. It is given IV with continuous monitoring of
the person.
Digoxin (see Chapter 44) is also used at times
to treat arrhythmias. This drug slows calcium from
KEY POINTS
Prototype summary: Diltiazem
Indications:
Treatment of paroxysmal
supraventricular tachycardia, atrial fibrillation and
atrial flutter.
Actions:
Blocks the movement of calcium ions across
the cell membrane, depressing the generation
of action potentials, delaying phases 1 and 2 of
repolarisation, and slowing conduction through the
AV node.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
30–60 mins 2–3 hours
6–8 hours
IV Immediate 2–3 mins
unknown
T
1/2
:
3.5 to 6 hours; metabolised in the liver and
excreted in urine.
Adverse effects:
Dizziness, light-headedness,
headache, asthenia, peripheral oedema,
bradycardia, AV block, flushing, nausea, hepatic
injury.
