702
P A R T 8
Drugs acting on the cardiovascular system
Heart, Lung and Blood Institute looked at the mortality
rate of people with asymptomatic, non-life-threatening
arrhythmias being treated with antiarrhythmics. The
results showed that long-term use of some antiarrhyth-
mics was associated with an increased risk of death. In
fact, the risk of death for some people was two to three
times greater than that for untreated individuals. These
results prompted more clinical trials to look at the effec-
tiveness of long-term use of antiarrhythmics.
It was found that antiarrhythmics may block some
reflex arrhythmias that help to keep the cardiovascular
system in balance, or they may precipitate new, deadly
arrhythmias. Therefore, it is important to document
the arrhythmia being treated and the rationale for treat-
ment and to monitor a person regularly when using
these drugs.
C
lass
I
antiarrhythmics
Class I antiarrhythmics (Table 45.1) are drugs that block
the sodium channels in the cell membrane during an
action potential. These drugs are further broken down
into three subclasses, reflecting the manner in which
their blockage of sodium channels affects the action
potential. These subclasses include the following:
• Class Ia antiarrhythmics: disopyramide
(
Rythmodan
)
• Class Ib antiarrhythmics: lignocaine (
Xylocaine
and
others)
• Class Ic antiarrhythmics: flecainide (
Flecatab
,
Tambocor
) and propafenone (
Rytmonorm
[available
in NZ])
Therapeutic actions and indications
The class I antiarrhythmics stabilise the cell membrane
by binding to sodium channels, depressing phase 0 of
the action potential and changing the duration of the
action potential (Figure 45.6).
Class Ia drugs
depress
phase 0 of the action potential and prolong the duration
of the action potential.
Class Ib drugs
depress phase 0
somewhat and actually shorten the duration of the action
potential.
Class Ic drugs
markedly depress phase 0, with
a resultant extreme slowing of conduction, but have
little effect on the duration of the action potential.
These drugs are local anaesthetics or membrane-
stabilising agents. They bind more quickly to sodium
channels that are open or inactive—ones that have been
stimulated and are not yet repolarised. This character-
istic makes these drugs preferable in conditions such as
tachycardia, in which the sodium gates are open fre-
quently. These drugs are indicated for the treatment of
potentially life-threatening ventricular arrhythmias and
should not be used to treat other arrhythmias because
of the risk of a proarrhythmic effect. See Table 45.1 for
usual indications for each class I antiarrhythmic agent.
Pharmacokinetics
These drugs are widely distributed after injection or
after rapid absorption through the gastrointestinal (GI)
tract. They undergo extensive hepatic metabolism and
are excreted in urine. These drugs cross the placenta
and are found in breast milk (see Contraindications and
cautions).
Disopyramide is available in oral form. Lignocaine
is administered by the IM or IV route, and can also be
given as a bolus injection in emergencies when monitor-
ing is not available to document the exact arrhythmia.
Flecainide is available in oral form.
Contraindications and cautions
Class I antiarrhythmics are contraindicated in the
presence of allergy to any of these drugs; with brady-
cardia or heart block unless an artificial pacemaker is
in place,
because changes in conduction could lead to
complete heart block
; with heart failure (HF), hypoten-
sion or shock,
which could be exacerbated by effects on
the action potential
; and with electrolyte disturbances,
which could alter the effectiveness of these drugs.
Caution should be used in people with renal or hepatic
dysfunction,
which could interfere with the biotrans
formation and excretion of these drugs.
These drugs cross the placenta, and although no
specific adverse effects have been associated with their
use, it is suggested that they be used in pregnancy only
if the benefits to the mother clearly outweigh the poten-
tial risks to the fetus. Class I antiarrhythmics enter
breast milk, and
because of the potential for adverse
effects on the neonate
, they should not be used during
TABLE 45.1
DRUGS IN FOCUS Antiarrhythmic agents
Drug name
Dosage/route
Usual indications
Class I antiarrhythmics
Class Ia
disopyramide
(Rythmodan)
Adult: 400–800 mg/day PO in divided doses
q 6–12 hours; use lower doses with older
people
Paediatric: 6–30 mg/kg per day PO in divided
doses q 6 hours, base dose on age
Treatment of life-threatening ventricular
arrhythmias
