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P A R T 8
Drugs acting on the cardiovascular system
breastfeeding. Another method of feeding the baby
should be chosen.
Adverse effects
The adverse effects of the class I antiarrhythmics are
associated with their membrane-stabilising effects and
effects on action potentials. Central nervous system
(CNS) effects can include dizziness, drowsiness, fatigue,
twitching, mouth numbness, slurred speech, vision
changes and tremors that can progress to convulsions.
GI symptoms include changes in taste, nausea and
vomiting. Cardiovascular effects include the proarrhyth-
mic effects that lead to the development of arrhythmias
(including heart blocks), hypotension, vasodilation and
the potential for cardiac arrest. Respiratory depression
progressing to respiratory arrest can also occur. Other
adverse effects include rash, hypersensitivity reactions,
loss of hair and potential bone marrow depression.
Flecainide is a class Ic drug that was found to
increase the risk of death in the CAST study.
Clinically important drug–drug interactions
Several drug–drug interactions have been reported
with these agents, so the possibility of an interaction
should always be considered before any drug is added
to a regimen containing an antiarrhythmic. The risk for
arrhythmia increases if these agents are combined with
other drugs that are known to cause arrhythmias, such
as digoxin and the beta-blockers.
Because quinidine competes for renal transport sites
with digoxin, the combination of these two drugs can
lead to increased digoxin levels and digoxin toxicity.
If these drugs are used in combination, the person’s
plasma digoxin level should be monitored and appro-
priate dose adjustment made. Serum levels and toxicity
of the class Ia antiarrhythmics increase if they are
combined with cimetidine; extreme caution should be
used if people are receiving this combination.
The risk of bleeding effects of these drugs increases
if they are combined with oral anticoagulants; people
receiving this combination should be monitored closely
and have their anticoagulant dose reduced as needed.
Check individual drug monographs for specific inter
actions associated with each drug.
phase 4
phase 0
phase
1
Sodium level equalises
Effects of Class Ic
antiarrhythmics:
markedly slow phase 0
Effects of Class Ia
antiarrhythmics:
block sodium channels
Effects of Class Ib
antiarrhythmics:
slower phase 0 of
action potential,
rapid repolarisation
Sodium
enters
cell
Calcium enters cell
Sodium and potassium
leave cell
Resting membrane
potential
phase
2
phase
3
0
–20
+20
–80
–100
FIGURE 45.6
The cardiac action potentials, showing the effects of
class Ia, Ib and Ic antiarrhythmics.
Prototype summary: Lignocaine
Indications:
Management of acute ventricular
arrhythmias during cardiac surgery or MI.
Actions:
Decreases depolarisation, decreasing
automaticity of the ventricular cells; increases
ventricular fibrillation threshold.
Pharmacokinetics:
Route Onset
Peak
Duration
IM 5–10 mins 5–15 mins
2 hours
IV Immediate Immediate
10–20 mins
T
1/2
:
10 minutes, then 1.5 to 3 hours; metabolised in
the liver and excreted in urine.
Adverse effects:
Dizziness, light-headedness, fatigue,
arrhythmias, cardiac arrest, nausea, vomiting,
anaphylactoid reactions, hypotension, vasodilation.
■■
Antiarrhythmics are drugs that alter the action
potential of the heart cells and interrupt arrhythmias.
The CAST study found that the long-term treatment
of arrhythmias may actually cause cardiac death, so
these drugs are now indicated only for the short-term
treatment of potentially life-threatening ventricular
arrhythmias.
■■
Class I antiarrhythmics block sodium channels,
depress phase 0 of the action potential and generally
prolong the action potential, leading to a slowing of
conduction and automaticity.
■■
Class I antiarrhythmics are membrane stabilisers; the
adverse effects seen are related to the stabilisation of
cell membranes, including those in the CNS and the
GI tract.
C
lass
II
antiarrhythmics
The class II antiarrhythmics are beta-adrenergic blockers
that block beta-receptors, causing a depression of phase 4
of the action potential (Figure 45.7). Several beta-
adrenergic blockers, such as esmolol (
Brevibloc
) and pro-
pranolol (
Deralin
,
Inderal
), are used as antiarrhythmics.
Therapeutic actions and indications
The class II antiarrhythmics competitively block beta-
receptor sites in the heart and kidneys. The result is a
KEY POINTS
