706
P A R T 8
Drugs acting on the cardiovascular system
C
lass
III
antiarrhythmics
The class III antiarrhythmics include amiodarone
(
Aratac
,
Cordarone X, Cardinorm
) and sotalol (
Cardol
,
Sotacor
).
Therapeutic actions and indications
The class III antiarrhythmics block potassium channels
and slow the outward movement of potassium
during phase 3 of the action potential, prolonging it
(Figure 45.7). All of these drugs are proarrhythmic and
have the potential of inducing arrhythmias. Although
amiodarone has been associated with such serious and
even fatal toxic reactions, in 2005 the American Heart
Association issued new guidelines for Advanced Cardiac
Life Support (ACLS) that named amiodarone the drug
of choice for treating ventricular fibrillation or pulseless
ventricular tachycardia in cardiac arrest situations. See
Table 45.1 for usual indications for each drug.
Pharmacokinetics
Amiodarone is available in an oral or intravenous form.
Sotalol is administered only in oral form. These drugs
are well absorbed after oral administration. Absorption
of sotalol is decreased by the presence of food. This drug
is metabolised in the liver and excreted in urine.
Contraindications and cautions
When these drugs are used to treat life-threatening
arrhythmias for which no other drug has been effective,
there are no contraindications.
Because sotalol is known
to be proarrhythmic
, individuals should be monitored
very closely at the initiation of therapy and periodically
during therapy. Caution should be used with all of these
drugs in the presence of shock, hypotension or respira-
tory depression; with a prolonged QTc interval,
which
could worsen due to the depressive effects on action
potentials
; and with renal or hepatic disease,
which
could alter the biotransformation and excretion of these
drugs.
Adverse effects
The adverse effects associated with these drugs are
related to the changes they cause in action potentials.
Nausea, vomiting and GI distress; weakness and dizzi-
ness; and hypotension, HF and arrhythmia are common.
Amiodarone has been associated with a potentially fatal
liver toxicity, ocular abnormalities and the development
of very serious cardiac arrhythmias.
Clinically important drug–drug interactions
These drugs can cause serious toxic effects if they
are combined with digoxin or quinidine. There is an
increased risk of proarrhythmias if they are combined
with antihistamines, phenothiazines or tricyclic anti
depressants. Sotalol may have a loss of effectiveness if
it is combined with non-steroidal anti-inflammatory
drugs, aspirin or antacids. Other specific drug–drug
interactions have been reported with individual drugs; a
drug reference should always be consulted when adding
a new drug to a regimen containing any of these agents.
Prototype summary: Amiodarone
Indications:
Treatment of life-threatening ventricular
arrhythmias.
Actions:
Acts directly on heart muscle cells to
prolong repolarisation and the refractory period,
increasing the threshold for ventricular fibrillation;
also acts on peripheral smooth muscle to decrease
peripheral resistance.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
2–3 days
3–7 hours
6–8 hours
IV Immediate 20 mins
Infusion
T
1/2
:
10 days; metabolised in the liver and excreted
in urine.
Adverse effects:
Malaise, fatigue, dizziness, HF,
cardiac arrhythmias, cardiac arrest, constipation,
nausea, vomiting, hepatotoxicity, pulmonary
toxicity, corneal microdeposits and vision changes.
■■
Class III antiarrhythmics block potassium channels
and prolong phase 3 of the action potential.
■■
Amiodarone is the drug recommended for use during
life support measures. It is associated with serious to
potentially fatal hepatotoxicity.
C
lass
IV
antiarrhythmics
Class IV antiarrhythmics include two calcium channel
blockers: diltiazem (
Cardizem
) and verapamil (
Anpec
,
Cordilox SR, Isoptin
).
Therapeutic actions and indications
The class IV antiarrhythmics block the movement of
calcium ions across the cell membrane, depressing the
generation of action potentials and delaying phases 1
and 2 of repolarisation, which slows automaticity and
conduction (see Figure 45.7). Both diltiazem and verapa-
mil are used as antihypertensives (see Chapter 43) and to
treat angina (see Chapter 46). Table 45.1 describes usual
indications for each drug.
KEY POINTS
