Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CLASS III ANTIARRHYTHMIC DRUGS
potential duration is caused by blockade of potassium
channels.
Sotalol, when administered intravenously or at high
doses orally, increases the Q-T interval on the ECG in
experimental dogs. As for any β-blocker, the heart rate
is decreased with sotalol administration. It also prolongs
the AV nodal refractory period and the P-R interval
because of its β-blocking effect. Sotalol increases the
atrial and the ventricular fibrillation threshold in experimental
dogs. The effect on atrial refractoriness should
make it a good drug for preventing atrial fibrillation in
dogs, especially those with primary atrial fibrillation
after cardioversion. The effect on the ventricular fibrillation
threshold should make it an effective agent for
preventing sudden death in dogs. Its effects on defibrillation
are less well understood. In one study, sotalol
decreased the success rate for defibrillation, while in
another study, it decreased the energy required for
defibrillation.
The hemodynamic effects of sotalol are mixed.
Because it is a β-blocker, a decrease in myocardial contractility
is expected and has been identified in anesthetized,
experimental dogs with normal hearts and in
experimental dogs after myocardial infarction. However,
in isolated cardiac tissues, sotalol does not have any
negative inotropic effect and may have a modest (20–
40% increase) positive inotropic effect in catecholamine-depleted
experimental cats. This effect may be
caused by the prolongation of the action potential
allowing more time for calcium influx in systole.
In experimental dogs, sotalol has less of a negative
inotropic effect than propranolol. In humans with compromised
myocardial function, sotalol can induce or
exacerbate heart failure but the incidence is much lower
than one might expect. In one study, heart failure was
aggravated by sotalol in only 3% of human patients.
The potential negative inotropic effects of sotalol could
theoretically produce myocardial depression and
produce or aggravate heart failure in small animal
patients. As in human patients, if one uses this drug, the
dose must be carefully titrated and canine or feline
patients with moderate to severe cardiac disease must
be monitored carefully.
Formulations and dose rates
Sotalol hydrochloride is supplied as tablets. Sotalol is marketed as
D,L-sotalol. Both the D-and L-isomers prolong action potential duration,
while the L-isomer is responsible for the β-blocking properties
of the drug.
Doses used in experimental dogs
In one study in experimental dogs, sotalol successfully converted
atrial fl utter to sinus rhythm in 14 of 15 dogs at a dose of 2 mg/kg IV
administered over 15 min. Quinidine only converted nine of the 15
dogs at a dose of 10 mg/kg IV over 15 min. In another study to
examine sotalol’s ability to terminate and to prevent atrial fi brillation,
it was administered intravenously to dogs with induced atrial fi brillation.
At a dose of 2 mg/kg IV, sotalol did not terminate or prevent atrial
fi brillation. At a cumulative dose of 8 mg/kg, however, it terminated
the arrhythmia in seven of eight dogs and prevented its reinduction
in all eight dogs. This effect was due to a prolongation of atrial refractory
period.
A high dose of D-sotalol is required to suppress the formation of
ventricular arrhythmias in experimental dogs. This compound has no
β-blocking activity and one would expect that a lower dose of the
racemic mixture would be effective. In one study of conscious experimental
dogs 3–5 d after myocardial infarction, four doses of 8 mg/kg
D-sotalol administered intravenously successfully prevented the
induction of ventricular tachycardia by programmed electrical stimulation
in six of nine dogs and slowed the rate of the tachycardia in
two of the three remaining dogs.
D-sotalol is also effective in increasing the ventricular fi brillation
threshold in experimental dogs with myocardial infarction. Again, the
dose required to produce this benefi cial effect appears to be quite
high, although the data are confl icting and lower doses were not used
in most studies. In one study that examined conscious dogs, four
doses of 8 mg/kg of D-sotalol PO were administered over 24 h. This
dose prevented ventricular fi brillation secondary to ischemia produced
distal to a previous myocardial infarction. The use of lower doses was
not reported. In another study using conscious dogs subjected to
distal myocardial ischemia and infarction, sotalol was administered
at 2 mg/kg and at 8 mg/kg intravenously. Although the two groups
were not reported separately, it appears that both doses prevented
ventricular fi brillation and sudden death. In the group of dogs given
sotalol, 13 of 20 dogs survived while only one of 15 dogs given a
placebo lived.
Clinical experience with sotalol doses
Boxers with severe ventricular arrhythmias and syncope
without severe myocardial failure often respond favorably to the
administration of sotalol. Syncopal episodes cease and a marked
reduction in ventricular arrhythmias occurs. The dose ranges from
40 mg to 120 mg q.12 h (approximately 1–4 mg/kg q.12 h) PO. This
dose is comparable to the human pediatric dose of 50 mg/m 2 of body
surface area q.12 h PO. The dose is generally titrated, starting at
40 mg q.12 h. If that dose is ineffective the dose is increased to 80 mg
in the morning and 40 mg in the evening, followed by 80 mg
q.12 h.
Sotalol may, in some circumstances, be used cautiously in dogs
with moderate to severe myocardial failure. The authors recommend
that patients with moderate to severe myocardial failure be monitored
very carefully during the initial stages of sotalol administration.
If this cannot be done, sotalol should not be used. In dogs
with myocardial failure, the most common response to a relative
overdose is weakness, presumably secondary to a low cardiac output.
In patients in heart failure, exacerbation of edema can occur. In most
cases, withdrawal of the drug should be the only action required if
evidence of low cardiac output or exacerbation of the edema becomes
apparent. If this does not suffi ce or if the clinical abnormalities are
severe, the administration of a bipyridine compound, calcium or glucagon
may be benefi cial. Administration of a catecholamine, such as
dobutamine or dopamine, will not produce the desired response, since
β-receptors are blocked by sotalol.
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