Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CLASS I ANTIARRHYTHMIC DRUGS
● There is one report in the literature of a case of
aplastic anemia in a dog treated with quinidine.
● The most important clinical problem is exacerbation
of heart failure after quinidine administration. Presumably
this is due to its negative inotropic effects.
In general, quinidine use should be avoided in dogs
with severe myocardial failure or in dogs that have,
or have had, heart failure.
● Quinidine should not be used in cats.
Known drug interactions
Quinidine displaces digoxin from binding sites throughout
the body and reduces digoxin renal clearance,
resulting in a higher serum digoxin concentration. This
is an important drug interaction and can lead to clinical
signs of digitalis intoxication. Most of the digitalis toxicity
in this situation is due to central nervous system
stimulation (e.g. vomiting due to stimulation of the
chemoreceptor trigger zone), since brain concentration
of digoxin increases by 50% when quinidine is administered
while digoxin concentration decreases in all
other tissues, including myocardium.
Procainamide
Clinical applications
Procainamide is effective against ventricular tachyarrhythmias
and may be effective against some supraventricular
tachyarrhythmias in dogs. The authors have no
experience using this drug in cats.
Although it is often effective at decreasing the frequency
and rate of ventricular tachyarrhythmias, procainamide
does not appear to be very effective at
preventing sudden death in patients with severe underlying
cardiac disease. It may have proarrhythmic effects in
certain patients. Consequently, we do not recommend its
use in Doberman pinschers and boxers with cardiomyopathy
or dogs with subaortic stenosis that are prone to
sudden death due to ventricular tachyarrhythmias.
Procainamide is more rationally used in dogs in the
intensive care unit with malignant ventricular tachycardia
that is unresponsive to lidocaine administration or
in anesthetized dogs that have a serious ventricular
tachyarrhythmia that is unresponsive to lidocaine.
Procainamide can also be used to treat a variety of
supraventricular arrhythmias, including atrial fibrillation
and supraventricular tachycardia due to pre-excitation
syndrome. However, it is almost never the drug of
choice for these arrhythmias.
Mechanism of action
Procainamide is a class Ia antiarrhythmic agent with
properties very similar to those of quinidine. Procainamide
decreases the upstroke velocity of phase 0 depolarization
in normal action potentials and in action
potentials produced by abnormal automaticity. This
slows conduction in these tissues.
Re-entrant tachyarrhythmias may be terminated by
procainamide either slowing conduction or producing a
bidirectional block in the abnormal segment of the reentrant
pathway. This effect is enhanced as extracellular
potassium concentration is increased. Therefore procainamide
may be more effective in a patient with hypokalemia
if the serum potassium concentration is normalized.
Procainamide shifts the threshold potential to more
positive values. This reduces the excitability of cardiac
tissue. It also increases the duration of repolarization and
the effective refractory period. The increase in effective
refractory period is greater than the increase in action
potential duration. Theoretically, this function should
increase fibrillation threshold and make procainamide an
effective drug for preventing sudden death due to ventricular
fibrillation. However, clinically this does not
appear to be the case in human or veterinary medicine.
Procainamide can suppress digitalis-induced DADs.
This should theoretically make it effective for treating
digitalis intoxication-induced tachyarrhythmias.
Although it does suppress these arrhythmias in dogs, a
very high serum concentration is required. Procainamide
was not effective against DADs produced by mechanisms
other than digitalis intoxication in one in vitro
study. The drug does not appear to suppress automatic
atrial arrhythmias. Procainamide has vagolytic properties
but these are less than those observed with quinidine
and are rarely clinically significant.
Formulations and dose rates
Procainamide hydrochloride is available for oral administration in
tablets or capsules and for parenteral administration. A sustainedrelease
oral preparation is available.
Clinically, a dose of 20–30 mg/kg q.6 h PO for procainamide hydrochloride
and q.8 h for the sustained-release preparation is generally
used. We rarely observe any clinically signifi cant toxicity at these
doses and can usually document effi cacy. There is a report of a young
adult male Labrador retriever that required a dose of procainamide in
the 30–40 mg/kg q.8 h PO range to control an arrhythmia associated
with pre-excitation. No untoward effects were reported in this dog.
Consequently, higher doses can be tried if the recommended dose is
not effective.
When administered intravenously, intermittent boluses of 2–4 mg/
kg should be injected slowly (over 2 min) up to a total dose of 12–
20 mg/kg until the arrhythmia is controlled. This can be followed by
a CRI of 10–40 µg/kg/min.
The sustained-release preparation has the same half-life as procainamide
but has a longer time to peak concentration (longer absorption
half-life). This enables 8-hourly administration. However, the
peak serum concentration achieved with the sustained-release preparation
is lower than the regular preparation when given at the same
dose. Consequently, it has been recommended that the dose of the
sustained-release preparation be higher.
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