Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
● Phenytoin may also decrease serum quinidine
concentration.
● Phenytoin should not be added to intravenous fluids
because of lack of solubility and resultant precipitation.
Quinidine
Quinidine is an optical isomer of quinine. It was originally
prepared by Pasteur to treat malaria in 1853. It was
not until 1918 that quinidine was recognized as an effective
agent for treating atrial fibrillation in humans.
Clinical applications
Quinidine has been used most commonly for the longterm
suppression of ventricular premature depolarizations
and ventricular tachyarrhythmias. Chronic oral
therapy of ventricular arrhythmias is most commonly
aimed at preventing sudden death. Because quinidine
does not appear to be very effective at preventing sudden
death in dogs and, in humans, may increase the incidence
of sudden death, use of this drug as a chronic
agent has plummeted in the past 10 years.
Quinidine can also be used acutely to abolish ventricular
arrhythmias and is occasionally effective in the
control of atrial premature depolarizations and paroxysmal
supraventricular tachycardia. However, other
drugs (e.g. digitalis, β-blockers, calcium channel blockers)
are generally more effective in the dog for supraventricular
arrhythmias. Quinidine is ineffective in dogs
with atrial fibrillation secondary to cardiac disease.
However, it can be effective at converting atrial fibrillation
to sinus rhythm in dogs without underlying
cardiac disease (primary atrial fibrillation).
Mechanism of action
Quinidine is a class Ia antiarrhythmic agent that can be
effective against automatic and re-entrant supraventricular
and ventricular tachyarrhythmias in dogs. Its
primary action is to decrease the movement of sodium
through the fast sodium channel during phase 0. This
results in a decrease in the upstroke velocity of the action
potential and a consequent decrease in cardiac electrical
impulse conduction velocity. This effect is enhanced
by increasing extracellular potassium concentration
because of the decreased resting membrane potential.
Quinidine prolongs the refractory period in atrial,
ventricular and Purkinje cells, which can effectively
interrupt re-entrant pathways. It also acts to decrease
the slope of phase 4 and increase the threshold potential
toward 0 in automatic cells. In so doing it suppresses
normal automaticity in Purkinje fibers and suppresses
cardiac excitability. Sinus node automaticity is
unchanged or may even be increased owing to decreased
vagal tone in normal patients (vagolytic effect).
There is a paucity of literature on the effects of quinidine
on abnormal automaticity. Quinidine can suppress
DADs in the Purkinje system but it can also increase the
amplitude of DADs in atrial myocardium. Quinidine is
used experimentally to produce EADs and so is unlikely
to have beneficial effects with rhythms generated by this
mechanism.
Formulations and dose rates
Quinidine is available as quinidine gluconate, quinidine sulfate and
quinidine polygalacturonate. Quinidine sulfate and quinidine polygalacturonate
are available as tablets. Quinidine gluconate comes as a
solution for parenteral use.
DOGS
• Chronic oral dose for treating ventricular tachyarrhythmias: 6–
16 mg/kg q.8 h. Quinidine sulfate is more rapidly absorbed than
quinidine gluconate
• To convert atrial fi brillation to sinus rhythm in primary atrial
fi brillation, doses ranging from 12.5 mg/kg q.6 h to 20 mg/kg
q.2 h can be used. These doses are continued until conversion
of the rhythm or until mild signs of toxicity are present
• Quinidine gluconate may be administered parenterally but rapid
intravenous injections may cause dangerous hypotension.
Lidocaine (lignocaine) and procainamide are preferred over
quinidine for parenteral administration. The parenteral dose is
5–10 mg/kg IM or IV
Pharmacokinetics
Quinidine is about 85% protein bound and has a halflife
of 5–6 h in the dog. A steady-state serum concentration
is achieved approximately 24 h after initiating
therapy but the serum concentration is commonly
within the therapeutic range following the first dose.
Pharmacokinetics have not been studied in cats.
Quinidine is metabolized in the liver to some cardioactive
and some inactive metabolites and is also excreted
by the kidneys. Renal disease and heart failure may
increase the serum concentration. Microsomal enzymeinducing
drugs, such as anticonvulsants, may shorten
the half-life of quinidine. Concomitant administration
of the antacids aluminum hydroxide or magnesium
oxide with quinidine decreases the maximum plasma
quinidine concentration in dogs.
Adverse effects
● Gastrointestinal side effects have been reported to
occur in approximately 25% of dogs administered
quinidine. These appear to be direct effects of the
drug on the gastrointestinal tract.
● Cardiovascular toxicity is frequently reported in
human medicine and these findings have often been
extrapolated to the veterinary literature. Quinidine
toxicity is manifested as QRS and Q-T interval prolongation.
However, clinically significant prolongation
in the Q-T interval or QRS complex duration
does not occur even in dogs that are seizuring due to
toxicity.
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