Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CLASS IV ANTIARRHYTHMIC DRUGS
relaxation of systemic arterioles, resulting in a decrease
in peripheral vascular resistance.
The ability of calcium channel blockers to affect these
sites varies tremendously. Verapamil binds equally well
to cardiac and vascular smooth muscle sites, producing
profound electrophysiological changes, depression in
myocardial contractility and vasodilation. The dihydropyridines
have very little effect on cardiac calcium channels
but have profound effects on vascular smooth
muscle. Diltiazem is somewhere between these two
extremes, with profound electrophysiological changes,
an intermediate effect on cardiac function and a mild
effect on vascular smooth muscle. In conscious dogs,
nifedipine and verapamil increase the heart rate. This is
presumably due to reflex increase in sympathetic tone
caused by vasodilation. Diltiazem has little effect.
Myocardial contractility is increased reflexly by nifedipine,
decreased directly by verapamil and not changed
by diltiazem in the normal cardiovascular system. When
the autonomic nervous system is blocked with propranolol
and atropine, all three drugs decrease contractility
and heart rate. The variable effects are due to slight
differences in L-type channel subunit structure between
different sites that result in marked differences in channel
pharmacology.
Calcium channel-blocking agents that affect myocardial
channels block the slow inward calcium current
during phase 2 of the cardiac cell action potential. This
results in a decrease in myocardial contractility. This
may be beneficial in certain circumstances, such as in
feline patients with HCM and dynamic subaortic stenosis.
In human patients with normal myocardial function,
the negative inotropic effect is generally offset by reflex
increase in sympathetic tone. However, in human
patients with myocardial dysfunction the negative inotropic
and negative chronotropic effects of a drug such
as verapamil cannot be offset by a sympathetic nervous
system that is already maximally stimulated. The resultant
decrease in contractility and heart rate following
calcium channel blockade can be clinically significant.
Slow calcium channel activity is responsible for depolarization
in the sinus and AV nodes. Calcium channel
blockers prolong AV conduction, slow the ventricular
response to supraventricular tachyarrhythmias such as
atrial fibrillation and abolish supraventricular arrhythmias
when caused by re-entry through the AV node. The
depolarizing currents of the sinus node and the atrioventricular
junction are, at least in part, carried by
calcium. Calcium channel blockers have the potential to
decrease sinus rate in patients with tachycardia but
reflex increases in sympathetic tone due to decreased
vascular resistance commonly overcome this effect. This
effect can be lethal in patients that are dependent on
escape rhythms to maintain heart rate (e.g. canine
patients with third-degree AV block).
Clinical applications
Calcium channel blockers are highly effective for treating
paroxysmal supraventricular tachycardia. Diltiazem
is particularly useful for slowing ventricular rate in
patients with atrial fibrillation. Experimentally, calcium
channel blockers are effective for suppressing accelerated
idioventricular rhythms in dogs following shockinduced
myocardial injury and myocardial infarction.
They have also been effective at suppressing digitalisinduced
ventricular arrhythmias in conscious experimental
dogs. To our knowledge, however, no reports
exist in the veterinary literature concerning the use of
calcium channel blockers to suppress ventricular
arrhythmias in canine patients.
The dihydropyridines are not useful for treating
arrhythmias. Instead, they are used to treat heart failure
secondary to mitral regurgitation as well as systemic
hypertension in dogs and cats.
Verapamil
Clinical applications
Verapamil is indicated for the acute termination of
supraventricular tachycardia in the dog. Although other
indications may exist, the authors have not used this
drug to treat any other arrhythmia and there are no
reports of its use for other indications in the veterinary
literature. The experimental literature suggests that
verapamil may be effective for terminating accelerated
idioventricular rhythm in intensive care patients and for
treating digitalis-induced ventricular tachyarrhythmias.
Mechanism of action
The ability of verapamil to terminate supraventricular
tachycardia is probably due to its effects on the AV
junctional tissue. Most probably, most supraventricular
tachycardias that respond to verapamil use the AV junction
as part or all of a re-entrant loop. Verapamil has
the ability to slow conduction through the AV junction
and to prolong the refractory period of this tissue at
clinically relevant doses and plasma concentrations.
Prolongation of conduction and refractoriness are classic
means of terminating re-entrant arrhythmias.
Formulations and dose rates
Verapamil hydrochloride is supplied for intravenous use in ampoules
and tablets for oral administration.
For the acute termination of supraventricular tachycardia, the intravenous
dose ranges from 0.05 to 0.15 mg/kg. The initial dose of
0.05 mg/kg should be administered over 1–2 min while the ECG is
monitored. If this initial dose is not effective, the same dose should
be repeated 5–10 min later. If the arrhythmia still is not terminated,
a last dose of 0.05 mg/kg (total dose = 0.15 mg/kg) should be
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