Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
Adverse effects
● At doses adequate to suppress arrhythmias:
– about 25% of dogs acutely develop anorexia
– about 10–15% develop central nervous signs of
ataxia or head tremor.
● Chronically, these doses produce the intolerable side
effects of:
– corneal dystrophy in 10–15% of dogs
– renal failure in about 25% of dogs within 4
months.
● Consequently, it does not appear that tocainide
should be used in dogs for the suppression of ventricular
arrhythmias and the prevention of sudden
death.
● In humans, tocainide produces little effect on the
electrocardiogram in patients without conduction
system disease. It has been documented to produce
asystole when administered concurrently with a β-
adrenergic blocking agent in human patients with
sinus node dysfunction. It produces no adverse effects
in human patients with pre-existing conduction
abnormalities.
CLASS II ANTIARRHYTHMIC DRUGS
(b-ADRENERGIC BLOCKERS)
Class II antiarrhythmic drugs competitively bind with β-
adrenergic receptors and so are termed β-blockers. All β-
blockers exert their antiarrhythmic effects by inhibiting
the effects of the adrenergic system on the heart. Cardiac
adrenergic stimulation increases the heart rate, increases
the conduction velocity through all regions of the
conduction system and myocardium and decreases the
refractoriness of cardiac tissues. In addition, it enhances
normal automaticity of subsidiary pacemaker tissue.
Three types of β-receptor, termed β 1 -, β 2 - and β 3 -
receptors, are present in the body. The β 1 - receptors are
primarily located within the heart and adipose tissue.
Stimulation of these receptors results in increases in
heart rate, myocardial contractility, atrioventricular
conduction velocity and automaticity of subsidiary
pacemakers.
The β 2 -receptors are primarily located in bronchial
and vascular smooth muscle, where they produce relaxation.
However, β 2 -receptors also occur in the sinus and
AV nodes, where they contribute to the increase in heart
rate and increased conduction velocity. They are also
present in myocardium, where stimulation results in
increased contractility. In addition, they are present in
kidney and pancreas, where they mediate renin and
insulin release.
The β 3 -receptors have only been recently discovered
and appear to depress myocardial contractility. See
Chapter 4 for further detail.
Classes
Numerous β-blockers are marketed for pharmacological
use. They differ in their abilities to block β-receptor
types. Some, in addition to their ability to block β-
receptors, can also stimulate β-receptors mildly. Some
are said to have membrane-stabilizing effects but these
effects occur only at very high doses. Consequently, this
is of no clinical significance. Some β-blockers also
weakly inhibit α-receptors and so have mild vasodilating
properties.
Many β-blockers have been developed to selectively
block β 1 -adrenergic receptors. This is primarily because
bronchospasm develops in humans with asthma who
receive a β 2 -adrenergic blocking drug. Dogs do not
develop asthma so there is no advantage in using a specific
β 1 -blocking drug in this species. However, it is a
reason to use a specific β 1 -blocking drug in cats with
asthma. Drugs that block β 2 -receptors also limit the
ability of patients with diabetes mellitus to respond to
hypoglycemia with glycogenolysis. Consequently, drugs
that block β 2 -receptors should be avoided in diabetic
patients. Drugs that block β 2 -receptors also have the
potential of blocking the peripheral vasodilating
response to β-agonists. As a result, peripheral vascular
resistance may increase.
In veterinary medicine, very few individuals have any
clinical experience with the vast majority of β-blockers.
The three primary drugs in veterinary use today are
propranolol, atenolol and carvedilol (see β blocker
section of this chapter p. 419). The drugs are equipotent
but their pharmacokinetics differ. Esmolol, a β-blocker
with a very short half-life, is also used on occasion as
an intravenous agent for short-term management of
arrhythmias.
Clinical applications
In veterinary medicine, β-blockers are used to treat both
supraventricular and ventricular tachyarrhythmias and
prevent sudden death due to ventricular tachyarrhythmias.
They are also used to treat HCM in cats. They
are occasionally used to treat systemic arterial hypertension
and more recently preclinical and clinical heart
disease. They may be more effective in cats than dogs
for controlling blood pressure. However, amlodipine is
more effective than propranolol for this purpose in cats.
β-Blockers are usually ineffective for treating systemic
hypertension secondary to renal disease in dogs.
As antiarrhythmic drugs, β-blockers are most commonly
used to slow the ventricular rate in patients with
atrial fibrillation, to abolish supraventricular tachycardia
and HCM, to slow the sinus rate in cats with hyperthyroidism,
to prevent sudden death in dogs with severe
subaortic stenosis and to chronically treat ventricular
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