Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
than drugs that specifically block β 1 -receptors. This is
probably because β 2 -receptors are also present in the
sinus node and help modulate the sinus rate.
Formulations and dose rates
Propranolol hydrochloride is available as tablets for oral administration
and ampoules for intravenous administration.
The dose of propranolol depends on the situation for which it is
used. In dogs with atrial fi brillation due to severe underlying cardiac
disease, the oral dose is 0.1–0.5 mg/kg q.8 h. At this dose range, the
negative inotropic effects of propranolol appear to be negligible. We
have never witnessed exacerbation of heart failure at this dose range
in dogs with dilated cardiomyopathy or severe mitral regurgitation,
even when the patient was not being administered a concomitant
positive inotropic agent, like digoxin.
In canine patients with supraventricular or ventricular tachyarrhythmias
and normal myocardial function, doses as high as 2 mg/kg
q.8 h are well tolerated and often required. Doses in this range are
contraindicated in patients with severe myocardial failure. Duration of
drug effect is longer than the drug’s half-life because of active propranolol
metabolites and receptor binding of the drug. Consequently,
administering the drug q.8 h appears to be effective. The feline oral
dose is 2.5–10 mg q.8 h for control of tachyarrhythmias.
The intravenous dose in dogs is administered as intermittent
boluses to effect. The initial IV dose is 0.02 mg/kg and the total dose
should not exceed 0.1 mg/kg. Intravenous doses of propranolol must
be administered cautiously to heart failure patients because a
decrease in contractility may acutely worsen hemodynamics. The
therapeutic endpoint is abolition or improvement of a tachyarrhythmia,
slowing of the sinus rate or slowing of the ventricular response
to atrial fi brillation.
Pharmacokinetics
Propranolol is lipid soluble and so is almost completely
absorbed by the small intestine. It is largely metabolized
by the liver. Oral propranolol undergoes a variable but
extensive first-pass hepatic metabolism. As a result, its
bioavailability for the first dose ranges from only 2%
to 17% for oral administration in the dog. Serum halflife
after the first dose is about 1.5 h in the dog. Chronic
oral dosing increases half-life to about 2 h and results
in serum concentrations 1.25–10 times greater than
after initial doses due to an increase in bioavailability.
This increase is probably due to saturation of first-pass
metabolism.
Adverse effects
● Patients with myocardial failure or heart failure due
to severe volume overload may have their heart
failure exacerbated by propranolol, especially if it is
administered intravenously. These patients usually
receive propranolol for control of heart rate and only
low oral doses are generally needed. If acute heart
failure is precipitated it cannot be reversed by catecholamines,
so calcium, glucagon or digitalis must
be used.
● Propranolol should not be administered to patients
with conduction disturbances or abnormal inherent
pacemaker function. Propranolol will exacerbate
sinus node dysfunction in patients with sick sinus
syndrome. It will also exacerbate AV nodal dysfunction
in patients with first- and second-degree AV
block, potentially creating third-degree AV block. In
patients with third-degree AV block, it will decrease
the rate of the subsidiary pacemaker, a potentially
lethal effect.
● Propranolol should not be used in patients with
asthma or chronic lower airway disease, as increases
in lower airway resistance may occur with
β-blockade.
● Propranolol should also be used with caution in
diabetic patients receiving insulin because propranolol
reduces sympathetic compensation for
hypoglycemia.
● Acute propranolol withdrawal may exacerbate the
original problem for which the drug was being
administered, so gradual withdrawal should be performed.
As an example, the authors have witnessed
sudden death in one boxer dog with ventricular
arrhythmia following the acute cessation of propranolol
administration.
● β-Blockers should not be administered to patients
with hyperkalemia because the β-blockade reduces
the potassium flux from intravascular to extravascular
spaces.
Known drug interactions
Digitalis plus propranolol can cause varying degrees of
AV block.
Special considerations
The intravenous preparation of the drug rapidly decomposes
in alkaline solutions.
Atenolol
Clinical applications
Atenolol has clinical indications in both dogs and cats.
In dogs, it is most commonly used in conjunction with
digoxin to slow the heart rate in patients with atrial
fibrillation. It is also used in dogs to treat supraventricular
tachycardia and ventricular tachyarrhythmias and
in an attempt to prevent sudden death in dogs with
severe subaortic stenosis. Its most common indication
in cats is to decrease systolic anterior motion of the
mitral valve in feline HCM and to treat ventricular
tachyarrhythmias.
Mechanism of action
Atenolol is a specific β 1 -adrenergic blocking drug. It
has the same potency as propranolol but different
pharmacokinetics.
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