Page 123 - Small Animal Internal Medicine, 6th Edition

CHAPTER 4 Cardiac Arrhythmias and Antiarrhythmic Therapy 95

improving cardiac function, and increasing survival time. Sotalol may worsen heart failure in animals with DCM.
These include the third-generation β-blocker, carvedilol; the However, sotalol is thought to have less negative inotro-
VetBooks.ir second-generation agent, metoprolol; and some others. pic effect than propranolol. Other adverse effects of sotalol
have included hypotension, depression, nausea, vomiting,
Despite theoretical and some experimental benefit, β-blocker
therapy has not been shown to delay CHF or increase sur-
reports of aggression that resolved after sotalol was discon-
vival in dogs and cats. diarrhea, and bradycardia. There are sporadic anecdotal
Carvedilol blocks β 1 -, β 2 -, and α 1 -adrenergic receptors; tinued. Sotalol may induce or worsen neurogenic brady-
has antioxidant effects; reduces endothelin release; has some cardia in some Boxers with ventricular tachycardia. Like
++
Ca -blocking effect; and is also thought to promote vasodi- other β-blockers, sotalol therapy should not be discontin-
lation by affecting either NO or prostaglandin mechanisms. ued abruptly.
Oral doses in dogs produce a wide range of peak plasma
concentrations. Carvedilol is eliminated mainly through Amiodarone
hepatic metabolism; the terminal half-life in dogs is less Amiodarone HCl is thought to produce its antiarrhythmic
than 1 to 2 hours (i.e., shorter than in people), and the drug effects by prolonging the action potential duration and effec-
is highly protein-bound. Its β-blocking effect lasts for 12 tive refractory period in both atrial and ventricular tissues.
hours, and some residual effect persists for up to 24 hours, Although considered a class III agent, it shares properties
consistent with active metabolite(s). In healthy dogs, low with all three other antiarrhythmic drug classes. Amioda-
doses of carvedilol cause minimal hemodynamic effect, but, rone is an iodinated compound that also has noncompetitive
++
as with all β-blockers, animals in heart failure may not toler- α 1 - and β-blocking effects, as well as Ca channel-blocking
ate even small doses. effects. The β-blocking effects occur soon after administra-
Metoprolol tartrate is another β 1 -selective agent. It is well tion, but maximal class III effects (and prolongation of action
absorbed orally, but bioavailability is reduced by a large first- potential duration and QT interval) are not achieved for
++
pass effect. There is minimal protein-binding. The drug is weeks with chronic administration. Its Ca -blocking effects
metabolized in the liver and excreted in the urine. Half-life may inhibit triggered arrhythmias by reducing afterdepo-
is 1.6 hours in dogs and 1.3 hours in cats. larizations. Therapeutic doses slow the sinus rate, decrease
AV conduction velocity, and minimally depress myocardial
CLASS III ANTIARRHYTHMIC DRUGS contractility and blood pressure. Indications for amiodarone
Common features of class III drugs include prolongation of include refractory atrial and ventricular tachyarrhythmias,
the cardiac action potential and effective refractory period especially reentrant arrhythmias using an accessory pathway.
without a decrease in conduction velocity. Their effects The IV form has been used for ventricular tachycardia and
are mediated by inhibition of potassium channels respon- AF. However, use of the standard (older) IV formulation
sible for repolarization (delayed rectifier current). These often precipitates hypotension and anaphylactoid reactions,
agents are useful against ventricular arrhythmias, especially related to the solvents (polysorbate 80 and benzyl alcohol)
those caused by reentry. Class III drugs have antifibrilla- used to keep the drug in solution. Therapy for acute hyper-
tory effects as well. They share some characteristics of other sensitivity reaction has included discontinuing the drug,
antiarrhythmic drug classes in addition to their class III and using diphenhydramine (e.g., 1 mg/kg IV), a cortico-
effects. steroid (e.g., prednisolone 1-2 mg/kg IV), IV fluids and
other supportive care as needed. Although antihistamine
Sotalol pretreatment, conservative dosing, and slow injection over
Sotalol HCl is a nonselective β-blocker that has class III 10 to 20 minutes have been helpful in some cases, use of
effects at higher doses. Its oral bioavailability is high, although standard amiodarone IV is NOT currently recommended.
absorption is reduced when given with food. Sotalol’s half- A newer amiodarone formulation (Nexterone) without poly-
life is about 5 hours in dogs. It is eliminated unchanged by sorbate 80 and benzyl alcohol is available and thought to
the kidneys, and renal dysfunction prolongs elimination. be safer.
Sotalol’s β-blocking effect outlasts its plasma half-life. The The pharmacokinetics of amiodarone are complex.
drug has minimal hemodynamic effects, although it can Chronic oral use is associated with a prolonged time to
cause slowed sinus rate, first-degree AV block, and hypoten- steady state (of several weeks), concentration of drug in
sion. Proarrhythmia can occur (as with all antiarrhythmic myocardial and other tissues, and accumulation of an active
agents), including torsades de pointes (a type of multiform metabolite (desethylamiodarone). Therapeutic serum con-
ventricular tachycardia). Sotalol’s class III effects occur at centration range is thought to be 1 to 2.5 µg/mL. Amioda-
higher doses in dogs than in people. Doses used clinically in rone has less of a proarrhythmic effect than other agents and
dogs may be producing primarily β-blocking effects. A high could reduce the risk of sudden death because of its uniform
incidence of proarrhythmia (especially torsades de pointes), prolongation of repolarization throughout the ventricles, as
which is of concern in people taking sotalol, has not been well as suppression of Purkinje fiber automaticity. In normal
reported clinically in dogs. Experimentally, in dogs with dogs IV amiodarone does not adversely affect contractility
hypokalemia, co-administration of mexiletine reduced the at cumulative doses less than 12.5 to 15 mg/kg. However, the
proarrhythmic potential. potential exists for more profound cardiac depression and