Page 121 - Small Animal Internal Medicine, 6th Edition

CHAPTER 4 Cardiac Arrhythmias and Antiarrhythmic Therapy 93

Phenytoin and increase AV conduction time and refractoriness. The
The only indication for phenytoin as an antiarrhythmic agent antiarrhythmic effect of β-blockers relates to β 1 -receptor
VetBooks.ir is for digoxin-induced ventricular tachyarrhythmias in dogs blockade rather than direct electrophysiologic effects. They
are often used in combination with a class I agent (such
that are not responsive to lidocaine or other agents. Thus it
is now almost never used. Electrophysiologically, it is similar
inotropic effect demands caution when used in animals
to lidocaine, but it also has some slow-calcium channel as procainamide or mexiletine), although their negative
inhibitory and CNS effects that contribute to its effectiveness with myocardial failure. β-receptor blockers are used in
against digitalis-induced arrhythmias. Slow IV infusion (of animals with supraventricular and ventricular tachyar-
10 mg/kg) and oral administration (of 20-50 mg/kg PO q8h) rhythmias (especially those induced by enhanced sympa-
have minimal hemodynamic effects; however, oral bioavail- thetic tone), certain congenital and acquired ventricular
ability is poor. Rapid IV injection can depress myocardial outflow obstructions, hyperthyroid heart disease, HCM,
contractility, exacerbate arrhythmias, and cause vasodilation, and other diseases or toxicities that cause excessive sym-
hypotension, or respiratory arrest related to the propylene pathetic stimulation. A β-blocker, rather than diltiazem,
glycol vehicle. The half-life of phenytoin in the dog is about sometimes is used in conjunction with digoxin to slow the
3 hours. The drug is metabolized in the liver; drugs that ventricular response rate to AF. A β-blocker, such as ateno-
inhibit CYP enzyme activity increases phenytoin’s serum lol or propranolol, is considered the first-line antiarrhyth-
concentration. IV administration of phenytoin has been mic agent in cats for both supraventricular and ventricular
associated with bradycardia, AV block, ventricular tachycar- tachyarrhythmias.
dia, and cardiac arrest. CNS toxicity signs include depres- β-adrenergic receptors have been classified into subtypes.
sion, nystagmus, disorientation, and ataxia. The drug is not β 1 -receptors are located mainly in the myocardium and
used in cats because of its long half-life (>40 hours) and mediate increases in contractility, heart rate, AV conduction
toxicity. velocity, and automaticity in specialized fibers. Extracardiac
β 2 -receptors mediate bronchodilation and vasodilation, as
Other Class I Agents well as renin and insulin release. There also are some β 2 - and
Flecainide and propafenone are class IC agents. Flecainide β 3 -receptors in the heart. “Nonselective” β-blockers inhibit
prolongs the sinus cycle length and AV conduction time and catecholamine binding to both β 1 - and β 2 -adrenergic recep-
refractoriness. It also has a potassium current (delayed recti- tors. Other β-blockers are more selective; they antagonize
fier, I κ ) blocking effect similar to class III agents; however, mainly one or the other receptor subtype (Table 4.3). The
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action potential prolongation is offset by its Na channel first-generation β-blockers (e.g., propranolol) have nonse-
blocking effect, so little change in action potential duration lective β-blocking effects. Second-generation agents (e.g.,
occurs. Because of its effects to prolong refractoriness and atenolol, metoprolol) are relatively β 1 selective. The third-
slow conduction, it can increase risk for proarrhythmia and generation β-blockers affect both β 1 and β 2 receptors but also
sudden death, especially at high doses and in patients with antagonize α 1 receptors and may have other effects. A few
prior myocardial damage. Propafenone increases AV node β-blockers have some degree of intrinsic sympathomimetic
refractory period, slows intraatrial conduction, and reduces activity.
ventricular excitability. It also has weak β- and calcium The clinical antiarrhythmic effect of class II drugs is
channel blocking activity, and a vagolytic effect. Adverse thought to relate to β 1 -receptor blockade rather than to
effects in people include lightheadedness, nausea, vomiting, direct electrophysiologic mechanisms. In normal animals
and proarrhythmia. Higher doses of these agents depress β-receptor blockers have little negative inotropic effect.
automaticity in the sinus node and specialized conducting However, they must be used cautiously in animals with
tissues. Vasodilation, myocardial depression, and severe underlying myocardial disease because increased sympa-
hypotension have occurred after IV injection. Bradycardia, thetic drive may be necessary to maintain cardiac output;
intraventricular conduction disturbances, and consistent marked depression of cardiac contractility, conduction, or
(although transient) hypotension, as well as nausea, vomit- heart rate can result in such cases, and CHF could be pre-
ing, and anorexia, have occurred in dogs. Proarrhythmia is cipitated. β-blockers generally are contraindicated in patients
a serious potential adverse effect of these agents. Flecainide with sinus bradycardia, sick sinus syndrome, high-grade AV
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can be useful against paroxysmal SVT or AF but is not used block, or severe CHF and in animals also receiving a Ca -
for long-term therapy of AF, or in patients with myocardial blocking drug. Nonselective β-blockers could increase
dysfunction, ventricular hypertrophy, valvular disease, or peripheral vascular resistance (because of unopposed
ischemic heart disease. Propafenone has been effective in α-adrenergic effects) and provoke bronchoconstriction.
suppressing various SVTs, including those involving an β-blockers also can mask the early signs of acute hypo-
accessory pathway. glycemia in diabetics (such as tachycardia, blood pressure
changes) and reduce the release of insulin in response to
CLASS II ANTIARRHYTHMIC DRUGS: hyperglycemia. Because the effect of β-blockers depends on
β-ADRENERGIC BLOCKERS the level of sympathetic activation, individual patient
Class II antiarrhythmic drugs act by blocking catecholamine response is quite variable. Therefore initial dosages should
effects. They slow heart rate, reduce myocardial O 2 demand, be low and titrated upward cautiously, as needed.