Page 120 - Small Animal Internal Medicine, 6th Edition

92 PART I Cardiovascular System Disorders

depolarizations and tachycardias. It is less effective than propensity to cause vasodilation (by means of nonspecific
quinidine for atrial tachyarrhythmias. Procainamide pro- α-adrenergic receptor blockade), cardiac depression, and
VetBooks.ir longs the effective refractory period and slows accessory hypotension. The oral and IM routes usually do not cause
adverse hemodynamic effects, but close monitoring is war-
pathway conduction in dogs with orthodromic AVRT. Pro-
cainamide should be used only with caution in animals with
mL) usually are achieved in 12 to 24 hours after oral or IM
hypotension. ranted initially. Therapeutic blood concentrations (2.5-5 µg/
Procainamide is well absorbed orally in the dog, with a administration. Slow-release sulfate (83% active drug), glu-
half-life of 2.5 to 4 hours; sustained-release procainamide’s conate (62% active drug), and polygalacturonate (80% active
half-life was 3 to 6 hours. Unfortunately, oral procainamide drug) salts of quinidine prolong the drug’s absorption and
is no longer available in the United States, but it may be elimination. The sulfate salt is more rapidly absorbed than
elsewhere. The drug undergoes hepatic metabolism and the gluconate; peak effect is usually achieved 1 to 2 hours
renal excretion in proportion to the creatinine clearance. after oral administration.
Procainamide can be given IM without marked hemody- Marked QT prolongation, right bundle branch block, or
namic effect, but rapid IV injection can cause hypotension QRS widening by more than 25% of pretreatment value sug-
and cardiac depression, although to a much lesser degree gests quinidine toxicity; various conduction blocks and ven-
than IV quinidine. Administration by CRI can be used if the tricular tachyarrhythmias are other manifestations. The QT
arrhythmia responds to an IV bolus; a steady state is reached prolongation implies increased temporal dispersion of myo-
in 12 to 22 hours. Therapeutic plasma concentration range is cardial refractoriness; this predisposes to torsades de pointes
thought to be 4 to 10 µg/mL. (see p. 41) and VF. Transient episodes of these serious
The toxic effects of procainamide are similar to those of arrhythmias are thought to underlie syncopal attacks in
quinidine (see later) but usually are milder. GI upset and people taking quinidine. Lethargy, weakness, and CHF can
prolongation of the QRS or QT intervals can occur. Procain- result from the negative inotropic and vasodilatory effects of
amide can enhance the ventricular response rate to AF (that the drug and subsequent hypotension. Cardiotoxicity and
is, the heart rate) if used without diltiazem, digoxin, or a hypotension can be partially reversed by sodium bicarbonate
+
β-blocker. More serious toxic effects include hypotension, (1 mEq/kg IV), which temporarily decreases serum K con-
depressed AV conduction (sometimes causing 2° or 3° AV centration, enhances quinidine’s binding to albumin, and
block), and proarrhythmia. The latter can cause syncope or reduces its cardiac electrophysiologic effects. GI signs (e.g.,
VF. Hypotension should respond to IV fluid, and cate- nausea, vomiting, diarrhea) are common with orally admin-
cholamine or calcium-containing solutions. istered quinidine. Thrombocytopenia (reversible after quini-
dine discontinuation) can occur in people and possibly in
Quinidine dogs and cats.
Quinidine, the prototype IA drug, has been used to treat
ventricular and some supraventricular tachyarrhythmias. In Mexiletine
large dogs with recent-onset AF and normal ventricular Mexiletine HCl is similar to lidocaine in its electrophysio-
function (lone AF), quinidine might cause conversion to logic, hemodynamic, toxic, and antiarrhythmic properties. It
sinus rhythm. This drug must be used cautiously in animals can be effective in suppressing ventricular tachyarrhythmias
with heart failure or hyperkalemia. The characteristic elec- in dogs. The combination of sotalol or a traditional β-blocker
trophysiologic effects of quinidine are depression of automa- with mexiletine may be more efficacious and associated with
ticity and conduction velocity, and prolongation of the fewer adverse effects than mexiletine alone (by allowing
effective refractory period. Corresponding dose-dependent lower dosage). The drug is easily absorbed when adminis-
ECG changes include PR, QRS, and QT prolongation. Quini- tered orally, but delayed gastric emptying, narcotics, and
dine also has indirect vagolytic effects. At low doses, these magnesium-aluminum hydroxide antacids reportedly slow
vagolytic effects can increase the sinus rate or the ventricular its absorption in people. Mexiletine undergoes hepatic
response rate to AF by antagonizing the drug’s direct effects. metabolism (influenced by liver blood flow) and some renal
As with other class I agents, hypokalemia reduces quinidine’s excretion (which is slower if the urine is markedly alkaline).
antiarrhythmic effectiveness. Cimetidine can have variable effects on mexiletine plasma
The drug is well absorbed orally but is rarely used now for concentration; however, omeprazole and famoditine are
chronic oral therapy because of its frequent adverse effects. unlikely to affect its metabolism. Moderate to severe liver
Quinidine is metabolized extensively by the liver; the half- disease can impair mexiletine’s metabolism. Hepatic micro-
life is about 6 hours in dogs and 2 hours in cats. Quinidine somal enzyme inducers can accelerate its clearance. The half-
is highly protein-bound; severe hypoalbuminemia can pre- life in dogs is from 4.5 to 7 hours (depending to some degree
dispose to toxicity. Cimetidine, amiodarone, and antacids on the urine pH). Approximately 70% of the drug is protein-
can also predispose to toxicity by slowing the drug’s elimi- bound. The therapeutic serum concentration is thought to
nation. Quinidine can precipitate digoxin toxicity (when range from 0.5 to 2 µg/mL (as in people). The effects of
used concurrently) by displacing digoxin from skeletal mexiletine in cats are not well known. Adverse effects have
muscle binding sites and reducing its renal clearance. IV included vomiting, anorexia, tremor, disorientation, sinus
administration is not recommended because of quinidine’s bradycardia, and thrombocytopenia.