Page 124 - Small Animal Internal Medicine, 6th Edition

96 PART I Cardiovascular System Disorders

hypotension in dogs with myocardial disease. Amiodarone myocardial failure (for agents with pronounced negative ino-
use is not described in cats. tropic effect), and digoxin toxicity. They usually are not pre-
VetBooks.ir effects. Hepatopathy, GI abnormalities, and a positive scribed in patients receiving a β-blocker because of additive
Amiodarone is associated with many potential adverse
negative effects on contractility, AV conduction, and heart
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Coombs test have been reported in Dobermans receiving
is treated with supportive care, including atropine for bra-
amiodarone. Other long-term adverse effects can include rate. An overdose or exaggerated response to a Ca -blocker
depressed appetite, GI upset, pneumonitis leading to pulmo- dycardia or AV block, dopamine or dobutamine (see Box
nary fibrosis, thyroid dysfunction, thrombocytopenia, and 3.1) and furosemide for heart failure, and dopamine or IV
neutropenia. Hypersensitivity reactions (with acute ery- calcium salts for hypotension.
thema, angioedema, pruritus, agitation), hypotension, or
tremors have occurred in dogs, especially with IV adminis- Diltiazem
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tration (of the older formulation). Other adverse effects Diltiazem HCl is a benzothiazepine Ca channel blocker. It
observed in people have included corneal microdeposits, slows AV conduction, causes potent coronary and mild
photosensitivity, bluish skin discoloration, and peripheral peripheral vasodilation, and has a lesser negative inotropic
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neuropathy. Amiodarone can increase the serum concentra- effect than the prototypical Ca entry blocker, verapamil.
tion of digoxin, diltiazem, and possibly procainamide and Diltiazem is often combined with digoxin to further slow the
quinidine. ventricular response rate to AF in dogs with heart failure. It
is indicated for other supraventricular tachyarrhythmias as
Other Class III Agents well. Diltiazem has been used in cats with HCM, based on
Ibutilide fumarate is somewhat effective for converting its potential to decrease heart rate, contractility, and myocar-
recent-onset AF in people, but there is little veterinary dial oxygen demand and to enhance myocardial relaxation
experience with this drug. In experimental dog studies, and perfusion. However, diltiazem has not been shown to
it suppressed sinus and AV node conduction, increased improve clinical outcome.
refractoriness, and prolonged the QT interval; it was only Peak effects are seen within 2 hours of oral dosing; effects
moderately effective in suppressing AF and has caused tor- last at least 6 hours in dogs. Extensive first-pass effect limits
sades de pointes. Dofetilide is another drug that selectively bioavailability, especially in dogs. The half-life of diltiazem
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blocks the rapid component of the repolarizing K current. in the dog is just over 2 hours, but chronic dosing prolongs
It too is used in people for converting AF and to maintain it because of enterohepatic circulation. In cats, the half-life
sinus rhythm, but it may be more effective in preventing is about 2 to 3 hours; plasma concentrations peak within 30
rather than terminating AF. Experimentally in dogs it pro- to 90 minutes and effects last for 8 hours, although much
longs the QT interval and can induce torsades de pointes, variability in pharmacokinetics exists among individual cats.
although it does not exacerbate left ventricular dysfunc- The therapeutic range is 50 to 300 ng/mL. Diltiazem is
tion. Dofetilide is metabolized in the liver and has both metabolized in the liver; active metabolites exist. Drugs that
hepatic and renal clearance; the half-life is about 4.5 hours inhibit hepatic CYP enzyme systems decrease the metabo-
in dogs. lism of diltiazem. Propranolol and diltiazem decrease each
other’s clearance when used simultaneously. Diltiazem ER is
a sustained-release preparation; the 240 mg capsules contain
CLASS IV ANTIARRHYTHMIC DRUGS: four tablets of 60 mg each. Doses of 30 to 60 mg q24h pro-
CALCIUM ENTRY BLOCKERS duced serum concentrations >200 ng/mL for 24 hours in
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The Ca entry blockers are a diverse group of drugs that cats, although some cats on the lower dose reached <50 ng/
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have the common property of decreasing cellular Ca influx mL by 24 hours. The 60-mg dose (~9-15 mg/kg) caused leth-
by blocking transmembrane L-type calcium channels. As a argy, GI signs, and weight loss in about one third of cats on
group, these drugs can cause coronary and systemic vasodi- chronic therapy. Another sustained-release preparation
lation, enhance myocardial relaxation, and reduce cardiac (Cardizem-CD capsules) at 10 mg/kg daily in cats produces
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contractility. The dihydropyridine group of Ca -blockers plasma concentrations that peak in 6 hours and remain in
(such as amlodipine) primarily have vasodilating effects and the therapeutic range for 24 hours. A dose of 45 mg per cat
do not appreciably alter cardiac conduction or contractility. is approximately equal to 105 mg of Cardizem-CD (or the
The nondihydropyridine group (including diltiazem) slows amount that fits into the small end of a No. 4 gelatin capsule;
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conduction in tissues dependent on the slow inward Ca a 300-mg capsule provides about 6.5 doses); this is given
current, such as the sinus and AV nodes, thereby exerting once daily.
some antiarrhythmic effects. Adverse effects of diltiazem are uncommon at therapeutic
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Possible adverse effects of Ca -blockers include reduced doses, although anorexia, nausea, and bradycardia may
contractility, hypotension, depression, anorexia, lethargy, occur. Rarely, other GI, cardiac, and neurologic adverse
bradycardia, and AV block. Low initial doses are used effects develop. High liver enzyme activities and anorexia
and increased as needed to effect or to maximal recom- occur sporadically in cats. Some cats have become aggressive
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mended dose. Contraindications to Ca channel blocker use or shown other personality change when treated with
include sinus bradycardia, AV block, sick sinus syndrome, diltiazem.