Page 99 - Small Animal Internal Medicine, 6th Edition

CHAPTER 3 Management of Heart Failure 71

OTHER VASODILATORS Hypotension is the most common adverse effect of
Vasodilators can affect arterioles, venous capacitance vessels, hydralazine therapy. GI upset also can occur, which may
VetBooks.ir or both (“balanced” vasodilators). Arteriolar dilators relax require drug discontinuation. High dosages have been asso-
ciated with a lupus-like syndrome in people, although this
arteriolar smooth muscle and thereby decrease systemic
vascular resistance and LV afterload. In patients with MR,
arteriolar dilators decrease the systolic pressure gradient has not been reported in animals.
across the mitral valve, reduce regurgitant flow, and enhance Amlodipine
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forward flow into the aorta. Reduced regurgitant flow can This dihydropyridine L-type Ca channel blocker causes
diminish LA pressure, pulmonary congestion, and possi- peripheral vasodilation as its major action. Amlodipine has
bly LA size. Arteriolar vasodilators are used in advanced little effect on AV conduction. Besides being used to treat
heart failure from MR and sometimes DCM, as an adjunct hypertension in cats, and sometimes in dogs (see Chapter
to ACEI and other therapy, to provide additional afterload 11), it is an adjunctive therapy for advanced stage C (and
reduction. stage D) heart failure. In dogs that cannot tolerate ACEIs,
Arteriolar (or mixed) vasodilator therapy is initiated amlodipine could be used in combination with a nitrate.
using low doses to avoid hypotension and reflex tachycardia. Amlodipine’s oral bioavailability is good. It has a long
Reduction in concurrent diuretic dosage may be advisable. duration of action (at least 24 hours in dogs). Plasma con-
Monitoring for signs of hypotension is especially important. centration peaks in 3 to 8 hours; half-life is about 30 hours.
Ideally, arterial blood pressure is measured multiple times Plasma concentrations increase with long-term therapy.
over several hours after starting therapy or dosage increase. Maximal effect develops over 4 to 7 days after therapy is
Dosage titration to a mean arterial pressure between 70 to begun in dogs. The drug is metabolized in the liver. Elimi-
80 mm Hg has been suggested as a therapeutic goal; however, nation is through the urine and feces. Because of the delay
systolic pressures of less than 90 to 100 mm Hg should be in achieving maximum effect, low initial doses and weekly
avoided. A venous pO 2 of greater than 30 mm Hg (from a blood pressure monitoring during up-titration are recom-
free-flowing jugular vein), as a means to indicate reduced mended. An initial dose of 0.05 to 0.1 mg/kg PO q24(-12)h
tissue oxygen extraction, also can help guide dosage titra- is suggested when used for additional afterload reduction in
tion. Clinical signs of drug-induced hypotension include dogs receiving other heart failure therapy. Chronic admin-
weakness, lethargy, tachycardia, and poor peripheral perfu- istration of amlodipine (for ≥ 5 months) has been associ-
sion. The vasodilator dose can be titrated upward, if neces- ated with development of gingival hyperplasia in a small
sary, while monitoring for hypotension with each increase number of dogs being treated for chronic degenerative valve
in dose. disease; the hyperplasia appears to resolve after amlodipine
Venodilators relax systemic veins, increase venous capaci- discontinuation.
tance, decrease cardiac filling pressures (preload), and reduce
pulmonary congestion. They are most often used in the Prazosin
setting of acute CHF. Prazosin selectively blocks α 1 -receptors in both arterial and
venous walls. It rarely is used for chronic CHF management
Hydralazine because drug tolerance develops over time, and the capsule
Hydralazine directly relaxes arteriolar smooth muscle dose size is inconvenient in small animals. Controlled clini-
when the vascular endothelium is intact, but it has little cal studies in dogs are lacking. Hypotension, especially after
effect on the venous system. The drug reduces arterial the initial dose, is the most common adverse effect. Tachy-
blood pressure, improves pulmonary edema, and increases cardia is less likely to occur than with hydralazine because
jugular venous oxygen tension (presumably from increased presynaptic α 2 -receptors, important in the feedback control
cardiac output) in dogs with MR and heart failure. The of norepinephrine release, are not blocked.
most common indication for hydralazine is acute, severe
CHF from MR when nitroprusside use is impractical. Nitrates
Hydralazine can cause marked reflex tachycardia. The Nitrates act as venodilators (although IV nitroprusside has
dosage should be reduced if this occurs. Hydralazine can mixed vasodilator effects; see p. 63). They are metabolized
contribute to the enhanced NH response in patients with in vascular smooth muscle to produce NO, which indirectly
heart failure, which makes it less desirable than ACEIs for mediates vasodilation. Nitroglycerin ointment or isosorbide
chronic use. dinitrate has been used occasionally in the management
Hydralazine has a faster onset of action than amlodipine. of chronic CHF, either combined with standard therapy
Its effect peaks within 3 hours and lasts up to 12 hours. for refractory CHF or with hydralazine or amlodipine in
Administration of hydralazine with food decreases bioavail- animals that cannot tolerate ACEIs. Nitrates affect blood
ability by more than 60%. There also is extensive first-pass redistribution in people, but there are few studies involving
hepatic metabolism of this drug. However, increased doses dogs, especially using the oral route for CHF management.
saturate this mechanism and increase bioavailability in dogs. There is extensive first-pass hepatic metabolism, and the
General precautions for initiating and titrating therapy are efficacy of oral nitrates is questionable. Nitroglycerin oint-
outlined in the preceding section. ment (2%) is applied cutaneously (see p. 63). Self-adhesive,