Page 246 - Small Animal Internal Medicine, 6th Edition

218 PART I Cardiovascular System Disorders

intraglomerular pressure and proteinuria. ACEI are rela- when ACEI monotherapy fails to achieve adequate BP
tively weak antihypertensive medications, leading to BP control; amlodipine should not be used as an antihyperten-
VetBooks.ir reduction in the realm of 10% to 20%, even at relatively sive monotherapy in dogs. A low dose is started initially and
titrated upward as needed. Amlodipine’s half-life is about 30
high doses. The efficacy of these agents likely is greater in
patients with glomerular hypertension (proteinuric renal
ing therapy. Oral bioavailability is high, and peak plasma
disease) and in patients with significant RAAS activation. hours in dogs; maximal effects occur 4 to 7 days after initiat-
ACEIs are the recommended first-line treatment for sys- concentrations are reached 3 to 8 hours after administration;
temic hypertension in dogs, as well as in cats with protein- plasma concentrations increase with chronic therapy. The
uric renal disease. In dogs, q12h dosing is recommended for drug undergoes hepatic metabolism, but there is not exten-
optimal RAAS suppression, whereas q24h dosing is adequate sive first-pass elimination; caution is warranted when liver
in cats. If BP remains elevated despite ACEI administration function is poor. The drug is excreted through the urine and
at a typical dose (0.5 mg/kg PO q12h for dogs, q24h for feces. In both dogs and cats, combination therapy of amlo-
cats), it is unlikely that dose escalation will further reduce dipine plus an ACEI can control BP while yielding a bal-
BP, and amlodipine is generally added. ACEI are generally anced effect on glomerular pressure and GFR through equal
very well tolerated, although GI upset, electrolyte distur- dilation of afferent and efferent arterioles.
bances, and hypotension are potential concerns. Worsen- β-adrenergic blockers potentially could reduce BP by
ing azotemia is possible in patients with CKD because decreasing heart rate, cardiac output, and renal renin release.
efferent arteriolar dilation reduces glomerular filtration Atenolol and propranolol have been used most often (see p.
rate (GFR). 94). A β-blocker can be considered for cats with hyperthyroid-
Angiotensin receptor blockers (ARBs), such as telmisar- induced hypertension, as increased activity of the sympa-
tan, losartan, and irbesartan, inhibit the RAAS system thetic nervous system could underlie hypertension in this
“downstream” from ACEI by selectively antagonizing the disease; furthermore, β-blockers can inhibit peripheral con-
AT 1 receptor to which angiotensin II binds. In experimental version of T 4 to active T 3 . However, atenolol therapy causes
studies, ARBs appear to lower BP more effectively than no change in BP in normotensive cats and only decreases BP
ACEI, although reported BP reduction with ARBs is only in by ~15 mm Hg in hypertensive hyperthyroid cats. In general,
the realm of 20 to 25 mm Hg. As with ACEI, these agents β-blockers are ineffective as a sole antihypertensive agent in
are also used for treatment of proteinuria and are likely to cats; adjunct amlodipine usually is required.
be particularly useful for systemic hypertension associated α 1 -adrenergic antagonists oppose the vasoconstrictive
with glomerular disease or in patients with RAAS activation. effects of α-receptors. Their main use is for hypertension
No studies have compared efficacy of ACEI to ARBs in clini- caused by pheochromocytoma. Phenoxybenzamine is a
cal patients with systemic hypertension. Telmisartan appears noncompetitive α 1 - and α 2 -blocker used most often for
to be the most effective ARB in dogs and cats, and has been pheochromocytoma-induced hypertension. Treatment is ini-
studied at doses of 1 to 3 mg/kg PO q24h in both dogs and tiated with a low dose titrated upward as needed. The selec-
cats. Losartan is not recommended due to inferior BP tive α 1 -blocker prazosin is another option. After α-blocker
control, likely due to failure of hepatic conversion to the dosing is begun, adjunctive therapy with a β-blocker can
active metabolite in dogs. help control reflex tachycardia or arrhythmias. In cases of
Amlodipine besylate is a long-acting dihydropyridine pheochromocytoma, β-blockade should not be initiated
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Ca -blocker that causes vasodilation without appreciable before α-blockade, because use of a β-blocker as the sole
cardiac effects. It is a more effective antihypertensive agent agent in this setting leaves α 1 -receptors unopposed and is
than ACEIs or ARBs. The drug usually is dosed once daily, likely to exacerbate hypertension.
although q12h administration can be used in patients that Hypotension is a potential adverse effect of any antihy-
do not respond sufficiently to the lower dose. Amlodipine pertensive drug. Hypotension usually is manifested as
dilates the glomerular afferent arterioles and can thereby act periods of lethargy or ataxia. Reduced appetite could be
synergistically with ACEI to reduce glomerular hyperten- another adverse effect. Conversely, rebound hypertension
sion. In dogs, amlodipine administration alone has been can occur if antihypertensive therapy is suddenly discontin-
shown to activate the RAAS. In cats with CKD, amlodipine ued. This especially is of concern when using β- or α 2 -
does not alter serum creatinine concentration, although blockers. If therapy with such agents is to be terminated, the
RAAS activation specifically has not been studied. dosage should be gradually tapered down first.
Amlodipine is an effective antihypertensive in both dogs
and cats. In cats, amlodipine monotherapy is effective in HYPERTENSIVE EMERGENCY
controlling hypertension secondary to various causes. Amlo- Urgent antihypertensive therapy is indicated when new or
dipine is initially dosed in cats as 0.625 mg/cat (one quarter progressive signs of severe hypertension are identified.
of a 2.5-mg tablet) q24h; this dose can be increased to q12h Examples include acute retinal detachment and hemorrhage,
(or to 1.25 mg/cat) if needed, based on rechecked BP. Cats encephalopathy, intracranial hemorrhage, acute renal failure,
with higher BP at diagnosis (>200 mm Hg) often require a aortic aneurysm, or acute left-sided congestive heart failure.
higher dose of amlodipine for eventual BP control. In hyper- The animal should be hospitalized until BP and other acute
tensive dogs, amlodipine is added to the treatment regimen signs are controlled.