Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
no benefit and may worsen clinical signs. PDE Vi
prevents degradation of cGMP resulting in relaxation
of pulmonary vascular smooth muscle and, to a lesser
degree, systemic vasodilation (preferential pulmonary
vasodilation). Sildenafil is currently the most extensively
researched of the PDE V inhibitors and has been shown
to improve both exercise tolerance and quality of life
in humans with pulmonary hypertension resulting in
its FDA approval for treatment of this disorder in
humans.
Viagra® was recently re-released as Revatio® (which
is more expensive). Sildenafil is now available as a
generic preparation in some countries further reducing
its cost although documentation of efficacy of the
generic formulations has not been reported. Clinical
improvement in humans has been documented at multiple
doses ranging from 20 mg to 80 mg three times a
day. Because higher doses do not increase the efficacy,
the currently recommended dose in humans is 20 mg
every 8 h.
Formulations and dose rates
CANINE
• 0.25–3.0 mg/kg PO
Empirically, the authors start at a dose of approximately 5 mg/dog
and titrate. In oxygen-dependent dogs, initiation of the target dose of
approximately 3 mg/kg may be indicated and well tolerated based on
the authors experience. Uptitration can occur over days to weeks if
patients are not oxygen dependent. Due to cost the authors have not
used doses greater then 25 mg/dog. Oral sildenafi l liquid dosage
forms have been reported to be stable and have been used in people.
Therefore suspension formulations can be used in dogs and greatly
facilitate cost effective accurate dosing.
Adverse effects
None have been documented in the dogs managed
by the author (>25 dogs). One retrospective canine
study also reported no adverse side effects and clinical
improvements in 10 dogs with PH receiving a median
dose of approximately 2 mg/kg every 8–24 h.
Known drug interactions
Due to the nature of canine PH, sildenafil has been used
in combination with many other medications including
conventional heart failure medications (diuretics, ACE
inhibitors, pimobendan) with no recognized adverse
effects.
NEUROENDOCRINE MODULATION
Agents in this group address the maladaptive changes
associated with the progression of heart disease in the
RAAS and sympathetic nervous system.
EXAMPLES
Oral: ACE inhibitors (preferred), aldosterone antagonist (e.g.
spironolactone) (preferred), β-blockers (preferred), digoxin,
neutral endopeptidase inhibitors, angiotensin receptor
blockers
Angiotensin-converting enzyme
(ACE) inhibitors
EXAMPLES
Enalapril (preferred), benazepril (preferred), ramipril
(preferred), lisinopril, captopril
There are five ACE inhibitors that have been used in
dogs and cats: captopril, enalapril, lisinopril, benazepril
and ramipril. Generally these drugs have similar effects.
The primary difference is in duration of effect and
potential side effects. Captopril, the original ACE inhibitor,
is short-acting, lasting less than 3–4 h, and has
more side effects than the other ACE inhibitors. It is
therefore now rarely used. The effects of enalapril and
ramipril last 12–14 h. Lisinopril and benazepril are
thought to be the longest-acting ACE inhibitors; oncedaily
use is advocated in humans and animals. Benazepril
is excreted primarily via hepatic metabolism versus
renal filtration (others) and thus may be better tolerated
in patients with pre-existing renal disease particularly
when a low dose is required.
Clinical applications
The primary clinical indication for ACE inhibitors is for
the treatment of heart failure in dogs, cats and people.
ACE inhibitors are also frequently used for the management
of systemic hypertension in people. However, their
efficacy in systemic hypertension in dogs and cats when
used as monotherapy has been disappointing.
A more recent indication for ACE inhibitors in dogs,
cats and people is in the treatment of a variety of renal
diseases with emphasis on protein-losing glomerulopathy.
Given the subject matter of this chapter, these indications
will not be discussed in detail but the reader is
directed to additional reading on the subject including
the ACVIM consensus statement on management of
proteinuria in dogs and cats. In brief, there is evidence
that use of ACE inhibitors (benazapril) will attenuate
the progression of renal failure in cats with significant
proteinuria. However, the evidence that they are beneficial
in cats with little proteinuria (the majority of cats)
has not yet been established by appropriate large-scale
clinical trials. There is probably no disadvantage to
using ACE inhibitors in cats with renal failure as there
may be some benefit provided the cat can be pilled easily
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