Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
Adverse effects
Anticipated adverse effects would be the same as for
other long-acting ACE inhibitors.
Lisinopril
Lisinopril is a lysine derivative of enalaprilat. It does not
require hydrolysis to become active. It has a higher
affinity for ACE than either captopril or enalapril.
Formulations and dose rates
Lisinopril is supplied as tablets.
DOGS AND CATS
• A clinically effective dose of lisinopril has not been identifi ed
• The generally used dose in dogs is 0.5 mg/kg q.24 h PO. From
pharmacodynamic data, a dose of 0.25–0.5 mg/kg q.12 h or
1.0 mg/kg q.24 h may be more effective
• The primary benefi t of lisinopril may be in dogs with impaired
liver function
• The major factor that retards its use is the fact that the studies
to document its pharmacodynamics and effi cacy in the dog and
cat have not been performed
Pharmacokinetics
Lisinopril’s bioavailability is 25–50% and is unaffected
by feeding. Peak plasma concentration occurs 4 h after
oral administration in dogs. Peak inhibition of the
pressor response to angiotensin I occurs 3–4 h after oral
administration. Peak ACE inhibition occurs 6–8 h after
administration. Elimination half-life of lisinopril in dogs
is about 3 h.
Lisinopril’s effects last for 24 h but are substantially
attenuated 24 h after oral administration in dogs. A
dose of 0.3 mg/kg orally to dogs results in approximately
75% inhibition of the pressor response to angiotensin
I 3 h after administration. This response decreases
to about 60% inhibition by 6 h and to approximately
10% at 24 h. When a dose of 1.0 mg/kg is administered
PO, more than 90% inhibition of the pressor response
to angiotensin I is achieved 4 h after drug administration.
This response is effectively unchanged 6 h after
administration and is still approximately 40% inhibited
24 h after administration.
Adverse effects
The adverse effects of lisinopril are the same as those of
the other long-acting ACE inhibitors.
Captopril
Formulations and dose rates
Captopril is supplied as tablets but is no longer a recommended ACE
inhibitor in dogs or cats as more suitable products are now available
on the veterinary market.
DOGS
• 0.5–1.0 mg/kg q.8 h PO
• Doses of 3.0 mg/kg q.8 h have been associated with glomerular
lesions and renal failure in experimental dogs and in clinical
canine patients
• In one study, the onset of activity of captopril was within 1 h
following the fi rst dose. Drug effect lasted less than 4 h. A dose
of 1 mg/kg produced slightly greater effects than a dose of
0.5 mg/kg. A dose of 2 mg/kg produced no additional benefi t
CATS
• 0.5–1.5 mg/kg q.8–12 h, determined from clinical experience
Pharmacokinetics
Captopril’s affinity for ACE is approximately 30,000
times greater than that of angiotensin I. Captopril has
a half-life in dogs of about 3 h. It is about 75% bioavailable
in fasted dogs and 30–40% in fed dogs.
Approximately 40% of circulating captopril is protein
bound. Captopril is metabolized in the liver but almost
all of the captopril and its metabolites are eliminated by
the kidneys, principally via tubular secretion. In patients
with decreased renal function, a decrease in dose interval
or dose is recommended. The average total body
clearance and the renal clearance of captopril are
600 mL/kg in the dog. The volume of distribution of
captopril in the dog is 2.6 L/kg; the volume of the
central compartment is about 0.5 L/kg.
Adverse effects
● Captopril is generally well tolerated in most patients.
However, side effects can occur and include anorexia,
vomiting, diarrhea, azotemia and hypotension.
● Gastrointestinal side effects appear to be more
common in dogs administered captopril than in dogs
administered other ACE inhibitors.
● In human patients, captopril produces fewer instances
of azotemia and hypotension than do the longeracting
ACE inhibitors. Doses in excess of 2.0 mg/kg
q.8 h can produce renal failure, hence should be
avoided.
ALDOSTERONE ANTAGONISTS
EXAMPLE
Spironolactone
Spironolactone is an aldosterone antagonist and potassium
sparing diuretic. It has potential beneficial effects
on the progression of heart disease. For a full discussion
of spironolactone see the diuretic section of this
chapter.
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