Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 17 DRUGS USED IN THE MANAGEMENT OF HEART DISEASE AND CARDIAC ARRHYTHMIAS
Formulations and dose rates
Hydralazine is available as tablets. The author (Kittelson) has witnessed
a lack of response to some generic hydralazine products and
does not recommend their use.
The effective dose is 0.5–3.0 mg/kg q.12 h PO. This dose must be
titrated, starting with a low dose and titrating upward to an effective
endpoint.
Dose titration
In dogs that are not being administered an ACE inhibitor,
the starting dose of hydralazine should be 1.0 mg/
kg. This can then be titrated up to as high as 3.0 mg/kg
if no response is observed at lower doses. Titration in
these animals can be performed with or without blood
pressure measurement. If blood pressure cannot be
monitored, titration is performed more slowly and
clinical and radiographic signs are monitored. Baseline
assessments of mucous membrane color, capillary refill
time, murmur intensity, cardiac size on radiographs and
severity of pulmonary edema are made.
A dose of 1 mg/kg is administered q.12 h PO and
repeat assessments are made in 12–48 h. If no response
is identified, the dose is increased to 2 mg/kg q.12 h and
then to 3 mg/kg q.12 h if no response is seen at the
previous dose. Mucous membrane color and capillary
refill time will become noticeably improved in about
50–60% of dogs. In most dogs with heart failure due
to mitral regurgitation, the severity of the pulmonary
edema will improve within 24 h. In many of these dogs
the size of the left ventricle and left atrium will decrease.
In some dogs, improvement will not be great enough to
identify with certainty. In those dogs the titration may
continue, with the realization that some dogs will be
mildly overdosed and clinical signs of hypotension may
become evident.
Owners should be warned to watch for signs of
hypotension and notify the clinician if they are identified.
If a dog becomes weak and lethargic following
hydralazine administration, the dog should be rechecked
by a veterinarian but in almost all situations the dog
should only be observed until the drug effect wears off
11–13 h later. The drug dose should then be reduced.
In the rare event that signs of shock become evident,
fluids and vasopressors may be administered. In human
medicine, there has never been a death recorded that
was secondary to the administration of hydralazine
alone. The dosage record is 10 g. The authors have
observed dogs becoming very weak following an overdose
of hydralazine but have never observed a serious
complication when the drug was not administered in
conjunction with another vasodilator such as an ACE
inhibitor.
More rapid titration can be performed if blood pressure
monitoring is available. In this situation, baseline
blood pressure is measured and 1.0 mg/kg hydralazine
administered. Blood pressure measurement should then
be repeated 1–2 h later. If blood pressure (systolic, diastolic
or mean) has decreased by at least 15 mmHg, the
dose administered (1.0 mg/kg) is effective and should be
administered q.12 h from then on. If no response is
identified, another 1.0 mg/kg dose should be administered
(cumulative dose of 2.0 mg/kg) and blood pressure
measured again 1–2 h later. This can continue until a
cumulative dose of 3.0 mg/kg has been administered
within a 12 h period. The resultant cumulative dose
then becomes the dose administered q.12 h.
In dogs that are already receiving an ACE inhibitor,
hydralazine must be added to the treatment regimen
cautiously. ACE inhibition depletes the body’s ability to
produce angiotensin II in response to hydralazineinduced
vasodilation. Severe hypotension can occur if
the hydralazine dose is not titrated carefully. In general,
the dosage should start at 0.5 mg/kg and the dose should
be titrated at 0.5 mg/kg increments until a response is
identified. Blood pressure monitoring is strongly encouraged
in this situation. Referral to a specialist cardiologist
or internist is also encouraged if feasible.
In dogs with acute, fulminant heart failure due to
severe mitral regurgitation that are not already receiving
an ACE inhibitor, hydralazine titration can be more
aggressive. An initial dose of 2.0 mg/kg may be administered
along with intravenous furosemide. This dose
should produce a beneficial response in more than 75%
of dogs. It may produce hypotension but the hypotension
is rarely fatal, whereas fulminant pulmonary edema
is commonly fatal.
Pharmacokinetics
Hydralazine is well absorbed from the gastrointestinal
tract but undergoes first-pass hepatic metabolism.
Although the kidney does not excrete hydralazine,
its biotransformation is affected by renal failure,
which may increase serum concentration. The vasodilating
effect of hydralazine occurs within 30–60 min
after oral administration and peaks within 3 h. The
effect is then stable for the next 8–10 h, after which it
rapidly dissipates. The net duration of effect is about
12 h.
Adverse effects
The most common side effects include first-dose hypotension
and anorexia, vomiting and diarrhea.
● Gastrointestinal. Anorexia and/or vomiting occur in
approximately 20–30% of patients. They are often
intractable as long as the drug is being administered.
Consequently, discontinuation of the drug may be
necessary. Reducing the dose to 0.25–0.5 mg/kg
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