Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

PURE VASODILATORS
q.12 h for 1–2 weeks and then increasing the
dose to its therapeutic range may be effective in some
cases.
● Hypotension. The most serious adverse effect is
hypotension, indicated by signs of weakness and
depression. In most cases, this does not require treatment
and the signs will abate within 10–12 h after
the last dose of hydralazine. The dose should then
be reduced.
● Reflex tachycardia. When hydralazine is used as the
only agent in patients with hypertension and normal
cardiac function, hydralazine induces a reflex increase
in sympathetic nervous system tone. The increased
sympathetic drive increases myocardial contractility
and heart rate. Consequently cardiac output increases
dramatically, offsetting the effect of the arteriolar
dilation. The net result is no change in systemic arterial
blood pressure. When an α-adrenergic receptor
blocker is added to the therapeutic regimen, the
reflex effect is blocked and systemic arterial blood
pressure decreases.
Although hydralazine is not commonly used to
treat hypertension in veterinary medicine, this same
response would be expected in a patient that is misdiagnosed
and receives hydralazine when it is not in
heart failure.
Reflex sympathetic tachycardia is not as common
in heart failure patients as in patients with systemic
hypertension. However, in one study, heart rate in
dogs with mild to moderate heart failure increased
from an average of 136 beats/min to 153 beats/min
following hydralazine administration. In patients
with heart failure, the sympathetic nervous system is
already activated but the heart’s ability to respond
to the sympathetic nervous system is blunted or abolished.
In fact, the heart’s ability to respond to any
type of stimulus is overwhelmed.
Therefore, when hydralazine is administered to a
patient with heart failure, systemic arterial blood
pressure does decrease and a less profound increase
in systemic blood flow is produced than that observed
when the drug is administered to patients with systemic
hypertension.
Reflex tachycardia may be controlled by the addition
of α-adrenergic blocking drugs or digoxin.
● Increased renin release. Rebound increases in renin
and aldosterone secretion and decreased sodium
excretion occur following hydralazine administration.
The beneficial effect on regurgitant fraction
usually outweighs these effects, however.
One should remember that drugs like furosemide
also increase renin release and so increase plasma
aldosterone concentration. In people, systemic lupus
erythematosus, drug fever and peripheral neuropathy
have been reported.
Known drug interactions
Hydralazine administration may have beneficial effects
on the pharmacokinetics and pharmacodynamics of
other drugs.
● Increased renal blood flow caused by hydralazine
administration can increase the glomerular filtration
rate (if initially depressed) and thereby enhance
digoxin excretion.
● Increased renal blood flow also improves furosemide
delivery to the nephron. This increases furosemide’s
renal effects (increases natriuresis and diuresis), especially
in patients that are refractory to furosemide
administration because of decreased renal flow due
to decreased cardiac output.
Prazosin
Clinical applications
Prazosin is an arteriolar and venodilatory agent. The
hemodynamic effects of prazosin have not been documented
in the dog or cat. In humans with heart failure,
its administration decreases right and left ventricular
filling pressures, edema and congestion and increases
stroke volume and cardiac output. Prazosin is effective
in reducing mean arterial blood pressure in some dogs
with renal hypertension.
Mechanism of action
Prazosin acts primarily by blocking α 1 -adrenergic receptors
but also peripherally inhibits phosphodiesterase.
Since prazosin does not block α 2 -adrenergic receptors,
noradrenaline (norepinephrine) release is still controlled
via negative feedback. Reflex tachycardia is generally
not seen. The vasodilating effects of prazosin become
attenuated after the first dose in humans and in rats.
This problem has markedly limited its use in human
medicine. In rats, it is thought that this effect is brought
about by stimulation of the RAAS.
Formulations and dose rates
Prazosin is supplied as capsules.
DOGS
• The starting dose is 1 mg q.8 h PO for dogs 15 kg
• The dose then needs to be titrated upward if the initial dose is
ineffective, or reduced if hypotension occurs
CATS
• The preparation is not amenable for use in cats
Pharmacokinetics
Elimination and metabolism are primarily hepatic. No
adjustment is made for renal insufficiency.
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