Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

POSITIVE INOTROPIC DRUGS
Pharmacokinetics
Dobutamine must be administered as a CRI. A plateau
plasma concentration is achieved within approximately
8 min of starting the infusion. Upon cessation of the
infusion, dobutamine rapidly clears from the plasma
with a terminal half-life of 1–2 min. The rapid clearance
is due primarily to degradation of the drug by
catechol-O-methyltransferase.
In experimental dogs, dobutamine produces doserelated
increases in myocardial contractility, cardiac
output, stroke volume and coronary blood flow, with
no change in systemic arterial blood pressure. When
administered to a patient with acute or chronic myocardial
failure, it should increase contractility and cardiac
output and decrease ventricular diastolic pressures,
leading to a decrease in edema formation and normalization
of systemic blood pressure if it is low. This has
been poorly documented in dogs and cats with chronic
myocardial failure but has been well documented in
human patients. Failing myocardium responds much
less avidly to positive inotropic agents than normal
myocardium. Consequently, it is not unusual for echocardiographic
measures of left ventricular function to
change minimally following dobutamine administration
in dogs with severe systolic dysfunction (e.g. DCM).
This statement is true of all positive inotropes.
Dobutamine’s effects on heart rate are generally less
than those of other catecholamines. When studied in
normal dogs and in dogs with experimental myocardial
infarction, the heart rate did not increase at infusion
rates less than 20 µg/kg/min. Dobutamine, however,
does increase heart rate in a dose-dependent manner in
dogs that are anesthetized.
Adverse effects
Dobutamine can exacerbate existing arrhythmias, especially
ventricular arrhythmias. It can also produce new
arrhythmias and increase heart rate.
Special considerations
The 12.5 mg/mL solution must be further diluted into
at least 50 mL for administration. Once in an intravenous
solution, the compound is stable at room temperature
for 24 h.
Dobutamine should not be mixed with bicarbonate,
heparin, hydrocortisone sodium succinate, cefalothin,
penicillin or insulin.
Dopamine
Clinical applications
In cardiovascular medicine, dopamine is recommended
for short-term use in animals with systolic dysfunction
and in the management of acute oliguric renal failure,
particularly in the dog. In addition, dopamine is
often used as a pressor agent to manage inappropriate
hypotension in both conscious and anesthetized
patients.
Mechanism of action
Dopamine is the precursor of noradrenaline (norepinephrine).
It stimulates cardiac α- and β-adrenergic
receptors as well as peripherally located dopaminergic
receptors. The reported effects of dopamine are dose
dependent: where dopaminergic effects on renal blood
flow occur at low doses 1–1.5 µg/kg/min, positive
inotropic responses predominate at doses 5–10 µg/kg/
min and pressor effects dominate at infusion rates
greater than 10 µg/kg/min. The pressor effects are undesirable
in the setting of decompensated heart failure and
thus dobutamine is preferred in this setting. Dopaminergic
receptors appear to be located most prevalently in
the renal and mesenteric vascular beds, where they
produce vasodilation and improve blood flow. As with
dobutamine, all effects are attenuated over time and are
reduced in dogs with heart failure relative to normal
dogs.
Formulations and dose rates
Dopamine is supplied as 40 mg/mL in a 10 mL single use vial
(400 mg/vial) and should be diluted appropriately for administration.
DOGS
• 1–10 µg/kg/min IV
• Low doses (1.0–1.5 µg/kg/min) cause renal vasodilation via
specifi c dopaminergic receptors; therefore, dopamine is often
used in the management of acute oliguric renal failure
• Medium doses (3–10 µg/kg/min) cause increased cardiac
output with little effect on peripheral resistance or heart rate
• Doses higher than 10 µg/kg/min can be used but result in
noradrenaline (norepinephrine) release and increased peripheral
vascular resistance and heart rate (pressor effect)
• An initial dose of 2 µg/kg/min may be started and titrated
upward to obtain the desired clinical effect (improved
hemodynamics)
Pharmacokinetics
All sympathomimetics have a very short half-life (1–
2 min). When administered orally, they experience rapid
and extensive first-pass hepatic metabolism before they
reach the circulation. Consequently, they must be
administered intravenously as a CRI.
Special considerations
Dopamine is inactivated when mixed with sodium
bicarbonate or other alkaline intravenous solutions. The
solution becomes pink or violet. The product should not
be used if it is discolored.
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