Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

INODILATORS
25% above baseline. Because of this marked species
difference, data obtained from human patients given
amrinone or milrinone cannot be extrapolated to dogs
or cats.
Milrinone
Clinical applications
Milrinone is the preferred bipyridine compound but is
rarely used clinically; for acute cardiovascular support,
dobutamine is preferred. It is a bipyridine compound
with pharmacological effects and clinical indications
that are almost identical to amrinone. Milrinone is currently
marketed for intravenous administration only. No
clinical studies of the effects of intravenous milrinone
administration for acute myocardial failure in dogs or
cats have been performed. Clinical studies of the effects
of chronic oral administration have been performed but
this form of the drug has not been approved for veterinary
use and is not available for human use.
Formulations and dose rates
Milrinone lactate is supplied in 10 mL and 20 mL single-dose vials
containing 1 mg/mL. It can be diluted in 0.45% and 0.9% sodium
chloride and 5% dextrose in water.
DOGS
• In normal anesthetized dogs, milrinone 30–300 µg/kg IV
increases contractility by 40–120% while decreasing diastolic
blood pressure by 10–30%
• Constant-rate intravenous infusions (1–10 µg/kg/min) increase
contractility by 50–140%, with peak effect in 10–30 min
• Dogs with systolic dysfunction (predominantly from DCM)
displayed improved echocardiographic parameters with
milrinone 0.5–1.0 mg/kg q.12 h PO during a 4-week treatment
regimen
Pharmacokinetics
Peak effect occurs within 1–2 min of starting an intravenous
infusion and is reduced to 50% of maximum
within 10 min of stopping the infusion. The effects are
essentially gone in 30 min.
Adverse effects
Ventricular arrhythmias worsen in a small percentage
of dogs.
Known drug interactions
Milrinone is chemically incompatible with furosemide
and thus should not be administered in the same intravenous
line without flushing adequately in between.
Amrinone
Clinical applications
Amrinone is used for short-term inotropic support in
small animal patients with myocardial failure. It may be
useful to supplant a sympathomimetic once β-receptor
downregulation has become a problem. It is not commonly
used as a first-line agent because of its expense.
Formulations and dose rates
Amrinone is supplied in 20 mL ampoules in a concentration of 5 mg/
mL for administration as supplied or for dilution in 0.9% or 0.45%
saline.
DOGS AND CATS
• Amrinone is marketed only as a solution for intravenous
administration and so is useful only for short-term
administration
• In dogs, the initial dose should be 1–3 mg/kg, administered as
a slow intravenous bolus, followed by a CRI of 10–100 µg/kg/
min. One-half the initial bolus may be administered 20–30 min
after the fi rst bolus
• The same regimen may be effective in the cat
Pharmacokinetics
In normal anesthetized dogs, an intravenous bolus of
amrinone (1.0–3.0 mg/kg) causes contractility to
increase 60–100%, systemic arterial blood pressure to
decrease 10–30% and heart rate to increase 5–10%.
The maximal contractility increase occurs within 5 min
after injection and decreases 50% by 10 min. Effects are
dissipated within 20–30 min. This short duration of
effect necessitates administering the drug by constant
intravenous infusion following the initial bolus injection.
Infusion rates of 10–100 µg/kg/min in anesthetized
experimental dogs increase contractility by 30–90%
above baseline and in unanesthetized dogs by
10–80%.
In anesthetized dogs, an infusion of 10 µg/kg/min
does not decrease systemic blood pressure, whereas
30 µg/kg/min decreases it by 10% and 100 µg/kg/min
decreases it by 30%. Heart rate does not increase at
10 µg/kg/min but elevates by 15% at 30 µg/kg/min and
increases by 20% at 100 µg/kg/min. In anesthetized
dogs with drug-induced myocardial failure, amrinone
infusions increase contractility by 40–200% above
baseline and increase cardiac output by 80%. Constant
infusions in dogs take about 45 min to reach peak effect.
In experimental cats, amrinone infused at 30 µg/kg/min
causes contractility to increase by 40% above baseline.
Peak effect occurs 90 min after starting an infusion.
Studies have not been performed to determine the
hemodynamic changes brought about by amrinone
administration in dogs or cats with naturally occurring
heart failure. On the basis of the information from
normal dogs, however, clinical recommendations can be
made. The drug has a wide margin of safety and the risk
of toxicity is low. With milrinone (which has similar
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