Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

INJECTABLE ANESTHETIC AGENTS
– Edema or hyperemia of ears and paws are commonly
encountered but these are of little clinical
significance. There are rare reports of necrosis of
the appendages.
– Of more concern are the reports of pulmonary
and laryngeal edema. These adverse events are
potentially fatal but the incidence is low. Prompt
treatment with corticosteroids and antihistamines
may be required and in the case of laryngeal
edema, a patent airway should be established and
maintained.
– Alphaxalone in cyclodextrin is not associated
with histamine release.
● Despite being steroidal anesthetics, alphaxalone and
alphadolone have no significant endocrine effect.
● Alphaxalone ± alphadolone crosses the placenta but
depression of kittens appears to be minimal if the
total dose is kept below 6 mg/kg.
Contraindications and precautions
Alphaxalone ± alphadolone should be avoided or used
cautiously in the following patients.
● Cremophor EL-based drug should not be
administered to dogs
● Cremophor EL-based drug should not be
administered to cats with asthma or mast cell tumors
● Hypovolemic and hypotensive patients
● Patients with heart disease
Known drug interactions
● Premedication may prolong and smooth the
recovery period. It also variably reduces the dose
required for induction of anesthesia.
● Antihistamines will reduce the side effects
associated with Cremophor EL administration.
Etomidate
Clinical applications
Etomidate can be used to induce anesthesia prior to
maintenance with an inhalant. Alternatively it can be
used as a maintenance agent for nonpainful procedures
of short duration. It has fewer adverse cardiovascular
effects than other injectable anesthetics and is frequently
recommended in patients that are hemodynamically
unstable. Fetal transfer is poor and there is less depression
of the neonate than with other agents, making this
agent useful in the patient requiring cesarean section. It
has a wide safety margin, with a therapeutic index of
16 in dogs.
Mechanism of action
Etomidate produces dose-dependent cortical depression.
It activates the GABA A receptor, which opens chloride
channels, resulting in cellular hyperpolarization.
Formulations and dose rates
Etomidate is a carboxylated imidazole. Commercial preparations
contain only the active dextrorotatory isomer. It has a pH-dependent
ring structure that is water soluble at low pH but becomes lipid soluble
at physiological pH. There are two formulations available. One preparation
contains etomidate dissolved in 35% propylene glycol (Hypnomidate®).
It forms a clear hypertonic solution that does not support
bacterial growth. The other preparation contains etomidate in an
aqueous emulsion of 10% soyabean oil, 2.25% glycerol and 1.25%
egg phosphatide (Etomidate-Lipuro®). It is milky white, slightly
viscous and does support bacterial growth. There is no bacteriostatic
agent in either preparation and any unused drug should be discarded.
Etomidate is currently unlicensed for use in animals.
• The recommended induction dose for etomidate is 0.5–2 mg/kg
IV in the premedicated animal. As with other induction agents,
the drug should be given to effect rather than as a single bolus.
• Etomidate should not be administered in the absence of
sedation because excitatory side effects are commonly seen.
• Anesthesia can be maintained for short periods with etomidate
given at a rate of 0.05–0.15 mg/kg/min in premedicated
animals. Prolonged infusion is not recommended. It may be
associated with adverse effects including adrenocortical
suppression and hemolysis.
Pharmacokinetics
Etomidate is moderately lipid soluble and in the dog
approximately 76% protein bound. After IV administration
it induces unconsciousness in less than 30
seconds. Anesthesia lasts for 5–10 min and recovery is
rapid. Termination of anesthesia is due to redistribution
and rapid hydrolysis by hepatic microsomal enzymes
and plasma esterases. The hepatic extraction ratio for
etomidate is about 0.5 and a decrease in hepatic blood
flow has a moderate effect on metabolism; however,
clearance in patients with intrinsic liver disease is
unchanged. The inactive metabolites are excreted mainly
in the urine.
Adverse effects
Central nervous system effects
● Etomidate decreases cerebral metabolic oxygen
requirement, cerebral blood flow and intracranial
pressure. Cerebral metabolic oxygen requirements
(CMRO 2 ) are decreased because neuronal function
is depressed by etomidate. The decrease in cerebral
blood flow is due to direct cerebral vasoconstriction
and is independent of the fall in CMRO 2 . Because
etomidate has a minimal effect on arterial blood
pressure, cerebral perfusion pressure is better maintained
than with thiopental and propofol.
● Etomidate has anticonvulsant properties and is
capable of controlling status epilepticus.
● Etomidate is tolerated well by the patient with
cerebral disease or epilepsy and those undergoing
myelography.
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