Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

INJECTABLE ANESTHETIC AGENTS
● Increased motor activity, hyperreflexia and secondary
hyperthermia may be seen during recovery
following use of ketamine alone and sometimes
following use of ketamine/benzodiazepine combinations.
Because of the effect on muscle tone,
ketamine has the potential to induce malignant
hyperthermia.
Other effects
● Ketamine causes hypersalivation and increased bronchial
secretions. In the past, concurrent administration
of atropine has been advocated but this is no
longer routinely recommended as tachycardia and an
increase in myocardial oxygen requirement may
result.
● Intraocular pressure rises after ketamine administration
and the drug should be avoided in animals with
glaucoma, penetrating eye injury, deep corneal ulcer
or descemetocele.
● Because the eye remains open corneal drying may
occur and application of an ocular lubricant is
recommended.
● Accidental perivascular injection does not result in
tissue necrosis but does cause a painful reaction. Pain
may also be evident on intramuscular injection.
Contraindications and precautions
Ketamine should be avoided in the following patients.
● Patients that have a pre-existing tachycardia and
those in which tachycardia would be detrimental
● Patients with elevated sympathetic tone, e.g. hyperthyroidism
and pheochromocytoma
● Patients with hypertrophic cardiomyopathy
● Patients with raised ICP (e.g. due to an intracranial
mass or head trauma)
● Epileptic patients or those undergoing myelography
● Patients with glaucoma, deep corneal ulcer or
descemetocele
● Patients susceptible to malignant hyperthermia
Tiletamine-zolazepam
Clinical applications
Tiletamine-zolazepam can be administered for sedation
or anesthesia of short-to-moderate duration or for
induction before gaseous anesthesia. Separately tiletamine
and zolazepam do not have ideal sedative or
anesthetic properties but together they produce
dissociative anesthesia, muscle relaxation and some
analgesia.
Induction is smooth when given by any route provided
that an adequate dose is administered. Analgesia
is adequate for minor procedures such as wound sutures
and cat castrations but not for major surgery such as
ovariohysterectomy or castration in dogs. About 40%
of animals retain some muscular tone.
Mechanism of action
Tiletamine probably has the same action as ketamine at
the NMDA receptor and zolazepam enhances the action
of GABA.
Formulations and dose rates
Tiletamine HCl belongs to the cyclohexamine group of dissociative
agents and zolazepam is a benzodiazepine related to diazepam and
midazolam. The combination is manufactured as a lyophilized powder
that can be added to water, saline or 5% dextrose for reconstitution.
The resulting solution is clear with a pH of 2.0–3.5.
The powder has a long shelf-life but the solution should be discarded
after 4 days if stored at room temperature or 14 days if stored
in a refrigerator.
• A 100 mg/mL solution contains 50 mg tiletamine and 50 mg
zolazepam. The dosage and route recommended by the
manufacturer for the cat are 9.7–15.8 mg/kg IM and for the
dog 6.6–13.2 mg/kg IM. The recommended dose is high,
producing a prolonged recovery, and the drug can be given by
the intravenous and subcutaneous routes also.
• Smaller doses than recommended are effective but the actual
dose appears to vary.
• In the USA, Telazol® administered at 2.5 mg/kg IM produces
heavy sedation to light anesthesia in cats and excitement is not
seen at lower doses. However, Zoletil® administered at 2.5 mg/
kg IM produces excitement in young, healthy cats and a dose of
5 mg/kg IM is required to produce sedation or anesthesia.
• In geriatric or compromised animals a lower dose can be given
for sedation.
Pharmacokinetics
After intravenous administration the onset of unconsciousness
is less than 30–60 seconds. After IM administration,
an effect can be seen in less than 2–5 min and
a peak effect is seen in about 10 min. The duration of
anesthesia after IM or SC administration is dose dependent,
with low doses (2–5 mg/kg) providing sedationanesthesia
for approximately 15–20 min. A single IV
dose lasts 10–20 min and full recovery takes 3–5
hours.
Recovery is initially due to redistribution and an infusion
or several boluses prolong the duration of recovery.
The drug is ultimately eliminated after hepatic metabolism
and metabolites of both tiletamine and zolazepam
are reported to be excreted by the kidneys.
Adverse effects
Very little work has been carried out to investigate the
effects of tiletamine-zolazepam in small animals. It can
probably be assumed that many of the effects of this
drug will be similar to those of a ketamine and diazepam
combination.
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