Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 6 SEDATIVES
Table 6.1 Suggested doses of specific antagonists for reversal of selected α2-agonists in the dog and cat
Dog (mg/kg)
Cat (mg/kg)
To
reverse
xylazine
To reverse
medetomidine
Atipamezole 0.2 0.05–0.2 (5 ×
medetomidine
dose)
To reverse
romifidine
0.2 (approx. 1.7 ×
romifidine
dose)
To
reverse
xylazine
To reverse
medetomidine
0.2 0.1–0.2 (2.5 ×
medetomidine dose)
To reverse
romifidine
0.4 (equal to
romifidine dose)
Yohimbine 0.10–0.15 – – 0.1–0.2 0.5 –
Tolazoline 0.5–1 – – 2 – –
of α 2 -agonist to be reduced without compromising
the quality of the sedation.
● In addition, α 2 -agonists greatly reduce the required
dose of intravenous and inhalation anesthetics, by
50% or more in some cases. Since they also tend
to slow the circulation it is relatively easy to overdose
a patient with the induction agent. Thus if α 2 -
agonists are used for premedication, the induction
drug should be given slowly and at a much reduced
dose.
● Fatalities have been documented in horses sedated
with detomidine that concurrently received intravenous
potentiated sulfonamides. This interaction has
not been reported following the use of other
α 2 -agonists.
Special considerations
● α 2 -Agonists can be absorbed through mucous membranes
or broken skin and so should be handled with
care. Should inadvertent self-administration occur,
medical attention should be sought immediately,
since serious CNS disturbance can result.
a2-Adrenoceptor antagonists
EXAMPLES
Yohimbine (Antagonil®, Yobine®), atipamezole
(Antisedan®), tolazoline (Tolazine®).
Clinical applications
α 2 -Adrenoceptor antagonists are used to reverse the
sedation induced by α 2 -agonists, allowing a more rapid
recovery. Unfortunately, not all properties of the α 2 -
agonists are reversed equally and higher doses may be
required to fully antagonize the adverse cardiopulmonary
effects of these drugs.
Atipamezole is the most specific of the α 2 -antagonists
available. It is generally licensed to reverse medetomi-
dine in dogs and cats but has been used to antagonize
other α 2 -agonists. Yohimbine and tolazoline have been
used primarily to reverse xylazine-induced sedation.
Formulations and dose rates
Atipamezole
Dogs and cats: 0.05–0.4 mg/kg IM
Yohimbine
Dogs and cats: 0.1–0.11 mg/kg IV to reverse xylazine
The actual dose required depends on the species and also which α 2 -
agonist is being reversed (Table 6.1).
Adverse effects
● A number of adverse effects have been documented
following administration of α 2 -antagonists to dogs
and cats. These are generally transient and include
apprehension or excitement, muscle tremors and in
some cases hypersalivation and vomiting.
● Convulsions have also been recorded but primarily
in patients that have been treated with ketamine.
This dissociative anesthetic, if unopposed by a suitable
sedative, is capable of inducing seizures, especially
in dogs.
● Hypotension and tachycardia may occur if atipamezole
is injected rapidly intravenously; the intramuscular
route is therefore preferred for this
antagonist.
● Tolazoline is the least specific of the antagonists. In
particular, it behaves as an agonist at H 2 -histamine
receptors and signs including nausea, abdominal
pain, diarrhea and gastrointestinal bleeding have
been recorded in humans.
Contraindications and precautions
● Patients with renal dysfunction
● Patients with a history of seizures
● Dogs that have also received ketamine
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