Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

INTRODUCTION
during short-term opioid use for acute pain relief but
management using stool softeners and other adjuncts
may prove necessary during prolonged opioid therapy.
Constipation results primarily from inhibitory actions
of opioids on neurones of the myenteric plexus, although
the CNS is also involved to a minor extent. Both µ- and
κ-opioid agonists (relative actions depend on species)
markedly inhibit the propulsive contractions of peristalsis,
slowing gastrointestinal transit and thereby increasing
water resorption. Biliary and pancreatic secretion is
inhibited and sphincter tone is increased, contributing
to constipation.
Urinary retention
Urinary retention is a minor and variable side effect of
opioids in most species, resulting from increased sphincter
tone. Where high concentrations are administered
intrathecally or into the extradural space, retention may
be significant, for a period of some hours, and regular
monitoring of urinary bladder tone should be performed.
Opioids with agonist activity at κ-receptors
produce diuresis, thus increasing urine flow.
Histamine release
Opioids are secretagogues and histamine release results
from a nonopioid receptor-mediated action on circulating
mast cells. Pethidine and to a lesser extent morphine
may produce significant histamine release on intravenous
administration of clinical doses. Intravenous use of pethidine
should be avoided. In contrast, fentanyl produces
little or no histamine release. Pruritus is a relatively
common sequel to extradural administration of morphine
(pethidine is not used via this route) and has been
reported in many species including man, the horse and
the dog. This is a receptor-mediated action (it is reversed
by opioid antagonists such as naloxone) but has a poorly
understood mechanism (it may be treated by subanesthetic
concentrations of the sedative-anesthetic propofol,
a drug with no known opioid receptor antagonism).
Excitatory motor effects
Motor excitation, muscular rigidity and explosive motor
behavior can occur with µ-opioid receptor agonists at
high doses in some species. These actions are dose
related and mediated by the CNS. They are thought to
arise from disinhibition of basal ganglia neural systems
and possibly midbrain emotional motor systems. Cats,
horses, pigs and ruminants are particularly susceptible
to excitatory motor effects. Opioids are routinely and
effectively used in these species and these effects are not
normally seen at even high-end clinical doses.
Tolerance and physical dependence
Repeated or continuous use of opioids results in development
of tolerance, or a need to administer an increased
dose to produce the same effect, and physical dependence
characterized by a withdrawal syndrome on cessation
of use.
Tolerance can usually be overcome by increasing the
dose of opioid used but this carries the risk of increasing
physical dependence. The maximum analgesic effect
achievable may be blunted in tolerant patients for partial
agonists such as buprenorphine, pentazocine and butorphanol,
regardless of dose. Tolerance and dependence
do not develop appreciably after a single opioid dose
but are of concern if therapy is continued for more than
several days. Both phenomena are dose related and
develop in parallel. Therefore, if there is need to escalate
doses of opioids over a period of days to produce adequate
control of pain then the likelihood increases that
a withdrawal syndrome will be manifested on cessation
of use.
Opioid withdrawal is intensely dysphoric if severe
and can be minimized by use of gradually diminishing
opioid doses. The syndrome differs somewhat among
species but can include agitation, violent escape attempts,
ptosis, yawning, lacrimation, rhinorrhea, diarrhea, urination,
ejaculation and piloerection.
Indications and techniques of opioid
use in small animals
Animals presenting in pain
Veterinary surgeons may be presented with an animal
in pain, most frequently following trauma. In these
cases moderate-to-high doses of opioid, often in combination
with sedation and a second mode of analgesia
(multimodal analgesia), are needed to overcome the preexisting
nociception. However, the most frequent indication
for opioid administration in veterinary practice
is perioperatively. This may be preoperative, intraoperative,
postoperative or a combination of any or all of
these.
Preoperative analgesia
Preoperative opioids regularly form part of the premedication
protocol, usually in combination with a sedative
or tranquilizer. Premedicants commonly used in companion
animal practice include acepromazine (ACP),
medetomidine and the benzodiazepines diazepam and
midazolam. All three agents have a synergistic effect
with most opioids in current usage. With α 2 -agonists
this may be explained by a co-localization of receptor
activity. Analgesic effects of medetomidine are principally
(but not exclusively) due to spinal antinociception
via binding to nonnoradrenergic receptors located on
the dorsal horn. There is also some evidence of supraspinal
analgesic mechanisms in the locus ceruleus.
In severely compromised animals in whom only lowlevel
sedation is required, a low dose of an opioid alone
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