Small Animal Clinical Pharmacology - CYF MEDICAL DISTRIBUTION

CHAPTER 14 OPIOID ANALGESICS
Contraindications and precautions
● Caution should be exercised when administering
morphine to animals with head trauma. It is important
to ensure that ventilation is adequate to avoid
problems associated with increased arterial CO 2 .
● Rapid intravenous administration of large doses
should be avoided in hypovolemic animals because
of the risk of histamine release and a further decrease
in arterial blood pressure.
● Epidural administration of any drug is best avoided
during sepsis and in the presence of clotting abnormalities
or localized skin infections.
Known drug interactions
● As with other opioids, morphine has a synergistic
action with ACP, the most commonly used sedative in
small animal practice. Because of the additive effect of
this and similar combinations, caution would suggest
that the individual dose of each drug be reduced from
that given alone. This will of course be tempered by
the animal’s temperament and the desired effect. Of
particular concern when using such combinations is
the exacerbation of ventilatory depression.
● Similarly, morphine has at least additive actions on
respiratory depression when used with other sedatives
such as benzodiazepines and barbiturates.
● Verapamil augments the analgesia produced by
morphine.
Pethidine (meperidine)
Clinical applications
Pethidine has only very mild sedative effects when given
alone to healthy animals but is unlikely to induce bradycardia,
unlike other opioids. Because of its short
duration of action (1–2 h at the most), pethidine is of
more practical use as a preanesthetic medication than
as a postoperative analgesic. Vomiting is less common
than with morphine when used as a premedicant.
Mechanism of action
Pethidine has a similar receptor selectivity profile to
morphine, is slightly less efficacious and has lower
potency. It has an extremely fast onset, even when given
by the subcutaneous route (less than 5 min).
Formulations and dose rates
DOGS AND CATS
• 2–10 mg/kg IM, SC
Although absorption of pethidine can be variable after IM
administration, this route is preferred to SC because of the
local irritation and pain that may be produced. Pethidine is
not to be administered IV in small animals because of
marked histamine release.
Pharmacokinetics
Pethidine is moderately lipid soluble and has an onset
of action shorter than that of morphine following IM
injection. About 70% is protein bound to albumin,
lipoprotein and α 1 -acid glycoprotein.
Most pethidine is metabolized in the liver to norpethidine,
pethidinic acid and norpethidinic acid, which are
then excreted via the kidneys. Norpethidine can accumulate
in renal failure and has about half the analgesic
potency of pethidine. Norpethidine also causes CNS
stimulation and may result in myoclonus and seizures,
a situation more common with prolonged administration
in the presence of renal impairment.
Adverse effects
● In equianalgesic doses, pethidine’s respiratory depressant
effects are comparable to morphine.
● Pethidine should not be given IV as it significantly
depresses myocardial contractility and causes histamine
release.
● Vomiting is rarely seen after administration and it
does not cause excitement in cats or horses.
● Bradycardia is rarely seen due to pethidine’s atropine-like
structure which may cause tachycardia.
● Large doses of pethidine, greater than 20 mg/kg, will
induce excitement and seizures in cats.
Known drug interactions
Pethidine should be used cautiously in conjunction with
monoamine oxidase inhibitors such as selegiline (see
Chapter 7). Use with monoamine oxidase inhibitors
leads to excessive metabolism to norpethidine, with
greatly increased risk of myoclonus and seizures.
Methadone
Methadone is a synthetic opioid with a pharmacological
profile similar to morphine.
Clinical applications
Similar use to morphine, although not for epidural use
as it is not available in preservative-free formulation.
Mechanism of action
The potency and efficacy of methadone are similar to
morphine and it is more selective for µ-receptors.
Its analgesic efficacy is similar to morphine after a
single dose but is several times greater after repeated
administration. This may result from its very long
plasma half-life, which in humans is on average 24 h;
however, this does not appear to be the case in
animals.
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