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InFocus

Options in perioperative analgesia: buprenorphine v. methadone

Miguel Martinez discusses the use of opioid analgesic drugs and compares two which are currently licensed for the provision of perioperative pain relief in cats and dogs

PAIN and analgesia is a fast
developing field of research.
However, new knowledge
translates slowly into changes in
clinical practice. Dogs and cats
often
undergo
painful
surgical
procedures
and
adequate
pain relief
is of
paramount importance in those
situations.

Nowadays, the concepts of
multimodal and pre-emptive analgesia
are well known and applied by the
veterinary profession. The
administration of analgesic drugs
with different mechanisms of action and, ideally, before the noxious
stimulus is applied, provides better
pain relief with fewer side effects.

Opioid analgesics and non-
steroidal anti-inflammatory drugs (NSAIDs) are the cornerstone of
many analgesic plans in general
veterinary practice. Other drugs such
as tramadol, gabapentin, paracetamol
and local analgesics are less
commonly used.

The majority of opioid analgesic
drugs used in clinical practice exert their analgesic effect through binding
and activation of μ opioid receptors.
Among these drugs, buprenorphine
and methadone are currently licensed
for the provision of perioperative
pain relief in cats and dogs.

Partial agonist

Buprenorphine is a semi-synthetic
partial μ opioid agonist widely used
in veterinary practice. As a partial
agonist, it binds to the μ receptor
producing sub-maximal activation
with a so-called “ceiling effect”. This
means that increasing doses may, at
some point, not increase analgesia.

It is also for this reason that the
potential risk of unwanted side
effects (bradycardia, respiratory
depression, etc.) is reduced. It has a
slow onset of action (30-40 minutes)
and a reasonably long duration of effect (6-12 hours) at the
manufacturer’s recommended dose.

Buprenorphine is often combined
with sedatives such as alpha 2
agonists and acepromazine as a
premedication previous to surgical
procedures. It is also frequently used
in the post-operative period to
provide pain relief, often in
combination with NSAIDs.

It is particularly efficacious in
feline patients where research has
shown it is as effective as morphine.
Besides, it is very convenient due to
its longer duration of action and it
can be administered by several
different routes (intravenous,
intramuscular, subcutaneous and
transmucosal) with excellent
bioavailability and results.

Finally, it is also advantageous
that buprenorphine is a Schedule 3
opioid with a lower level of legal
restrictions and controls and a lower
potential for human abuse.

Attractive choice

All these qualities make
buprenorphine a very attractive
choice for the veterinary practitioner
and this is the reason why currently it
is probably the number one opioid
used in general practice.

In recent years, however, other
opioid analgesics have been tested in
clinical research settings and finally
have made it into the veterinary
market. One of these opioids is
methadone.

Methadone is an “old” drug that
has suffered for years from a bad
reputation, because it is automatically
linked to drug abuse and drug
addicts. However, it is an excellent
analgesic with a fantastic
pharmacological profile.

Unlike buprenorphine, methadone
is a pure μ opioid agonist, meaning
that its efficacy augments as we
increase the dose without a ceiling effect at doses used
clinically. Unfortunately,
this also means there are
more chances of seeing
side-effects such as
dysphoria, nausea,
reduced gastrointestinal
motility, respiratory
depression and
bradycardia.

It is not uncommon
to see dogs panting after
receiving methadone,
especially via the
intravenous route. Cats
are more prone to show
behavioural effects.

Short onset of action

Methadone is quite lipid soluble and
crosses the brain barrier very quickly,
meaning it has a very short onset of
action. It provides at least 4-6 hours
of analgesia at the doses
recommended by the manufacturer.

It also binds to the NMDA
receptor in the central nervous system
where it works as an antagonist. This
action prevents central sensitisation
and “wind up”, two phenomena
involved in the development of
chronic and neuropathic pain.

It is for these reasons that
methadone is an excellent choice for analgesia in the perioperative period
(before, during and after surgery). In
the premedication it works
synergistically with sedative drugs and
does not stimulate vomiting, unlike
morphine.

During surgery it can be used for
“top-ups” with an extremely fast
onset of action. Post-operatively it
can be titrated easily to effect
following regular pain scores.
Methadone is the author’s first choice
opioid for perioperative analgesia.

Methadone is a controlled drug
(Schedule 2) and the usual
precautions and rules for these types
of drugs have to be followed (storage,
record keeping, etc.).

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