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Options in perioperative analgesia: buprenorphine v. methadone

01 May 2014, at 1:00am

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.).