Buprenorphine: an additional option in the fight against pain in dogs and cats
Buprenorphine hydrochloride is a partial μ-opioid agonist with a structure very similar to morphine. The receptor pharmacology and pharmacokinetics profile of buprenorphine is complex but unique and contributes to its distinct safety and efficacy. It is a highly lipophilic molecule with high affinity for μ-receptor, thus binding to the μ-opioid receptor slowly but with an extremely big strenght. Once bound to the receptor, buprenorphine activates only partially the receptor, producing part of its potential activity and providing moderate analgesia and variable sedation and is associated with few adverse effects.
Buprenorphine is 25-30 times more potent than morphine, the original opiate narcotic that all others are compared to in terms of potency and effectiveness. While potency is greater, efficacy, especially in acute pain, is lesser than that of morphine and other pure μ-agonists. This means that lower doses are needed to determine a given analgesic effect, but the maximum effect that the drug can produce is lower.
In veterinary medicine, buprenorphine is used primarily as an analgesic for relieving mild-to-moderate pain in dogs and cats following minor surgical procedures such as routine ovariohysterectomy, castration, dental procedures and simple orthopedic procedures. Given the long duration of action, lower sedation and lesser side effects associated with the use of buprenorphine, it is suitable for analgesia in hospitalised patients after treatment of acute postoperative pain with more effective techniques and drugs. Buprenorphine should not be considered the opioid of choice for surgical procedures involving severe pain, where locoregional techniques or more effective drugs must be taken into account.
We discourage the use of buprenorphine also as premedication in patients scheduled for surgery or scheduled for diagnostic procedures that are likely to end up with a surgery. Patients having received buprenorphine will need considerably higher doses of μ-agonist to reach a given analgesic effect as receptors will be occupied by the partial agonist with higher affinity and lower efficacy. It is recommended withholding buprenorphine therapy for at least 4-6 hours before administering anaesthesia when incorporating a pure μ-receptor agonist.
Combination with NSAIDs is recommended in healthy patients as the analgesic effect is greatly enhanced.
Pharmacodynamic of IV and IM buprenorphine is characterized by a negative hysteresis, indicating that buprenorphine’s effective plasma levels are not necessarily associated with the drug’s antinociceptive effects and that the drug after administration will have a delayed onset: approximately 30 minutes to peak effect, after IV administration and 45 to 60 minutes after IM administration.
Recommended dosing for dogs and cats ranges between 0.01 and 0.04 mg/kg with duration of antinociceptive effect increasing proportionally with the dose administered. Duration of effect varies between 3 to 4 hours at 0.01 mg/kg up to 10 hours at 0.04 mg/kg, for normal formulations, while it can reach up to 72 hours of analgesic effect with sustained-release formulations.
In cats, different studies have shown that bioavailability is comparable whether given IV, IM, or via buccal oral mucosa (the molecule is not absorbed into the GI tract, where bioavailability is poor, but directely through oral mucosa). This transmucosal absorption seems to be influenced by the alkaline pH of feline saliva and there is, as yet, no support for effective oral absorption by the dog.
Buprenorphine has minimal sedative and respiratory depressant effects and is not associated with clinically significant hyperthermia in cats. Larger doses of buprenorphine are not associated with an increased level of sedation or adverse effects. These characteristics of the molecule can be used in order to antagonize pure μ-opioid agonist induced side effects preserving a moderate degree of analgesia.
Buprenorphine has many unique characteristics that distinguish it from other μ-opioid agonists and it is necessary to clearly understand its PK and PD features to obtain the greatest clinical advantages. Long duration of action with moderate analgesia and few side effects together with multiple efficient routes of administration, including the oral transmucosal way, make it a viable option for long-term pain management in dogs and cats.
If you have noted any problems with your animal, please consult your veterinarian.
Text by Tommaso Pilla