Pharmacology Notes

Buprenorphine is a partial opioid agonist at mu receptors and an antagonist at kappa receptors, with a prolonged duration of action. It is available as sublingual, parenteral and transdermal preparations. Sublingual buprenorphine is indicated for use in acute and chronic pain, for cancer pain, and opioid detoxification.

Buprenorphine is subject to considerable first-pass metabolism following oral administration. Buprenorphine is metabolised by cytochrome P450 3A4. Drugs which inhibit CYP3A4 (eg ketoconazole, erythromycin) may cause significant increases in serum buprenorphine levels and drugs which induce CYP3A4 (eg carbamazepine) may cause significant decreases in serum buprenorphine levels.

Buprenorphine has high receptor affinity and slow dissociation from the receptor, with the analgesic effect persisting longer than the elimination half-life. Hence, there is no direct correlation between plasma level and clinical effect. After higher doses of buprenorphine, respiratory depression can occur that may be unresponsive to naloxone. A ceiling effect for respiratory depression may give buprenorphine a better safety profile than full opioid agonists. It can precipitate withdrawal reactions in patients taking pure opioid receptor agonists (eg morphine, oxycodone). Because of this adverse effect, it has a very limited use for pain management in palliative care.

The 7-day transdermal patch is indicated for use in moderate to severe pain. It reaches steady state after 3 days, and plasma levels decrease by 50% approximately 12 hours after the patch is removed. Buprenorphine patches are not suitable for the management of acute pain or for use in patients with rapidly changing analgesic requirements.

Buprenorphine should not be considered a first-line analgesic agent, because there is limited evidence about, and experience of, its use compared to other opioids.

In the treatment of opioid dependence, buprenorphine has the advantage of lower overdose risk than methadone and lesser physical dependence.

The bioavailability of sublingual buprenorphine is about 30%. While normally administered sublingually once-daily, many people find that alternate-day administration provides satisfactory relief of withdrawal symptoms. As with methadone, the dose needs to be determined individually. 

Buprenorphine can precipitate withdrawal if used too soon in a person who has taken a high dose of an opioid. This needs to be considered when commencing treatment. Buprenorphine can cause typical opioid effects such as sedation, nausea, itching and constipation, but in high doses it can cause withdrawal symptoms such as sweating, flu-like symptoms, abdominal pain, insomnia and mood swings in patients dependent on opioids. Allergic reactions, including angioedema and anaphylaxis, have been reported.

Reversal of buprenorphine overdose with naloxone may require considerably higher doses than those used for heroin or methadone overdose, possibly because buprenorphine binds very firmly to opioid receptors.