Buprenorphine

[SH4:p119]

Usage

• Effective in relieving moderate to severe pain
• Effective as epidural opioid
  * Higher lipid solubility and higher affinity for MOP receptors than morphine
  --> Limited cephalad spread
  --> Less likelihood for delayed respiratory depression

Structure

• Derived from thebaine

Pharmacodynamics

Potency

• Analgesic potency is high
  * Buprenorphine 0.3mg IM is equivalent to 10mg of morphine

Mechanism of action

• Buprenorphine - partial agonist action at MOP and NOP receptors
  --> Bell-shaped response curve
• At low and intermediate doses --> Analgesia (due to action at MOP receptors)
• At high doses --> Decreased analgesia (due to action at NOP receptors)
• Affinity at MOP receptors is high
  = 50 times that of morphine
  --> Slow dissociation from receptor
  --> Prolonged duration, and resistance to antagonism with naloxone
• Antagonist effect is mainly due to ability to displace opioid agonists from MOP receptors

Side effects

Side effects similar to morphine
--> But may be resistant to antagonism with naloxone

Side effects include:

• Drowsiness
• N&V
• Respiratory depression
• Pulmonary oedema

NB:

• Dysphoria is unlikely
  * Unlike other agonist-antagonists
• Can precipitate withdrawal symptoms
• Withdrawal from buprenorphine is mild
  * Like withdrawal from other agonist-antagonists
• Risk of abuse is low

Pharmacokinetics

Elimination

• About 2/3 of the drug excreted unchanged in bile
• Rest in urine as inactive metabolites

Action profile

• Onset of action after IM = in 30 minutes
• Duration of action = >8 hours

Physicochemical properties

• High lipid solubility
  * 5 times that of morphine

Clinical