3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.5. Opioids
                      3.1.3.5.4. Opioid agonist-antagonists
 3.1.3.5.4.2. Buprenorphine 

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