Clinical Actions of Fentanyl and Buprenorphine

Abstract

Receptor binding assays were undertaken in an attempt to elucidate the opioid binding characteristics of fentanyl and buprenorphine, and to investigate some of the differences between them. Buprenorphine showed slow receptor association (30 min), but with high affinity to multiple sites from which dissociation was very slow (T 1/2 = 166 min) and incomplete (50% binding after 1 h). This contrasted with the receptor binding of fentanyl, which achieved rapid equilibrium (within 10 min) and dissociated equally rapidly (T 1/2 = 6.8 min) and completely (100% by 1 h). Competitive displacement showed buprenorphine displacement of fentanyl binding was concentration- and time-dependent over ranges encountered in clinical use, but buprenorphine binding was displaced with only very high concentrations of other opioids. These findings offer pharmacodynamic explanations for the differences in fentanyl and buprenorphine analgesic response profiles and suggest how binding interactions might be applied to therapeutic use.

The Use of Sublingual Buprenorphine–naloxone for Reversing Heroin Overdose: A High‐risk Strategy That Should Not Be Recommended

“…In addition to this, the slow binding kinetics of buprenorphine suggest that a full response may not occur for up to half an hour [6], which is consistent with clinical experience that precipitated withdrawal does not occur immediately, with a time of onset of approximately 20 minutes. This is clearly too long to wait for a response in an overdose situation.…”

“…In Baltimore, Maryland, a recent review of the city's intoxication deaths over the past 13 years found that a very small percentage of opioid-related deaths also involved benzodiazepines [6,7]. The majority involved no other substance except cocaine.…”

Comparison of effect of intrathecal dexmedetomidine and clonidine as an adjuvant to hyperbaric bupivacaine in patients undergoing surgery for fracture femur and tibia

“…[4][5][6][7] These opioids produce satisfactory analgesia for 24hours postoperatively, but are frequently associated with side effects like respiratory depression, itching, nausea, vomiting and urinary retention. [8][9][10][11][12] Other adjuvants like ketamine, neostigmine has been tried but none has become established in regular clinical practice. Various studies have shown that intrathecal clonidine produces prolongation of spinal anaesthesia and reduces the need of post-operative analgesic requirement and there is now adequate evidence that clonidine given intrathecally produces antinociceptive effects without any neurotoxicity and may be useful in the treatment of somatic pain.…”

Pharmacological mechanisms underlying the antinociceptive and tolerance effects of the 6,14-bridged oripavine compound 030418

“…This feature may lead to the persistent occupation of the opioid receptors by 030418. Several early reports have also demonstrated that 6,14-bridged oripavine compounds have very powerful binding interactions with opioid receptors and thus slow receptor kinetics, which causes a long-lasting effect [35][36][37] .…”