Mechanisms of respiratory depression induced by the combination of buprenorphine and diazepam in rats.
Animals
Male
Rats
Analgesics, Opioid
/ pharmacokinetics
Benzodiazepines
/ pharmacokinetics
Blood Gas Analysis
/ methods
Buprenorphine
/ adverse effects
Diazepam
/ adverse effects
Drug Interactions
/ physiology
Flumazenil
/ pharmacokinetics
Narcotic Antagonists
/ pharmacokinetics
Rats, Sprague-Dawley
Receptors, Opioid
/ metabolism
Respiratory Insufficiency
/ chemically induced
PET imaging
benzodiazepine
buprenorphine
diazepam
pharmacodynamic interaction
rat
respiratory depression
Journal
British journal of anaesthesia
ISSN: 1471-6771
Titre abrégé: Br J Anaesth
Pays: England
ID NLM: 0372541
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
21
06
2021
revised:
05
10
2021
accepted:
28
10
2021
pubmed:
8
12
2021
medline:
8
3
2022
entrez:
7
12
2021
Statut:
ppublish
Résumé
The safety profile of buprenorphine has encouraged its widespread use. However, fatalities have been attributed to benzodiazepine/buprenorphine combinations, by poorly understood mechanisms of toxicity. Mechanistic hypotheses include (i) benzodiazepine-mediated increase in brain buprenorphine (pharmacokinetic hypothesis); (ii) benzodiazepine-mediated potentiation of buprenorphine interaction with opioid receptors (receptor hypothesis); and (iii) combined effects of buprenorphine and benzodiazepine on respiratory parameters (pharmacodynamic hypothesis). We studied the neuro-respiratory effects of buprenorphine (30 mg kg In contrast to diazepam and buprenorphine alone, diazepam/buprenorphine induced early-onset sedation (P<0.05) and respiratory depression (P<0.001). Diazepam did not alter Pharmacodynamic parameters and antagonist pretreatments indicate that diazepam/buprenorphine-induced respiratory depression results from a pharmacodynamic interaction between both drugs on ventilatory parameters.
Sections du résumé
BACKGROUND
The safety profile of buprenorphine has encouraged its widespread use. However, fatalities have been attributed to benzodiazepine/buprenorphine combinations, by poorly understood mechanisms of toxicity. Mechanistic hypotheses include (i) benzodiazepine-mediated increase in brain buprenorphine (pharmacokinetic hypothesis); (ii) benzodiazepine-mediated potentiation of buprenorphine interaction with opioid receptors (receptor hypothesis); and (iii) combined effects of buprenorphine and benzodiazepine on respiratory parameters (pharmacodynamic hypothesis).
METHODS
We studied the neuro-respiratory effects of buprenorphine (30 mg kg
RESULTS
In contrast to diazepam and buprenorphine alone, diazepam/buprenorphine induced early-onset sedation (P<0.05) and respiratory depression (P<0.001). Diazepam did not alter
CONCLUSIONS
Pharmacodynamic parameters and antagonist pretreatments indicate that diazepam/buprenorphine-induced respiratory depression results from a pharmacodynamic interaction between both drugs on ventilatory parameters.
Identifiants
pubmed: 34872716
pii: S0007-0912(21)00701-7
doi: 10.1016/j.bja.2021.10.029
pii:
doi:
Substances chimiques
Analgesics, Opioid
0
Benzodiazepines
12794-10-4
Buprenorphine
40D3SCR4GZ
Diazepam
Q3JTX2Q7TU
Flumazenil
40P7XK9392
Narcotic Antagonists
0
Receptors, Opioid
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
584-595Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.