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Article Dans Une Revue Clinical Toxicology Année : 2022

Effect of the first wave of COVID-19 on Poison Control Centre activities in 21 European countries: an EAPCCT initiative

L. Hondebrink
M. Zammit
L. Høgberg
M. Hermanns-Clausen
D. Lonati
K. Faber
T Arif
  • Fonction : Auteur
Z Babić
G Bacis
  • Fonction : Auteur
L Bahtić
  • Fonction : Auteur
N Bates
M Brvar
E Burbienė
  • Fonction : Auteur
B Cagáňová
  • Fonction : Auteur
P Casey
N Delcourt
Am Descamps
A Descatha
V Eagling
  • Fonction : Auteur
F Eyer
F Gambassi
L Gray
P Jagpal
  • Fonction : Auteur
J Jovic-Stosic
  • Fonction : Auteur
M Labadie
T Lilius
H Líndal
Ca Locatelli
M Midtervoll
  • Fonction : Auteur
P Nisse
Df Palmqvist
  • Fonction : Auteur
Am Patat
Z Pereska
E Puskarczyk
  • Fonction : Auteur
G Ricci
A Salierno
N Simon
M Tellerup
  • Fonction : Auteur
R Thanacoody
A van Velzen

Résumé

Tramadol overdose is frequently associated with the onset of seizures, usually considered as serotonin syndrome manifestations. Recently, the serotoninergic mechanism of tramadol-attributed seizures has been questioned. This study’s aim was to identify the mechanisms involved in tramadol-induced seizures in overdose in rats. The investigations included (1) the effects of specific pretreatments on tramadol-induced seizure onset and brain monoamine concentrations, (2) the interaction between tramadol and γ-aminobutyric acid (GABA)A receptors in vivo in the brain using positron emission tomography (PET) imaging and 11C-flumazenil. Diazepam abolished tramadol-induced seizures, in contrast to naloxone, cyproheptadine and fexofenadine pretreatments. Despite seizure abolishment, diazepam significantly enhanced tramadol-induced increase in the brain serotonin (p < 0.01), histamine (p < 0.01), dopamine (p < 0.05) and norepinephrine (p < 0.05). No displacement of 11C-flumazenil brain kinetics was observed following tramadol administration in contrast to diazepam, suggesting that the observed interaction was not related to a competitive mechanism between tramadol and flumazenil at the benzodiazepine-binding site. Our findings do not support the involvement of serotoninergic, histaminergic, dopaminergic, norepinephrine or opioidergic pathways in tramadol-induced seizures in overdose, but they strongly suggest a tramadol-induced allosteric change of the benzodiazepine-binding site of GABAA receptors. Management of tramadol-poisoned patients should take into account that tramadol-induced seizures are mainly related to a GABAergic pathway.

Dates et versions

hal-03905686 , version 1 (18-12-2022)

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Citer

L. Hondebrink, M. Zammit, L. Høgberg, M. Hermanns-Clausen, D. Lonati, et al.. Effect of the first wave of COVID-19 on Poison Control Centre activities in 21 European countries: an EAPCCT initiative. Clinical Toxicology, 2022, 60 (10), pp.1145-1155. ⟨10.1080/15563650.2022.2113094⟩. ⟨hal-03905686⟩

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