Effects of dexmedetomidine and MK-467 on plasma glucose, insulin and glucagon in a glibenclamide-induced canine hypoglycaemia model

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Kallio-Kujala , I J , Bennett , R C , Raekallio , M R , Yatkin , E , Meierjohann , A , Savontaus , E , Scheinin , M , Spillmann , T & Vainio , O M 2018 , ' Effects of dexmedetomidine and MK-467 on plasma glucose, insulin and glucagon in a glibenclamide-induced canine hypoglycaemia model ' , Veterinary Journal , vol. 242 , pp. 33-38 . https://doi.org/10.1016/j.tvjl.2018.09.012

Title: Effects of dexmedetomidine and MK-467 on plasma glucose, insulin and glucagon in a glibenclamide-induced canine hypoglycaemia model
Author: Kallio-Kujala, I. J.; Bennett, R. C.; Raekallio, M. R.; Yatkin, E.; Meierjohann, A.; Savontaus, E.; Scheinin, M.; Spillmann, T.; Vainio, O. M.
Contributor: University of Helsinki, Small Animal Hospital
University of Helsinki, Small Animal Hospital
University of Helsinki, Marja Raekallio / Principal Investigator
University of Helsinki, Thomas Spillmann / Principal Investigator
University of Helsinki, Outi Vainio / Principal Investigator
Date: 2018-12
Language: eng
Number of pages: 6
Belongs to series: Veterinary Journal
ISSN: 1090-0233
URI: http://hdl.handle.net/10138/294741
Abstract: The commonly used sedative alpha(2)-adrenoceptor agonist dexmedetomidine has adverse cardiovascular effects in dogs that can be prevented by concomitant administration of the peripherally acting alpha(2)-adrenoceptor antagonist MK-467. An ancillary effect of dexmedetomidine is to decrease insulin release from the pancreas, whereas MK-467 stimulates insulin release. This study assessed the effects of co-administered dexmedetomidine and MK-467 in a canine glibenclamide-induced hypoglycaemia model. In a randomised, cross-over experiment, eight beagle dogs received five intravenous treatments, comprising two administrations of saline, with dexmedetomidine or dexmedetomidine and MK-467, and three administrations of glibenclamide, with saline, dexmedetomidine or dexmedetomidine and MK-467. Plasma concentrations of glucose, lactate, insulin, glucagon and the test drugs were monitored. Administration of glibenclamide significantly increased insulin secretion and decreased blood glucose concentrations. Dexmedetomidine counteracted glibenclamide-evoked hypoglycaemia. This was opposed by the alpha(2)-adrenoceptor antagonist MK-467, but the glibenclamide-evoked hypoglycaemia was not potentiated by co-administration of dexmedetomidine and MK-467. None of the dogs developed uncontrolled hypoglycaemia. Thus, the combination of dexmedetomidine and MK-467 appeared to be safe in this canine hypoglycaemia model. Nevertheless, when MK-467 is used to alleviate the undesired cardiovascular effects of alpha(2)-adrenoceptor agonists in dogs, it should be used with caution in animals at risk for hypoglycaemia because of its insulin-releasing and hypoglycaemic effects. (C) 2018 The Author(s). Published by Elsevier Ltd.
Subject: Canine
Dexmedetomidine
Glibenclamide
Hypoglycaemia
MK-467
ALPHA(2)-ADRENERGIC RECEPTOR ANTAGONIST
INTRAVENOUS DEXMEDETOMIDINE
MEDETOMIDINE
PHARMACOKINETICS
CARDIOPULMONARY
SECRETION
LACTATE
DOG
413 Veterinary science
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