Kallio-Kujala I J, Bennett R C, Raekallio M R, Yatkin E, Meierjohann A, Savontaus E, Scheinin M, Spillmann T, Vainio O M
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Viikintie 49, FI-00014 Helsinki, Finland.
Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, Viikintie 49, FI-00014 Helsinki, Finland.
Vet J. 2018 Dec;242:33-38. doi: 10.1016/j.tvjl.2018.09.012. Epub 2018 Sep 21.
The commonly used sedative α-adrenoceptor agonist dexmedetomidine has adverse cardiovascular effects in dogs that can be prevented by concomitant administration of the peripherally acting α-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 α-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 α-adrenoceptor agonists in dogs, it should be used with caution in animals at risk for hypoglycaemia because of its insulin-releasing and hypoglycaemic effects.
常用的镇静性α-肾上腺素能受体激动剂右美托咪定在犬类中具有不良心血管效应，可通过同时给予外周作用的α-肾上腺素能受体拮抗剂MK-467来预防。右美托咪定的一个辅助作用是减少胰腺释放胰岛素，而MK-467则刺激胰岛素释放。本研究评估了联合使用右美托咪定和MK-467在犬类格列本脲诱导的低血糖模型中的作用。在一项随机交叉实验中，八只比格犬接受了五种静脉治疗，包括两次给予生理盐水、右美托咪定或右美托咪定与MK-467，以及三次给予格列本脲、生理盐水、右美托咪定或右美托咪定与MK-467。监测血浆葡萄糖、乳酸、胰岛素、胰高血糖素和受试药物的浓度。给予格列本脲显著增加胰岛素分泌并降低血糖浓度。右美托咪定抵消了格列本脲诱发的低血糖。α-肾上腺素能受体拮抗剂MK-467对此起相反作用，但联合使用右美托咪定和MK-467并未增强格列本脲诱发的低血糖。没有一只犬出现失控的低血糖。因此，在该犬类低血糖模型中，右美托咪定和MK-467的组合似乎是安全的。然而，当MK-467用于减轻犬类中α-肾上腺素能受体激动剂的不良心血管效应时，由于其胰岛素释放和降血糖作用，在有低血糖风险的动物中应谨慎使用。
