Peripherally acting α-adrenoceptor antagonist MK-467 with intramuscular medetomidine and butorphanol in dogs: A prospective, randomised, clinical trial

Kallio-Kujala, Ira Janika; Turunen, Heta; Raekallio, Marja; Honkavaara, Juhana; Salla, Kati; Casoni, Daniela; Hautajärvi, Heidi; Vainio, Outi

doi:10.1016/j.tvjl.2018.08.007

Cited by 12 publications

(8 citation statements)

References 21 publications

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“…Even if the initial haemodynamic effects of medetomidine are not entirely prevented by intramuscularly (IM) coadministered vatinoxan, their intensity and duration are reduced (Restitutti et al 2017). Similarly, when IM medetomidineevatinoxan is further combined with butorphanol, lesser reductions in HR (Salla et al 2014;Kallio-Kujala et al 2018a) and CI have been observed (Salla et al 2014).…”

mentioning

confidence: 99%

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol, on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

Turunen

Raekallio

Honkavaara

et al. 2020

Veterinary Anaesthesia and Analgesia

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Objective To investigate the impact of intramuscular (IM) co-administration of the peripheral a 2 -adrenoceptor agonist vatinoxan (MK-467) with medetomidine and butorphanol prior to intravenous (IV) ketamine on the cardiopulmonary and anaesthetic effects in dogs, followed by atipamezole reversal.Study design Randomized, masked crossover study.Animals A total of eight purpose-bred Beagle dogs aged 3 years.Methods Each dog was instrumented and administered two treatments 2 weeks apart: medetomidine (20 mg kg e1 ) and butorphanol (100 mg kg e1 ) premedication with vatinoxan (500 mg kg e1 ; treatment MVB) or without vatinoxan (treatment MB) IM 20 minutes before IV ketamine (4 mg kg e1 ). Atipamezole (100 mg kg e1 ) was administered IM 60 minutes after ketamine. Heart rate (HR), mean arterial (MAP) and central venous (CVP) pressures and cardiac output (CO) were measured; cardiac (CI) and systemic vascular resistance (SVRI) indices were calculated before and 10 minutes after MVB or MB, and 10, 25, 40, 55, 70 and 100 minutes after ketamine. Data were analysed with repeated measures analysis of covariance models. A p-value <0.05 was considered statistically significant. Sedation, induction, intubation and recovery scores were assessed.Results At most time points, HR and CI were significantly higher, and SVRI and CVP significantly lower with MVB than with MB. With both treatments, SVRI and MAP decreased after ketamine, whereas HR and CI increased.MAP was significantly lower with MVB than with MB; mild hypotension (57e59 mmHg) was recorded in two dogs with MVB prior to atipamezole administration. Sedation, induction, intubation and recovery scores were not different between treatments, but intolerance to the endotracheal tube was observed earlier with MVB.Conclusions and clinical relevance Haemodynamic performance was improved by vatinoxan co-administration with medetomidineebutorphanol, before and after ketamine administration. However, vatinoxan was associated with mild hypotension after ketamine with the dose used in this study. Vatinoxan shortened the duration of anaesthesia.

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confidence: 99%

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol, on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

Turunen

Raekallio

Honkavaara

et al. 2020

Veterinary Anaesthesia and Analgesia

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“…Classical haemodynamic effects of medetomidine can be attenuated by the co-administration of MK-467 IM in dogs (Restitutti et al, 2017). MK-467 when combined with medetomidine and butorphanol minimize the bradycardia induced by medetomidine in dogs as well advocate the adequate sedation required for diagnostic procedures (Kallio-Kujala et al, 2018a). In cats as well, the combinations of vatinoxan and α 2 -agonists have the potential to lessen the α 2 -agonist-induced adverse effects with little or no impact on the desired outcome.…”

Section: Effects Of Mk-467 In Different Animal Speciesmentioning

confidence: 99%

“…MK-467 markedly influence the early disposition of dexmedetomidine without obvious effects on the plasma concentrations of the later in dogs, cats as well as sheep, whereas dexmedetomidine does affects the disposition of MK-467, but only minimally (Honkavaara et al, 2011;Pypendop et al, 2016;Adam et al, 2018). It has been analyzed that MK-467 elevates the early stage plasma concentration of both medetomidine and butorphanol when administrated IM in the same syringe and thereby results in deeper initial sedation for a shorter duration (Kallio-Kujala et al, 2018a;Restitutti et al, 2017). Bennett et al (2016) outlined the plasma disposition of dexmedetomidine in dogs when given together with MK-467.…”

Section: Pharmacokinetic Effectsmentioning

confidence: 99%

Various Systemic Effects of MK-467, A Peripherally Acting α2-adrenoceptor Antagonist in Different Animal Species: An Overview

Akash

Hoque

Amarpal

2020

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Most commonly used α2-adrenoceptor agonist shows adverse cardiovascular effects during anaesthesia. They mainly depress the cardiovascular system by provoking vasoconstriction followed by bradycardia. Although α2-adrenoceptor antagonist like atipamezole can reverse these effects along with that they also reverse the sedation and nociception. Concomitant administration of peripherally acting α2-adrenoceptor antagonist MK-467 can reverse the adverse cardiovascular effect of α2-adrenoceptor agonists without affecting the sedation and nociception. MK-467 has been successfully used in different animals like dogs, cats, sheep, horses along with different α2-adrenoceptor agonist drugs. This review aims to summarize the effects of MK-467 on sedation, cardiopulmonary system, the minimum alveolar concentration of different inhalant anaesthetics, plasma drug concentration, plasma glucose and insulin in different animals.

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“…α2-AM reduces gastric secretion, increases the duration of food transit [9], and inhibits colon motility [44].…”

Section: Effect On the Digestive Tractmentioning

confidence: 99%

Tendencies and perspectives of central alpha2-adrenomimetic application in medicobiological research

et al. 2019

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The pharmacodynamic effects of the administration of 2-adrenergic agonists both in a monovariant and in combination with drugs of other pharmacological groups are considered. Based on analysis of safety nonclinical studies the characteristics of main physiological effects of 2-adrenergic receptors as well as physiological effects of 2-agonists on various organs and systems are presented. For the determination of tendencies and directions in research of central 2-AM (dexmedetomidine) the analysis of bibliographical data, accumulated and extracted from Medline database with 5 year time-filter (VOSviewer, 1.6.11 version) has been carried out. For the further research of central 2-adrenomimetics and their application in clinical practice the following perspective directions have been determined: the study of effects and mechanisms of cytoprotectant and antioxidant action, the study of the use of drugs in a monovariant and in combinations for the development of analgesic drugs, anesthesia and development of combined formulations with a delayed release of antagonists designed to mitigate side effects.

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Peripherally acting α-adrenoceptor antagonist MK-467 with intramuscular medetomidine and butorphanol in dogs: A prospective, randomised, clinical trial

Cited by 12 publications

References 21 publications

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol, on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

Effects of intramuscular vatinoxan (MK-467), co-administered with medetomidine and butorphanol, on cardiopulmonary and anaesthetic effects of intravenous ketamine in dogs

Various Systemic Effects of MK-467, A Peripherally Acting α2-adrenoceptor Antagonist in Different Animal Species: An Overview

Tendencies and perspectives of central alpha2-adrenomimetic application in medicobiological research

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