Changes in energy metabolism, and levels of stress-related hormones and electrolytes in horses after intravenous administration of romifidine and the peripheral α-2 adrenoceptor antagonist vatinoxan.
Abstract: Romifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan (previously known as MK-467), in turn, is an antagonist of α-2 adrenoceptors. Because vatinoxan does not cross the blood brain barrier in significant amounts, it has only minor effect on sedation induced by α-2 adrenoceptor agonists. Previously, vatinoxan is shown to prevent the hyperglycaemia, increase of plasma lactate concentration and the decrease of insulin and non-esterified free fatty acids (FFAs) caused by α-2 adrenoceptor agonists in different species. The aim of our study was to investigate the effects of intravenous romifidine and vatinoxan, alone and combined, on plasma concentrations of glucose and some stress-related hormones and metabolites in horses. Results: Plasma glucose concentration differed between all intravenous treatments: romifidine (80 μg/kg; ROM), vatinoxan (200 μg/kg; V) and the combination of these (ROM + V). Glucose concentration was the highest after ROM and the lowest after V. Serum FFA concentration was higher after V than after ROM or ROM + V. The baseline serum concentration of insulin varied widely between the individual horses. No differences were detected in serum insulin, cortisol or plasma adrenocorticotropic hormone (ACTH) concentrations between the treatments. Plasma lactate, serum triglyceride or blood sodium and chloride concentrations did not differ from baseline or between the treatments. Compared with baseline, plasma glucose concentration increased after ROM and ROM + V, serum cortisol, FFA and base excess increased after all treatments and plasma ACTH concentration increased after V. Serum insulin concentration decreased after V and blood potassium decreased after all treatments. Conclusions: Romifidine induced hyperglycaemia, which vatinoxan partially prevented despite of the variations in baseline levels of serum insulin. The effects of romifidine and vatinoxan on the insulin concentration in horses need further investigation.
Publication Date: 2018-05-09 PubMed ID: 29743097PubMed Central: PMC5944056DOI: 10.1186/s13028-018-0380-xGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The researchers studied the effects of a commonly used equine sedative, romifidine, on stress-related hormones and electrolyte levels in horses while also examining the potential mitigating effects of the drug vatinoxan. They discovered that romifidine can cause high blood sugar levels, which vatinoxan can somewhat counteract. However, variations in how horses’ insulin levels respond require additional investigation.
Introduction
- The study aimed to observe the effects of romifidine, a common sedative used in equine medicine, and vatinoxan, an α-2 adrenoceptor antagonist, on the plasma concentrations of glucose, stress-related hormones, and metabolites in horses.
- Romifidine functions by activating α-2 adrenoceptors; however, its use may also alter plasma levels of glucose and certain stress-related hormones and metabolites.
- On the other hand, vatinoxan, which has minimal effect on sedation, has been shown to counteract hyperglycaemia and disturbances in lactate, insulin, and fatty acid levels.
Methodology
- The research was conducted using intravenous treatments of romifidine, vatinoxan, and a combination of both.
- Changes in glucose, serum fatty acid (FFA), and insulin concentrations were recorded for each treatment, among other measures.
Results
- A difference was observed in plasma glucose concentration between all treatments, with the highest seen after administering romifidine and the lowest after vatinoxan.
- The serum FFA concentration was higher in horses after vatinoxan compared to those after romifidine or the combination treatment.
- Plasma lactate, serum triglyceride, or blood sodium and chloride concentrations remained unchanged between treatments.
- Post treatment, increases were noted in plasma glucose concentration after the romifidine and combination treatment, while decreases were observed in insulin concentration after vatinoxan, and blood potassium after all treatments.
Conclusions
- The study found that romifidine induced hyperglycaemia in horses, a condition somewhat mitigated by vatinoxan.
- Due to varying levels of insulin observed across horses, further investigation is required to understand the effects of romifidine and vatinoxan on insulin concentration in horses.
Cite This Article
APA
Pakkanen SAE, de Vries A, Raekallio MR, Mykkänen AK, Palviainen MJ, Sankari SM, Vainio OM.
(2018).
Changes in energy metabolism, and levels of stress-related hormones and electrolytes in horses after intravenous administration of romifidine and the peripheral α-2 adrenoceptor antagonist vatinoxan.
Acta Vet Scand, 60(1), 27.
https://doi.org/10.1186/s13028-018-0380-x Publication
Researcher Affiliations
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland. soile.pakkanen@fimnet.fi.
- Davies Veterinary Specialists, Manor Farm Business Park, Higham Gobion, Hertfordshire, UK.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.
- Department of Equine and Small Animal Medicine, Faculty of Veterinary Medicine, University of Helsinki, P.O. Box 57, 00014, Helsinki, Finland.
MeSH Terms
- Administration, Intravenous / veterinary
- Adrenergic alpha-2 Receptor Agonists / administration & dosage
- Adrenocorticotropic Hormone / blood
- Animals
- Blood Glucose / metabolism
- Drug Combinations
- Energy Metabolism / drug effects
- Female
- Horses / metabolism
- Hydrocortisone / blood
- Imidazoles / administration & dosage
- Insulin / blood
References
This article includes 46 references
- Kullmann A, Sanz M, Fosgate GT, Saulez MN, Page PC, Rioja E. Effects of xylazine, romifidine, or detomidine on hematology, biochemistry, and splenic thickness in healthy horses.. Can Vet J 2014 Apr;55(4):334-40.
- Thurmon JC, Neff-Davis C, Davis LE, Stoker RA, Benson GJ, Lock TF. Xylazine hydrochloride-induced hyperglycemia and hypoinsulinemia in thoroughbred horses.. J Vet Pharmacol Ther 1982 Dec;5(4):241-5.
- Carroll GL, Matthews NS, Hartsfield SM, Slater MR, Champney TH, Erickson SW. The effect of detomidine and its antagonism with tolazoline on stress-related hormones, metabolites, physiologic responses, and behavior in awake ponies.. Vet Surg 1997 Jan-Feb;26(1):69-77.
- Angel I, Bidet S, Langer SZ. Pharmacological characterization of the hyperglycemia induced by alpha-2 adrenoceptor agonists.. J Pharmacol Exp Ther 1988 Sep;246(3):1098-103.
- Raekallio M, Vainio O, Karjalainen J. The influence of atipamezole on the cardiovascular effects of detomidine in horses.. J Ass vet Anaesth 1990;17:50–53.
- Raekallio M, Leino A, Vainio O, Scheinin M. Sympatho-adrenal activity and the clinical sedative effect of detomidine in horses.. Equine Vet J Suppl 1992 Feb;(11):66-8.
- Raekallio M, Vainio O, Scheinin M. Detomidine reduces the plasma catecholamine, but not cortisol concentrations in horses.. Zentralbl Veterinarmed A 1991 Apr;38(3):153-6.
- Alexander SL, Irvine CH. The effect of the alpha-2-adrenergic agonist, clonidine, on secretion patterns and rates of adrenocorticotropic hormone and its secretagogues in the horse.. J Neuroendocrinol 2000 Sep;12(9):874-80.
- Nuñez E, Steffey EP, Ocampo L, Rodriguez A, Garcia AA. Effects of alpha2-adrenergic receptor agonists on urine production in horses deprived of food and water.. Am J Vet Res 2004 Oct;65(10):1342-6.
- DeFronzo RA, Sherwin RS, Dillingham M, Hendler R, Tamborlane WV, Felig P. Influence of basal insulin and glucagon secretion on potassium and sodium metabolism. Studies with somatostatin in normal dogs and in normal and diabetic human beings.. J Clin Invest 1978 Feb;61(2):472-9.
- Ambrisko TD, Hikasa Y. The antagonistic effects of atipamezole and yohimbine on stress-related neurohormonal and metabolic responses induced by medetomidine in dogs.. Can J Vet Res 2003 Jan;67(1):64-7.
- Ueoka N, Hikasa Y. Effects in cats of atipamezole, flumazenil and 4-aminopyridine on stress-related neurohormonal and metabolic responses induced by medetomidine, midazolam and ketamine.. J Feline Med Surg 2015 Aug;17(8):711-8.
- Ranheim B, Horsberg TE, Søli NE, Ryeng KA, Arnemo JM. The effects of medetomidine and its reversal with atipamezole on plasma glucose, cortisol and noradrenaline in cattle and sheep.. J Vet Pharmacol Ther 2000 Dec;23(6):379-87.
- Carroll GL, Hartsfield SM, Champney TH, Geller SC, Martinez EA, Haley EL. Effect of medetomidine and its antagonism with atipamezole on stress-related hormones, metabolites, physiologic responses, sedation, and mechanical threshold in goats.. Vet Anaesth Analg 2005 May;32(3):147-57.
- Luna SP, Taylor PM, Carregaro AB. Atipamezole antagonism of an ACTH stimulation test in ponies sedated with detomidine.. J Vet Pharmacol Ther 2011 Oct;34(5):508-11.
- Ramseyer B, Schmucker N, Schatzmann U, Busato A, Moens Y. Antagonism of detomidine sedation with atipamezole in horses.. Vet Anaesth Analg 1998;25:47–51.
- Hubbell JA, Muir WW. Antagonism of detomidine sedation in the horse using intravenous tolazoline or atipamezole.. Equine Vet J 2006 May;38(3):238-41.
- DiMaio Knych HK, Covarrubias V, Steffey EP. Effect of yohimbine on detomidine induced changes in behavior, cardiac and blood parameters in the horse.. Vet Anaesth Analg 2012 Nov;39(6):574-83.
- Clineschmidt BV, Pettibone DJ, Lotti VJ, Hucker HB, Sweeney BM, Reiss DR, Lis EV, Huff JR, Vacca J. A peripherally acting alpha-2 adrenoceptor antagonist: L-659,066.. J Pharmacol Exp Ther 1988 Apr;245(1):32-40.
- Warren JB, Dollery CT, Sciberras D, Goldberg MR. Assessment of MK-467, a peripheral alpha 2-adrenergic receptor antagonist, with intravenous clonidine.. Clin Pharmacol Ther 1991 Jul;50(1):71-7.
- Goldman ME, Pettibone DJ, Reagan JE, Clineschmidt BV, Baldwin JJ, Huff JR. Blockade of peripheral α2-adrenoceptors by L-659,066 enhances glucose tolerance and insulin release in mice.. Drug Develop Res 1989;17:141–151.
- Restitutti F, Raekallio M, Vainionpää M, Kuusela E, Vainio O. Plasma glucose, insulin, free fatty acids, lactate and cortisol concentrations in dexmedetomidine-sedated dogs with or without MK-467: a peripheral α-2 adrenoceptor antagonist.. Vet J 2012 Aug;193(2):481-5.
- Sciberras DG, Reed JW, Elliott C, Blain PG, Goldberg MR. The effects of a peripherally selective alpha 2-adrenoceptor antagonist, MK-467, on the metabolic and cardiovascular response to exercise in healthy man.. Br J Clin Pharmacol 1994 Jan;37(1):39-44.
- Schafers RF, Elliott HL, Howie CA, Reid JL. A preliminary, clinical pharmacological assessment of L-659,066, a novel alpha 2-adrenoceptor antagonist.. Br J Clin Pharmacol 1992 Dec;34(6):521-6.
- Vainionpää MH, Raekallio MR, Pakkanen SA, Ranta-Panula V, Rinne VM, Scheinin M, Vainio OM. Plasma drug concentrations and clinical effects of a peripheral alpha-2-adrenoceptor antagonist, MK-467, in horses sedated with detomidine.. Vet Anaesth Analg 2013 May;40(3):257-64.
- de Vries A, Pakkanen SA, Raekallio MR, Ekiri A, Scheinin M, Taylor PM, Vainio OM. Clinical effects and pharmacokinetic variables of romifidine and the peripheral α(2) -adrenoceptor antagonist MK-467 in horses.. Vet Anaesth Analg 2016 Nov;43(6):599-610.
- Honkavaara JM, Raekallio MR, Kuusela EK, Hyvärinen EA, Vainio OM. The effects of L-659,066, a peripheral alpha2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia in dogs.. Vet Anaesth Analg 2008 Sep;35(5):409-13.
- Restitutti F, Honkavaara JM, Raekallio MR, Kuusela EK, Vainio OM. Effects of different doses of L-659'066 on the bispectral index and clinical sedation in dogs treated with dexmedetomidine.. Vet Anaesth Analg 2011 Sep;38(5):415-22.
- Rolfe NG, Kerr CL, McDonell WN. Cardiopulmonary and sedative effects of the peripheral α2-adrenoceptor antagonist MK 0467 administered intravenously or intramuscularly concurrently with medetomidine in dogs.. Am J Vet Res 2012 May;73(5):587-94.
- Ambrisko TD, Hikasa Y. Neurohormonal and metabolic effects of medetomidine compared with xylazine in beagle dogs.. Can J Vet Res 2002 Jan;66(1):42-9.
- Raekallio MR, Kuusela EK, Lehtinen ME, Tykkyläinen MK, Huttunen P, Westerholm FC. Effects of exercise-induced stress and dexamethasone on plasma hormone and glucose concentrations and sedation in dogs treated with dexmedetomidine.. Am J Vet Res 2005 Feb;66(2):260-5.
- Honkavaara JM, Restitutti F, Raekallio MR, Kuusela EK, Vainio OM. The effects of increasing doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs.. J Vet Pharmacol Ther 2011 Aug;34(4):332-7.
- Warren JB, Dollery CT, Sciberras D, Goldberg MR. Assessment of MK-467, a peripheral alpha 2-adrenergic receptor antagonist, with intravenous clonidine.. Clin Pharmacol Ther 1991 Jul;50(1):71-7.
- Schafers RF, Elliott HL, Howie CA, Reid JL. A preliminary, clinical pharmacological assessment of L-659,066, a novel alpha 2-adrenoceptor antagonist.. Br J Clin Pharmacol 1992 Dec;34(6):521-6.
- Johnson PJ, Wiedmeyer CE, LaCarrubba A, Ganjam VK, Messer NT 4th. Laminitis and the equine metabolic syndrome.. Vet Clin North Am Equine Pract 2010 Aug;26(2):239-55.
- Benson GJ, Grubb TL, Neff-Davis C, Olson WA, Thurmon JC, Lindner DL, Tranquilli WJ, Vanio O. Perioperative stress response in the dog: effect of pre-emptive administration of medetomidine.. Vet Surg 2000 Jan-Feb;29(1):85-91.
- Wojtasiak-Wypart M, Soma LR, Rudy JA, Uboh CE, Boston RC, Driessen B. Pharmacokinetic profile and pharmacodynamic effects of romifidine hydrochloride in the horse.. J Vet Pharmacol Ther 2012 Oct;35(5):478-88.
- Muir WW. Anxiolytics, nonopioid sedative-analgesics, and opioid analgesics. In: Muir WW, Hubbel JAE, editors. Equine anesthesia. St Louis: Saunders Elsevier; 2009. pp. 185–209.
- Keen JA, McGorum BC, Hillier C, Nally JE. Short-term incubation of equine laminar veins with cortisol and insulin alters contractility in vitro: possible implications for the pathogenesis of equine laminitis.. J Vet Pharmacol Ther 2013 Aug;36(4):382-8.
- Zolovick A, Upson DW, Eleftheriou BE. Diurnal variation in plasma gluco-corticosteroid levels in the horse (Equus caballus).. J Endocrinol 1966 Jul;35(3):249-53.
- Hemmann K, Raekallio M, Kanerva K, Hänninen L, Pastell M, Palviainen M, Vainio O. Circadian variation in ghrelin and certain stress hormones in crib-biting horses.. Vet J 2012 Jul;193(1):97-102.
- Bohák Z, Szabó F, Beckers JF, Melo de Sousa N, Kutasi O, Nagy K, Szenci O. Monitoring the circadian rhythm of serum and salivary cortisol concentrations in the horse.. Domest Anim Endocrinol 2013 Jul;45(1):38-42.
- van Dijk P, Lankveld DP, Rijkenhuizen AB, Jonker FH. Hormonal, metabolic and physiological effects of laparoscopic surgery using a detomidine-buprenorphine combination in standing horses.. Vet Anaesth Analg 2003 Apr;30(2):72-80.
- Wright EE, Simpson ER. Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists.. J Lipid Res 1981 Nov;22(8):1265-70.
- Langin D, Holm C, Lafontan M. Adipocyte hormone-sensitive lipase: a major regulator of lipid metabolism.. Proc Nutr Soc 1996 Mar;55(1B):93-109.
- Weiner ID, Wingo CS. Hypokalemia--consequences, causes, and correction.. J Am Soc Nephrol 1997 Jul;8(7):1179-88.
Citations
This article has been cited 1 times.- Gehlen H, Jaburg N, Merle R, Winter J. Can Endocrine Dysfunction Be Reliably Tested in Aged Horses That Are Experiencing Pain?. Animals (Basel) 2020 Aug 14;10(8).
Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
