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Jon M Arnemo - One of the best experts on this subject based on the ideXlab platform.
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the effects of Medetomidine and its reversal with atipamezole on plasma glucose cortisol and noradrenaline in cattle and sheep
Journal of Veterinary Pharmacology and Therapeutics, 2000Co-Authors: Birgit Ranheim, Tor Einar Horsberg, N E Soli, Kathrine A Ryeng, Jon M ArnemoAbstract:In the present study, we report the effect of Medetomidine followed by atipamezole on plasma glucose, cortisol and noradrenaline in calves, cows and sheep. Eight calves, eight lactating dairy cows and eight adult female sheep were included in a crossover trial. The animals were injected i.v. with Medetomidine (40 microg/kg), followed 60 min later by atipamezole i.v. (200 microg/kg) or saline. The wash-out period between experiments was 1 or 2 weeks. In every animal, Medetomidine induced a marked hyperglycaemia, which was reversed by atipamezole. Cortisol levels increased significantly in cows and sheep, reaching levels 4-8-fold higher than the baseline levels 25-45 min after injection of Medetomidine. Atipamezole did not affect the cortisol levels, except in sheep where an increase was observed. Plasma levels of noradrenaline decreased in cows and sheep after Medetomidine injection, reflecting the inhibition of sympathetic activity by the drug. After injection of the antagonist, there was a large increase in noradrenaline levels. In conclusion, a high dose of Medetomidine does not seem to reduce the overall endocrine stress response in cattle and sheep, which has previously been reported in other species.
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Pharmacokinetics of Medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction.
Journal of veterinary pharmacology and therapeutics, 1998Co-Authors: Birgit Ranheim, N E Soli, Jon M Arnemo, Kathrine A Ryeng, Tor Einar HorsbergAbstract:Medetomidine and atipamezole are licensed for use in dogs and cats in several countries and are highly selective and specific alpha2-adrenoceptor agents. The pharmacokinetics of the agonist Medetomidine and the antagonist atipamezole were studied in a cross-over trial in eight dairy calves. The animals were injected intravenously (i.v.) with Medetomidine (40 microg/kg i.v.), followed by atipamezole (200 microg/kg i.v.) or saline after 60 min. The wash-out period between experiments was 1 week. Drug concentrations in plasma were determined using HPLC. Atipamezole significantly (P < 0.05) increased the AUMC and MRT of Medetomidine due to an increase in the Medetomidine concentration when atipamezole was injected i.v. The mean increment in Medetomidine concentration was 6.4 ng/mL, increased levels having a mean duration of 39.4 min. Other pharmacokinetic parameters of Medetomidine were not significantly altered by atipamezole. Sedative effects of the agonist, and the effectiveness of the antagonist were recorded. All the animals relapsed into sedation on average 80 min after reversal with atipamezole. It is likely that the increase in Medetomidine concentration after the injection of atipamezole i.v. results from displacement of Medetomidine from alpha2-adrenoceptors in highly perfused tissues.
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reversal of Medetomidine induced sedation in reindeer rangifer tarandus tarandus with atipamezole increases the Medetomidine concentration in plasma
Journal of Veterinary Pharmacology and Therapeutics, 1997Co-Authors: Birgit Ranheim, Tor Einar Horsberg, U Nymoen, N E Soli, Nicholas J. C. Tyler, Jon M ArnemoAbstract:The pharmacokinetics of two potent alpha 2-adrenoceptor agents that can be used for immobilization (Medetomidine) and reversal (atipamezole) of the sedation in mammals, were studied in three reindeer (Rangifer tarandus tarandus) in winter and again in summer. Medetomidine (60 micrograms/kg) was injected intravenously (i.v.), followed by atipamezole (300 micrograms/kg) intravenously 60 min later. Drug concentrations in plasma were measured by HPLC. The administration of atipamezole resulted in an immediate 2.5-3.5 fold increase in the Medetomidine concentration in plasma. Clearance for Medetomidine (median 19.3 mL/min.kg) was lower than clearance for atipamezole (median 31.0 mL/min.kg). The median elimination half-lives of Medetomidine and atipamezole in plasma were 76.1 and 59.9 min, respectively. The animals became resedated 0.5-1 h after the reversal with atipamezole. Resedation may be explained by the longer elimination half-life of Medetomidine compared to atipamezole.
Peter Daszak - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Intravenous Medetomidine and Medetomidine/Ketamine for Immobilization of Free-Ranging Variable Flying Foxes (Pteropus hypomelanus)
PloS one, 2011Co-Authors: Jonathan H. Epstein, Jennifer A. Zambriski, Melinda K. Rostal, Darryl J. Heard, Peter DaszakAbstract:Medetomidine (0.03 mg/kg) and Medetomidine/ketamine (0.05/5.0 and 0.025/2.5 mg/kg), administered by intravenous injection, were evaluated for short-term immobilization of wild-caught variable flying foxes (Pteropus hypomelanus). Medetomidine alone produced incomplete chemical restraint and a stressful, prolonged induction. Both ketamine/Medetomidine doses produced a smooth induction and complete immobilization. The combined Medetomidine/ketamine dose of 0.025/2.5 mg/kg produced a rapid induction (232±224 sec) with minimal struggling and vocalization, a complete and effective immobilization period, and tended to lead to a faster and better quality recovery than Medetomidine alone or a higher dose of Medetomidine and ketamine (0.05/5.0 mg/kg), thus reducing holding time and permitting an earlier release of the bat back into the wild.
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comparison of intravenous Medetomidine and Medetomidine ketamine for immobilization of free ranging variable flying foxes pteropus hypomelanus
PLOS ONE, 2011Co-Authors: Jonathan H. Epstein, Jennifer A. Zambriski, Melinda K. Rostal, Darryl J. Heard, Peter DaszakAbstract:Medetomidine (0.03 mg/kg) and Medetomidine/ketamine (0.05/5.0 and 0.025/2.5 mg/kg), administered by intravenous injection, were evaluated for short-term immobilization of wild-caught variable flying foxes (Pteropus hypomelanus). Medetomidine alone produced incomplete chemical restraint and a stressful, prolonged induction. Both ketamine/Medetomidine doses produced a smooth induction and complete immobilization. The combined Medetomidine/ketamine dose of 0.025/2.5 mg/kg produced a rapid induction (232±224 sec) with minimal struggling and vocalization, a complete and effective immobilization period, and tended to lead to a faster and better quality recovery than Medetomidine alone or a higher dose of Medetomidine and ketamine (0.05/5.0 mg/kg), thus reducing holding time and permitting an earlier release of the bat back into the wild.
Birgit Ranheim - One of the best experts on this subject based on the ideXlab platform.
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the effects of Medetomidine and its reversal with atipamezole on plasma glucose cortisol and noradrenaline in cattle and sheep
Journal of Veterinary Pharmacology and Therapeutics, 2000Co-Authors: Birgit Ranheim, Tor Einar Horsberg, N E Soli, Kathrine A Ryeng, Jon M ArnemoAbstract:In the present study, we report the effect of Medetomidine followed by atipamezole on plasma glucose, cortisol and noradrenaline in calves, cows and sheep. Eight calves, eight lactating dairy cows and eight adult female sheep were included in a crossover trial. The animals were injected i.v. with Medetomidine (40 microg/kg), followed 60 min later by atipamezole i.v. (200 microg/kg) or saline. The wash-out period between experiments was 1 or 2 weeks. In every animal, Medetomidine induced a marked hyperglycaemia, which was reversed by atipamezole. Cortisol levels increased significantly in cows and sheep, reaching levels 4-8-fold higher than the baseline levels 25-45 min after injection of Medetomidine. Atipamezole did not affect the cortisol levels, except in sheep where an increase was observed. Plasma levels of noradrenaline decreased in cows and sheep after Medetomidine injection, reflecting the inhibition of sympathetic activity by the drug. After injection of the antagonist, there was a large increase in noradrenaline levels. In conclusion, a high dose of Medetomidine does not seem to reduce the overall endocrine stress response in cattle and sheep, which has previously been reported in other species.
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Pharmacokinetics of Medetomidine and atipamezole in dairy calves: an agonist-antagonist interaction.
Journal of veterinary pharmacology and therapeutics, 1998Co-Authors: Birgit Ranheim, N E Soli, Jon M Arnemo, Kathrine A Ryeng, Tor Einar HorsbergAbstract:Medetomidine and atipamezole are licensed for use in dogs and cats in several countries and are highly selective and specific alpha2-adrenoceptor agents. The pharmacokinetics of the agonist Medetomidine and the antagonist atipamezole were studied in a cross-over trial in eight dairy calves. The animals were injected intravenously (i.v.) with Medetomidine (40 microg/kg i.v.), followed by atipamezole (200 microg/kg i.v.) or saline after 60 min. The wash-out period between experiments was 1 week. Drug concentrations in plasma were determined using HPLC. Atipamezole significantly (P < 0.05) increased the AUMC and MRT of Medetomidine due to an increase in the Medetomidine concentration when atipamezole was injected i.v. The mean increment in Medetomidine concentration was 6.4 ng/mL, increased levels having a mean duration of 39.4 min. Other pharmacokinetic parameters of Medetomidine were not significantly altered by atipamezole. Sedative effects of the agonist, and the effectiveness of the antagonist were recorded. All the animals relapsed into sedation on average 80 min after reversal with atipamezole. It is likely that the increase in Medetomidine concentration after the injection of atipamezole i.v. results from displacement of Medetomidine from alpha2-adrenoceptors in highly perfused tissues.
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reversal of Medetomidine induced sedation in reindeer rangifer tarandus tarandus with atipamezole increases the Medetomidine concentration in plasma
Journal of Veterinary Pharmacology and Therapeutics, 1997Co-Authors: Birgit Ranheim, Tor Einar Horsberg, U Nymoen, N E Soli, Nicholas J. C. Tyler, Jon M ArnemoAbstract:The pharmacokinetics of two potent alpha 2-adrenoceptor agents that can be used for immobilization (Medetomidine) and reversal (atipamezole) of the sedation in mammals, were studied in three reindeer (Rangifer tarandus tarandus) in winter and again in summer. Medetomidine (60 micrograms/kg) was injected intravenously (i.v.), followed by atipamezole (300 micrograms/kg) intravenously 60 min later. Drug concentrations in plasma were measured by HPLC. The administration of atipamezole resulted in an immediate 2.5-3.5 fold increase in the Medetomidine concentration in plasma. Clearance for Medetomidine (median 19.3 mL/min.kg) was lower than clearance for atipamezole (median 31.0 mL/min.kg). The median elimination half-lives of Medetomidine and atipamezole in plasma were 76.1 and 59.9 min, respectively. The animals became resedated 0.5-1 h after the reversal with atipamezole. Resedation may be explained by the longer elimination half-life of Medetomidine compared to atipamezole.
Fouad K. Mohammad - One of the best experts on this subject based on the ideXlab platform.
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Developmental and behavioral effects of Medetomidine following in ovo injection in chicks.
Neurotoxicology and teratology, 2011Co-Authors: Fouad K. Mohammad, Gada A.-m. Faris, Anwar Z. Al-zubeadyAbstract:Developmental and behavioral effects of Medetomidine were assessed in chicks following in ovo exposure on incubation day 4. Medetomidine at 25 and 50 μg/egg injected once into the air cell on incubation day 4, dose-dependently decreased the number of viable chick embryos starting on day 10 of the incubation. The percentages of successful hatching in the control and Medetomidine treated groups were 93, 60 and 47%, respectively. Embryo lethalities in these groups were 7, 40 and 53%, respectively. In ovo exposure of the chicks to Medetomidine at 25 and 50 μg/egg did not significantly affect the body weight of the chicks as well as their morphometric measurements. In another experiment, 3- and 8-day old chicks exposed to Medetomidine in ovo (25 μg/egg) were monitored in the open-field for 5 min. Medetomidine suppressed the open-field activity of both 3- and 8-day old chicks. This was manifested by a significant increase in the latency to move from the central square of the open-field arena and a decrease in the number of lines crossed (ambulation) with an additional decrease in vocalizations of the 3-day old chicks when compared with respective age-matched control values. In the same Medetomidine-exposed chicks the duration of tonic immobility significantly increased in comparison with respective control values. Pharmacological challenge of the Medetomidine-exposed chicks (8-day old) with Medetomidine at 25 μg/kg, intramuscularly significantly increased the latencies to onset of sedation and loss of righting reflex and decreased the duration of sleep when compared with the saline-control group challenged in the same manner. The data suggest that Medetomidine could be a behavioral teratogen in chicks following in ovo exposure.
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Medetomidine protection against diazinon-induced toxicosis in mice.
Toxicology letters, 1997Co-Authors: Luay K. Yakoub, Fouad K. MohammadAbstract:Abstract The protective effect of the α2-agonist Medetomidine against the organophosphorus insecticide diazinon-induced toxicosis was examined in male mice. Oral dosing of diazinon at 75 and 100 mg/kg produced signs of toxicosis in mice characteristic of cholinergic over-stimulation, and the percentages of deaths were 90 and 100%, respectively. Subcutaneous (s.c.) injection of Medetomidine at 0.05, 0.1 and 0.3 mg/kg, 15 min before diazinon (75 mg/kg, orally) significantly and dose-dependently decreased the incidence of toxic manifestations, delayed the onset of tremors and death, and increased the 24 h survival rates to 70, 80 and 100%, respectively. Similarly Medetomidine pretreatments (0.1 and 0.3 mg/kg s.c) significantly protected the mice from the toxicity of a high dose (100 mg/kg, orally) of diazinon, and increased the 24 h survival rates to 38 and 50%, respectively. The α2-antagonist atipamezole significantly abolished the protective effect of Medetomidine. When atropine sulfate (6 mg/kg s.c.) was combined with Medetomidine (0.3 mg/kg s.c.) the degree of protection against diazinon toxicosis was more than that produced by either drug alone. The data suggest that Medetomidine protected mice against diazinon-induced toxicosis, and a combination of Medetomidine and atropine produced an even greater degree of protection.
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Reversal of Medetomidine sedation in sheep by atipamezole and yohimbine.
Veterinary and Human Toxicology, 1995Co-Authors: Fouad K. Mohammad, I.k. Zangana, A.r. Abdul-latifAbstract:The antagonistic effect of the alpha 2-adrenoceptor antagonists atipamezole and yohimbine on Medetomidine-induced sedation was studied in male Awassi sheep. The animals were sedated with an im injection of 40 micrograms Medetomidine/kg bw. After recumbency, the sheep were injected iv with either 5 ml physiological saline solution (control), 0.2 mg atipamezole/kg or 0.2 mg yohimbine/kg. The saline-treated animals remained sedated and recumbent for 61.3 +/- 3.0 (mean +/- SE) min. Atipamezole or yohimbine significantly reduced the recumbency period to 2.8 +/- 0.9 or 4.3 +/- 0.9 min, respectively. Atipamezole or yohimbine significantly increased the Medetomidine-induced reductions in the heart rate, respiratory rate and ruminal contractions. Rectal temperature was neither affected by Medetomidine nor by the subsequent administrations of antagonists. These data suggest the usefulness of atipamezole or yohimbine in antagonizing the sedative effects of Medetomidine in sheep.
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Medetomidine Sedation in Sheep
Zentralblatt fur Veterinarmedizin. Reihe A, 1993Co-Authors: Fouad K. Mohammad, I.k. Zangana, A.r. Abdul-latifAbstract:The sedative effect of Medetomidine was evaluated in 6 male Awassi sheep. Medetomidine at 40 micrograms/kg, i.m. induced sedation and recumbency in the sheep within 9 +/- 1 and 17 +/- 4 minutes, respectively. The duration of recumbency was 58 +/- 1 minutes. Medetomidine produced good analgesia and marked muscle relaxation in the recumbent animals for 30 to 45 minutes. The side effects of Medetomidine were bradycardia, respiratory depression, stasis of the rumen with tympany, salivation and polyuria. The animals recovered from the sedative and side effects of Medetomidine 1.5 to 2 hours after gaining the righting reflex without any apparent adverse effect. The results suggested that Medetomidine could be a useful sedative analgesic in sheep.
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Clinical observations in Shami goat kids sedated with Medetomidine
Small Ruminant Research, 1991Co-Authors: Fouad K. Mohammad, I.k. Zangana, N.a. Al-kassimAbstract:Abstract The sedative action and side effects of Medetomidine were recorded in five Shami goat kids. Intramuscular injection of Medetomidine at 15 μg/kg caused recumbency in the kids in 11 ± 4 min (mean ± SD). The duration of recumbency and latency to onset of standing were 59 ± 13 and 17 ± 15 min, respectively. In the recumbent animals, the major side effects of Medetomidine were bradycardia, hypothermia and stasis of the rumen. Other clinical side effects were salivation, bloating, frequent urination, jugular pulsation, mydriasis, polypnea and dyspnea. The side effects of Medetomidine disappeared after standing for 1.5–2 h. The results suggested that Medetomidine reliably induced sedation and recumbency in goat kids, and the animals recovered from the sedative effect of Medetomidine without any apparent adverse effect.
K W Clarke - One of the best experts on this subject based on the ideXlab platform.
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Pharmacokinetics of Medetomidine in ponies and elaboration of a Medetomidine infusion regime which provides a constant level of sedation.
Research in veterinary science, 1999Co-Authors: Regula Bettschart-wolfensberger, Outi Vainio, K W Clarke, F. S. Aliabadi, D C DemuthAbstract:Abstract The pharmacokinetics of intravenous (i.v.) Medetomidine (7 mcg kg –1 ) were best described by a two-compartment model in five ponies. Total body clearance was 4 (SD 0.60) 1 kg h, –1 t 1/2α 7.6 (0.91) minutes and t 1/2β 51.3 (13.09) minutes. In one pony the one-compartmental model was best fit, and total body clearance was 4.2 l kg h –1 and t 1/2 was 11 minutes. Medetomidine plasma levels had fallen below the limits of quantification (0.05 ng ml –1 ) within 4 hours. Medetomidine 5 mcg kg –1 i.v. followed by an infusion of 3.5 mcg kg h –1 for two hours provided a constant level of sedation reaching steady state plasma Medetomidine levels of 1–1.5 ng ml –1 within 30 minutes. Sedation was reversed effectively by atipamezole (60 mcg kg –1 ) i.v. The pharmacokinetics of Medetomidine make it suitable for prolonged use by infusion, such as is required as part of a total intravenous anaesthetic technique in horses.
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Characterisation of the cardiovascular pharmacology of Medetomidine in the horse and sheep
Research in veterinary science, 1998Co-Authors: C.e. Bryant, J. Thompson, K W ClarkeAbstract:Abstract Medetomidine was administered to sheep and horses at a dose rate of 5 Pg kg −1 (i.v.). Heart rate and blood pressure were recorded. Medetomidine induced bradycardia and a biphasic blood pressure response consisting of a transient hypertension followed by hypotension. Administration of prazosin (an alpha, adrenoceptor antagonist; 100μg kg 1, i.v.) had no effect on the cardiovascular response to Medetomidine (5 Vg kg −1 , i.v.), but inhibited the cardiovascular response of methoxamine (an alpha, adrenoceptor agonist; 75 pg kg −1 , i.v.). L-659,066 (an alpha2 adrenoceptor antagonist which does not cross the blood brain barrier; 264 μg kg − , i.v.) attenuated the Medetomidine induced bradycardia, but had no effect on the cardiovascular response to methoxamine. L-659,066 also reduced the Medetomidine induced hypertension in sheep, but had less effect on the horse. It is concluded that both alpha 1 and alpha 2 adrenoceptors are important in the control of cardiovascular function in horses and sheep. Medetomidine appears to act on alpha2 adrenoceptors alone in the sheep. The cardiovascular effects of Medetomidine in the horse are complex and may be influenced by central alpha2 adrenoceptor regulation or effects on other receptor subtypes as well as direct stimulation of peripheral alpha 2 adrenoceptors.
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cardiopulmonary effects of combinations of Medetomidine hydrochloride and atropine sulphate in dogs
Veterinary Record, 1996Co-Authors: H I K Alibhai, K W Clarke, Y H Lee, J. ThompsonAbstract:Medetomidine and xylazine are alpha 2 adrenoceptor agonists which are used as sedatives and premedicants in small animals. However, bradycardia is a side effect and the use of atropine sulphate has been recommended to counteract it. This study investigated the effects of combining Medetomidine (40 μg/kg) and atropine (30 μg/kg) on the cardiopulmonary function of six dogs. Medetomidine administered alone caused severe bradycardia, but hypertension was mild and transient. Medetomidine and atropine administered together caused an initial bradycardia, but within 15 minutes there was tachycardia accompanied by a mean arterial blood pressure of 210 mm Hg. When atropine was administered 30 minutes before Medetomidine, tachycardia and hypertension were observed within five minutes of the Medetomidine injection. Thus, although atropine will counteract Medetomidineinduced bradycardia, its use results in prolonged and severe hypertension, in association with the tachycardia. Although atropine may be life-saving when bradycardia is profound, its indiscriminate use in combination with alpha 2 adrenoceptor agonists may be disadvantageous.
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Comparison of the sedative effects of Medetomidine and xylazine in horses
The Veterinary record, 1991Co-Authors: C.e. Bryant, Gary C.w. England, K W ClarkeAbstract:The sedative effects in horses of the new alpha 2 agonist Medetomidine were compared with those of xylazine. Four ponies and one horse were treated on separate occasions with two doses of Medetomidine (5 micrograms/kg bodyweight and 10 micrograms/kg bodyweight) and with one dose of xylazine (1 mg/kg bodyweight) given by intravenous injection. Medetomidine at 10 micrograms/kg was similar to 1 mg/kg xylazine in its sedative effect but produced more severe and more prolonged ataxia, and one animal fell over during the study. Medetomidine at 5 micrograms/kg produced less sedation but a similar degree of ataxia to 1 mg/kg xylazine.
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A COMPARISON OF THE SEDATIVE EFFECTS OF Medetomidine AND XYLAZINE IN THE HORSE
Journal of Veterinary Anaesthesia, 1991Co-Authors: C.e. Bryant, Gary C.w. England, K W ClarkeAbstract:Summary The sedative effects in horses of the new α2-agonist Medetomidine were compared with those of xylazine. Four ponies and one horse were treated on separate occasions with two doses of Medetomidine (5 mμ/kg bodyweight and 10 μg/kg bodyweight) and with one dose of xylazine (1 μg/kg bodyweight) given by intravenous injection. Medetomidine at 10 μg/kg was similar to 1 mg/kg xylazine in sedative effect but produced greater and more prolonged ataxia. Ataxia was so severe following 10 μg/kg of Medetomidine that one animal fell over during the study. Medetomidine (5 μg/kg) produced less sedation but a similar degree of ataxia to 1 mg/kg xylazine.