首页 | 本学科首页   官方微博 | 高级检索  
相似文献
 共查询到20条相似文献,搜索用时 15 毫秒
1.
The cardiovascular effects of detomidine and xylazine were compared in six chronically instrumented, conscious ponies. Ponies were instrumented with a micromanometer in the left ventricular chamber, a Doppler flow probe on a coronary artery and sonomicrometer crystals in the left ventricular free wall. Heart rate, ventricular systolic pressure, stroke work, dP/dtmax, minute work and coronary blood flow were measured for 4 h following intravenous injection of detomidine at several doses or xylazine at 1.1 mg/kg. Both drugs caused a profound hypertensive response at 15 s post-injection. The magnitude of the pressure change did not increase with detomidine doses greater than 20 micrograms/kg. There was a dose-dependent effect on the duration of the hypertension. Bradycardia and A-V blockade of similar magnitude followed the hypertension at all drug doses. Both drugs caused a negative inotropic effect on the heart at all doses. Minute work, a mechanical index of myocardial O2 demand, and coronary flow decreased to a similar extent following all drug treatments. With the exception of a greater hypertensive response, detomidine at the dosages studied, produced cardiovascular effects that were very similar to those of the recommended dosage of xylazine.  相似文献   

2.
Acute pharmacodynamic effects of the α2-adrenoceptor agonists, xylazine and guanfacine, were investigated in nine healthy calves in an open crossover trial. Xylazine (100 μg/kg body weight intravenously (i.v.)) and guanfacine (20 μg/kg body weight i.v.) were equi-effective in lowering heart rate by 25–30% at 5 min. Under these conditions, xylazine induced strong sedation and increased plasma growth hormone levels, indicating central nervous system mediated actions, whereas guanfacine was not sedative and did not induce release of growth hormone. Oxygen consumption was decreased by both drugs, but respiratory exchange ratio decreased only in response to xylazine. However, in response to both drugs, plasma levels of noradrenaline, adrenaline, insulin and non esterified fatty acids decreased similarly and glucose increased comparably. These results demonstrate marked differences in the central nervous system-mediated effects of the two α2-adrenoceptor agonists, whereas peripheral actions are similar.  相似文献   

3.
The sedative effects of a new alpha 2-adrenoceptor agonist, romifidine, were compared with those of xylazine and detomidine. Five horses were treated with two doses of romifidine (40 micrograms/kg body weight and 80 micrograms/kg body weight), two doses of detomidine (10 micrograms/kg body weight and 20 micrograms/kg body weight) and one dose of xylazine (1 mg/kg body weight) given by intravenous injection using a Latin-square design. The dose of 80 micrograms/kg romifidine appeared equipotent to 1 mg/kg xylazine and 20 micrograms/kg detomidine, although at these doses both xylazine and detomidine had a shorter action. Detomidine 20 micrograms/kg and xylazine both produced greater lowering of the head and a greater degree of ataxia than romifidine at either dose. Romifidine produced sedation similar to that of the other drug regimes. The effect upon imposed stimuli was similar.  相似文献   

4.
5.
The cardiopulmonary effects of the intravenous administration of clonidine (15 μg/kg), ST-91 (30 μg/kg) and diazepam (0.4 mg/kg) were compared in five healthy sheep using a randomized cross-over design, to determine whether the hypoxaemic effects of α2 adrenoceptor agonists are due to sedation, or to peripheral α2 adrenoceptor stimulation. All three drugs significantly lowered arterial oxygen tension (PaO2) levels within 2 min of their administration; however, clonidine and ST-91 produced long lasting and severe hypoxaemia with mean PaO2 levels of ≈40 mm Hg and 50 mm Hg (5.3 kPa and 6.6 kPa), respectively. The fall in PaO2 was considerably less with diazepam (63 mm Hg or 8.4 kPa at 2 min) and by 15 min the values did not differ from placebo treated animals. None of the drugs increased arterial carbon dioxide tension (PaCO2) levels when compared to saline treatment and the acid base variables did not show any significant change. A significant increase was recorded in the packed cell volume of the ST-91 treated group throughout the study. Within 2 min of their administration, all drugs caused a significant increase in mean arterial pressure (MAP) as compared to the placebo treated group. The MAP remained significantly increased for 5 and 60 min after clonidine and ST-91 treatment, respectively. The study shows that ST-91 and clonidine produce a greater degree of hypoxaemia than occurs with diazepam sedation, and that the hypoxaemic effect of α2 adrenoceptor agonists in sheep are mainly mediated by peripheral α2 adrenoceptors.  相似文献   

6.
Xylazine (0.2 mg/kg, iv) alone or preceded by atipame-zole (0.125 μg/kg, iv) or by aspirin (10 μg/kg, iv) was administered to 18 sheep. Medetomidine (60 μg/kg, iv) was also administered to 12 sheep. Xylazine, but not medetomidine, significantly reduced the number of platelets. Both atipamezole and aspirin prevented this reduction. It was concluded that α2-agonists would seem to produce platelet aggregation that may contribute to the development of the respiratory changes that follow the administration of α2-agonists in sheep, but probably not always to a degree that could result in a significant decrease in the number of circulating platelets.  相似文献   

7.
In the present study, the hypoxaemic potential of four α2 agonists possessing different selectivity for α2 adrenoceptors and of a saline placebo was studied in five clinically healthy sheep using a randomized Latin square design and equipotent sedative doses. Baseline values for heart rate (HR), mean arterial pressure (MAP), arterial oxygen (PaO2) and carbon dioxide (PaCO2) tensions, respiration rate and maximum change in pleural pressure (ΔPpl) were obtained, followed by the intravenous administration of either: xylazine (150 μg/kg); romifidine (50 μg/kg); detomidine (30 μg/kg); medetomidine (10 μg/kg) or placebo. Subsequent recordings were made up to 60 min after drug administration. No significant (P 0.05) alterations in any variable occurred with placebo. All the α2 agonists significantly (P 0.05) decreased PaO2 levels without a significant (P 0.05) change in PaCO2. The lowest PaO2 values were 29–42 mm Hg (3.9–5.5 kPa) with no significant difference between drugs. Respiratory rate and ΔPpl increased significantly within 2 min of drug administration; the duration of this effect varied with the α2 agonist, lasting longest with romifidine. As compared to the saline treated group, a significant increase in MAP was observed up to 10 min after administration of romifidine and detomidine, however, a significant decrease was seen at 10 and 45 min after xylazine and medetomidine, respectively. The α2 agonists studied induced a similar change in PaO2 at peak effect, despite their reported variable selectivity for α2 vs. α1 adrenoceptors.  相似文献   

8.
The analgesic effects of the non-steroidal anti-Inflammatory drugs (NSAIDs) flunixin and dipyrone were assessed in healthy sheep with no pre-existing inflammation, and in sheep with a chronic inflammatory lesion, using a mechanical noxious stimulus. Saline and dexamethasone were given as controls. Blood taken from healthy sheep after NSAID administration was assayed for thromboxane B2 (TxB2) to compare the ability of these drugs to inhibit cyclo-oxygenase. Both flunixin and dipyrone produced a small but statistically significant rise in pain thresholds (18% and 21% of maximum possible effect respectively) in the healthy sheep which peaked at 30 min and had returned to pre-drug values by 2–3 h. In the lame sheep a similar effect occurred but the response was smaller, much more variable and tended to be prolonged. Saline and dexamethasone had no effect on thresholds over 6 h in either group of sheep. The rise in thresholds was prevented by pre-treatment with naloxone (an opioid antagonist) or attpamezole (an α2-adrenergic antagonist) in the healthy sheep. Naloxone and atipamezole had no effect on thresholds when given alone to healthy sheep. Both NSAIDs Inhibited the production of TxB2 to a similar extent. These results indicate that central mechanisms may be involved in NSAID analgesia.  相似文献   

9.
Medetomidine, a novel alpha 2-agonist drug intended for small animal sedation, was injected intramuscularly at dose rates of 0.02, 0.06 and 0.18 mg/kg. Xylazine (3.0 mg/kg) and saline were used for comparison. The five treatments were tested in a Latin square design in five cats. Treatments differed significantly in three-way analysis of variance, medetomidine inducing an increase in drowsiness with a corresponding decrease in both aroused waking and sleep determined by polygraphical criteria. The duration of effect was dose-dependent. The effect of 0.18 mg/kg medetomidine was comparable to 3.0 mg/kg of xylazine. The drugs also induced bradycardia.  相似文献   

10.
11.
The antinociceptive activity of the intravenously administered alpha 2-adrenoceptor agonists, clonidine and xylazine, was measured in sheep using thermal and mechanical pressure threshold detection systems. Both drugs demonstrated clear antinociceptive activity for both forms of threshold stimuli and clonidine at 6 micrograms/kg i.v. was more potent and longer lasting than xylazine at 50 micrograms/kg i.v. The antinociceptive effects were reversed by idazoxan (0.1 mg/kg i.v.), but were not affected by naloxone at 0.2 mg/kg i.v. indicating that these effects were mediated by alpha 2-adrenoceptors.  相似文献   

12.
Spirals of endothelially denuded equine saphenous vein were used to study the pre- and post-junctional effects of medetomidine in vitro . The pD2 values were calculated for noradrenaline (6.7 /pm 0.1), phenylephrine (5.6 /pm 0.1), BHT 920 (6.2 /pm 0.2) and UK 14304 (5.7 /pm 0.2). Medetomidine produced a biphasic response, with a pD21 of 8.2 /pm 0.1 and a pD22 of 5.7 /pm 0.1 in the equine saphenous vein ( n = 6 ). Prazosin (10−7 m) significantly shifted the second phase of the medetomidine concentration-response curve to the right (pD21 was 8.1 /pm 0.2 and pD22 was 5.0 /pm 0.2, P < 0.05). Rings of equine saphenous vein were electrically stimulated to investigate the pre-junctional effects of medetomidine. Increasing concentrations of the α2-adrenoceptor agonist BHT 920 reduced the response to electrical stimulation in a concentration dependent manner to a maximum of 40 /pm 5%. whereas medetomidine (0.1-100 nm) caused a concentration dependent enhancement to a maximum of 490 /pm 150%. These results suggest α1- and α2-adrenoceptors are functional in the equine saphenous vein, but that medetomidine is not acting exclusively as an α2-adrenoceptor agonist.  相似文献   

13.
α2-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep. It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet aggregation were to follow platelet activation in response to the administration of α2 agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B2 concentrations before and after the intravenous administration of the α2-agonist drug xylazine at a dose of 0.1 mg/kg. It was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride (0.125 mg/kg), an α2-adrenoceptor antagonist.  相似文献   

14.
Protein binding kinetics of lincomycin (LM) and clindamycin (CM) were studied using plasma, albumin and α1-acid glycoprotein (AGP) derived from humans, dogs, cattle and sheep. Based on Rosenthal plots of LM and CM, drug-binding property in plasma presented specific and non-specific binding, except for LM in cattle and sheep and for CM in sheep, where only non-specific binding was demonstrated. Dissociation constant (Kd) and binding capacity (Bmax) for specific binding and proportionality constant (PC) for non-specific binding were as follows: Kd = 3.14 μmol/L, Bmax = 15.28 μmol/L, PC = 0.19 for humans; Kd = 3.84 μmol/L, Bmax = 6.55 μmol/L, PC = 0.14 for dogs; PC = 0.12 for cattle; PC = 0.16 for sheep in LM and Kd = 0.94 μmol/L, Bmax = 12.24 μmol/L, PC = 4.98 for humans; Kd = 1.48 μmol/L, Bmax = 9.52 μmol/L, PC = 2.91 for dogs; Kd = 1.22 μmol/L, Bmax = 4.45 μmol/L, PC = 2.40 for cattle; PC = 1.48 for sheep in CM. The specific binding for each species was different, showing more difference in Bmax compared with Kd. The non-specific binding of LM was similar among species whereas that of CM was different, implying species difference. The drug-binding property of AGP for each species was all specific binding and the Kd was comparable to that obtained from plasma, indicating that AGP is a major specific binder in plasma. The lack of detection of specific binding for LM in cattle and sheep and for CM in sheep plasma could be attributable to a higher Kd and lower plasma AGP concentration compared with other species. The drug-binding property of albumin was characterized as all non-specific, without a great difference among species. Except for CM in sheep, the lower PC in albumin solution compared with that in plasma suggested the presence of another non-specific binder in plasma, i.e. lipoprotein. From the simulation of drug-binding percentage to AGP concentrations, AGP could be a major contributor to drug-plasma protein binding in pathological states. The degree of AGP-drug binding for each species could vary according to the degree of increase of AGP concentrations from a healthy to a pathological state, inducing a decrease in the unbound fraction (fp): 6.1 fold for dogs, 4.6 fold for humans, 1.8 fold for sheep and 1.4 fold for cattle in LM; 5.8 fold for dogs, 5.7 fold for cattle, 4.0 fold for humans and 1.5 fold for sheep in CM. Therefore, the disposition and efficacy of lincosamides affected by fp can be modified differently by the change of fp attributable to the alteration of plasma AGP concentration in each species.  相似文献   

15.
Inter-individual variation in drug serum protein binding was studied in healthy dogs and in dogs with inflammatory diseases for lidocaine, oxprenolol and propranolol, which bind mainly to alpha 1-acid glycoprotein (alpha 1-AGP), and for diazepam, digitoxin and phenytoin, which bind mainly to albumin. For the drugs mostly bound to alpha 1-AGP, in both groups of dogs binding varied considerably, and it was markedly higher in dogs with inflammatory disease. For the other drugs, the variation in binding was smaller and did not differ between the two groups of dogs. In both groups of dogs, the alpha 1-AGP concentration varied widely; it was higher in the serum of the dogs with inflammation, while the concentration of albumin was lower in these animals. There was a significant negative correlation between percentage free lidocaine, oxprenolol or propranolol and alpha 1-AGP concentration, suggesting that the inter-individual variation in binding of these drugs is due to the variation in alpha 1-AGP concentration. There was a marked intra-individual variation in lidocaine binding and in serum alpha 1-AGP concentration, studied over a period of 3 weeks in healthy dogs; a significant negative correlation between percentage free lidocaine and alpha 1-AGP concentration was obtained.  相似文献   

16.
The effects of medetomidine and atipamezole were examined in rainbow trout. Medetomidine proved to be an effective sedative but not an anaesthetic; its effects were antagonised by atipamezole. The clinical signs of medetomidine sedation were rapid settling to the bottom of the tank followed by progressive ataxia. The sedative effect was dose-dependent: at 1 mg/l, one of 6 fish rested on its side after 10 min, whereas at 20 mg/l all 6 rested on their sides. No loss of consciousness occurred. Atipamezole at 6 times the medetomidine concentration antagonised sedation. The average time before fish exposed to medetomidine alone showed avoidance reactions was 10 h, more than 5 times longer than the mean time in fish exposed to medetomidine and then atipamezole. During exposure to medetomidine (5 mg/l) opercular movement rate decreased from 80/min to 20/min. The nature of opercular excursions also changed from being rapid and shallow to slow and deep. Respiratory movements increased after transfer to the bath containing atipamezole. Medetomidine had a marked effect upon skin colour, with fish becoming very pale a few min after exposure. Normal pigmentation was not restored until 4.5 days after exposure to medetomidine alone, but returned to normal after 10 min exposure to atipamezole solution. The half-life (t1/2 lambdaz) for medetomidine was 5.5 h. For atipamezole, it was 8.6 h.  相似文献   

17.
The present studies were undertaken to examine the effect of tumour necrosis factor (TNF) alpha on prostaglandins (PGs) F(2alpha) and E(2) release by cultured porcine endometrial cells harvested on days 13-16 after oestrus in comparison to stimulation with oxytocin (OT) and luteinizing hormone (LH). A time-dependent effect of TNFalpha (10 ng/ml) on PGF(2alpha) release was observed in stromal and luminal epithelial cells. Moreover, TNFalpha increased PGF(2alpha) secretion from both endometrial cell types with effective concentrations of 1 (p < 0.05), 10 and 50 ng/ml (p < 0.01). The effect of TNFalpha (10 ng/ml) on endometrial PGF(2alpha) and PGE(2) release was compared with OT (100 nmol/l) and LH (100 ng/ml). All factors affected PGF(2alpha) secretion from stromal cells, however, the stimulation tended to be more potent after OT and LH (p < 0.01) than after TNFalpha (p < 0.05) treatment. In epithelial cells, only TNFalpha was able to stimulate PGF(2alpha) release (p < 0.001). PGE(2) secretion from stromal cells increased after incubation with TNFalpha and OT (p < 0.05). Only LH stimulated PGE(2) release from epithelium (p < 0.001), and its action was very effective when compared with TNFalpha or OT (p < 0.01). Summarizing, TNFalpha induces both PGs secretion from cultured porcine endometrium, but preferentially stimulates PGF(2alpha) release from luminal epithelial cells. Therefore, similarly to OT and LH, TNFalpha may be considered as a potential modulator of endometrial PGF(2alpha) production during luteolysis in the pig.  相似文献   

18.
The pharmacokinetics and metabolic fate of labelled compounds were investigated after intramuscular administration of 3H-radiolabelled etiproston to nine cows. Elimination was rapid ( t 1/2β= 2.8 h). Forty-eight h after administration 92.6% of the radioactivity had been eliminated, mainly via the urinary (66% at 48 h) and faecal routes (26% at 48 h). In comparison, little elimination in milk occurred (less than 0.034% dose/l by 24 h). Radioactivity at the injection site 48 h after administration was seen in one cow (< 4.68 × 10-5% dose/g). No radioactivity was detected in the tissues. Urinary metabolites were purified and isolated using XAD-2 extraction and preparative HPLC in reverse and normal phases. The main urinary metabolite, identified by mass spectrometry, was the tetranor acid derivative in equilibrium with its lactone form.  相似文献   

19.
The effect of flunixin meglumine on prostaglandin synthesis and metabolism was evaluated in the pig in vivo. It was found that the prostaglandin metabolite, 15-ketodihydro-PGF2 alpha, was decreased in the peripheral circulation within 20 min of injection of the drug. In therapeutic doses in the pig the drug had no effect on the metabolism of PGF2 alpha. Flunixin was compared with some other non-steroidal anti-inflammatory drugs in an in vitro test system utilizing sheep vesicular gland microsomes. It was concluded that this drug is a potent inhibitor of prostaglandin synthesis.  相似文献   

20.
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号