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1.
This study quantitatively investigated the analgesic action of a low-dose constant-rate-infusion (CRI) of racemic ketamine (as a 0.5 mg kg−1 bolus and at a dose rate of 10 μg kg−1 min−1) in conscious dogs using a nociceptive withdrawal reflex (NWR) and with enantioselective measurement of plasma levels of ketamine and norketamine. Withdrawal reflexes evoked by transcutaneous single and repeated electrical stimulation (10 pulses, 5 Hz) of the digital plantar nerve were recorded from the biceps femoris muscle using surface electromyography.Ketamine did not affect NWR thresholds or the recruitment curves after a single nociceptive stimulation. Temporal summation (as evaluated by repeated stimuli) and the evoked behavioural response scores were however reduced compared to baseline demonstrating the antinociceptive activity of ketamine correlated with the peak plasma concentrations. Thereafter the plasma levels at pseudo-steady-state did not modulate temporal summation. Based on these experimental findings low-dose ketamine CRI cannot be recommended for use as a sole analgesic in the dog.  相似文献   

2.
The rate of reversal of neuromuscular block was compared in 36 sheep receiving either edrophonium (500 μg kg−1) and atropine (80 μg kg−1), neostigmine (50 μg kg−1) and atropine (80 μg kg−1) or saline (10 ml), using the train of four count (TO4C) recorded at n. facialis - m. levator nasolabialis. Neuromuscular block was produced with mivacurium (200 μg kg−1) followed later by a single incremental dose of 70 μg kg−1. Antagonists or saline were given when spontaneous recovery from the incremental dose (T04C = 1) = 1 begun. The T04C increased from 1 to 4 in all animals, in all treatment groups within 10 minutes of reversal. The T04C was 4 in all animals five minutes after edrophonium, and seven minutes after neostigmine; differences were not statistically significant. The T04C was significantly higher with edrophonium two and three minutes after antagonism compared with saline. The data show that spontaneous recovery from mivacurium is rapid in sheep, although reversal is accelerated by anticholinesterase drugs.  相似文献   

3.
Fluconazole (100 mg) was administered to six adult cats as an intravenous infusion over 30 minutes, and the same cats received 100 mg of the drug orally 16 weeks later. The cats were bled repeatedly through an indwelling jugular catheter, the plasma fluconazole concentrations were assayed by high performance liquid chromatography, and the concentration-time data were subjected to a non-compartmental pharmacokinetic analysis. The mean (SD) intravenous half-life (13·8 [2·6] hours) was similar to that observed after oral dosing (12·4 [3·0] hours). The plasma clearances (intravenous 0·9 [0·1], oral 0·9 [0·2] ml min−1 kg−1) and the volumes of distribution at steady state (intravenous 1·1 [0·1], oral 1·0 [0·1] litre kg−1) were also similar after the two routes of dosing. The peak plasma concentration was reached 2·6 hours after oral dosing and the drug was completely bioavailable (1·09 [0·05]). On the basis of this single dose study, the administration of 50 mg fluconazole every eight hours to a 4 kg cat should produce average steady state plasma fluconazole concentrations of approximately 33 mg litre−1.  相似文献   

4.
Medetomidine was administered intravenously to six sheep at 5, 10 and 20 μg kg−1 and to one horse and four ponies at 5 and 10 μg kg−1. In both species medetomidine resulted in significant decreases in heart rate and cardiac output and, initially, in an increase in arterial blood pressure. In the ponies this increase in blood pressure was followed by a significant and prolonged decrease, but in the sheep the secondary decrease in blood pressure was not statistically significant. In the sheep, the three doses of medetomidine resulted in profound and significant decreases in arterial oxygen tensions, which were significantly dose related, but in the ponies the arterial blood oxygen tensions were not significantly decreased. In both species medetomidine caused a small but significant increase in arterial blood carbon dioxide tensions.  相似文献   

5.
The influence of training on blood lactate concentrations during treadmill exercise and a 40-minute inactive recovery period was examined in seven trained and seven detrained thorough-bred horses. Lactate concentrations were measured in venous blood collected at the end of each exercise state, and at intervals for 40 minutes afterwards. Measurements were made of maximum oxygen uptake (V̇O2max, ml kg−1 min−1), VLA4 (velocity at which blood lactate concentration was 4 mmol litre−1); LA8 (lactate concentration [mmol litre−1] during exercise at 8 m sec−1), peak lactate (highest lactate concentration after exercise), LA40 (lactate concentration 40 minutes after exercise), the time of peak lactate concentration (minutes after exercise) and the rate of disappearance of blood lactate (Rtd). The trained horses had a significantly lower LA8 (2·1 ± 0·1 vs 6·5 ± 1 mmol litre−1, P<0·01), higher VLA4 (9·8 ± 0·2 vs 5·8 ± 0·6 m sec−1, P<0·01) and higher V̇02max (156·3 ± 3·8 vs 107·1 ± 3·9 ml kg−1 min−1, P<0·001). The value of Rtd and the time of peak lactate concentration were not significantly different.  相似文献   

6.
Gentamycin sulphate ( ) and gentamycin oleate ( ) were encapsulated in liposomes composed of phosphatidylcholine ( ) and cholesterol ( ) (molar ratio 7:7:2 and 5:5:l, respectively), and were administered via intramuscular injection to rabbits, to evaluate their potential use as sustained release formulations. Five groups of five animals each were used for the pharmacokinetic study, and treatments were established as follows: 3 mg kg−1 of i.v., 3 mg kg−1 of i.m., 3 mg kg−1 of liposome-containing gentamycin sulphate ( ) i.m., 3 mg kg−1 of i.m., and 3 mg kg−1 of liposome-containing gentamycin oleate ( ) i.m. Gentamycin plasma concentrations after i.m. administration of LGS were extremely low compared with those obtained after the i.m. administration of ; the peak plasma concentration ( max) showed an eight-fold decrease with , and the area under the concentration-time curve ( ) was four-fold lower for the liposomal form. The apparent elimination half-life estimated after administration of showed a three-fold increase compared with values calculated for free . After the administration of the same dose of , max obtained showed a 2·5-fold decrease in relation to peak concentrations of free , and the apparent β-half life of encapsulated showed a three-fold increase compared with i.m. . Large-size liposomes containing gentamycin administered i.m. to rabbits gave sustained drug release from the injection site, providing prolonged plasma concentrations of the drug in the body.  相似文献   

7.
The serotonergic regulation of feeding behaviour has not so far been studied in ruminants. Therefore, the effects of some serotonin (5-HT) receptor agonists and antagonists on food intake and forestomach motility were studied in dwarf goats.Goats ate less food when treated intravenously (IV) with the 5-HT precursor 5-HTP (25 µg, 50 µg or 100 µg kg–1 min–1 over 15 min) than when they were treated with 5-HT (which does not pass the blood-brain barrier) or with saline. Accordingly, IV dexfenfluramine infusions (50 µg or 100 µg kg–1 min–1 over 15 min), which induces release of brain 5-HT, also led to dose-related reductions in food intake. In contrast, no anorectic effects were observed after IV infusions with the selective 5-HT reuptake inhibitor fluoxetine (100 µg kg–1 min–1 over 15 min), the selective 5-HT1A agonist 8-OH-DPAT (0.5 µg kg–1 min–1 over 15 min), or eltoprazine (4 or 8 µg kg–1 min–1 over 15 min), a mixed 5-HT1A/5HT1B receptor agonist. None of the 5-HT antagonists tested gave any increase in food consumption in this model. Interestingly, the non-selective 5-HT receptor antagonist methysergide (360 µg/kg IV) reduced food intake. This effect was most noticeable at 3 h after injection. The 5-HT3 receptor antagonist ondansetron (IV 10 µg kg–1 min–1 over 15 min) and the peripheral 5-HT2 receptor antagonist xylamidine (IV 100 µg kg–1 min–1 over 10 min) failed to modify food intake. These results provide evidence for central serotonergic involvement in the control of feeding. However, this control system differs markedly in goats and rodents.Dexfenfluramine, 5-HTP and eltoprazine administered at similar dose rates to those used in the food intake experiments induced some clinical signs including inhibition of forestomach contractions. These results, together with our earlierin vivo andin vitro observations, suggest that the inhibitory effects of serotonin receptor agonists on forestomach contractions are due to interactions with both peripheral and central serotonergic receptors. The change in smooth muscle tension, which leads to a change in the signals transmitted via vagal afferents to the central nervous system, appears not to modify feeding behaviour in dwarf goats.  相似文献   

8.
These studies were undertaken to examine the systemic and renal effects of the pharmacological inhibition of endothelium-derived nitric oxide (EDNO) in cats. In six healthy cats, the intravenous infusion of nitro-L-arginine at a dose of 100 μg kg−1 bodyweight min−1 resulted in a marked increase (P<0·001) in mean arterial pressure from the control value of 116·7 ± 4·6 mmHg to 154·2 ± 6·8 mmHg and an increase (P<0·05) in renal vascular resistance from the control value of 3·69 ± 0·33 mmHg min ml−1 to 6·83 ± 1·15 mmHg min ml−1. The increase in renal vascular resistance was generalised, with comparable increments in preglomerular and postglomerular vascular resistance. Mean values for glomerular capillary pressure (61·1 ± 61·9 vs 1·9 ± 1·6 mmHg), calculated from the sum of arterial colloid osmotic pressure plus proximal tubule stop-flow pressure, did not change in response to the infusion of nitro-L-arginine. However, there was a marked reduction in renal blood flow (29·4 ± 3·1 to 16·9 ± 2·3 ml min−1, P<0·01) and glomerular filtration rate (5·22 ± 0·57 to 3·52 ± 0·45 ml min−1, P<0·01). These results provide evidence that EDNO plays an important role in the basal regulation of systemic arterial blood pressure and renal haemodynamics in cats.  相似文献   

9.
Holtenius, K.: Effects of the long-acting somatostatin analogue octreotide on abomasal function and plasma level of insulin and glucagon in sheep. Acta vet. scand. 1994, 35, 235-241.– The effects of the long-acting somatostatin analogue octreotide were studied in sheep. Octreotide was given subcutaneously at a dose of 0.75 ug/kg body-weight and, as a control, 0.9% saline solution was injected in a change-over design. Octreotide inhibited abomasal acid secretion and retarded the turnover time of digesta through the abomasum. The plasma levels of insulin and glucagon decreased due to the octreotide injection, while the plasma glucose level was not affected. The effects of octreotide lasted for 3-4h. There were no significant effects of the saline injection. The effects of octreotide showed similarities with results from previous studies on monogas-tric species.  相似文献   

10.
Serum glucose and plasma C-peptide response to IV glucagon administration was evaluated in 24 healthy dogs, 12 dogs with untreated diabetes mellitus, 30 dogs with insulin-treated diabetes mellitus, and 8 dogs with naturally acquired hyperadrenocorticism. Serum insulin response also was evaluated in all dogs, except 20 insulin-treated diabetic dogs. Blood samples for serum glucose, serum insulin, and plasma C-peptide determinations were collected immediately before and 5,10,20,30, and (for healthy dogs) 60 minutes after IV administration of 1 mg glucagon per dog. In healthy dogs, the patterns of glucagon-stimulated changes in plasma C-peptide and serum insulin concentrations were identical, with single peaks in plasma C-peptide and serum insulin concentrations observed approximately 15 minutes after IV glucagon administration. Mean plasma C-peptide and serum insulin concentrations in untreated diabetic dogs, and mean plasma C-peptide concentration in insulin-treated diabetic dogs did not increase significantly after IV glucagon administration. The validity of serum insulin concentration results was questionable in 10 insulin-treated diabetic dogs, possibly because of anti-insulin antibody interference with the insulin radioimmunoassay. Plasma C-peptide and serum insulin concentrations were significantly increased (P < .001) at all blood sarnplkg times after glucagon administration in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Five-minute C-peptide increment, C-peptide peak response, total C-peptide secretion, and, for untreated diabetic dogs, insulin peak response and total insulin secretion were significantly lower (P < .001) in diabetic dogs, compared with healthy dogs, whereas these same parameters were significantly increased (P < .011 in dogs with hyperadrenocorticism, compared with healthy dogs, and untreated and insulin-treated diabetic dogs. Although not statistically significant, there was a trend for higher plasma C-peptide concentrations in untreated diabetic dogs compared with insulin-treated diabetic dogs during the glucagon stimulation test. Baseline C-peptide concentrations also were significantly higher (P < .05) in diabetic dogs treated with insulin for less than 6 months, compared with diabetic dogs treated for longer than 1 year. Finally, 7 of 42 diabetic dogs had baseline plasma C-peptide concentrations greater than 2 SD (ie, >0.29 pmol/mL) above the normal mean plasma C-peptide concentration; values that were significantly higher, compared with results in healthy dogs (P < .001) and with the other 35 diabetic dogs (P < .001). In summary, measurement of plasma C-peptide concentration during glucagon stimulation testing allowed differentiation among healthy dogs, dogs with impaired β-cell function (ie, diabetes mellitusl, and dogs with increased β-cell responsiveness to glucagon (ie, insulin resistance). Plasma C-peptide concentrations during glucagon stimulation testing were variable in diabetic dogs and may represent dogs with type-1 and type-2 diabetes or, more likely, differences in severity of β-cell loss in dogs with type-1 diabetes. J Vet Intern Med 1996;10:116–122. Copyright © 1996 by the American College of Veterinary Internal Medicine.  相似文献   

11.
Intravenous infusions of hydrocortisone sodium succinate (HSS) were given at 0·625 mg kg−1 hour−1 and 0·312 mg kg−1 hour−1 to six dogs. Plasma cortisol concentrations were measured by radioimmunoassay at 0, 15, 30, 45 and 60 minutes and then every 30 minutes for a further five hours. Chronic hypocortisolaemia was induced and maintained with mitotane and the HSS infusions were repeated after 31 and 50 days. No statistically significant difference was observed in the plasma cortisol concentrations after either period of hypocortisolaemia, but the plasma cortisol concentrations tended to be higher in most of the dogs.  相似文献   

12.
The concentration of ivermectin in the plasma of reindeer was measured after it was administered either topically as a pour-on preparation at 500 μg kg−1 bodyweight at different seasons to animals of different ages, or after subcutaneous and oral doses of 200 μg kg−1 bodyweight. The plasma concentrations of ivermectin were highest and least variable after it was administered subcutaneously.  相似文献   

13.
The effect of dietary chloride content (0·2, 0·4 and 1·3 per cent chloride on a dry matter basis) on the disposition of a single oral dose of bromide (14 mg kg−1 was evaluated in normal beagles. Increasing the dietary chloride content from 0·2 to 1·3 per cent resulted in a significant decrease in the mean apparent elimination half-life from 69 ± 22 days to 24 ± 7 days. The mean area under the concentration curve ( ) for dogs fed 1·3 per cent chloride was significantly smaller than the for dogs fed 0·2 per cent chloride. Dietary chloride had no effect on the maximum serum concentrations (Cmax) or on the time (Tmax) to reach the maximum concentrations. The steady-state serum bromide concentrations predicted from the single dose data for daily doses of 14 mg kg−1 of bromide were significantly lower in dogs fed 1·3 per cent chloride (310 ± 150 mg litre−1) than in dogs fed 0·2 per cent chloride (1950 ± 1140 mg litre−1). The predicted mean daily doses of bromide necessary to maintain serum levels within the therapeutic range for dogs fed 1·3 per cent chloride (43 ± 13 mg kg−1) were almost twice as high as the dose estimated for dogs fed 0·4 per cent chloride (22 ± 3 mg kg−1) and nearly three times as high as the dose estimated for dogs fed 0·2 per cent chloride (15 ± 4 mg kg−l). These differences were statistically significant (P=0·002).  相似文献   

14.
The influence of methimazole on the plasma disposition kinetics of fenbendazole, oxfendazole and their metabolites, was investigated in adult sheep. The two anthelmintics were administered by oral drench at 5 mg kg−1 either alone (control treatments) or together with methimazole given orally at 3 mg kg−1. Blood samples were taken serially for 144 hours. Fenbendazole parent drug and its sulphoxide and sulphone metabolites were the three analytes observed by high performance liquid chromatography ( ) after the administration of both anthelmintics. The disposition of each analyte followed a similar pattern after the administration of the two anthehnintics alone. Oxfendazole was the main component recovered in plasma between four and 120 to 144 hours after the administration of both anthelmintics either with or without methimazole. A modified pattern of disposition, with significantly higher Cmax and values for fenbendazole parent drug, and a delayed appearance in plasma with retarded Tmax values for the sulphoxide and sulphone metabolites, were the main pharmacokinetic changes observed when the drugs were administered with methimazole.  相似文献   

15.
The aim of this study was to determine the cardiac performance of conscious healthy dogs during stimulation with dobutamine. Eight healthy unsedated beagle dogs were used. Cardiac output was measured by the thermodilution technique and blood pressures by extravascular pressure transducers. Dobutamine challenge at a dosage ranging from 275 to 50 pg kg−1 min−1 -1 induced a significant rise in cardiac power index ( ), cardiac index ( ), stroke index ( ) and heart rate ( ) and a significant decrease in pulmonary vascular resistance ( ) and systemic vascular resistance ( ). The highest CPI was 2·05 times greater than its basal resting value. The CI was primarily responsible for this increase in . The si and HR contributed approximately 55 per cent and 45 per cent respectively of the maximal increase in .  相似文献   

16.
Susceptibility to equine hyperlipaemia is increased by poor food intake. To assess the contribution of changes in insulin sensitivity, plasma glucose and cortisol responses to an intravenous insulin challenge (0·4 kg−1 bodyweight) were compared with those observed after saline administration in six donkeys fasted either overnight or for three days. Three days of fasting decreased both the rate of insulin-induced hypoglycemia and the maximal hypoglycemic response. A transitory increase in plasma cortisol which peaked within one to four hours of insulin administration was observed in three of the six overnight-fasted donkeys and in all of the three-day fasted donkeys; inter-animal variation appeared to exist in the responsiveness of the hypothalamic-pituitary-adrenocortical ( ) axis to stimulation by insulin-induced hypoglycemia. Fasting is likely to present a risk of equine hyperlipaemia, at least in part, by the reduction in tissue sensitivity to the glucoregulatory action of insulin.  相似文献   

17.
Five days after the induction of acute systemic inflammation in greyhounds by intramuscular and subcutaneous injections of Freund's adjuvant, the hepatic concentrations of cytochromes P-450 and b5, the activities of the hepatic microsomal enzymes aniline p-hydroxylase and aminopyrine n-demethylase and the disposition and urinary excretion of phenylbutazone were determined. The mean plasma concentrations of phenylbutazone after intravenous administration were described by the bi-exponential equations: Cp = 144·2e−34·6t + 171·5e−0·104t for five normal greyhounds and Cp = 113·6e−16·13t + 163·1e−0·108t for five febrile greyhounds. The elimination half-lives, total body clearances and apparent volumes of distribution were 6·7 hours, 18·4 ml kg−1 hour−1 and 0·18 litre kg−1, for the normal greyhounds, and 6·4 hours, 19·5 ml kg−1 hour−1 and 0·18 litre kg−1, for the febrile greyhounds. There were no significant differences between the pharmacokinetic parameters describing the distribution and elimination of phenylbutazone, or between the quantities of phenylbutazone, oxyphenbutazone and hydroxyphenylbutazone excreted in the urine. In the febrile greyhounds, there were significant decreases in the hepatic microsomal concentrations of cytochromes P-450 and b5 and in the activities of aniline p-hydroxylase and aminopyrine n-demethylase.  相似文献   

18.
The dose response relationship for the intermediateacting non-depolarising muscle relaxant, atracurium besylate in the pig was determined using evoked electromyography. An incremental dose technique was used in seven Large White/Landrace crossbred pigs anaesthetised with nitrous oxide and halothane. ED50 and ED95 were 510 ± 87 μg kg−1 and 1150 ± 270 μg kg−1, respectively. Although these values may represent an overestimate, they provide a reasonable guideline for the use of atracurium by veterinary anaesthetists.  相似文献   

19.
The pharmacokinetics of propofol were investigated in two groups of five Scottish blackface sheep undergoing surgery for the implantation of subcutaneous tissue pouches. After premedication with acepromazine and papaveretum, anaesthesia was induced with either propofol at 4 mg kg−1 intravenously (group 1) or with a mixture of propofol at 3 mg kg−1 and ketamine at 1 mg kg −1 intravenously (group 2). Anaesthesia was maintained with a variable infusion rate of either propofol alone (group 1) or propofol and ketamine (group 2). Both regimens produced satisfactory conditions for superficial surgery of the body surface. The mean (SD) duration of anaesthesia was 64·8 (3·1) minutes for group 1 and 60 (0) minutes for group 2; the mean total dose of propofol given to the sheep in group 1 was 801 (84) mg, and the sheep in group 2 received 470 (46) mg of propofol and 267 (30) mg of ketamine. The mean elimination half-life of propofol was 56·6 (13·1) minutes in group 1 and 50·3 (21·4) minutes in group 2; the mean volume of distribution at steady state was 1037 (0480) litre kg−1 in group 1 and 1·515 (0939) litre kg−1 in group 2; the mean body clearance was 85·4 (28·0) ml kg−1 min−1 in group 1 and 1280 (35·0) ml kg−1 min−1 in group 2; the mean residence time corrected for a bolus injection was 12·1 (4·2) minutes in group 1 and 11·9 (6·6) minutes in group 2; for the infusion, the mean residence time was 72·1 (4·2) minutes in group 1 and 69·9 (7·9) minutes in group 2. There were wide variations in the blood propofol concentrations reached in individual sheep by using this standard dosing regimen. All the sheep recovered quickly from anaesthesia; the mean times to extubation, sternal recumbency and standing for the animals in group 1 were 2·8 (0·4) 6·3 (1·2) and 10·9 (1·6) minutes from the end of the infusion, and the times for group 2 were 5·3 (0·9), 11·2 (1·7) and 15·1 (2·2) minutes.  相似文献   

20.
Ureaplasma species were isolated from semen samples collected sequentially from one Awassi and three Assaf breeding rams. Each ram was injected subcutaneously with an aqueous solution of lincomycin and spectinomycin for five consecutive days at a dose equivalent to 4·5 mg kg−1 lincomycin and 9·0 mg kg−1 spectinomycin daily. Serum and semen samples were collected at intervals during the treatment and assayed for lincomycin. No Ureaplasma species were isolated from semen samples collected during the course of the treatment and at intervals for 17 days after the last treatment. The concentration of lincomycin in semen ranged from 0·51 μg ml−1 four hours after treatment to 0·08 μg ml−1 24 hours after treatment, and these levels were three to nine times higher than the corresponding serum concentrations.  相似文献   

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