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1.
To improve the sensitivity and specificity of screening for etorphine in horses, an 125I-labeled etorphine analog was synthesized and an antibody to etorphine was raised in rabbits. A radioimmunoassay (RIA) for etorphine was developed, using these reagents. Bound and free 125I-labeled etorphine was separated by a double-antibody method that reduced interference from materials associated with equine urine. The 125I-labeled etorphine binding was rarely greater than 250 pg of background etorphine equivalents/ml in raw urine and was 100 pg/ml in hydrolyzed urine. The 125I-RIA was capable of detecting etorphine equivalents in urine above these background values. Etorphine equivalents were detected in equine urine samples for about 7 days after 4 mares were dosed with 0.22 microgram of etorphine/kg of body weight, IV. The stability of etorphine in urine from these mares was evaluated. Urine from these dosed mares was held in constant -20 C storage, and aliquots were repeatedly frozen and thawed. When analyzed for etorphine equivalents using an 125I-RIA, etorphine and its metabolites in urine samples were stable for less than or equal to 38 days if continuously frozen and also were resistant to repeated freezing and thawing.  相似文献   

2.
OBJECTIVE: To determine the cardiorespiratory effects of an i.v. infusion of propofol alone or in association with fentanyl, alfentanil, or sufentanil in cats and, for each combination, the minimal infusion rate of propofol that would inhibit a response to noxious stimuli. DESIGN: Randomized crossover study. ANIMALS: 6 cats. PROCEDURE: Cats were anesthetized 4 times in random order. After i.v. administration of fentanyl, alfentanil, sufentanil, or saline (0.9% NaCl) solution, anesthesia was induced with propofol (7 mg/kg 13.2 mg/lb], i.v.) and maintained for 90 minutes with a continuous infusion of propofol in conjunction with fentanyl (0.1 microg/kg/min [0.045 microg/lb/min]), alfentanil (0.5 microg/kg/min [0.23 microg/lb/min]), sufentanil (0.01 microg/kg/min [0.004 microg/lb/min]), or saline solution (0.08 mL/kg/min [0.036 mL/lb/min]). RESULTS: Minimal infusion rate of propofol required to prevent a response to a noxious stimulus was higher when cats received saline solution. After 70 minutes, minimal infusion rate of propofol was significantly higher with fentanyl than with sufentanil. Decreases in heart rate, systolic blood pressure, rectal temperature, and respiratory rate were detected with all treatments. Oxygen saturation did not change significantly, but end-tidal partial pressure of carbon dioxide increased with all treatments. There were no significant differences in recovery times or sedation and recovery scores among treatments. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that infusion of propofol in combination with fentanyl, alfentanil, or sufentanil results in satisfactory anesthesia in cats.  相似文献   

3.
The aim of this study was to compare the pharmacokinetics of fentanyl, alfentanil, and sufentanil in isoflurane‐anesthetized cats. Six adult cats were used. Anesthesia was induced and maintained with isoflurane in oxygen. End‐tidal isoflurane concentration was set at 2% and adjusted as required due to spontaneous movement. Fentanyl (10 μg/kg), alfentanil (100 μg/kg), or sufentanil (1 μg/kg) was administered intravenously as a bolus, on separate days. Blood samples were collected immediately before and for 8 h following drug administration. Plasma drug concentration was determined using liquid chromatography/mass spectrometry. Compartment models were fitted to concentration–time data. A 3‐compartment model best fitted the concentration–time data for all drugs, except for 1 cat in the sufentanil group (excluded from analysis). The volume of the central compartment and the volume of distribution at steady‐state (L/kg) [mean ± SEM (range)], the clearance (mL/min/kg) [harmonic mean ± pseudo‐SD (range)], and the terminal half‐life (min) [median (range)] were 0.25 ± 0.04 (0.09–0.34), 2.18 ± 0.16 (1.79–2.83), 18.6 ± 5.0 (15–29.8), and 151 (115–211) for fentanyl; 0.10 ± 0.01 (0.07–0.14), 0.89 ± 0.16 (0.68–1.83), 11.6 ± 2.6 (9.2–15.8), and 144 (118–501) for alfentanil; and 0.06 ± 0.01 (0.04–0.10), 0.77 ± 0.07 (0.63–0.99), 17.6 ± 4.3 (13.9–24.3), and 54 (46–76) for sufentanil. Differences in clearance and volume of distribution result in similar terminal half‐lives for fentanyl and alfentanil, longer than for sufentanil.  相似文献   

4.
Six performance bred (Thoroughbred or Standardbred) mares were fed the anthelmintic pyrantel tartrate as a daily supplement for a period of 21 days to assure steady state concentrations would be achieved. The forensic "clearance times" and potential for analytical interference of pyrantel tartrate were then investigated. This investigation was intend- ed to enable guidelines to be established for veterinarians and trainers to avoid a "positive" test result for pyrantel which might violate existing rules or regulations. The analysis of blood and urine samples from these horses was conducted by the University of Kentucky Equine Drug Testing Laboratory, and were performed on samples obtained on days -3, -2, -1, 7, 14, 21, +1, +2, +3 and +4. Pyrantel tartrate was readily detected by standard thin layer chromatography analysis in urine samples on days 7, 14 and 21 during the administration portion of the study, and on day + 1 of the post-adminislxation time period. Further analysis of the positive urine samples by direct probe mass spectrometry confirmed the presence of pyrantel. In our analysis of equine serum samples pyrantel tartrate was not detected. Pyrantel positive urine samples were additionally ana- lyzed using enzyme-linked immunosorbent assays designed to detect fluphenazine,butorphanol, morphine, oxymorphone, fentanyl, sufentanil and etorphine, with no cross-reactivity found. We concluded that, from a drug testing perspective, the use of pyrantel is unlikely to interfere with normal post- race drug testing.  相似文献   

5.
A radioiodinated analog of fentanyl was synthesized for use with a commercially available radioimmunoassay for fentanyl. The sensitivity of the modified assay was at least 100 times greater than that of the original assay. Using this modified assay, concentrations of fentanyl as low as 1 pg/ml of fentanyl or fentanyl equivalents in equine urine were detected. Doses of fentanyl 100 times smaller than the minimum dose for a pharmacologic effect were detectable and a pharmacologically effective dose of fentanyl was detectable for up to 96 hours or more. The high sensitivity of the assay indicated that large numbers of urine samples (ie, 10 to 20) probably could be pooled and screened simultaneously, which would result in an economical analysis for fentanyl in the urine of horses after a race. Sufentanil and its metabolites also were detectable, using this assay, but at only about 1% of the efficiency at which fentanyl was detectable.  相似文献   

6.
Abstract: Protocols for utilizing intravenous infusions of sufentanil were developed for experimental cardiac surgery in swine and dogs. After initial experiences with fentanyl, sufentanil was selected for these procedures due to its increased potency and shorter half life thus requiring a smaller volume for infusion and more control. In dogs with experimental mitral valve regurgitation, an initial bolus of sufentanil 3 γg/kg IV was followed by a continuous IV infusion at a rate of 9–13 γg/kg/hr. Swine used in experiments involving cardiac conduction system ablation received ketamine 33 mg/kg IM and acepromazine 1.1 mg/kg IM as a preanesthetic combination. Following the preanesthetic, an initial infusion of sufentanil 15 γg/kg/hr was started and a loading dose of sufentanil 7 γg/kg IV was administered as a bolus for induction. They were then maintained by a continuous IV infusion at a rate of 15–30 γg/kg/hr. Dogs but not pigs required periodic supplementation of anaesthesia with isoflurane and/or nitrous oxide during portions of the experimental protocol. No anaesthetic related deaths have occurred in either species using these anaesthetic protocols for cardiac procedures.  相似文献   

7.
Mycotoxins may affect animal health, including reproduction. Little is known about the clinical relevance of exposure of horses to contaminated feed. This study aimed at (i) monitoring the levels of the mycotoxins zearalenone (ZEN), with its metabolites α‐ and β‐zearalenol (α‐ and β‐ZOL), and sterigmatocystin (STC) in urine samples from thoroughbred mares in Japan and (ii) relating these findings to the potential effects on reproductive efficacy of breeding mares. Sixty‐three urine samples of breeding mares from 59 breeding farms were used. Urine samples and reproductive records were collected from each mare when it was presented to the stallion station. Urinary concentrations of ZEN, α‐ and β‐ZOL, and STC were measured using liquid chromatography‐tandem mass spectrometry (LC‐MS/MS). ZEN, α‐ and β‐ZOL were measurable in the urine of all examined mares, indicating the prevalence of ZEN in equine feeds. In seven of the 63 samples, STC was also detected at levels ranging from 1.3 to 18.0 pg/mg creatinine. No significant correlation between the concentrations of mycotoxins and pregnancy status was observed. In conclusion, measurement of mycotoxins in urine samples is a useful non‐invasive method for monitoring the systemic exposure of mares to multiple mycotoxins.  相似文献   

8.
Foetal death was induced in 10 Standardbred mares at day 45 of gestation by injecting 20 to 45 ml of hypertonic (24% W/V) saline into the conceptus at surgery. Ten mares underwent sham treatment and acted as controls. Blood and urine samples were collected every other day between days 30 and 45 post ovulation and at 0, 3 and 6 h relative to the infusion of saline in the treated mares, or sham treatment in control mares. Blood and urine samples were then collected daily between days 46 and 55 post ovulation. Urine oestrone sulphate (E1S) concentrations, measured by radioimmunoassay, increased between day 34 and day 36 of gestation in treated and control groups. In mares in which foetal death was induced, urine E1S concentrations declined post-operatively and were significantly (p less than .05) lower than controls by day 50. In plasma, E1S concentrations showed a major increase between days 36 and 40 in both groups. This was followed by a rapid decline after treatment in saline-injected mares, so that by day 48 plasma E1S concentrations in treated mares were significantly (P less than .05) lower than the controls. The results show that urinary and plasma E1S concentrations rise rapidly during early pregnancy, and are associated with a viable foetus after day 45 of pregnancy.  相似文献   

9.
Different structurally related phenylpiperidine opioids exhibit different isoflurane-sparing effects in cats. Because minimum alveolar concentration (MAC) in cats is affected only by very high plasma concentrations of some phenylpiperidine opioids, we hypothesized these effects are caused by actions on nonopioid receptors. Using a prospective, randomized, crossover design, six cats were anesthetized with isoflurane, intubated, ventilated, and instrumented. Isoflurane MAC was measured in triplicate using a tail-clamp and bracketing technique. A computer-controlled intravenous infusion using prior pharmacokinetic models targeted plasma concentrations of 60 ng/ml fentanyl, 10 ng/ml sufentanil, or 500 ng/ml alfentanil, and isoflurane MAC was measured in duplicate. Next, naltrexone 0.6 mg/kg was administered to cats hourly during the opioid infusion, and isoflurane MAC was measured in duplicate. Blood was collected during MAC determinations to measure opioid concentrations. Responses were analyzed using repeated measures ANOVA with significance at p < .05. Alfentanil and sufentanil decreased isoflurane MAC by 16.4% and 6.4%, respectively, and these effects were completely reversed by naltrexone. Fentanyl had no significant effect on isoflurane MAC. Alfentanil and sufentanil modestly reduce isoflurane MAC via agonist effects on opioid receptors. However, these effects are too small to justify clinical use of phenylpiperidine opioids as single agents to reduce MAC in cats.  相似文献   

10.
To determine the behavioral and antinociceptive effects of narcotic and non-narcotic analgesics administered by intravenous injection in horses, 10 thoroughbred mares weighing between 450 and 550 kg and ranging in age from 8 to 13 years old were analyzed. The effects of alfentanil, butorphanol, flunixin, and saline solution on the general activity of the horses were investigated by measuring spontaneous locomotor activity (SLA) and head height (HH) in two behavior stalls. The antinociceptive effects of alfentanil (0.02 mg kg−1), butorphanol (0.1 mg kg−1), flunixin meglumine (0.5 mg kg−1), and saline were determined by measuring skin twitch reflex latency (STRL) after thermal cutaneous nociceptive stimulation. A paired Student t-test was used to compare SLA and HH between the groups of horses receiving different doses of the same drug at various time points. The Tukey test was used to compare the antinociceptive effect of the treatments. Differences were considered significant when P value was <.05. Horses treated with opioid analgesics demonstrated excitation, as shown by a significant increase in SLA at all doses tested and by neighing and demonstrating attentive attitudes with movement of the ears, stereotypical walking, and ataxia in most of the animals. HH was elevated only in animals treated with alfentanil. Antinociception was observed at 5 and 30 minutes after administration of alfentanil and butorphanol, respectively. Increased SLA was observed at 30 and 90 minutes after administration of alfentanil and butorphanol, respectively. We observed no effect on antinociception in horses given flunixin. In conclusion, this study suggests that alfentanil has a faster onset and a shorter duration than butorphanol; however, both drugs are able to stimulate the central nervous system.  相似文献   

11.
Background: Evaluation of serial urine protein:creatinine (UPC) ratios is important in prognosticating chronic kidney disease and monitoring response to therapeutic interventions. Owing to random biologic variation in dogs with stable glomerular proteinuria, multiple determinations of UPC ratios often are recommended to reliably assess urine protein loss. This can be cost‐prohibitive. Objective: The purpose of this study was to evaluate agreement between the mean of 3 UPC ratios obtained on 3 separate urine samples per dog and a single UPC ratio obtained when aliquots of the separate samples were pooled and analyzed as 1 sample. Methods: Three separate urine samples were collected from each of 25 dogs, both client‐owned and members of a research colony. Protein and creatinine concentrations were measured in the supernatant of each sample using a biochemical analyzer, and the mean of the 3 UPC ratios was calculated. A 1.0 mL aliquot of each of the 3 samples from each dog was pooled to create a fourth sample for that dog, and the UPC ratio of the pooled sample was similarly determined. Agreement and correlation between the mean and pooled UPC ratios were assessed using Bland–Altman difference plots and regression analysis, respectively. Results: The UPC ratio in the pooled samples was highly correlated (r=.9998, P<.0001) with the mean UPC ratio of the 3 separate samples. Strong agreement between results was demonstrated; a UPC ratio from a pooled sample was at most ±20% different than the mean UPC ratio obtained from 3 separate samples. Conclusions: Measuring the UPC ratio in a pooled sample containing equal volumes of several different urine specimens from the same dog provides a reliable and cost‐effective alternative to assessing multiple UPC ratios on several specimens from the same dog.  相似文献   

12.
The prototype of a commercial ELISA test kit designed for fentanyl determination in human urine has been evaluated for screening fentanyl in horse urine and plasma. The measurement of fentanyl after intravenous (2 mg) and intramuscular (0.25 mg) administration in undiluted plasma was not reproducible while accurate quantification of fentanyl in urine greatly depends on the composition of the horse urine. The ELISA assay, however, is simple and could be successfully used for quantitative measurements in diluted urine and for rapid qualitative screening for fentanyl in large numbers of urine samples.  相似文献   

13.
Six healthy adult mares were each given an oral loading dose of ormetoprim(OMP)-sulfadimethoxine (SDM) at a dosage of 9.2 mg of OMP/kg and 45.8 mg of SDM/kg, followed by four maintenance doses of 4.6 mg of OMP/kg and 22.9 mg of SDM/kg, at 24 h intervals. Ormetoprim and SDM concentrations were measured in serum, synovial fluid, peritoneal fluid, cerebrospinal fluid, urine and endometrium. The highest mean serum OMP concentration was 0.92 micrograms/mL 0.5 h after the first dose; the highest mean SDM concentration was 80.9 micrograms/mL 8 h after the first dose. The highest mean synovial fluid concentrations were 0.14 microgram of OMP/mL and 28.5 micrograms of SDM/mL 12 h after the first dose. The highest mean peritoneal fluid concentrations were 0.19 micrograms of OMP/mL 6 h after the first dose and 25.5 micrograms of SDM/mL 8 h after the fifth dose. The highest mean endometrial concentrations were 0.56 micrograms of OMP/g and 28.5 micrograms of SDM/g 4 h after the fifth dose. The mean cerebrospinal fluid concentrations were 0.08 micrograms of OMP/mL and 2.1 micrograms of SDM/mL 5 h after the fifth dose. Mean trough urine drug concentrations were greater than or equal to 0.4 micrograms of OMP/mL and greater than or equal to 172 micrograms of SDM/mL. Two of the mares were each given a single intravenous (IV) injection of OMP and SDM at a dosage of 9.2 mg of OMP/kg and 45.8 mg of SDM/kg. Excitation and muscle fasciculations were observed in both mares after IV administration and all scheduled blood samples could be collected from only one of the two mares.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

14.
24-hour renal clearance and excretion of endogenous substances in the mare   总被引：1，自引：0，他引：1  
Urine samples were obtained from 6 healthy mares. During a 2-day acclimation period, mares were kept in stalls, fed sweet feed and mixed grass hay, and allowed free access to water and trace mineral salt. The mares were crosstied in their stalls within reach of hay, salt, and water for 24 hours during which urine was obtained by constant flow via indwelling Foley catheters. Twenty-four-hour urine production was 7,649 to 11,904 ml/day (mean = 9,212 +/- 1,9285) or 14.7 to 25.1 ml?/day. (mean = 19.3 +/- 4.1). Urinary excretion and clearance of electrolytes and protein were determined from aliquots of well-mixed, pooled 24-hour urine samples. These values were sodium (Na) = 0 to 1.7 mEq/kg/day (mean = 0.4 +/- 0.7), chloride (Cl) = 2.0 to 4.2 mEq/kg/day (mean = 3.0 +/- 0.8), phosphorous (P) = 0.03 to 0.12 mg/kg/day (mean = 0.07 +/- 0.3), potassium (K) = 3.7 to 6.5 mEq/kg/day (mean = 5.3 +/- 1.4), and creatinine (Cr) = 32.1 to 53.9 mg/kg/day (mean = 40.3 +/- 8.5). Fractional excretions of electrolytes were Na = 0% to 0.46% (mean = 0.1 +/- 0.2), Cl = 0.48% to 1.64% (mean = 1.14 +/- 0.45), P = 0.04% to 0.16% (mean = 0.08 +/- 0.04), and K = 23.9% to 75.1% (mean = 51.7 +/- 17.3). Average clearances (ml/hr/kg) were Na = 0.12 +/- 0.19, K = 64.1 +/- 17.1, Cl = 1.21 +/- 0.33, and P = 0.09 +/- 0.51. Average endogenous Cr clearance (ml/min/kg) was 1.92 +/- 0.51.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

15.
OBJECTIVE: To test horses for serologic evidence of an association between vesiviral antibodies and abortion. SAMPLE POPULATION: Sera from 141 horses. PROCEDURES: 2 experiments were conducted. Experiment 1 comprised sera obtained in 2001 and 2002 from 3 groups of horses (58 mares from farms with a history of abortion problems, 25 mares between 3 and 13 years of age with unknown reproductive histories that were sold at auction [breeding-age control mares], and 29 mixed-age males and yearling females sold at auction [negative control population]). Experiment 2 comprised sera from 3 groups of pregnant mares (10 pregnant mares fed Eastern tent caterpillars [ETCs], 9 pregnant mares fed ETC frass only, and 10 pregnant control mares). Sera were analyzed for antibodies against vesivirus by use of a validated recombinant vesivirusspecific peptide antigen in an indirect ELISA. RESULTS: For experiment 1, 37 of 58 (63.8%) mares from farms with abortion problems were seropositive for vesivirus antibodies, whereas 10 of 25 (40%) breeding-age control mares were seropositive. All 29 mixed-age males and yearling females were seronegative for vesivirus antibodies. For experiment 2, 17 of 29 mares aborted (some from each group). Seropositive status for vesivirus antibodies increased from 47.1% (8/17) to 88.2% (15/17) for the pregnant mares that aborted during the experiment. CONCLUSION AND CLINICAL RELEVANCE: Significant association was detected between seropositive status for vesivirus and abortion in mares; consequently, vesivirus appears to be a pathogenic virus associated with abortion in mares. These data support adding vesivirus antibody testing into diagnostic screening to determine the cause for abortion in mares.  相似文献   

16.
The ability of an immunomodulator, mycobacterial cell wall extract (MCWE), to clear uterine infection in susceptible mares after an experimental challenge withStreptococcus zooepidemicus was evaluated. Thirty mares susceptible to endometritis, based on the presence of uterine fluid during both diestrus and estrus, were selected from a herd of 896 and inoculated with a live culture of 5 × 106 CFU of S. zooepidemicus on day 1 of estrus. Twenty-four hours later, mares were evaluated by ultrasonography, bacteriology, exfoliative cytology, and uterine biopsy to confirm infection. Forty-eight hours after inoculation, and on confirmation of uterine infection, mares were randomly assigned to one of four unbalanced experimental treatments to receive 1500 μg MCWE IU (n = 10) or IV (n = 10), or placebo IU (n = 5) or IV (n = 5). Mares were examined at ovulation and 7 days post-ovulation for uterine fluid via transrectal ultrasonography and for bacteriology, exfoliative cytology, and uterine biopsy. Efficacy was based on the ability of the mare to clear endometritis as determined by negative bacteriology and reduced numbers of polymorphonuclear cells (PMNs) on uterine biopsy. Because no statistical difference was detected between routes of administration on day 7 post-ovulation, the data sets were combined and re-analyzed to evaluate overall efficacy. Endometritis was observed in all placebo-treated mares 7 days post-ovulation, whereas treatment with MCWE resulted in the elimination of endometritis in 35% of the mares by the time of ovulation, and 70% of the mares by 7 days post-ovulation. Treatment with MCWE, compared with the placebo group, resulted in a significant decrease in the number of mares positive for endometritis at ovulation based on exfoliative cytology and bacteriology (P < .01) and at 7 days post-ovulation based on biopsy, exfoliative cytology, and bacteriology (P < .001). Results indicate that MCWE was an effective treatment for the elimination of endometritis caused by S. zooepidemicus in mares.  相似文献   

17.
This study was designed to determine the interactive effects of mu and kappa opioid agonists on locomotor behavior in the horse. Three doses of a mu agonist, fentanyl (5, 10, 20 micrograms/kg) and a kappa agonist U50,488H (30, 60, 120 micrograms/kg) were administered in a random order to six horses. Locomotor activity was measured using a two minute footstep count. Each dose of U50,488H was then combined with 20 micrograms/kg of fentanyl to determine the interactive effects of the drugs on locomotor activity. A significant increase in locomotor activity was seen with 20 micrograms/kg of fentanyl and all the drug combinations. The combination of U50,488H with fentanyl resulted in an earlier onset of locomotor activity. At the highest doses of the combination (U50,488H 120 micrograms/kg, fentanyl 20 micrograms/kg), the duration of locomotor activity was significantly increased when compared to the other doses. We conclude that locomotor activity is maintained or enhanced in horses when a receptor specific kappa agonist is combined with a mu receptor agonist.  相似文献   

18.
OBJECTIVE: To determine daily variation in urinary clearance and fractional excretion (FE) of electrolytes and minerals within and between horses and to compare volumetric and single-sample urine collection for determining FE values of diets with a range of dietary cation-anion balance (DCAB). ANIMALS: 5 Thoroughbred and 6 mixed-breed mares. PROCEDURE: 3 isocaloric diets with low, medium, and high DCAB values (85, 190, and 380 mEq/kg of dry matter, respectively) were each fed for 14 days. Daily blood samples, single urine samples collected by using a urinary catheter (5 mares), and volumetric urine collections (6 mares) were obtained during the last 72 hours of each diet. RESULTS: Urine and plasma pH values, plasma concentrations, and FE values of sodium, chloride, potassium, magnesium, phosphorus, and calcium were altered by varying the DCAB. Noticeable variation in clearance and FE values was detected within horses from day-to-day on the same diet as well as between horses. Fractional excretion values were not significantly different between single-sample and volumetric methods, except for magnesium in the high DCAB diet. Volumetric and single-sample collections revealed similar patterns of change in urinary FE values with varying DCAB, except for calcium and magnesium. CONCLUSIONS AND CLINICAL RELEVANCE: Substantial variation in clearance and FE of electrolytes and minerals are evident within horses between 24-hour periods as well as between horses fed a specific diet. Three daily urine samples provide similar information regarding dietary-induced changes in clearance and FE values (excluding calcium and magnesium) as that obtained by volumetric urine collection.  相似文献   

19.
The locomotor responses of horses given morphine and fentanyl were blocked or lessened by administration of naloxone or acepromazine. Naloxone given at the dosage of 0.015 mg/kg completely blocked the locomotor activity induced in horses given fentanyl (0.020 mg/kg of body weight). The locomotor stimulation produced by morphine given at the dosage of 2.4 mg/kg was reduced by 75% of naloxone (0.020 mg/kg). Acepromazine partially blocked the locomotor responses to fentanyl and morphine. This blockade activity reached its peak about 30 minutes after acepromazine was given (IV) and lasted more than 6 hours. Simultaneous administration of acepromazine and morphine was associated with substantial respiratory depression for more than 4 hours after administration of both drugs. In other experiments, fentanyl did not add to the partial locomotor response observed after large doses of pentazocine were given--this being consistent with the concept that pentazocine possesses both antagonist and agonist actions at the narcotic receptor. Furosemide and phenylbutazone, given at usually used clinical doses, had no effect on the locomotor response to fentanyl, indicating that the usual clinical dosages of neither drug exerted stimulant or depressant actions.  相似文献   

20.
Objective To determine whether specific dopamine receptor antagonists block alfentanil‐induced locomotor stimulation in horses. Study design Randomized, prospective, crossover experiment. Animals Eight adult horses (462–604 kg). Methods Doses of dopamine‐1 (D1) (NNC 01–0756) and dopamine‐2 (D2) antagonists (eticlopride) were selected in a pilot study prior to a three part, blinded, cross‐over study. In part 1, horses received 7.5 µg kg?1 eticlopride, 5 µg kg?1 NNC 01–0756 or an equal volume of saline. In part 2, they received both antagonists and in part 3, acepromazine at 0.05 mg kg?1. Locomotor activity was assessed by counting the steps taken by a marked forefoot per 2 minutes. The D antagonist was injected IV after a 20‐minute control period. The horses were observed for 10 minutes before alfentanil (20 µg kg?1) was injected IV. Locomotor activity was then monitored for 60 minutes. Statistical analysis was performed on step counts following alfentanil normalised by subtracting the mean control step count from each value recorded after alfentanil. Data were analysed using Friedman tests and Tukey‐Kramer comparisons. Results Alfentanil increased locomotor activity for 10 minutes. NNC 01–0756 tended to reduce locomotor activity between 0 and 10 minutes (p = 0.261), but neither D antagonist suppressed it significantly. The combination of D antagonists induced more step counts than saline or acepromazine (p = 0.0265) in the 20–40‐minute period and more than saline, acepromazine or eticlopride between 40 and 60 minutes (p = 0.0003). Conclusions Neither D1 nor D2 antagonists inhibited alfentanil‐induced locomotor activity. Both drugs appeared to cause locomotor stimulation of their own. Clinical relevance D1 and D2 antagonism did not reduce opioid‐induced excitement in horses and is not suitable for reducing the incidence of this unwanted side‐effect of opioids.  相似文献   

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