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BDX Lascelles † SA Robertson ‡ PM Taylor§ J Hauptman¶ 《Veterinary anaesthesia and analgesia》2003,30(2):108-108
Little is known about the analgesic action of buprenorphine (BUP) in cats. Relative to man, the cat has a more alkaline oral pH, which may make this an effective route for administering BUP in this species. This study aimed to assess and compare the pharmacokinetics and pharmacodynamics of sublingual (S‐L) and IV administration of BUP. Thermal threshold (TT) was measured and blood samples were collected following IV or S‐L administration (20 µg kg?1) of the injectable formulation. Six cats (five spayed females, one castrated male, 4.1–6.6 kg) were used. Each cat received both treatments in a randomized cross‐over study design with 1 month between experiments. Twenty‐four hours prior to each study, the lateral thorax of each of the cats was shaved, cephalic and jugular catheters placed, and oral pH measured. On the day of the study, TT was measured using a ‘thorax‐mounted’ thermal threshold‐testing device specifically developed for cats. The cats were free to move around. Skin temperature was recorded before each test, then the heater activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. The thermal threshold cut‐off point was 55.5 °C. Three baseline thresholds were recorded before treatment with S‐L or IV (via cephalic catheter) BUP (20 µg kg?1). Blood was withdrawn (jugular) at 1, 2, 4, 6, 10, 15, 30, 45, 60 minutes and at 2, 4, 6, 8, 12, and 24 hours post‐administration. TT was measured every 30 minutes?6 hours, 1–12 hours, and at 24 hours post‐administration. Plasma was immediately separated, stored at ?20.5 °C, and assayed within 4 months using a commercially available 125I radioimmunoassay. Threshold data were analyzed using anova with a repeat factor of time. No adverse effects were noted. Pupils were dilated for up to 9 hours post‐BUP. Behavioral changes were calm euphoria. Measured oral pH was 9 in each cat. Pre‐treatment mean threshold (±SD) was 41.2 ± 0.9 °C in the S‐L group and 40.8 ± 0.85 °C in the IV group. There were no significant differences between the groups with respect to thresholds over time (p = 0.72). Thresholds were significantly increased from 30 to 360 minutes in both the groups (>44.615 °C). Peak plasma BUP (Cmax) was lower (11 ± 6.7 ng mL?1vs. 92.9 ± 107.9 ng mL?1) and occurred later (Tmax) (30 minutes vs. 1 minute) after S‐L compared to IV administration, respectively. BUP (20 µg kg?1)‐administered S‐L or IV provided antinociception between 30 and 360 minutes after administration. Plasma levels did not correspond to TT. 相似文献
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Many cats do not receive analgesics for treatment of perioperative pain, but when they do, the opioid agonist–antagonist butorphanol (B) is widely used. B is reported to provide long‐lasting visceral analgesia, but its somatic actions are not well documented. This study aimed to assess B by using a thermal threshold (TT) model. Six cats (four spayed females, two castrated males, 4.4–6.9 kg) participated in the study. The day before each study, the lateral thorax of each of the cats was shaved and a cephalic catheter was placed. TT was measured using a thermal threshold testing device specifically developed for cats. A heater element and temperature sensor housed in a small probe was held against the cat's thorax with an elastic band and pressure bladder to assure consistent contact. Skin temperature was recorded before each test, then the heater was activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature recorded. A cut‐out temperature was set at 55.5 °C. Three baseline measurements were recorded before IV injections of 0.1, 0.2, 0.4, or 0.8 mg kg?1 of B. Each cat received all doses in a randomized order at least 1 week apart, and the investigator was blinded to the treatments. TT was measured at every 15 minutes for 6 hours. Data were analyzed using a three‐factor anova , and the critical mean difference was calculated. Pre‐treatment threshold was 40.8 ± 2.25 °C in all cats. There was a significant increase in threshold in all groups from 15 to 90 minutes, but no dose‐related differences were observed. Peak threshold achieved was 48.35 °C, 60 minutes after 0.4 mg kg?1 of B was injected. Mydriasis was present in all cats after treatment, and many exhibited dysphoric behavior. In this model, B had a short duration of action and no dose–response relationship. Compared to other opioids tested under similar conditions, the intensity of the effect of B was small and of shorter duration. 相似文献
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Morphine is considered the prototypical opiate analgesic. Despite the common use of morphine in dogs, ideal dosing strategies have not been formulated due to the difficulty in assessing its analgesic effects. The purpose of this study was to: 1) evaluate a noninvasive mechanical threshold device (von Frey device) to measure antinociceptive responses (pharmacodynamics) of opiates in dogs and 2) evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of intravenous (IV) morphine in dogs. Six healthy Beagle dogs were used. The von Frey threshold (vFT) response was evaluated hourly for 8 hours in each dog to examine the effect of repeated testing (controls). PK and PD (vFT) measurements were then made following a 1 mg kg–1 IV bolus of morphine sulfate. A two way blinded crossover consisted of an 8 hour IV constant rate infusion of saline or morphine with hourly PD measurements. The individual CRI was based on individual PK data and adjusted every 2 hours to attain targeted plasma concentrations of morphine of 10, 20, 30, and 40 ng mL–1. Blood samples were taken hourly in all phases, except the controls. No significant (p > 0.05) intraindividual changes in vFT occurred in the controls over 8 hours. The morphine bolus produced increased vFT at 1, 2, 3, and 4 hours post injection (p < 0.05). The EMAX and EC50 following the IV bolus were 213 ± 104% (increase from baseline) and 13.9 ± 5.8 ng mL–1, respectively. The CRI produced increased vFT at plasma concentrations >30 ng mL–1, when compared to saline controls (p < 0.05). Targeted plasma concentrations were inconsistent at higher infusion rates, suggesting the PK of morphine may change during CRI. The actual mean ± SD CRI plasma concentrations (ng ml–1) were 10.8 ± 3.0, 22.7 ± 7.4, 32.4 ± 13.9, 35.7 ± 16.9. Morphine dosing protocols should be re‐evaluated, as sufficient analgesia may not be obtained from published dosages. Intravenous boluses may be more predictable than CRI. 相似文献
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BDX Lascelles † SA Robertson‡ PM Taylor§ J Hauptman¶ 《Veterinary anaesthesia and analgesia》2003,30(2):107-108
Hydromorphone (HY) has not been objectively assessed as an analgesic in cats. It has been suggested that butorphanol (B) can have a synergistic action with pure μ‐agonists. The aim of this study was to assess the antinociceptive activity of a single dose of HY, and to examine the effect of concurrent B administration on the thermal threshold (TT). Thermal thresholds were measured following IM administration of HY, B, a combination of B and HY (HY‐B), or saline (S). Six cats (four spayed females, two castrated males, 4.75–6.8 kg) were used. Each cat received HY (0.1 mg kg?1), B (0.4 mg kg?1), HY (0.1 mg kg?1), and B (0.4 mg kg?1) (HY‐B), or S (0.05 mL kg?1) in a randomized, blinded, cross‐over study design. Each cat received each treatment, with at least 12 days interval between the treatments. All injections were IM randomized to left or right quadriceps using a 24 SWG needle. Twenty‐four hours prior to each study, the thorax of each of the cats was shaved. On the day of the study, TT was measured using a thorax‐mounted thermal threshold‐testing device specifically developed for cats. Skin temperature was recorded before each test and then the heater was activated. When the cat responded by flinching, turning, or jumping, the stimulus was terminated and the threshold temperature was recorded. Three baseline thresholds were recorded over 1 hour before IM injection of test drug. Thermal threshold cut‐off was 55.5 °C. TT was measured at 5 and 15 minutes, every 15 to 360 minutes, every 30 minutes to 8 hours, every hour to 12 hours, and at 24 hours post‐injection. Threshold data were analyzed using an anova with a repeat factor of time. Behavioral adverse effects (dysphoria) were associated with B administration, but not with HY or HY‐B administration (these produced calm euphoria). The control group was stable over time (p = 0.22) (mean threshold 40.15 °C). Overall, there was no period effect, no significant effect of administering B, but a significant effect (raised TT) of administering HY or HY‐B. If the mean value of one of the experimental groups differed from the control group (40.075 °C) by more than 2.355 °C (>42.425 °C), that mean was significantly different from control at p < 0.05 (Bonferroni's t‐tests). This occurred between 15 and 165 minutes for B, from 15 to 345 minutes for HY, and between 15 and 540 minutes for HY‐B. In this model, HY provided up to 5.75 hours of antinociception at 0.1 mg kg?1, and concurrent administration of butorphanol (0.4 mg kg?1) decreased the intensity of antinociception over the first 2 hours, but extended the duration of significant antinociception to about 9 hours. 相似文献
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AIM: To investigate the attitudes of veterinary practitioners in New Zealand to pain and analgesia, and their use of analgesic drugs, in dogs and cats. METHODS: A questionnaire posted to 1,200 practising veterinarians was used to gather information about the use of analgesia in dogs and cats, assessment of pain, attitudes to pain relief, analgesic drugs and procedures used, factors affecting choice of analgesic agent, and veterinary demographics, continuing education and staffing. RESULTS: Three hundred and twenty questionnaires with useable data were returned, a response rate of 28%. Male and female veterinarians were evenly represented. The analgesic agents most commonly used were morphine (opioids) and carprofen (a non-steroidal anti-inflammatory drug; NSAID). Use of peri-operative pain relief ranged from 50% for castration of cats to 91% for fracture repair in dogs. For most procedures, female veterinarians scored pain at a significantly higher level than their male colleagues. Fifty-eight percent of respondents considered their knowledge in the area of assessment and treatment of pain was adequate. CONCLUSIONS: This survey was considered representative of veterinarians working in companion animal practice in New Zealand. Results indicated a relatively high use of peri-operative analgesia, including both pre-emptive and multi-modal analge- sia, in cats and dogs, although there was still some disparity between the perception of how painful a procedure was and the consequent use of pain relief. CLINICAL RELEVANCE: The establishment of current attitudes and practices indicates to practising veterinarians how their own use of analgesics compares with that of their colleagues. It also provides information to educators on potential areas of focus, given that 42% of respondents felt their knowledge in the area of assessment and treatment of pain was inadequate. 相似文献
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