Effects of buprenorphine, carprofen and saline on thermal and mechanical nociceptive thresholds in cats

To evaluate a prototype pressure stimulus device for use in the cat and to compare with a known thermal threshold device.Eight healthy adult cats weighing between 3.0 and 4.9 kg.Pressure stimulation was given via a plastic bracelet taped around the forearm. Three 2.4 mm diameter ball bearings, in a 10-mm triangle, were advanced against the craniolateral surface of the antebrachium by manual inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was also tested. Stimuli were stopped if they reached 55 degrees C or 450 mmHg without response. After four pressure and thermal threshold baselines, each cat received SC buprenorphine 0.01 mg kg(-1), carprofen 4 mg kg(-1) or saline 0.3 mL in a three period cross-over study with a 1-week interval. The investigator was blinded to the treatment. Measurements were made at 0.25. 0.5, 0.75, 1, 2, 3, 4, 6, 8, and 24 hours after injection. Data were analyzed by using ANOVA.There were no significant changes in thermal or pressure threshold after administration of saline or carprofen, but thermal threshold increased from 60 minutes until 8 hours after administration of buprenorphine (p < 0.05). The maximum increase in threshold from baseline (Delta T-max) was 3.5 +/- 3.1 degrees C at 2 hours. Pressure threshold increased 2 hours after administration of buprenorphine (p < 0.05) when the increase in threshold above baseline (Delta P-max) was 162 +/- 189 mmHg.This pressure device resulted in thresholds that were affected by analgesic treatment in a similar manner but to a lesser degree than the thermal method. Pressure stimulation may be a useful additional method for analgesic studies in cats.

Analgesia for cats after ovariohysterectomy with either buprenorphine or carprofen alone or in combination

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Postoperative analgesic effects of intravenous, intramuscular, subcutaneous or oral transmucosal buprenorphine administered to cats undergoing ovariohysterectomy

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Efeitos do meloxicam e do carprofeno administrados por diferentes vias no controle da uveíte em cães (Canis familiaris - Linnaeus, 1758)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Avaliação da dor crônica e locomoção de cães com displasia coxofemoral submetidos à acupuntura

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Carprofen and buprenorphine prevent hyperalgesia in a model of inflammatory pain in cats

A model of nociceptive threshold determination was developed for evaluation of NSAID analgesia in cats. In a crossover study, eight cats received carprofen (4 mg/kg), buprenorphine (0.01 mg/kg) or saline (0.3 ml) subcutaneously before intradermal kaolin injection on the antebrachium to induce mild inflammation. Pressure thresholds were measured at the injected site using blunt-ended pins advanced by manual inflation of a bladder within a bracelet. Bladder pressure was recorded as threshold (PT) at the behavioural end point. Baseline PT were recorded before kaolin injection (time 0). PT was measured at 2-10 h intervals for 52 h. PT below the lower 95% confidence interval (CI) of baseline values indicated hyperalgesia. After saline, hyperalgesia was detected from 2-6 h, 22-26 h, and at 30 and 36 h. After carprofen, PT remained within the 95% CI. After buprenorphine, PT remained within the 95% CI except at 2 h. Carprofen and to some extent buprenorphine, prevented inflammatory hyperalgesia. (C) 2007 Elsevier Ltd. All rights reserved.

Effects of subcutaneous methadone, morphine, buprenorphine or saline on thermal and pressure thresholds in cats

This study compared pressure and thermal thresholds after administration of three opioids in eight cats. Pressure stimulation was performed via a bracelet taped around the forearm. Three ball-bearings were advanced against the forearm by inflation of a modified blood pressure bladder. Pressure in the cuff was recorded at the end point (leg shake and head turn). Thermal threshold was tested as previously reported using a heated probe held against the thorax [Dixon et al. (2002) Research in Veterinary Science, 72, 205]. After baseline recordings, each cat received subcutaneous methadone 0.2 mg/kg, morphine 0.2 mg/kg, buprenorphine 0.02 mg/kg or saline 0.3 mL in a four period cross-over study. Measurements were made at 15, 30, 45 min and 1, 2, 3, 4, 8, 12 and 24 h after the injection. Data were analysed by ANOVA (P < 0.05). There were no significant changes in thresholds after saline. Thermal threshold increased at 45 min after buprenorphine (maximum 2.8 +/- 3 degrees C), 1-3 h after methadone (maximum 3.4 +/- 1.9 degrees C) and 45 min to 1 h (maximum 3.4 +/- 2 degrees C) after morphine. Pressure threshold increased 30-45 min (maximum 238 +/- 206 mmHg) after buprenorphine, 45-60 min after methadone (maximum 255 +/- 232 mmHg) and 45-60 min and 3-6 h (maximum 255 +/- 232 mmHg) after morphine. Morphine provided the best analgesia, and methadone appears a promising alternative. Buprenorphines limited effect was probably related to the subcutaneous route of administration. Previously, buprenorphine has produced much greater effects when given by other routes.

Continuous infusion in adult females dogs submitted to ovariohysterectomy with midazolam-xylazine and/or medetomidine pre-treated with methotrimeprazine and buprenorphine

OBJETIVO: Comparar através de infusão contínua de xilazina ou medetomidina associada à metotrimeprazina e buprenorfina, cetamina e midazolam, o grau de hipnose, miorrelaxamento e qualidade anestésica e a viabilidade cirúrgica, avaliando eventuais alterações paramétricas e qualidade de recuperação. MÉTODOS: Foram utilizados 20 cães fêmeas, adultas, hígidas (3 a 5 anos de idade) com peso corporal entre 7 e 15 quilos, escolhidas e distribuídas aleatoriamente de forma homogênea em 2 grupos de 10 animais cada, (n=10) sendo estes designados por Grupo 1 (G1), e Grupo 2 (G 2). em G1, os animais foram submetidos a um pré-tratamento com metotrimeprazina na dose de 1,0 mg/kg e buprenorfina na dose de 0,003mg/kg ou 3 µg/kg intravenoso. Decorridos 15 minutos, administrou-se cetamina na dose de 5,0 mg/kg e midazolam na dose de 0,2 mg/kg intravenoso. Imediatamente após a indução iniciou-se administração contínua, por um período de 30 minutos, da associação anestésica de midazolam 0,4 mg/kg/h, cetamina 20mg/kg/h e xilazina 1,0 mg/kg/h IV. em G 2 utilizou-se a mesma técnica empregada em G1 substituindo-se, a xilazina pela medetomidina na dose de 30µg/kg/h. RESULTADOS: Verificou-se em G1 bloqueio átrio-ventricular de primeiro e segundo grau, período de recuperação mais longo além de menor qualidade. em G 2 observou-se bloqueio átrio-ventricular de primeiro grau isolado e de ação fugaz. CONCLUSÕES: Ao se aplicar o método de infusão contínua, além da redução dos fármacos aplicados, evitaram-se efeitos colaterais permitindo uma recuperação mais tranqüila e isenta de excitações, ambos os protocolos permitiram a realização do ato cirúrgico (ovário-salpingo-histerectomia), causando uma redução da hipnose e um miorrelaxamento acentuado. A xilazina e a medetomidina apresentam um comportamento farmacodinâmico semelhante, porém com aspectos clínicos diferentes, as alterações eletrocardiográficas observadas em G 2 e em menor grau em G1 devem ser melhor estudadas.

Effects of buprenorphine on nociception and spontaneous locomotor activity in horses

Objective-To investigate spontaneous locomotor activity (SLA) and antinociceptive effects of buprenorphine in horses.Animals-6 healthy adult horses.Procedures-Horses received each of 3 treatments (10 mL of saline [0.9% NaCl] solution, 5 mu g of buprenorphine/kg, or 10 mu g of buprenorphine/kg). Treatments were administered IV Order of treatments was randomized, and there was a 10-day interval between subsequent treatments. Spontaneous locomotor activity was investigated in a behavioral box by use of infrared photoelectric sensors connected to a computer, which detected movement of each horse. Antinociceptive effect was investigated by hoof-withdrawal reflex latency (HWRL) and skin-twitching reflex latency (STBL) after painful stimulation with a heat lamp.Results-Moderate excitement was observed in all horses from 5 to 10 minutes after the administration of both dosages of buprenorphine. The SLA increased significantly for 6 and 14 hours after IV administration of 5 and 10 mu g of buprenorphine/kg, respectively. Values for HWRL increased significantly only at 30 minutes after injection of 5 mu g of buprenorphine/kg, whereas STRL and HWRL each increased significantly from 1 to 6 hours (except at 2 and 4 hours) and 11 hours, respectively, after injection of 10 mu g of buprenorphine/kg.Conclusions and Clinical Relevance-IV injection of buprenorphine caused a dose-dependent increase in SLA, but only the dose of 10 mu g/kg induced analgesia on the basis of results for the experimental method used.

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

Objective - To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. Animals - 36 adult dogs. Procedures - Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. Results - For serum γ-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. Conclusions and Clinical Relevance - Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.

Pharmacokinetic and pharmacodynamic modelling of intravenous, intramuscular and subcutaneous buprenorphine in conscious cats

Objective To describe simultaneous pharmacokinetics (PK) and thermal antinociception after intravenous (IV), intramuscular (IM) and subcutaneous (SC) buprenorphine in cats. Study design Randomized, prospective, blinded, three period crossover experiment. Animals Six healthy adult cats weighing 4.1±0.5kg. Methods Buprenorphine (0.02mgkg-1) was administered IV, IM or SC. Thermal threshold (TT) testing and blood collection were conducted simultaneously at baseline and at predetermined time points up to 24hours after administration. Buprenorphine plasma concentrations were determined by liquid chromatography tandem mass spectrometry. TT was analyzed using anova (p<0.05). A pharmacokinetic-pharmacodynamic (PK-PD) model of the IV data was described using a model combining biophase equilibration and receptor association-dissociation kinetics. Results TT increased above baseline from 15 to 480minutes and at 30 and 60minutes after IV and IM administration, respectively (p<0.05). Maximum increase in TT (mean±SD) was 9.3±4.9°C at 60minutes (IV), 4.6±2.8°C at 45minutes (IM) and 1.9±1.9°C at 60minutes (SC). TT was significantly higher at 15, 60, 120 and 180minutes, and at 15, 30, 45, 60 and 120minutes after IV administration compared to IM and SC, respectively. IV and IM buprenorphine concentration-time data decreased curvilinearly. SC PK could not be modeled due to erratic absorption and disposition. IV buprenorphine disposition was similar to published data. The PK-PD model showed an onset delay mainly attributable to slow biophase equilibration (t1/2ke0=47.4minutes) and receptor binding (kon=0.011mL ng-1minute-1). Persistence of thermal antinociception was due to slow receptor dissociation (t1/2koff=18.2minutes). Conclusions and clinical relevance IV and IM data followed classical disposition and elimination in most cats. Plasma concentrations after IV administration were associated with antinociceptive effect in a PK-PD model including negative hysteresis. At the doses administered, the IV route should be preferred over the IM and SC routes when buprenorphine is administered to cats. © 2012 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

Effects of carprofen administered by different routes to control experimental uveitis in dogs

Estudaram-se os efeitos do carprofeno, aplicado por diferentes vias, em uveítes experimentais em cães. Realizou-se paracentese de câmara anterior em dois momentos (M0 e M1), com intervalo de cinco horas entre si. em M0 e M1, colheram-se 0,2mL de humor aquoso e determinaram-se as concentrações de proteína total e de prostaglandina E2 (PGE2). Constituíram-se quatro grupos (n = 8), que receberam carprofeno ao final de M0 pelas vias subcutânea (GI), subconjuntival (GII) e tópica (GIII). Um quarto grupo não recebeu tratamento (controle). Procedeu-se à avaliação histopatológica nos indivíduos do GII. em todos os grupos, encontrou-se aumento significativo dos níveis proteicos e de PGE2 em M1. Não se observou diferença significativa, em M1, entre os grupos para nenhum dos parâmetros estudados. Exsudado inflamatório de caráter agudo e hemorragia discreta foram vistos à histopatologia após a aplicação do fármaco. O carprofeno foi ineficaz em inibir a síntese de PGE2 e o influxo de proteínas para a câmara anterior, por qualquer uma das vias testadas. Contudo, a redução de 44% nos níveis de proteínas (via tópica), sugere que por esta via ele pode ser utilizado como adjuvante no controle da uveíte em cães.

Evaluation of the adverse effects of subcutaneous carprofen over six days in healthy cats

This study evaluated the adverse effects of carprofen in seven healthy cats. Values for CBC, biochemical profiles and platelet aggregation were measured before and at seven days after SID treatment with subcutaneous carprofen: 4 mg/kg (day 1), 2 mg/kg (day 2 and 3) and 1 mg/kg (day 4 and 6) (CG) or 0.35 ml of saline (SG) for six days in a randomized, blinded, cross-over study with a four-week washout period. No treatment was given on day 5. Endoscopy of the GI tract was performed pre-treatment and on day 7 post-treatment. There were no significant changes in hematological profiles, biochemical profiles and endoscopy grading scores within nor between groups, except for lower albumin values at baseline than on day 7 (CG), and globulin and ALP values were higher at baseline than on day 7 in CG and SG. SC administration of carprofen over six days did not cause any adverse effects on gastrointestinal, hematological, or serum biochemical variables. (c) 2008 Elsevier Ltd. All rights reserved.

Hemodynamics and bispectral index (BIS) of dogs anesthetized with midazolam and ketamine associated with medetomidine or dexmedetomidine and submitted to ovariohysterectomy

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Effect of tranquilization and anesthesia on high-resolution electrocardiographic indices of dogs in the chronic chagasic myocardiopathy

Avaliou-se o efeito da tranquilização e da anestesia sobre os índices da eletrocardiografia de alta resolução (ECGAR) em cães portadores de doença-de-chagas na fase crônica indeterminada. Foram utilizados oito cães, adultos, sem raça definida, fêmeas, submetidas a seis protocolos (grupos). No grupo 1, os animais estavam sem efeito de tranquilização ou anestesia; no grupo 2, foram tranquilizados com acepromazina; no 3, foram tranquilizados com a associação acepromazina e buprenorfina; no 4, estavam sob anestesia geral inalatória com isofluorano; no 5, sob anestesia geral inalatória com sevofluorano; e no 6, sob anestesia com propofol. Os animais foram submetidos a todos os protocolos, com um período de 15 dias entre cada avaliação. Não se verificou alteração significativa na duração do complexo QRS e do LAS40 entre os grupos, e o RMS40 permaneceu sem alteração significativa. O nível de ruído foi significativamente menor nos grupos 4, 5 e 6 em relação ao grupo 1. A anestesia facilitou o registro da ECGAR sem alterar os índices eletrocardiográficos .