Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice / Composição química do óleo essencial de Zhumeria majdae e seus efeitos na expressão da síndrome de abstinência de morfina e tolerância ao efeito anticonvulsivante da morfina em crises induzidas por pentilenotetrazol em camundongos

Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.(AU)

Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.(AU)

Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice

Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.

Uso de dexmedetomidina em Medicina Veterinária: revisão de literatura / Use of dexmedetomidine in Veterinary Medicine: literature review

Os fármacos agonistas alfa-2 adrenérgicos são empregados há décadas na rotina anestesiológica veterinária, e recentemente destacou-se no mercado a dexmedetomidina, que possui maior especificidade, seletividade e segurança em relação a fármacos como a xilazina, clonidina, romifidina e detomidina. O objetivo deste estudo foi revisar os efeitos, aplicações e vantagens do uso da dexmedetomidina com base na literatura. Este novo fármaco é de grande interesse ao anestesiologista por promover sedação, analgesia e relaxamento muscular mais potentes que outros sedativos, além de proporcionar outros efeitos benéficos, como a redução do consumo de oxigênio durante o período trans e pós-operatório e da quantidade de anestésicos gerais e analgésicos. Assim como os outros fármacos da classe dos agonistas alfa-2 adrenérgicos, a dexmedetomidina causa depressão do sistema cardiovascular de forma menos acentuada e, no sistema respiratório, ocorre discreta alteração na frequência respiratória e no volume/minuto. A dexmedetomidina pode ser utilizada associada a fármacos opioides e na anestesia dissociativa. Ainda possui a capacidade de ser revertida com fármacos antagonistas alfa-2 adrenérgicos, como o atipamezol.

Alpha-2-adrenergic agonist drugs have been used for decades in the veterinary anesthesiology routine and recently dexmedetomidine has been well-regarded commercially due to its greater specificity, selectivity and safety compared to drugs such as xylazine, clonidine, romifidine and detomidine. The aim of this study was to review the effects, feasibility and advantages of using dexmedetomidine based on the literature. This new drug is of great interest to the anesthesiologist for providing sedation, analgesia and more potent muscle relaxation compared to other sedatives, in addition to providing other beneficial effects, such as a decrease in the trans- and postoperatively oxygen consumption and in anesthetics and analgesics dosages. Similar to other alpha-2 adrenergic agonists, dexmedetomidine causes cardiovascular depression, although less acute, as well as affecting the respiratory system by a slight change in respiratory rate and minute volume. Dexmedetomidine can be used in combination with opioid drugs and in dissociative anesthesia. It also has the ability to be reversed with alpha-2 adrenergic antagonist drugs, such as atipamezole.

Uso de dexmedetomidina em Medicina Veterinária: revisão de literatura / Use of dexmedetomidine in Veterinary Medicine: literature review

Os fármacos agonistas alfa-2 adrenérgicos são empregados há décadas na rotina anestesiológica veterinária, e recentemente destacou-se no mercado a dexmedetomidina, que possui maior especificidade, seletividade e segurança em relação a fármacos como a xilazina, clonidina, romifidina e detomidina. O objetivo deste estudo foi revisar os efeitos, aplicações e vantagens do uso da dexmedetomidina com base na literatura. Este novo fármaco é de grande interesse ao anestesiologista por promover sedação, analgesia e relaxamento muscular mais potentes que outros sedativos, além de proporcionar outros efeitos benéficos, como a redução do consumo de oxigênio durante o período trans e pós-operatório e da quantidade de anestésicos gerais e analgésicos. Assim como os outros fármacos da classe dos agonistas alfa-2 adrenérgicos, a dexmedetomidina causa depressão do sistema cardiovascular de forma menos acentuada e, no sistema respiratório, ocorre discreta alteração na frequência respiratória e no volume/minuto. A dexmedetomidina pode ser utilizada associada a fármacos opioides e na anestesia dissociativa. Ainda possui a capacidade de ser revertida com fármacos antagonistas alfa-2 adrenérgicos, como o atipamezol.(AU)

Alpha-2-adrenergic agonist drugs have been used for decades in the veterinary anesthesiology routine and recently dexmedetomidine has been well-regarded commercially due to its greater specificity, selectivity and safety compared to drugs such as xylazine, clonidine, romifidine and detomidine. The aim of this study was to review the effects, feasibility and advantages of using dexmedetomidine based on the literature. This new drug is of great interest to the anesthesiologist for providing sedation, analgesia and more potent muscle relaxation compared to other sedatives, in addition to providing other beneficial effects, such as a decrease in the trans- and postoperatively oxygen consumption and in anesthetics and analgesics dosages. Similar to other alpha-2 adrenergic agonists, dexmedetomidine causes cardiovascular depression, although less acute, as well as affecting the respiratory system by a slight change in respiratory rate and minute volume. Dexmedetomidine can be used in combination with opioid drugs and in dissociative anesthesia. It also has the ability to be reversed with alpha-2 adrenergic antagonist drugs, such as atipamezole.(AU)

Chemical composition of Zhumeria majdae essential oil and its effects on the expression of morphine withdrawal syndrome and tolerance to the anticonvulsant effect of morphine on pentylenetetrazole-induced seizures in mice

Abstract Regarding the proven anticonvulsant effect of Zhumeria majdae essential oil (ZMEO) in previous studies we were prompted to investigate the ZMEO effects on the tolerance to the anticonvulsant effects of morphine and the morphine withdrawal syndrome. Tolerance to the morphine anticonvulsant effect was induced in mice by subcutaneous injection of 2.5 mg/kg of morphine for 4 days. Subsequent doses of ZMEO (20 mg/kg) were used to study the expression and development of morphine tolerance. Clonidine was used as the standard drug to inhibit the morphine withdrawal syndrome symptoms. To study the ZMEO effect on withdrawal syndrome, mice received appropriate morphine values for 4 days and on the fifth day, 60 min before administration of naloxone. The effective dose of ZMEO was determined and the number of jumps, stands and changes in the dry stool weight, as symptoms of withdrawal syndrome were evaluated. The dose of 20 mg/kg of ZMEO decreased the tolerance in development and expression groups significantly. Counting the number of jumping, standing and defecation were assessed 30 min after morphine and 1 h after the vehicle and clonidine. The dose of 40 mg/kg ZMEO decreased all the signs of withdrawal syndrome significantly. ZMEO was analyzed by GC/MS and linalool (53.1%) and camphor (23.8%) were characterized as the main components. The results suggest that ZMEO possesses constituent(s) that have activity against tolerance to the anticonvulsant effects of morphine and the morphine withdrawal symptoms.

Resumo Em relação ao efeito anticonvulsivante comprovado do óleo essencial de Zhumeria majdae (ZMEO) em estudos anteriores, fomos instigados a investigar os efeitos do ZMEO em relação à tolerância aos efeitos anticonvulsivantes da morfina e da síndrome de abstinência de morfina. A tolerância ao efeito anticonvulsivante da morfina foi induzida em camundongos por injeção subcutânea de 2,5 mg/kg de morfina por 4 dias. Doses subsequentes de ZMEO (20 mg/kg) foram utilizadas para estudar a expressão e o desenvolvimento da tolerância à morfina. A clonidina foi usada como droga padrão para inibir os sintomas da síndrome de abstinência da morfina. Para estudar o efeito do ZMEO na síndrome de abstinência, os camundongos receberam valores apropriados de morfina por 4 dias e, no 5º dia, 60 minutos antes da administração de naloxona. A dose efetiva de ZMEO foi determinada, e o número de saltos e de permanência e as alterações no peso das fezes secas, conforme os sintomas da síndrome de abstinência, foram avaliados. A dose de 20 mg/kg de ZMEO diminuiu significativamente a tolerância nos grupos de desenvolvimento e expressão. A contagem do número de saltos, permanência e defecação foi avaliada 30 minutos após a morfina e 60 minutos após o veículo e a clonidina. A dose de 40 mg/kg de ZMEO diminuiu significativamente todos os sinais da síndrome de abstinência. O ZMEO foi analisado por GC/MS, e linalol (53,1%) e cânfora (23,8%) foram caracterizados como os principais componentes. Os resultados sugerem que o ZMEO apresenta constituintes que possuem atividade contra a tolerância aos efeitos anticonvulsivantes da morfina e aos sintomas de abstinência da morfina.

EFEITOS DA CLONIDINA E DA RILMENIDINA SOBRE OS SISTEMAS CARDIORRESPIRATÓRIO E GASTROINTESTINAL DE EQUINOS

Abstract: Clonidine and rilmenidine are drugs used in human medicine as central acting antihypertensive agents due to their actions on the alpha2-adrenoceptor and I1 imidazoline receptors in the central nervous system. Currently, clonidine is also used as a pre-anesthetic medication and in spinal anesthesia, and rilmenidine, despite the lower selectivity for alpha2-adrenergic receptors than clonidine, has also shown antinociceptive potential in experimental pain models. In this study, six horses were submitted to four treatments: R1 group (0.014 mg/kg of rilmenidine); R2 group (0.021 mg/kg of rilmenidine); Clo group (0.002 mg/kg of clonidine), and a control group. The assessment comprehended their heart and respiratory rates, systolic blood pressure and intestinal motility at basal levels and, then, 60 and 120 minutes after the oral administration of the drugs. Rilmenidine decreased heart rate on the two tested doses, which did not occur in the clonidine treatment; slight variations in systolic blood pressure in all treatments and respiratory rate reduction in treatments with rilmenidine at 0.021 mg/kg and clonidine at 0.002 mg/kg were also observed. Further studies with different dosages and varied administration routes are still necessary in order to elucidate more effects of these drugs on horses.

Resumo: Clonidina e rilmenidina são fármacos utilizados em medicina humana como agentes anti-hipertensivos de ação central devido às suas ações sobre os receptores alfa2-adrenérgicos e imidazolínicos I1 no SNC. Atualmente a clonidina é também utilizada como medicação pré-anestésica e em anestesias espinhais e a rilmenidina, apesar da menor seletividade pelo receptor alfa2-adrenérgico, também tem demonstrado potencial antinociceptivo em modelos experimentais de dor. Neste estudo, seis equinos foram submetidos a quatro tratamentos: grupo R1 (0,014 mg/kg de rilmenidina); grupo R2 (0,021 mg/kg de rilmenidina); grupo Clo (0,002 mg/kg de clonidina) e um grupo controle. Foram avaliadas as frequências cardíaca e respiratória, a pressão arterial sistólica e motilidade intestinal em níveis basais e, em seguida, 60 e 120 minutos após a administração oral dos fármacos. A rilmenidina reduziu a frequência cardíaca nas duas doses testadas, o que não ocorreu com a clonidina; variações discretas na pressão arterial sistólica em todos os tratamentos e redução na frequência respiratória nos tratamentos com 0,021 mg/kg de rilmenidina e 0,002 mg/kg de clonidina também foram observadas. São ainda necessários maiores estudos com doses e vias de administração diferentes para se elucidar maiores efeitos destes fármacos na espécie equina.

Efeitos da clonidina e da rilmenidina sobre os sistemas cardiorrespiratório e gastrointestinal de equinos / Effects of clonidine and rilmenidine on cardiorespiratory and gastrointestinal systems of horses

Clonidine and rilmenidine are drugs used in human medicine as central acting antihypertensive agents due to their actions on the alpha2-adrenoceptor and I1 imidazoline receptors in the central nervous system. Currently, clonidine is also used as a pre-anesthetic medication and in spinal anesthesia, and rilmenidine, despite the lower selectivity for alpha2-adrenergic receptors than clonidine, has also shown antinociceptive potential in experimental pain models. In this study, six horses were submitted to four treatments: R1 group (0.014 mg/kg of rilmenidine); R2 group (0.021 mg/kg of rilmenidine); Clo group (0.002 mg/kg of clonidine), and a control group. The assessment comprehended their heart and respiratory rates, systolic blood pressure and intestinal motility at basal levels and, then, 60 and 120 minutes after the oral administration of the drugs. Rilmenidine decreased heart rate on   the two tested doses, which did not occur in the clonidine treatment; slight variations in systolic blood pressure in all treatments and respiratory rate reduction in treatments with rilmenidine at 0.021 mg/ kg and clonidine at 0.002 mg/kg were also observed. Further studies with different dosages and varied administration routes are still necessary in order to elucidate more effects of these drugs on horses.

Clonidina e rilmenidina são fármacos utilizados em medicina humana como agentes anti-hipertensivos de ação central devido às suas ações sobre os receptores alfa2-adrenérgicos e imidazolínicos I1 no SNC. Atualmente a clonidina é também utilizada como medicação pré-anestésica e em anestesias espinhais e a rilmenidina, apesar da menor seletividade pelo receptor alfa2-adrenérgico, também tem demonstrado potencial antinociceptivo em modelos experimentais de dor. Neste estudo, seis equinos foram submetidos a quatro tratamentos: grupo R1 (0,014 mg/kg de rilmenidina); grupo R2 (0,021 mg/ kg de rilmenidina); grupo Clo (0,002 mg/kg de clonidina) e um grupo controle. Foram avaliadas as frequências cardíaca e respiratória, a pressão arterial sistólica e motilidade intestinal em níveis basais e, em seguida, 60 e 120 minutos após a administração oral dos fármacos. A rilmenidina reduziu a frequência cardíaca nas duas doses testadas, o que não ocorreu com a clonidina; variações discretas na pressão arterial sistólica em todos os tratamentos e redução na frequência respiratória nos tratamentos com 0,021 mg/kg de rilmenidina e 0,002 mg/kg de clonidina também foram observadas. São ainda necessários maiores estudos com doses e vias de administração diferentes para se elucidar maiores efeitos destes fármacos na espécie equina.

Efeitos da clonidina e da rilmenidina sobre os sistemas cardiorrespiratório e gastrointestinal de equinos / Effects of clonidine and rilmenidine on cardiorespiratory and gastrointestinal systems of horses

Clonidine and rilmenidine are drugs used in human medicine as central acting antihypertensive agents due to their actions on the alpha2-adrenoceptor and I1 imidazoline receptors in the central nervous system. Currently, clonidine is also used as a pre-anesthetic medication and in spinal anesthesia, and rilmenidine, despite the lower selectivity for alpha2-adrenergic receptors than clonidine, has also shown antinociceptive potential in experimental pain models. In this study, six horses were submitted to four treatments: R1 group (0.014 mg/kg of rilmenidine); R2 group (0.021 mg/kg of rilmenidine); Clo group (0.002 mg/kg of clonidine), and a control group. The assessment comprehended their heart and respiratory rates, systolic blood pressure and intestinal motility at basal levels and, then, 60 and 120 minutes after the oral administration of the drugs. Rilmenidine decreased heart rate on   the two tested doses, which did not occur in the clonidine treatment; slight variations in systolic blood pressure in all treatments and respiratory rate reduction in treatments with rilmenidine at 0.021 mg/ kg and clonidine at 0.002 mg/kg were also observed. Further studies with different dosages and varied administration routes are still necessary in order to elucidate more effects of these drugs on horses. (AU)

Clonidina e rilmenidina são fármacos utilizados em medicina humana como agentes anti-hipertensivos de ação central devido às suas ações sobre os receptores alfa2-adrenérgicos e imidazolínicos I1 no SNC. Atualmente a clonidina é também utilizada como medicação pré-anestésica e em anestesias espinhais e a rilmenidina, apesar da menor seletividade pelo receptor alfa2-adrenérgico, também tem demonstrado potencial antinociceptivo em modelos experimentais de dor. Neste estudo, seis equinos foram submetidos a quatro tratamentos: grupo R1 (0,014 mg/kg de rilmenidina); grupo R2 (0,021 mg/ kg de rilmenidina); grupo Clo (0,002 mg/kg de clonidina) e um grupo controle. Foram avaliadas as frequências cardíaca e respiratória, a pressão arterial sistólica e motilidade intestinal em níveis basais e, em seguida, 60 e 120 minutos após a administração oral dos fármacos. A rilmenidina reduziu a frequência cardíaca nas duas doses testadas, o que não ocorreu com a clonidina; variações discretas na pressão arterial sistólica em todos os tratamentos e redução na frequência respiratória nos tratamentos com 0,021 mg/kg de rilmenidina e 0,002 mg/kg de clonidina também foram observadas. São ainda necessários maiores estudos com doses e vias de administração diferentes para se elucidar maiores efeitos destes fármacos na espécie equina. (AU)

AVALIAÇÃO DO USO DOS AGONISTAS ALFA-2 DEXMEDETOMIDINA E CLONIDINA COM ASSOCIAÇÕES NA MEDICAÇÃO PRÉ-ANESTÉSICA, PARA MANUTENÇÃO DE ANESTESIA INTRAVENOSA TOTAL EM PRIMATAS NÃO-HUMANOS

Atualmente os centros zoológicos deixaram de ser apenas um espaço de lazer, passando a ser considerados ambientes importantes para a conservação da biodiversidade. Desta maneira, para o manejo dos animais selvagens, são realizados diversos procedimentos, incluindo anestesias. Os primatas não-humanos (PNH), entre eles o macaco prego, que é pertencente ao gênero Sapajus Nigritus é utilizado como modelo biológico em diversas pesquisas aplicadas aos humanos, sendo, portanto, uma espécie de interesse conservacionista. Todavia, o manejo físico de PNH é considerado difícil devido ao seu comportamento agressivo e força física. Neste contexto a medicação pré-anestésica (MPA) e a anestesia geral são importantes ferramentas para diminuir o estresse, risco de injúrias e proporcionar segurança para a equipe e para o paciente. Assim, o objetivo deste trabalho foi realizar uma monitoração anestésica em macacos prego, submetidos a procedimentos de avaliação física geral. Para isso, nove animais sendo quatro machos e cinco fêmeas, de idade relativos à jovem e adulto, foram anestesiados sob variações de dois grupos na pré-anestesia. Em cinco destes animais, foi utilizado dexmedetomidina na dose de 10 g/kg associada a 2 mg/kg de cetamina, 0,3mg/kg de midazolan e 0,5mg/kg de morfina por via intramuscular (IM). A seleção deste fármaco para este grupo de animais se deve ao grau de seletividade em receptores alfa-2, sendo que há seletividade alfa2:alfa1 de 1620:1, o que confere ao fármaco maior potência em relação à sedação. Em quatro animais, foi empregada clonidina na dose de 10 g/kg associada a 2 mg/kg de cetamina, 0,3mg/kg de midazolan e 0,5mg/kg de morfina por via IM. A clonidina tem menor seletividade que a dexmedetomidina, sendo alfa2:alfa1 de 1200:1. Após a medicação pré-anestésica os animais foram mantidos sob anestesia intravenosa total (AIVT), com propofol em uma taxa fixa de 0,1/mg/kg/min (titulada dose-efeito), para realização de avaliação física geral e exames complementares. Durante a monitoração anestésica os pacientes mantiveram todos os parâmetros fisiológicos normais, incluindo frequência respiratória, capnografia, saturação por oxigênio, pressão arterial invasiva, pressão arterial não-invasiva, coloração de mucosas, tempo de preenchimento capilar e temperatura corpórea. Ocorreu alteração na frequência cardíaca (bradicardia) em decorrência da ação dos agonistas alfa-2 nos barorreceptores. Embora tenha ocorrido diminuição da frequência cardíaca, não houve quaisquer intercorrências adversas graves e persistentes ou óbitos. Todos os animais se recuperaram satisfatoriamente. Concluiu-se que na medicação pré-anestésica de Sapajus Nigritus podem ser utilizados fármacos agonistas alfa-2 com segurança. Além disso, a monitoração anestésica detalhada, utilizando-se o maior número possível de indicadores fisiológicos é fundamental para se anestesiar primatas não-humanos com segurança.

Currently, zoological centers stand out from being just a leisure space, starting to be considered important environments for the conservation of biodiversity. Thus, for the handling of wild animals, several procedures are performed, including anesthesia. Non-human primates (PNH), including the capuchin monkey, which belongs to the Sapajus Nigritus genus, is used as a biological model in several researches applied to humans, and is, therefore, a species of conservation interest. However, the physical management of the PNH is considered difficult due to aggressive behavior and physical strength. In this context, pre-anesthetic medication (MPA) and general anesthesia are important tools to reduce stress, risk of injuries and provide safety for the team and for the patient. Thus, the objective of this work was to perform anesthetic monitoring in capuchin monkeys, general physical assessment procedures. For this purpose, nine animals, four males and five years, of relative age, one young and one adult, were anesthetized under variations of two groups in pre-anesthesia. In five of these animals, dexmedetomidine was used at a dose of 10 g / kg associated with 2 mg / kg of ketamine, 0.3 mg / kg of midazolam and 0.5 mg / kg of morphine intramuscularly (IM). A drug selection for this group of animals is due to the degree of selectivity in alpha-2 receptors, with alpha2: alpha1 selectivity of 1620:1, which gives the drug greater potency in relation to sedation. In four animals, clonidine was used at a dose of 10 g / kg associated with 2 mg / kg of ketamine, 0.3 mg / kg of midazolane and 0.5 mg / kg of morphine via IM. Clonidine has lower selectivity than dexmedetomidine, being alpha2: alpha1 of 1200: 1. After pre-anesthetic medication, the animals were collected under total intravenous anesthesia (TAI), with propofol at a fixed rate of delivery of 0.1 / mg / kg / min (titrated dose-effect), for general physical evaluation and complementary exams. During anesthetic monitoring, patients maintained all normal physiological parameters, including respiratory rate, capnography, oxygen saturation, invasive blood pressure, non-invasive blood pressure, mucosal staining, capillary refill time, and body temperature. There was a change in heart rate due to the action of alpha-2 agonists on baroreceptors. Although there was a decrease in heart rate, there were no serious and persistent adverse events or deaths. All animals recovered satisfactorily. It was concluded that in the pre-anesthetic medication of Sapajus Nigritus, alpha-2 agonist drugs can be used safely. In addition, detailed anesthetic monitoring, using as many physiological indicators as possible, is essential to safely anesthetize non-human primates.

Agonistas Alfa-2 pela via epidural na analgesia de cães e gatos - revisão de literatura / Alpha-2 agonists by epidural analgesia in dogs and cats ­ review abstract / Alfa-2 agonistas en la analgesia epidural en perros y gatos - revisión de la literatura

O tratamento da dor pós-operatória vem ganhando novo enfoque, principalmente no que se refere à administração de analgésicos pela via epidural, visto que esta modalidade resulta em uma analgesia mais duradoura, com a utilização de doses menores em relação às doses sistêmicas, resultando em mínimos efeitos colaterais. Dentre os analgésicos utilizados, os agentes agonistas alfa-2 de receptores adrenérgicos tem sido uma opção para o tratamento da dor devido a sua potente característica analgésica, sedativa e miorrelaxante. Os fármacos pertencentes a esta classe incluem a xilazina, clonidina, detomidina, romifidina, medetomidina e dexmedetomidina. Objetiva-se com esta revisão de literatura abordar informações sobre o uso dos agonistas alfa-2 pela via epidural em cães e gatos, abrangendo a técnica e os fármacos utilizados na Medicina Veterinária.

The treatment of postoperative pain has made a new focus, especially in regard to epidural injection of analgesic drugs, because it results in a longer lasting analgesia with smaller doses when compare to systemic doses, with minimum collateral effects. Among the used of analgesic drugs, the alpha-2 agonists agents of adrenergic receptors have been an option to the pain treatment due their potent sedative, analgesics and muscle relaxation properties. Xylazine, clonidine, detomidine, romifidine, medetomidine and dexmedetomidine are some drugs of this class. The goal of this review is focuses some information about the use of enidural olnho 2 agonists in dogs and cats, including the techniques and the agents used in the Veterinary Medicine.

El tratamiento del dolor postoperatorio ha cobrado nuevo enfoque, especialmente en lo que se refere a la administración de analgesicos epidurales. Esta se ha distinguido, pues da lugar a una analgesia de mayor duración con el uso de dosis más bajas en comparación con dosis sistémicas, con efectos secundarios mínimos. Entre los analgésicos utilizados, los agentes agonistas alfa-2 adrenérgico ha sido una opción para el tratamiento del dolor debido a sus, analgésicos, sedantes y relajantes musculares. Los medicamentos en este grupo incluyen xilazina, clonidina, detomidina, romifidina, medetomidina y dexmedetomidina. Objetivo con esta revisión de la literatura a la información sobre el uso de alfa-2 agonistas por la vía epidural en perros y gatos, incluso su técnica y las drogas utilizadas en medicina veterinaria.

Bloqueio peribulbar com associação de clonidina e hialuronidase à ropivacaína em cães submetidos à facectomias

Diversas oftalmopatoias afetam a qualidade visual dos animais de companhia, dentre elas a opaficificação dos cristalino ou catarata. Sob essas demandas de procedimentos corretivos eficazes e seguros, opta-se pela técnica de facectomia, que exige uma anestesia geral e bulbo ocular centralizado, midríase, acinesia do bulbo ocular, manutenção da pressão intraocular (PIO) e inibição do reflexo óculo-cardíaco (ROC) e como alternativa têm se empregado os bloqueios locais para realizar as exigências, afim de promover conforto e segurança para o paciente. Foi estudado a associação entre ropivacaína-clonidina-hialuronidase na anestesia peribulbar em cirurgias de facectomia em cães, avaliando-se parâmetros oculares e fisiológicos sistêmicos. O teste foi realizado em oito animais, utilizando-se dezesseis olhos, oito para o bloqueio anestésico (OB) e oito contralaterais para controle (OC). Realizou-se o bloqueio peribulbar em um único ponto com volume de 1 mL, contendo clonidina (1 g/kg), ropivacaína 1% (10 mg/mL) e hialuronidase (25 UTR) seguido da pré-medicação, indução e anestesia geral inalatória. Os parâmetros avaliados: PIO (medidas nos tempos 0, 1 e 10 minutos), diâmetro pupilar, centralização do bulbo ocular, latência e duração do bloqueio motor, frequência cardíaca, frequência respiratória, pressão arterial média, ritmo cardíaco, capnometria e temperatura retal. Os pacientes eram ASA 2 (75%) e ASA 3 (25%). O tempo cirúrgico foi de cerca de 72,87 ± 17,41 minutos no qual o tempo de midríase ocorreu em 67,75 ± 43,38 segundos, a centralização do bulbo ocular em 89,13 ± 38,23 segundos e a duração do bloqueio motor de 162 ± 18,9 minutos. A dilatação pupilar foi significativa após o bloqueio. Não houve mudanças significativas nos valores da PIO - T0 (OC: 13,13 ± 3,37 OB: 12,13 ± 1,76), TBP1 (OC: 13,50 ± 2,96 OB: 12,13 ± 2.37) e TBP10 (OC: 13,53 ± 4,18 OB: 12,75 ± 2,17). Não houve correlação significativa entre as doses recebidas de ropivacaína e o seu efeito no bloqueio, contudo, destacamos que as doses de ropivacaína foram todas abaixo dos limites terapêuticos. Os parâmetros fisiológicos foram esperados de um procedimento anestésico e retornaram aos valores basais após o despertar, sem complicações. Não foi relatada ocorrência de ROC ou qualquer complicação referente à técnica do bloqueio peribulbar em quaisquer pacientes. Conclui-se que o bloqueio peribulbar para facectomia utilizando-se a associação ropivacaína 1% - clonidina (1 g/kg) hialuronidase (25UTR) numa solução de 1 mL promove baixa latência, boa duração, midríase adequadas para a facectomia e sem efeitos adversos.

A wide range of ophtalmopathies affects animals visual quality as in lens opacification or cataract. To adress this, safer and efficient corrections are demanded and facectomy is the ellected thecnique, which, demands a general anesthesia, centralization and acenesia of ocular bulb, mydriasis, maintenance do intraocular pressure (IOP) and inhibition of ocularcardiac reflexes (OCR). Alternatively, to general anesthesia, local block is preferred bacause if promotes the other signs safely and provides more comfort to the patient. WE investigated the association of clonidine-hyaluronidase-ropivacaine in peribulbar anesthesia in dogs evaluating ocular and sistemic physiological parameters. Eight animals were investigated, counted 16 eyes, arrangeg 8 eyes for local block (OB) and the controlateral was defined as control (n=8, OC) . We performed a single-point low-volume (1.0 ml) thechnique. Injection volume contained clonidine (1 g/kg), hyaluronidase (25 UTR) and ropivacaine 1% (10mg/mL) and was followed by premedication, induction and inhalatory general anesthesia. We evaluated parameters at time 0 (T0) before peribulbar block, and post peribulbar block at 1 minute (T1) and at 10 mintues for IOP; we measured pupilar diameter, latency and time duration of motor block, akinesia and centralization of eye bulb as well as physiological parameters as cardiac and respiratory rate and frequency, mean arterial pressure, cardiac rhythm, capynometry and rectal temperature. Patients were rated as ASA 2 (75%) and ASA 3 (25%). Facectomy time extended for 72.87± 17.41 minutes, in which, mydriasis ocorrued at 67.75 ± 43.38 seconds; bulb centralizations at 67.75 ± 43.38 seconds; motor block extended for 162 ± 18.9 minutes. Pupilar dialation was significant after peribulbar block. No significant rate was observed for IOP - T0 (OC: 13.13 ± 3.37 OB: 12.13 ± 1.76), TBP1 (OC: 13.50 ± 2.96 OB: 12.13 ± 2.37) e TBP10 (OC: 13.53 ± 4.18 OB: 12.75 ± 2.17). No positive correlation between ropivacaine dose and peribulbar block effect could be determined, however, we detach that ropivacaine dosage for each animal was below the indicated therapeutcis limits for the specie. Physiological parameter were considered normally observed along the anesthesia procedure and reverted to basal rates at recovery and no complications were diagnosed. In all patientes, OCR or any complication relationed to peribulbar block were not observed. We conclude that periblubar block for facectomy using clonidine-hyaluronidase-ropivacaine (C-H-R) association in a 1 mL volume promotes low latency, long duration and mydriasis with no side effects.

O uso da Dexmedetomidina ou Xilazina associadas ao butorfanol na sedação de Gatos Pediátricos: Estudo dos parâmetros Clínicos e Ecocardiográficos.

O emprego de agonistas adrenérgicos dos receptores 2 traz benefícios na Anestesiologia clínica, em especial a dexmedetomidina, por seu aspecto farmacológico e alta especificidade. Contudo, suas vantagens e desvantagens devem ser melhor elucidadas por meio de estudos clínicos tanto na Medicina Humana quanto na Veterinária. São também do grupo dos agonistas de receptores 2 adrenérgicos fármacos como xilazina, detomidina, medetomidina, clonidina e romifidina, sendo os dois primeiros os mais utilizados na rotina da Medicina Veterinária no Brasil. Desta forma, o presente estudo teve por objetivos avaliar clinicamente os felinos por meio da frequência cardíaca, frequência respiratória, pressão arterial sistólica, SpO2, ETCO2, temperatura retal, glicemia, qualidade da sedação por meio de escalas descritivas simples de escores de sedação, relaxamento muscular e postura e avaliar por meio de ecocardiograma os efeitos cardiovasculares dos agentes 2 associados ao butorfanol. Foram selecionados 18 felinos, com pesos em torno de 1,5 +/- 0,14 kg, sem distinção de raça e sexo, e com idade aproximada de 4 semanas a 6 meses. Os parâmetros foram avaliados por ausculta torácica; capnografia; oxímetro de pulso; Doppler vascular; termômetro clínico; amostra em soro congelado e ecocardiograma. No presente estudo, os fármacos 2 agonistas em felinos neonatos, não afetaram os parâmetros clínicos avaliados, excetuando-se a glicemia, que apresentou aumento em até 60 minutos após a administração intramuscular. Ecocardiograficamente, a xilazina demonstrou-se mais deletéria em relação à dexmedetomidina na maioria dos parâmetros avaliados, levando a redução importante do débito cardíaco

The use of the 2 adrenergic agonists has benefits in clinical anesthesiology, especially dexmedetomidine, because of its pharmacological aspect and high specificity. However, its advantages and disadvantages should be better elucidated through clinical studies in both Human and Veterinary Medicine. It is also of the group of 2 adrenergic agonists drugs such as xylazine, detomidine, medetomidine, clonidine and romifidine, the first two being the most used in veterinary medicine routine in Brazil. The aim of the present study was to evaluate the cat's heart rate, respiratory rate, systolic blood pressure, SpO2, ETCO2, rectal temperature, glycemia, sedation quality by means of simple descriptive scales of sedation scores, relaxation muscle and posture and to evaluate by echocardiogram the cardiovascular effects of 2 agents associated with butorphanol. Eighteen cats were selected, with weights around 1.5 +/- 0.14 kg, without distinction of brand and sex, and approximately 4 weeks to 6 months of age. The parameters were evaluated by thoracic auscultation; capnography; pulse oximeter; vascular Doppler; thermometer; frozen serum and echocardiogram. In the present study, 2 agonist drugs in neonatal cats did not affect the clinical parameters evaluated, except for glycemia, which increased up to 60 minutes after intramuscular administration. Echocardiography showed that xylazine was more deleterious to dexmedetomidine in most of the parameters evaluated, leading to a significant reduction in cardiac output

Efeitos comportamental, clínico e analgésico promovidos pela injeção epidural preventiva de morfina, xilazina ou clonidina, em equinos

Opioids and 2-agonists have analgesic effect and preventive administration by epidural route can minimize undesirable and clinical effects. So, behavioral, clinical and analgesic effects were evaluated for 24 hours after preventive epidural injection of morphine (0,1mg kg-1), xylazine (0,17mg kg-1) or clonidine (3µg kg-1) in 18 horses subjected to incisional model of inflammatory pain evaluated by von Frey filaments. Behavioral changes and changes in heart rate, respiratory rate, rectal temperature and height of head were minimum and transitory. Cutaneous sensivity in injured skin was similar to complete skin for 24, 8 and 12 hours after preventive epidural injection of morphine, xylazine and clonidine, respectively. Moreover, clinical and behavioral changes were not severe along 24 hours.

Os agonistas dos receptores adrenérgicos 2 e os opioides tem ação analgésica e a aplicação preventiva pela via epidural pode minimizar os efeitos clínicos e comportamentais indesejáveis. Assim, avaliaram-se os efeitos comportamental, clínico e analgésico promovidos pela injeção epidural preventiva de morfina (0,1mg kg-1), xilazina (0,17mg kg-1) ou clonidina (3µg kg-1) durante 24 horas, em 18 equinos submetidos a um modelo incisional de dor inflamatória e avaliados pelos filamentos de von Frey. As alterações comportamentais, de frequência cardíaca, frequência respiratória, temperatura retal e altura de cabeça em relação ao solo foram mínimas e transitórias. A sensibilidade cutânea em pele incisada foi semelhante à sensibilidade da pele íntegra por 24, 8 e 12 horas após a administração epidural preventiva de morfina, xilazina ou clonidina, respectivamente, em equinos submetidos ao modelo incisional de dor inflamatória e avaliados com filamentos de von Frey. Além disso, não ocorreram alterações clínicas ou comportamentais importantes ao longo de 24 horas.

Efeitos comportamental, clínico e analgésico promovidos pela injeção epidural preventiva de morfina, xilazina ou clonidina, em equinos

Opioids and 2-agonists have analgesic effect and preventive administration by epidural route can minimize undesirable and clinical effects. So, behavioral, clinical and analgesic effects were evaluated for 24 hours after preventive epidural injection of morphine (0,1mg kg-1), xylazine (0,17mg kg-1) or clonidine (3µg kg-1) in 18 horses subjected to incisional model of inflammatory pain evaluated by von Frey filaments. Behavioral changes and changes in heart rate, respiratory rate, rectal temperature and height of head were minimum and transitory. Cutaneous sensivity in injured skin was similar to complete skin for 24, 8 and 12 hours after preventive epidural injection of morphine, xylazine and clonidine, respectively. Moreover, clinical and behavioral changes were not severe along 24 hours.

Os agonistas dos receptores adrenérgicos 2 e os opioides tem ação analgésica e a aplicação preventiva pela via epidural pode minimizar os efeitos clínicos e comportamentais indesejáveis. Assim, avaliaram-se os efeitos comportamental, clínico e analgésico promovidos pela injeção epidural preventiva de morfina (0,1mg kg-1), xilazina (0,17mg kg-1) ou clonidina (3µg kg-1) durante 24 horas, em 18 equinos submetidos a um modelo incisional de dor inflamatória e avaliados pelos filamentos de von Frey. As alterações comportamentais, de frequência cardíaca, frequência respiratória, temperatura retal e altura de cabeça em relação ao solo foram mínimas e transitórias. A sensibilidade cutânea em pele incisada foi semelhante à sensibilidade da pele íntegra por 24, 8 e 12 horas após a administração epidural preventiva de morfina, xilazina ou clonidina, respectivamente, em equinos submetidos ao modelo incisional de dor inflamatória e avaliados com filamentos de von Frey. Além disso, não ocorreram alterações clínicas ou comportamentais importantes ao longo de 24 horas.

Analgesia epidural com clonidina ou sufentanil epidural em cadelas submetidas à ovariosalpingohisterectomia sob anestesia geral inalatória / Epidural analgesia with clonidine or sufentanil in dogs submitted to ovariohysterectomy under general anesthesia

Background: Epidural administration of opioids and a2-adrenergic agonists allows the use of smaller doses when administered by other routes, providing analgesia during trans and post-anesthetic periods, reducing side effects and postoperative stress. Sufentanil in higher doses caused minimal hemodynamic changes in dogs. When given epidurally, clonidine produces analgesia without motor block by a non-opioid mechanism of action. The aim of this study was to evaluate the quality and duration of analgesia as well the cardiorespiratory changes resulting from administration of epidural clonidine or sufentanil in dogs anesthetized with halothane. Materials, Methods & Results: Twenty adult health dogs were used divided into two groups, clonidine (CLO) group and sufentanil (SUF) receiving 150 µg and 50 µg respectively epidural. After induction with thiopental and propofol in a mixture of equal parts (0.8 mg/kg), general anesthesia was maintained with halothane in a Bain circuit for further epidural administration of drugs. Heart rate and cardiac rhythm, respiratory rate, tidal volume, min volume, systolic arterial pressure, body temperature, oxygen saturation of oxyhemoglobin, halothane vaporization were evaluated at times T0 (baseline) and every 15 min until the end of the procedure (T1, T2, T3, T4). The arterial blood gas analysis was performed at T0G (baseline) and 30 min and 2 h after epidural (T1G, T2G) evaluating pH, PaO2 , PaCO2 , BE, HCO3 - and TCO2 . Postoperative analgesia was assessed by the scale of Firth & Haldane (1999) every hour for five hours, starting one hour after the surgery. All parametric variables were analyzed by use of a 1-way ANOVA for repeated measures, followed by a Dunnet test to compare all sample collection times with baseline data (0 min). For comparisons among groups, for each time, test t was used. Differences were considered significant when P < 0.05. The results showed a significant reduction in heart rate after 15 min lasting for 60 min with a reduction in SAP, but no signs of hypotension. A reduction in respiratory rate was also observed in the SUF group and vaporization of halothane in both groups with increase in SpO2 . There was no difference in cardiac rhythm and tidal volume, there was only an increase in minute volume at 60 min in the SUF group. Body temperature also decreases at all times. Discussion: The reduction in heart rate was observed since sufentanil have discrete sympatholytic and vagotonic activity and a2-adrenergic agonists may also cause bradycardia by vagomimetic effect. The drugs used can also cause a reduction in blood pressure, but hypotension was not observed in this study, corroborating with several authors. The lipophilic opioids suffer greater absorption by the blood vessels in the epidural region resulting in peak plasma concentration and early respiratory depression, while the a2-adrenergic agonists cause respiratory depression secondary to central nervous system depression. The observed reduction in vaporization is due to potentiation of drugs used. Analgesia in the intraoperative period can be proved since tachycardia, tachypnea, or hypertension during clamping of the ovarian pedicles was not observed and in the immediate postoperative period, both drugs proved effective with Firth & Haldane numerical scale. The doses employed by epidural reduced the need for halothane demonstrating intra-operative analgesic effect. Furthermore, sufentanil caused severe respiratory depression, however it is suggested greater efficacy when compared to clonidine in the immediate postoperative period.(AU)

Efeito sedativo e alterações fisiológicas da administração de clonidina por via intramuscular em cães intramuscular em cães / Physiologic alterations and sedative effect of intramuscular administration of clonidine in dogs

Background: α2-adrenergic agonists stand out for their intense acting in the respiratory and hemodynamic parameters, which sometimes aggravates the already compromised patient. Clonidine is widely used in humans due to its sedation, minimal hemodynamic and respiratory changes and for analgesia. In veterinary medicine, clonidine has been studied recently specially for epidural analgesia. The study aimed to evaluate the physiological changes and the sedative effect of the intramuscular administration of clonidine in dogs, once there are no reports of intramuscularly use of clonidine. Materials, Methods & Results: Six adult healthy mongrel dogs (5 females and 1 male) were used, after hematological evaluation (complete hemogram) with an average weight of 12 ± 2.5 kg. The animals were randomly divided into four groups with a minimum interval of 10 days, where: control group (GC) received 5 mL of saline IM with the other three groups receiving different doses of clonidine, 5 µg/kg (CLO5), 15 ìg/kg (CLO15) and 30 µg/kg (CLO30) intramuscularly. Heart and respiratory rate, oxygen saturation, systolic arterial pressure, rectal temperature and sedation by analogical descriptive scale were evaluated before administration (baseline), after 5 and 15 min and at 15 min intervals for a period of 90 min. For each group, all parametric variables were analyzed by use of a 1-way ANOVA for repeated measures, followed by a Dunnet test to compare all sample collection times with baseline data (0 min). For comparisons among groups, for each time, 1-way ANOVA was performed, followed by a Tukey test. Score sedation non parametrical variable were analyzed by Friedman test, followed by Dunn’s. Differences were considered significant at P < 0.05. The results showed that clonidine caused a reduction in heart rate 5 min after administration lasting for 90 min with the three doses studied, with a reduction in systolic arterial pressure but with no signs of hypotension. There were respiratory reduction, but between normal values and decreased rectal temperature was observed, with no changes in oxygen saturation. Sedation scores were higher with the higher doses of clonidine. Discussion: The cardiovascular and respiratory effects of administration of α2-adrenergic agonists are characteristic, noting reduction in heart rate which is due mostly to decrease in sympathetic nervous system tonus, which was observed in all treated groups where a significant reduction in heart rate in a gradual manner and tending to be dose dependent since lower values were observed with higher doses, reaching bradycardia (HR <60 bpm) in group CLO30. Another common alteration of α2- adrenergic agonists are the changes in blood pressure, such as hypertension and subsequent hypotension and respiratory depression, frames not observed in this study. Reduction in body temperature is especially due to decrease in muscular activity as well interfering with thermoregulatory mechanisms. Another factor that may contribute is the room temperature, which remained close to 25o C. Intramuscular administration of clonidine caused light and mild sedation with the studies doses and cardiorrespiratory changes should be used in healthy animals. Further studies should be conducted with associations of other pharmacological class to promote a more pronounced level of sedation.

Analgesia epidural com clonidina ou sufentanil epidural em cadelas submetidas à ovariosalpingohisterectomia sob anestesia geral inalatória / Epidural analgesia with clonidine or sufentanil in dogs submitted to ovariohysterectomy under general anesthesia

Background: Epidural administration of opioids and a2-adrenergic agonists allows the use of smaller doses when administered by other routes, providing analgesia during trans and post-anesthetic periods, reducing side effects and postoperative stress. Sufentanil in higher doses caused minimal hemodynamic changes in dogs. When given epidurally, clonidine produces analgesia without motor block by a non-opioid mechanism of action. The aim of this study was to evaluate the quality and duration of analgesia as well the cardiorespiratory changes resulting from administration of epidural clonidine or sufentanil in dogs anesthetized with halothane. Materials, Methods & Results: Twenty adult health dogs were used divided into two groups, clonidine (CLO) group and sufentanil (SUF) receiving 150 µg and 50 µg respectively epidural. After induction with thiopental and propofol in a mixture of equal parts (0.8 mg/kg), general anesthesia was maintained with halothane in a Bain circuit for further epidural administration of drugs. Heart rate and cardiac rhythm, respiratory rate, tidal volume, min volume, systolic arterial pressure, body temperature, oxygen saturation of oxyhemoglobin, halothane vaporization were evaluated at times T0 (baseline) and every 15 min until the end of the procedure (T1, T2, T3, T4). The arterial blood gas analysis was performed at T0G (baseline) and 30 min and 2 h after epidural (T1G, T2G) evaluating pH, PaO2 , PaCO2 , BE, HCO3 - and TCO2 . Postoperative analgesia was assessed by the scale of Firth & Haldane (1999) every hour for five hours, starting one hour after the surgery. All parametric variables were analyzed by use of a 1-way ANOVA for repeated measures, followed by a Dunnet test to compare all sample collection times with baseline data (0 min). For comparisons among groups, for each time, test t was used. Differences were considered significant when P < 0.05. The results showed a significant reduction in heart rate after 15 min lasting for 60 min with a reduction in SAP, but no signs of hypotension. A reduction in respiratory rate was also observed in the SUF group and vaporization of halothane in both groups with increase in SpO2 . There was no difference in cardiac rhythm and tidal volume, there was only an increase in minute volume at 60 min in the SUF group. Body temperature also decreases at all times. Discussion: The reduction in heart rate was observed since sufentanil have discrete sympatholytic and vagotonic activity and a2-adrenergic agonists may also cause bradycardia by vagomimetic effect. The drugs used can also cause a reduction in blood pressure, but hypotension was not observed in this study, corroborating with several authors. The lipophilic opioids suffer greater absorption by the blood vessels in the epidural region resulting in peak plasma concentration and early respiratory depression, while the a2-adrenergic agonists cause respiratory depression secondary to central nervous system depression. The observed reduction in vaporization is due to potentiation of drugs used. Analgesia in the intraoperative period can be proved since tachycardia, tachypnea, or hypertension during clamping of the ovarian pedicles was not observed and in the immediate postoperative period, both drugs proved effective with Firth & Haldane numerical scale. The doses employed by epidural reduced the need for halothane demonstrating intra-operative analgesic effect. Furthermore, sufentanil caused severe respiratory depression, however it is suggested greater efficacy when compared to clonidine in the immediate postoperative period.

Efeito sedativo e alterações fisiológicas da administração de clonidina por via intramuscular em cães intramuscular em cães / Physiologic alterations and sedative effect of intramuscular administration of clonidine in dogs

Background: α2-adrenergic agonists stand out for their intense acting in the respiratory and hemodynamic parameters, which sometimes aggravates the already compromised patient. Clonidine is widely used in humans due to its sedation, minimal hemodynamic and respiratory changes and for analgesia. In veterinary medicine, clonidine has been studied recently specially for epidural analgesia. The study aimed to evaluate the physiological changes and the sedative effect of the intramuscular administration of clonidine in dogs, once there are no reports of intramuscularly use of clonidine. Materials, Methods & Results: Six adult healthy mongrel dogs (5 females and 1 male) were used, after hematological evaluation (complete hemogram) with an average weight of 12 ± 2.5 kg. The animals were randomly divided into four groups with a minimum interval of 10 days, where: control group (GC) received 5 mL of saline IM with the other three groups receiving different doses of clonidine, 5 µg/kg (CLO5), 15 ìg/kg (CLO15) and 30 µg/kg (CLO30) intramuscularly. Heart and respiratory rate, oxygen saturation, systolic arterial pressure, rectal temperature and sedation by analogical descriptive scale were evaluated before administration (baseline), after 5 and 15 min and at 15 min intervals for a period of 90 min. For each group, all parametric variables were analyzed by use of a 1-way ANOVA for repeated measures, followed by a Dunnet test to compare all sample collection times with baseline data (0 min). For comparisons among groups, for each time, 1-way ANOVA was performed, followed by a Tukey test. Score sedation non parametrical variable were analyzed by Friedman test, followed by Dunns. Differences were considered significant at P < 0.05. The results showed that clonidine caused a reduction in heart rate 5 min after administration lasting for 90 min with the three doses studied, with a reduction in systolic arterial pressure but with no signs of hypotension. There were respiratory reduction, but between normal values and decreased rectal temperature was observed, with no changes in oxygen saturation. Sedation scores were higher with the higher doses of clonidine. Discussion: The cardiovascular and respiratory effects of administration of α2-adrenergic agonists are characteristic, noting reduction in heart rate which is due mostly to decrease in sympathetic nervous system tonus, which was observed in all treated groups where a significant reduction in heart rate in a gradual manner and tending to be dose dependent since lower values were observed with higher doses, reaching bradycardia (HR <60 bpm) in group CLO30. Another common alteration of α2- adrenergic agonists are the changes in blood pressure, such as hypertension and subsequent hypotension and respiratory depression, frames not observed in this study. Reduction in body temperature is especially due to decrease in muscular activity as well interfering with thermoregulatory mechanisms. Another factor that may contribute is the room temperature, which remained close to 25o C. Intramuscular administration of clonidine caused light and mild sedation with the studies doses and cardiorrespiratory changes should be used in healthy animals. Further studies should be conducted with associations of other pharmacological class to promote a more pronounced level of sedation.(AU)

Participação da via alfa-2 adrenérgica no controle da secreção do hormônio do crescimento no período pré-púbere em novilhas da raça Nelore / Participation of the pathway alfa-2: adrenergic in the control of growth hormone secretion in the pre-puberty period of the Nellore heifers

O objetivo deste trabalho foi investigar a variação na secreção de GH em resposta ao tratamento com clonidina, agonista alfa-2 adrenérgico, no período pré-púbere de novilhas da raça Nelore, e desta forma obter informações neuroendócrinas envolvidas no processo de maturação sexual destes animais. A administração de clonidina (10 µg/kg, I.V., amostras 15 min por 4h) foi feita nas novilhas aos oito (n =4), 12(n = 5) e 15 meses de idade (n = 4). A concentração de GH foi quantificada por radioimunoensaio (sensibilidade = 0,25 ng/mL, CV = 16%). Aos oito meses, a administração do estimulador alfa-2 adrenérgico aumentou a concentração de GH, área total de picos, área total de secreção de GH e amplitude do maior pico e reduziu o tempo para aparecimento de pico (P < 0,05). A administração de clonidina aumentou a concentração de GH aos 15 meses, e aos 12 meses, em intervalos restritos (P < 0,05). O uso da clonidina estimulou a secreção de GH em novilhas Nelore pré-púberes. Este efeito foi mais evidente nas novilhas aos oito meses, comparado aos 12 e 15 meses de idade.(AU)

This study investigated GH secretion after clonidine (alpha-2 adrenergic agonist) treatmentin pre-pubertal Nelore heifers. Clonidine (10mg/kg, IV, 15 min samples for 4h) was administrated in the same Nelore heifers at eight (n = 4), 12 (n = 5) and 15 (n = 4) months of age. The GH concentration was measured by radioimmunoassay (sensivity = 0.25 ng/mL, CV = 16%). At eight months, clonidine increased GH average concentration, total area of peaks, the total area of GH secretion and increased peak amplitude and reduced time to onset of peak (P < 0.05). At 15 months, the administration of clonidine increased the GH average concentration and at 12 months the increased occurred only in restricted intervals (P <0.05). Clonidine injection stimulated GH secretion in prepubertal heifers and this effect was more evident in Nelore heifers at eight months compared to 12 and 15 months of age.(AU)

Efeito da Clonidina e Hialuronidase Associada à Lidocaína na Anestesia Peribulbar em Cães Submetidos à Cirurgia de Catarata

O objetivo desse estudo foi o de avaliar o efeito da clonidina e hialuronidase associada à lidocaína na anestesia peribulbar em cães submetidos à cirurgia de catarata.