Efeitos determinados pela amitriptilina, administrada pela via subaracnóidea, sobre a medula e as meninges: estudo experimental em cães
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Data
2008-10-21
Autores
Fukushima, Fernanda Bono [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
A amitriptilina é o protótipo dos antidepressivos tricíclicos, classe de fármaco muito utilizada no tratamento da dor neuropática. Tem por propriedade principal a inibição da recaptação de serotonina e noradrenalina, além de interagir com diversos outros receptores. Estudos recentes demonstraram que os antidepressivos tricíclicos são potentes bloqueadores dos canais de sódio, potássio e cálcio, apresentando propriedades semelhantes aos anestésicos locais. Assim existe potencial para que esta classe farmacológica possa ser utilizada no neuroeixo como adjuvante anestésico local ou no tratamento de síndromes dolorosas neuropáticas refratárias. Entretanto, até o presente momento, não há consenso quanto a neurotoxicidade desta classe farmacológica sobre a medula e as meninges. O objetivo desta pesquisa foi avaliar a toxicidade da amitriptilina sobre a medula e as meninges quando administrada pela via subaracnóidea em cães. Método: Vinte e um animais foram randomizados em três grupos que receberam pela via subaracnóidea: Grupo 1 - Solução fisiológica 0,9%; Grupo 2 - solução de amitriptilina 5 mmol.ml-1; Grupo 3- solução de amitriptilina 10 mmol.ml-1. A punção subaracnóidea foi realizada no espaço intervertebral L6-L7. O volume da solução injetada foi de 1 ml. Os animais foram avaliados após uma hora da administração do fármaco e durante os 21 dias que permaneceram em cativeiro quanto ao tônus do esfíncter anal, bloqueio motor e sensibilidade dolorosa. Os animais foram sacrificados por eletrocussão sob anestesia. A medula e as meninges fixadas com solução de formalina 10%, coradas pelos métodos hematoxilina-eosina e tricrômico de Masson, para posterior analise histológica. O estudo foi duplamente encoberto. Para avaliação estatística foi utilizada a análise de variância. Resultados: Durante o período de observação de 21 dias os animais...
Amitriptyline is the prototype drug of the tricyclic antidepressants, which are commonly used as adjuvant medications in the treatment of neuropathic pain syndromes. It is an inhibitor of the reuptake of serotonin and norepinephrine, as well as a blocking agent for great number of receptors. Recent reports have demonstrated tricyclic antidepressants as potent blocking agents for voltage-dependent ionic Na+, K+ and Ca++ channels. Presenting a local anesthetic property. Hence there is a potential role for the intra-spinal use of amitriptyline as an adjuvant in neuroaxial anesthesia and in the treatment of refractory neuropathic pain. Nevertheless, to our knowledge there is no known information regarding the possible neural and meningeal effects of neuraxial amitriptyline administration. Therefore, we conducted a study to evaluate the neural and meningeal toxicities profiles of the intraspinal administration of amitriptyline to dogs. Methods: 21 Dogs were randomly selected for one of three groups: Group 1- 0,9% saline; Group 2- amitriptyline 5 mmol.ml-1 solution; Group 3- amitriptyline 10 mmol.ml-1 solution. In each of the groups one milliliter of the randomized solution was intraspinally administered by an investigator blinded for the intervention group. The dogs were evaluated one hour after awaking from the anesthesia and the following 21 days in the three following domains: anal sphincter tone, motor blockage and pain. The dogs were sacrificed by electrocution under anesthesia, the spinal cords were removed, fixed in 10% Formalin solution, stained by hematoxylin and eosin and Masson's trichrome technique for posterior histological analysis. We used analysis of variance to assess for differences among the treatment groups. Results: During the 21 days of observation after the procedure, all dogs recovered motor function and anal sphincter tone. With the exception of one dog... (Complete abstract, click electronic access below)
Amitriptyline is the prototype drug of the tricyclic antidepressants, which are commonly used as adjuvant medications in the treatment of neuropathic pain syndromes. It is an inhibitor of the reuptake of serotonin and norepinephrine, as well as a blocking agent for great number of receptors. Recent reports have demonstrated tricyclic antidepressants as potent blocking agents for voltage-dependent ionic Na+, K+ and Ca++ channels. Presenting a local anesthetic property. Hence there is a potential role for the intra-spinal use of amitriptyline as an adjuvant in neuroaxial anesthesia and in the treatment of refractory neuropathic pain. Nevertheless, to our knowledge there is no known information regarding the possible neural and meningeal effects of neuraxial amitriptyline administration. Therefore, we conducted a study to evaluate the neural and meningeal toxicities profiles of the intraspinal administration of amitriptyline to dogs. Methods: 21 Dogs were randomly selected for one of three groups: Group 1- 0,9% saline; Group 2- amitriptyline 5 mmol.ml-1 solution; Group 3- amitriptyline 10 mmol.ml-1 solution. In each of the groups one milliliter of the randomized solution was intraspinally administered by an investigator blinded for the intervention group. The dogs were evaluated one hour after awaking from the anesthesia and the following 21 days in the three following domains: anal sphincter tone, motor blockage and pain. The dogs were sacrificed by electrocution under anesthesia, the spinal cords were removed, fixed in 10% Formalin solution, stained by hematoxylin and eosin and Masson's trichrome technique for posterior histological analysis. We used analysis of variance to assess for differences among the treatment groups. Results: During the 21 days of observation after the procedure, all dogs recovered motor function and anal sphincter tone. With the exception of one dog... (Complete abstract, click electronic access below)
Descrição
Palavras-chave
Anestesia - Estudos experimentais, Anestesicos - Efeitos fisiológicos, Amitriptyline, Neurotoxicity
Como citar
FUKUSHIMA, Fernanda Bono. Efeitos determinados pela amitriptilina, administrada pela via subaracnóidea, sobre a medula e as meninges: estudo experimental em cães. 2008. 68 f. Tese (doutorado) - Universidade Estadual Paulista, Faculdade de Medicina de Botucatu, 2008.