Indiana University-Purdue University Indianapolis (IUPUI) / Voltage-gated sodium channels (VGSCs) are transmembrane proteins responsible for the initiation of action potentials in excitable tissues by selectively allowing Na+ to flow through the cell membrane. VGSC subtype Nav1.7 is highly expressed in nociceptive (pain-sensing) neurons. It has recently been shown that individuals lacking the Nav1.7 subtype do not experience pain but otherwise function normally. In addition, dysfunction of Nav1.7 caused by point mutations in the channel is involved in two inherited pain disorders, primary erythromelalgia (PE) and paroxysmal extreme pain disorder (PEPD). This indicates Nav1.7 is a very important component in nociception. The aims of this dissertation were to 1) investigate if the antipsychotic drug, trifluoperazine (TFP), could modulate Nav1.7 current; 2) examine changes in Nav1.7 properties produced by the PE mutation N395K including sensitivity to the local anesthetic (LA), lidocaine; and 3) determine how different inactivated conformations of Nav1.7 affect lidocaine inhibition on the channel using PEPD mutations (I1461T and T1464I) that alter transitions between the different inactivated configurations of Nav1.7. Standard whole-cell electrophysiology was used to determine electrophysiological and pharmacological changes in WT and mutant sodium currents. Results from this dissertation demonstrate 1) TFP inhibits Nav1.7 channels through the LA interaction site; 2) the N395K mutation alters electrophysiological properties of Nav1.7 and decreases channel sensitivity to the local anesthetic lidocaine; and 3) lidocaine stabilizes Nav1.7 in a configuration that decreases transition to the slow inactivated state of the channel. Overall, this dissertation answers important questions regarding the pharmacology of Nav1.7 and provides insight into the changes in Nav1.7 channel properties caused by point mutations that may contribute to abnormal pain sensations. The results of this dissertation on the function and pharmacology of the Nav1.7 channel are crucial to the understanding of pain pathophysiology and will provide insight for the advancement of pain management therapies.

The perioperative use of regional anesthesia and local anesthetics is part of almost every anesthesiologist’s daily clinical practice. Retrospective analyses and results from experimental studies pointed towards a potential beneficial effect of the local anesthetics regarding outcome—i.e., overall and/or recurrence-free survival—in patients undergoing cancer surgery. The perioperative period, where the anesthesiologist is responsible for the patients, might be crucial for the further course of the disease, as circulating tumor cells (shed from the primary tumor into the patient’s bloodstream) might form new micro-metastases independent of complete tumor removal. Due to their strong anti-inflammatory properties, local anesthetics might have a certain impact on these circulating tumor cells, either via direct or indirect measures, for example via blunting the inflammatory stress response as induced by the surgical stimulus. This narrative review highlights the foundation of these principles, features recent experimental and clinical data and provides an outlook regarding current and potential future research activities.

No description available.

Submitted by CAIO JOSÉ XAVIER ABIMUSSI null (caioabimussi@fmva.unesp.br) on 2016-01-17T16:54:36Z No. of bitstreams: 1 TESE_VERSÃO FINAL_CORRIGIDA.pdf: 2286468 bytes, checksum: 496c8f6ffc7595636c5c52c061679bc7 (MD5) / Approved for entry into archive by Juliano Benedito Ferreira (julianoferreira@reitoria.unesp.br) on 2016-01-18T15:52:49Z (GMT) No. of bitstreams: 1 abimussi_cjx_dr_araca.pdf: 2286468 bytes, checksum: 496c8f6ffc7595636c5c52c061679bc7 (MD5) / Made available in DSpace on 2016-01-18T15:52:49Z (GMT). No. of bitstreams: 1 abimussi_cjx_dr_araca.pdf: 2286468 bytes, checksum: 496c8f6ffc7595636c5c52c061679bc7 (MD5) Previous issue date: 2015-12-14 / Não recebi financiamento / Objetivou-se avaliar a anestesia raquidiana com ropivacaína em cães alterando a baricidade do anestésico local, investigando as alterações hemodinâmicas e complicações. Foram utilizados seis cães, Beagle, 4 anos, submetidos a anestesia inalatória com isofluorano e aos tratamentos: Ghipo = anestesia raquidiana hipobárica (0,5 mL NaCl 0,9% + 0,5 mL ropivacaína 0,75%); Giso = anestesia raquidiana isobárica (0,5 mL NaCl 1,53% + 0,5 mL ropivacaína 0,75%); Ghiper = anestesia raquidiana hiperbárica (0,5 mL glicose 10% + 0,5 mL ropivacaína 0,75%). Após indução anestésica e manutenção com isofluorano, os animais foram posicionados em decúbito lateral direito para a passagem de um cateter de artéria pulmonar pela veia jugular esquerda. Após esse procedimento, a punção subaracnóide foi realizada entre L5-L6 com uma agulha espinhal 22G, seguida da administração de 1 mL de anestésico local em 1 min. Os animais foram mantidos por 60 minutos anestesiados em decúbito ventral. A FC, f, PAM, DC, PAPm e TºC apresentaram aumento progressivo em todos os grupos enquanto que a PCPm, apenas no GHIPO, aumentou ao longo de todos os momentos. O IRPT no GISO apresentou valores significativamente superiores no M1, M5 e M10 comparado aos demais grupos, exceto no M5, em que o GISO diferiu somente do GHIPER. O IRVP no GISO aumentou no M5 em comparação ao MB. Foram observados efeitos adversos como déficit motor unilateral, atonia vesical, excitação, dor aguda e quemose. Conclui-se que as alterações hemodinâmicas não foram relevantes, embora a anestesia inalatória com isofluorano tenha influído sobre os resultados obtidos. / The aim of the study was to assess spinal anesthesia with ropivacaine in dogs altering the local anesthetic agent’s baricity in order to investigate hemodynamic changes and complications. Six beagle dogs aged 4 years old were anesthetized with isoflurane and subjected to the treatments: Ghypo = spinal anesthesia with hypobaric ropivacaine (0.5 mL of 0.9% NaCl + 0.5 mL ropivacaine at 0,75%); Giso = isobaric spinal anesthesia (0.5 mL of 0,906% NaCl + 0.5 mL ropivacaine at 0,75%); Ghyper = hyperbaric spinal anesthesia (0.5 mL of 10% glucose + 0.5 mL ropivacaine at 0.75%). After induction to anesthesia and maintenance with isoflurane, animals were positioned in right lateral recumbency for pulmonary artery catheterization through the left jugular vein. Rightafter, spinal anesthesia was performed between L5-L6 using a 22G Quincke tip needle, followed by administration of 1 mL of local anesthetic during 1 minute. Animals were maintained under anesthesia for 60 minutes in ventral recumbency. HR, FR, MAP, CO, mPAP and body temperature progressively increased in all groups. whereas PCWP increased only in GHYPO at all time points. The TPRI showed significantly higher values in GISO at M1, M5 and M10 compared to the other groups, except for M5, during which GISO differed only from GHYPER. The PVRI increased at M5 compared to MB in GISO. Side effects such as unilateral motor deficit, bladder atony, excitation, acute pain and chemosis were observed. In conclusion, the hemodynamic changes were not relevant, although inhalation anesthesia with isoflurane might have influenced the results.

Orientadores: Eneida de Paula, Daniele Ribeiro de Araújo / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-24T00:52:12Z (GMT). No. of bitstreams: 1 Barbosa_RaqueldeMelo_D.pdf: 5424104 bytes, checksum: a7f0888c7fb32138387068083d5bf74f (MD5) Previous issue date: 2013 / Resumo: Nanopartículas lipídicas sólidas (SLN) e carreadores lipídicos nanoestruturados (NLC) têm sido utilizados com sucesso como sistemas de liberação modificada. O anestésico local dibucaína (DBC) foi encapsulado em SLN e NLC objetivando aplicação tópica, para melhora de sua disponibilidade redução de efeitos adversos. As nanopartículas lipídicas foram preparadas pelas técnicas de sonicação (Son) ou homogeinização à alta pressão (HP), sendo utilizados palmitato de cetila (CP) ou miristato de miristila (MM) como matrizes lipídicas sólidas, acrescidos (NLC) ou não (SLN) de uma mistura de triglicerídeos de ácido cáprico e caprílico; poloxamer 188 foi usado como tensoativo. A DBC encapsulada foi quantificada por metodologia validada por cromatografia líquida de alta eficiência. As análises físico-químicas compreenderam diâmetro médio, potencial zeta, distribuição de tamanhos e morfologia das nanopartículas, percentual de encapsulação além de medidas de calorimetria exploratória de varredura (DSC), espectroscopia de infravermelho (FTIR), ressonância paramagnética eletrônica (RPE) e difração de raios X à baixo ângulo (SAXS). Medidas in vitro do perfil de liberação do fármaco, da estimativa de fluxo, deformação e elasticidade das partículas através de membranas artificiais e de toxicidade em cultura de células (fibloblastos 3T3 e queratinócitos HaCat) foram feitas. A estabilidade das amostras foi avaliada em função do tempo e testes de antinocicepção (tail flick, em ratos Wistar) foram usados para avaliar a atividade terapêutica in vivo. O diâmetro médio das partículas de SLN e NLC produzidas foi similar (ca. 200nm). A estabilidade física das nanopartículas foi satisfatória por até 240 dias de armazenamento a 4 ºC, principalmente para NLCMM/HP com e sem DBC, sugerindo que a metodologia de HP produz partículas mais estáveis. Todas as formulações apresentaram eficiência de encapsulação maior que 70%, sendo que NLCMMDBC/HP apresentou a maior encapsulação (90,54 ± 0,95%). Medidas de FTIR e DSC revelaram a DBC molecularmente dispersa na matriz lipídica das nanopartículas. Quanto à organização molecular das SLN e NLC, resultados de SAXS indicaram a existência de arranjos lipídicos lamelares no interior das SLN, não alterados pela adição da DBC; as medidas de RPE com marcadores de spin doxil-estearato revelaram espectros compatíveis com bicamadas, com maior organização molecular dos lipídios das SLN e NLC, após inserção da DBC. Ensaios in vitro confirmaram a liberação modificada da dibucaína associada às partículas, governada por difusão de Fick. Tanto a elasticidade quanto o fluxo das partículas in vitro apresentaram baixos valores evidenciando deposição das mesmas nas membranas com poros de 30 nm. A citotoxicidade intrínsica da DBC sobre ambos os tipos celulares foi reduzida após encapsulação nas SLN e NLC. O efeito analgésico in vivo da DBC a 0,05% aplicada topicamente (dispersa em gel de carbopol) aumentou significativamente após encapsulação nas formulações, em particular para SLNCPDBC liofilizada com o crioprotetor maltose. Assim, formulações de dibucaína em SLN ou NLC, preparadas com MM ou CP mostraram-se promissoras como bases para produtos farmacêuticos de liberação modificada, para anestesia dérmica / Abstract: Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), intended for topical application, were successfully prepared as sustained release systems for the encapsulation of the local anesthetic dibucaine (DBC), aiming to reduce its toxic effects and to improve its availability. The particles were prepared by two differents procedures: sonication (Son) or high pressure homogenization (HP), employing either cetyl palmitate (CP) or myristyl myristate (MM) as the solid lipid matrix, in the presence (NLC) or absence (SLN) of a mixture of capric and caprylic acids; poloxamer 188 was used as surfactant. DBC was quantified through a validated HPLC procedure. Physico-chemical analysis of the nanoparticles included measurements of size distribution, zeta potential, morphology, DBC encapsulation efficiency, as well as exploratory scanning calorimetry (DSC), infrared spectroscopy (FTIR), electron paramagnetic resonance (EPR) and small angle X-ray scattering (SAXS) tests. In vitro analysis of the release profile, flow and elasticity of the particles were performed through artificial membranes while toxicity was tested in 3T3 fibroblasts and HaCaT keratinocytes in culture. Stability of the formulations as a function of time was also measured. The therapeutic activity of the formulations was determined using antinociception tests (tail flick) in Wistar rats. SLN and NLC produced by both methodologies were similar (~200 nm), but HP produced more stable nanoparticles. The physical stability of the nanoparticles was satisfactory during a storage period of 240 days, especially for NLCMM/HP with or without DBC. All formulations showed encapsulation efficiencies higher than 70%, the greatest being assigned for NLCMMDBC/HP (90.54 ± 0.95%). FTIR and DSC revealed that DBC was molecularly dispersed in the lipid matrix of the nanoparticles. As for the SLN and NLC molecular packing, SAXS diffractrograms indicated the existence of lamellar repeats in SLN core region, which were not disturbed by the addition of DBC while EPR data with doxyl stearate probes revealed spectra compatible with bilayers, with higher molecular order in the presence of DBC. In vitro assays confirmed the prolonged release of dibucaine from the nanoparticles, by Fickian diffusion. Nanoparticles's elasticity and flow were low showing deposition on the surface of 30 nm pore membranes. The intrinsic cytotoxicity of DBC against both cell types was decreased, when encapsulated in SLN and NLC. The in vivo analgesic effect of 0.05% DBC topically applied (dispersed in carbopol gel) was significantly prolonged in the nanoparticle formulations, largely for SLNCPDBC lyophilized with maltosis as crioprotector. In conclusion, dibucaine formulations in SLN or NLC prepared with MM or CP are promising for the development of pharmaceutical products intended for prolonged dermal anesthesia / Doutorado / Bioquimica / Doutora em Biologia Funcional e Molecular

La douleur post-opératoire chez les patients constitue un défi thérapeutique important pour les cliniciens. Le traitement de la douleur post-opératoire n’est pas accessoire ni optionnel, puisqu’il permet de donner un congé de l’hôpital plus rapide aux patients et ainsi, il contribue à des économies importantes pour notre système de santé. Parmi les approches thérapeutiques utilisées pour la prise en charge de la douleur post-opératoire, cette thèse s’intéresse particulièrement aux blocs de nerfs périphériques par les anesthésiques locaux et à l’administration de la néostigmine par voie épidurale. Ces médicaments sont utilisés en clinique sans avoir préalablement établi, en se basant sur leur propriétés pharmacocinétiques et pharmacodynamiques spécifiques, leurs doses optimales. Ces doses devraient également tenir en considération les particularités anatomiques du site d’injection par rapport au site d’action. Cette thèse inclut des études exploratoires qui ont contribué à caractériser la pharmacocinétique de la ropivacaïne et de la bupivacaïne ainsi que la pharmacocinétique et la pharmacodynamie de la néostigmine. La première étude portait sur seize patients subissant une chirurgie orthopédique avec un bloc combiné des nerfs fémoral et sciatique par la ropivacaïne (n=8) ou la bupivacaïne (n=8). C’était la première étude qui a inclu des temps d’échantillons pharmacocinétiques allant jusqu’à 32 h après le bloc et ces résultats ont démontré une variabilité interindividuelle considérable. La modélisation par approche de population a aidé à expliquer les sources de la variabilité et démontré que l’absorption systémique des anesthésiques locaux était très lente. De plus, les concentrations plasmatiques demeuraient mesurables, et dans certains cas présentaient un plateau, 32 h après le bloc. Dans les prochaines études, un échantillonnage allant jusqu’à 4 ou 5 jours sera nécessaire afin d’atteindre la fin de l’absorption. La deuxième étude a établi le développement d’un modèle animal en étudiant la pharmacocinétique de la ropivacaïne après administration intraveineuse ainsi que son degré de liaison aux protéines plasmatiques chez le lapin (n=6). Les résultats ont démontré que, chez le lapin la ropivacaïne est beaucoup moins liée aux protéines plasmatiques comparativement à l’humain. Ce résultat important sera utile pour planifier les prochaines études précliniques. La troisième étude a exploré, pour la première fois, la pharmacocinétique et la pharmacodynamie de la néostigmine administrée par voie épidurale et a essayé de caractériser la courbe dose-réponse en utilisant trois doses différentes : 0.5, 1 et 1.5 mg. Bien que les concentrations de la néostigmine dans le liquide céphalo-rachidien fussent très variables une relation inverse entre la consommation de mépéridine et la dose de néostigmine a été démontrée. La dose de 1.5 mg a donné une meilleure réponse pharmacodynamique sur la douleur, mais elle a été considérée comme dangereuse puisqu’elle a résulté en deux cas d’hypertension. Nous avons conclu que des doses plus faibles que 1.5 mg devront être utilisées lors de l’utilisation de la néostigmine par voie épidurale. En conclusion, les études rapportées dans cette thèse ont exploré les propriétés pharmacocinétiques et/ou pharmacodynamiques de certains médicaments utilisés pour le traitement de la douleur post-opératoire. Ceci mènera au but ultime qui est la meilleure prise en charge de la douleur post-opératoire chez les patients. / Post-operative pain in surgical patients remains a challenging problem for the clinicians. The treatment of post-operative pain is no longer an accessory or nice to have, since it can significantly shorten hospital stays and lead to important savings for our health system. Amongst the therapeutic approaches used in the management of post-operative pain, we will focus on peripheral nerve blocks with local anesthetics and epidural neostigmine. These drugs are currently used in the clinic, without the prior characterization of an optimal dose that took into consideration their specific pharmacokinetic and pharmacodynamic properties. Optimal doses will need to consider the specific regional anatomy of the site of drug administration with respect to the site of action. This thesis included exploratory studies that helped to characterize the pharmacokinetics of ropivacaine and bupivacaine as well as the pharmacokinetics and pharmacodynamics of neostigmine. The first study included sixteen patients undergoing orthopedic surgeries with a combined femoral and sciatic nerve blocks technique using ropivacaine (n=8) or bupivacaine (n=8). The study was the first to include pharmacokinetic sampling up to 32 h after the block and results have shown that large between subject variability was present. Population modeling helped to explain and separate the various sources of variability and showed that systemic absorption was very slow. In addition, plasma concentrations were still measurable, and in some cases, plateaued at 32 h after the block. Future studies should extend sampling times to 4 or 5 days after the block in order to wait for the completion of the absorption. The second study attempted to establish an animal model by studying the intravenous pharmacokinetics and protein binding of ropivacaine in the rabbit (n=6). Results have shown that ropivacaine is much less bound to plasma protein in rabbits as compared to humans. This important information will be useful in future preclinical and clinical research. The third study explored, for the first time, the pharmacokinetics and the pharmacodynamics of epidural neostigmine (n=15) and attempted to characterize the dose effect relationship by testing the following doses: 0.5, 1 and 1.5 mg. Although the CSF pharmacokinetics of neostigmine were variable, a relationship between dose and meperidine consumption could be shown. The dose of 1.5 mg resulted in a better pharmacodynamic response on pain but it was deemed unsafe since it led to hypertension in two patients. We conclude that doses below 1.5 mg should be used for an epidural block with neostigmine. In conclusion, this research work investigated the pharmacokinetic and/or the pharmacodynamic characteristics of some drugs used for the treatment of post-operative pain. The gathered information will be essential to be able to reliably characterize the pharmacokinetic-pharmacodynamic relationships. This will help in achieving the ultimate goal which is a better management of post operative pain in surgical patients.

La douleur post-opératoire chez les patients constitue un défi thérapeutique important pour les cliniciens. Le traitement de la douleur post-opératoire n’est pas accessoire ni optionnel, puisqu’il permet de donner un congé de l’hôpital plus rapide aux patients et ainsi, il contribue à des économies importantes pour notre système de santé. Parmi les approches thérapeutiques utilisées pour la prise en charge de la douleur post-opératoire, cette thèse s’intéresse particulièrement aux blocs de nerfs périphériques par les anesthésiques locaux et à l’administration de la néostigmine par voie épidurale. Ces médicaments sont utilisés en clinique sans avoir préalablement établi, en se basant sur leur propriétés pharmacocinétiques et pharmacodynamiques spécifiques, leurs doses optimales. Ces doses devraient également tenir en considération les particularités anatomiques du site d’injection par rapport au site d’action. Cette thèse inclut des études exploratoires qui ont contribué à caractériser la pharmacocinétique de la ropivacaïne et de la bupivacaïne ainsi que la pharmacocinétique et la pharmacodynamie de la néostigmine. La première étude portait sur seize patients subissant une chirurgie orthopédique avec un bloc combiné des nerfs fémoral et sciatique par la ropivacaïne (n=8) ou la bupivacaïne (n=8). C’était la première étude qui a inclu des temps d’échantillons pharmacocinétiques allant jusqu’à 32 h après le bloc et ces résultats ont démontré une variabilité interindividuelle considérable. La modélisation par approche de population a aidé à expliquer les sources de la variabilité et démontré que l’absorption systémique des anesthésiques locaux était très lente. De plus, les concentrations plasmatiques demeuraient mesurables, et dans certains cas présentaient un plateau, 32 h après le bloc. Dans les prochaines études, un échantillonnage allant jusqu’à 4 ou 5 jours sera nécessaire afin d’atteindre la fin de l’absorption. La deuxième étude a établi le développement d’un modèle animal en étudiant la pharmacocinétique de la ropivacaïne après administration intraveineuse ainsi que son degré de liaison aux protéines plasmatiques chez le lapin (n=6). Les résultats ont démontré que, chez le lapin la ropivacaïne est beaucoup moins liée aux protéines plasmatiques comparativement à l’humain. Ce résultat important sera utile pour planifier les prochaines études précliniques. La troisième étude a exploré, pour la première fois, la pharmacocinétique et la pharmacodynamie de la néostigmine administrée par voie épidurale et a essayé de caractériser la courbe dose-réponse en utilisant trois doses différentes : 0.5, 1 et 1.5 mg. Bien que les concentrations de la néostigmine dans le liquide céphalo-rachidien fussent très variables une relation inverse entre la consommation de mépéridine et la dose de néostigmine a été démontrée. La dose de 1.5 mg a donné une meilleure réponse pharmacodynamique sur la douleur, mais elle a été considérée comme dangereuse puisqu’elle a résulté en deux cas d’hypertension. Nous avons conclu que des doses plus faibles que 1.5 mg devront être utilisées lors de l’utilisation de la néostigmine par voie épidurale. En conclusion, les études rapportées dans cette thèse ont exploré les propriétés pharmacocinétiques et/ou pharmacodynamiques de certains médicaments utilisés pour le traitement de la douleur post-opératoire. Ceci mènera au but ultime qui est la meilleure prise en charge de la douleur post-opératoire chez les patients. / Post-operative pain in surgical patients remains a challenging problem for the clinicians. The treatment of post-operative pain is no longer an accessory or nice to have, since it can significantly shorten hospital stays and lead to important savings for our health system. Amongst the therapeutic approaches used in the management of post-operative pain, we will focus on peripheral nerve blocks with local anesthetics and epidural neostigmine. These drugs are currently used in the clinic, without the prior characterization of an optimal dose that took into consideration their specific pharmacokinetic and pharmacodynamic properties. Optimal doses will need to consider the specific regional anatomy of the site of drug administration with respect to the site of action. This thesis included exploratory studies that helped to characterize the pharmacokinetics of ropivacaine and bupivacaine as well as the pharmacokinetics and pharmacodynamics of neostigmine. The first study included sixteen patients undergoing orthopedic surgeries with a combined femoral and sciatic nerve blocks technique using ropivacaine (n=8) or bupivacaine (n=8). The study was the first to include pharmacokinetic sampling up to 32 h after the block and results have shown that large between subject variability was present. Population modeling helped to explain and separate the various sources of variability and showed that systemic absorption was very slow. In addition, plasma concentrations were still measurable, and in some cases, plateaued at 32 h after the block. Future studies should extend sampling times to 4 or 5 days after the block in order to wait for the completion of the absorption. The second study attempted to establish an animal model by studying the intravenous pharmacokinetics and protein binding of ropivacaine in the rabbit (n=6). Results have shown that ropivacaine is much less bound to plasma protein in rabbits as compared to humans. This important information will be useful in future preclinical and clinical research. The third study explored, for the first time, the pharmacokinetics and the pharmacodynamics of epidural neostigmine (n=15) and attempted to characterize the dose effect relationship by testing the following doses: 0.5, 1 and 1.5 mg. Although the CSF pharmacokinetics of neostigmine were variable, a relationship between dose and meperidine consumption could be shown. The dose of 1.5 mg resulted in a better pharmacodynamic response on pain but it was deemed unsafe since it led to hypertension in two patients. We conclude that doses below 1.5 mg should be used for an epidural block with neostigmine. In conclusion, this research work investigated the pharmacokinetic and/or the pharmacodynamic characteristics of some drugs used for the treatment of post-operative pain. The gathered information will be essential to be able to reliably characterize the pharmacokinetic-pharmacodynamic relationships. This will help in achieving the ultimate goal which is a better management of post operative pain in surgical patients.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

The objective was to evaluate the efficacy of lidocaine and bupivacaine in spinal turtles by species Phrynops geoffroanus to promote sensory and motor block in the regions of the tail, vent and later members. Ten females with average weight of 2.14 kilograms (kg) were submitted to two anesthetic protocols, with an interval of 10 days: 4.6 milligrams (mg) / kg of lidocaine 2% and 1.15 mg / kg of bupivacaine 0.5% deposited in the spinal region of space proximal intercoccígeo. The anesthetic action in the tail for the two anesthetics was instantaneous, that is less than 1 min. Regarding the latency period in later members (PM), we obtained 4.5 ± 4.37 min and instant messaging as their average values for lidocaine and bupivacaine. The presence of maximum muscle relaxation and analgesia was 34.50 ± 33.28 min and 114.55 ± 39.89 min in the tail / vent to 2% lidocaine. and bupivacaine 0.5%, respectively. Medium corresponding to 24 ± 23.42 min and 110.50 ± 28.81 min was obtained by the later members use of anesthetics in the same sequence. The recovery period, equivalent to the time required to return to preanesthetic parameters from the start scoring 2 for muscle relaxation, was 37.00 ± 23.63 min for lidocaine and 61.5 ± 36.59 min for bupivacaine. Times skillful anesthesia achieved with the use of both anesthetic protocols are sufficient to perform simple surgical procedures and routine, such as amputation of the penis and suturing of skin lacerations. The choice of anesthetic to be applied will depend on the average time the procedure was performed to average 2% lidocaine and bupivacaine half-hour average of one hour. / Objetivou-se avaliar a eficácia da utilização de lidocaína e bupivacaína por via espinhal em cágados da espécie Phrynops geoffroanus para a promoção de bloqueios motor e sensitivo nas regiões dos membros pelvinos, cauda e cloaca. Dez fêmeas, com peso médio de 2,14 quilogramas (Kg), foram submetidas a dois protocolos anestésicos, com intervalo de 10 dias: 4,6 miligramas (mg)/Kg de lidocaína 2% e 1,15 mg/Kg de bupivacaína 0,5%, depositadas na região espinhal do espaço intercoccígeo proximal. A ação anestésica na cauda para os dois anestésicos foi instantânea, isto é menor que 1 min. Em relação ao período de latência nos membros pelvinos (MP), obteve-se 4,5 ±4,37 min e instantâneo como valores médios respectivos para lidocaína e bupivacaína. A presença de relaxamento muscular máximo com analgesia foi de 34,50±33,28 min e 114,55±39,89 min na cauda/cloaca para lidocaína 2%. e bupivacaína 0,5%, respectivamente. Médias correspondentes a 24±23,42 min e 110,50±28,81 min foram obtidas nos membros pelvinos mediante utilização dos anestésicos, na mesma sequência. O período de recuperação, equivalente ao tempo necessário para retorno aos parâmetros pré-anestésicos a partir do início de escore 2 para relaxamento muscular, foi de 37,00±23,63 min para lidocaína e 61,5±36,59 min para a bupivacaína. Os tempos hábeis de anestesia, conseguidos com a utilização de ambos os protocolos anestésicos, são suficientes para execução de procedimentos cirúrgicos mais simples e rotineiros, como amputação de pênis e sutura de lacerações de pele. A escolha do anestésico a ser aplicado vai depender do tempo médio do procedimento realizado, para lidocaína 2% tempo médio de meia hora e bupivacaína tempo médio de uma hora. / Mestre em Ciências Veterinárias

We aimed to investigate the efficacy of lidocaine and bupivacaine via spinal injection in promoting sensory and motor block in the regions of the tail/cloaca and pelvic members of Trachemys dorbignyi. Ten females with average weight of 1.375 kilograms (kg) were submitted to two anesthetic protocols, with an interval of 10 days: 4.6 milligrams (mg)/kg of lidocaine 2% and 1.15 mg/kg of bupivacaine 0, 5%, deposited via spinal in the coccyx region. The animals were evaluated for latent period, reasonable period and recovery period of anesthesia. For the period of latency of the tail (Lca), we obtained an average of 28.80 ± 2.29 seconds (sec) and 56.80 ± 4.78 sec for lidocaine and bupivacaine. Since the average latency of pelvic limb was 448.00 ± 48.51 sec and 487.70 ± 30.25 sec for both anesthetics. The reasonable period of anesthesia was 79.29 ± 33.11 minutes (min) for lidocaine and 116.55 ± 41.03 min in the tail/cloaca for bupivacaine. Averages corresponding to 112.03 ± 45.12 min and 150.87 ± 53.36 min were obtained in the pelvic members through use of anesthetics in the same sequence. Finally, the recovery period was 76.30 ± 32.18 min and 68.00 ± 43.35 min for lidocaine and bupivacaine, respectively. The heart rate remained within the range considered normal for reptiles. It was concluded that the use of lidocaine 2% and 0.5% bupivacaine via spinal injection is safe and effective in promoting anesthesia in the tail/cloaca and pelvic members in Trachemys dorbignyi. The duration of anesthetic effect in the tail/cloaca was significantly higher by using bupivacaine 0.5%. The times of reasonable periods of anesthesia achieved with the use of both anesthetic protocols are sufficient to perform simple and routine surgical procedures, such as amputation of the penis and suturing of skin lacerations. / Objetivou-se avaliar a eficácia da utilização de lidocaína e bupivacaína por via espinhal em cágados da espécie Trachemys dorbignyi para a promoção de bloqueios motor e sensitivo nas regiões da cauda/cloaca e membros pelvinos. Dez fêmeas, com peso médio de 1,375 quilogramas (Kg), foram submetidas a dois protocolos anestésicos, com intervalo de 10 dias: 4,6 miligramas (mg)/Kg de lidocaína 2% e 1,15 mg/Kg de bupivacaína 0,5%, depositadas na região espinhal do espaço intercoccígeo proximal. Os animais foram avaliados quanto a período de latência, período hábil de anestesia e período de recuperação. Em relação ao período de latência da cauda (Lca), obteve-se 28,80±2,29 segundos (seg) e 56,80±4,78 seg como valores médios respectivos para lidocaína e bupivacaína. Já o período médio de latência do membro pelvino foi 448,00±48,51 e 487,70±30,25 seg para ambos os anestésicos. O período hábil de anestesia foi de 79,29±33,11 minutos (min) para lidocaína e 116,55±41,03 min na cauda/cloaca para bupivacaína. Médias correspondentes a 112,03±45,12 min e 150,87±53,36 min foram obtidas nos membros pelvinos mediante utilização dos anestésicos, na mesma sequencia. Por fim, o período de recuperação foi de 76,30±32,18 min para lidocaína e 68,00±43,35 min para a bupivacaína. A freqüência cardíaca se manteve dentro do intervalo considerado normal para os répteis. Concluiu-se que utilização de lidocaína 2% e bupivacaína 0,5% por via espinhal mostra-se uma técnica segura e eficaz na promoção de anestesia na região da cauda/cloaca e nos membros pelvinos, em Trachemys dorbignyi. O tempo de efeito anestésico na região da cauda/cloaca foi significativamente maior mediante utilização da bupivacaína 0,5%. Os tempos hábeis de anestesia, conseguidos com a utilização de ambos os protocolos anestésicos, são suficientes para execução de procedimentos cirúrgicos mais simples e rotineiros, como amputação de pênis e sutura de lacerações de pele. / Mestre em Ciências Veterinárias