RESUMO
BACKGROUND: The aim of this study was to investigate the effects of intracerebroventricularly administered rocuronium bromide on the central nervous system, determine the seizure threshold dose of rocuronium bromide in rats, and investigate the effects of rocuronium on the central nervous system at 1/5, 1/10, and 1/100 dilutions of the determined seizure threshold dose. METHODS: A permanent cannula was placed in the lateral cerebral ventricle of the animals. The study was designed in two phases. In the first phase, the seizure threshold dose of rocuronium bromide was determined. In the second phase, Group R 1/5 (n=6), Group 1/10 (n=6), and Group 1/100 (n=6) were formed using doses of 1/5, 1/10, and 1/100, respectively, of the obtained rocuronium bromide seizure threshold dose. RESULTS: The rocuronium bromide seizure threshold value was found to be 0.056±0.009µmoL. The seizure threshold, as a function of the body weight of rats, was calculated as 0.286µmoL/kg-1. A dose of 1/5 of the seizure threshold dose primarily caused splayed limbs, posturing, and tremors of the entire body, whereas the dose of 1/10 of the seizure threshold dose caused agitation and shivering. A dose of 1/100 of the seizure threshold dose was associated with decreased locomotor activity. CONCLUSIONS: This study showed that rocuronium bromide has dose-related deleterious effects on the central nervous system and can produce dose-dependent excitatory effects and seizures.
Assuntos
Androstanóis/farmacologia , Sistema Nervoso Central/efeitos dos fármacos , Epilepsia/tratamento farmacológico , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Feminino , Injeções Intraventriculares , Locomoção/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Distribuição Aleatória , Ratos Wistar , RocurônioRESUMO
AIMS: Endogenous ouabain is elevated in patients and experimental models of hypertension and is associated with elevated mortality. In this context, it is reasonable to assume that a new antihypertensive drug that inhibits the deleterious effects of endogenous ouabain may be a specific pharmacological tool for hypertension treatment. Here, we investigated the effects of rostafuroxin (ROSTA), an ouabain inhibitor, on SBP, endothelial dysfunction and oxidative stress in deoxycorticosterone acetate (DOCA)-salt rats. METHODS AND RESULTS: A hypertensive model was established in uninephrectomized Wistar rats using DOCA-salt. After SBP stabilization, DOCA-salt rats were divided into two groups: DOCA-salt (control) and DOCA-salt treatment with ROSTA (1 mg/kg per day gavage, 3 weeks). The SBP was measured using the tail-cuff method, and vascular function was assessed in mesenteric-resistance arteries (MRAs) using a wire myograph. Nitric oxide and reactive oxygen species production were investigated. Western blot was performed to quantify protein expression. Our results indicated that ROSTA treatment decreased SBP, improved acetylcholine-induced relaxation via enhanced nitric oxide synthesis and bioavailability, decreased superoxide anion generation from NAD(P)H oxidase and cyclooxygenase-2 and reduced cytoplasmic tyrosine kinase Src phosphorylation without changes in NaKATPase activity in MRA from DOCA-salt rats. CONCLUSION: This study reports the critical role of endogenous ouabain in volume-dependent hypertension. In MRA from DOCA-salt rats, the binding of endogenous ouabain to NaK-ATPase results in downstream c-SRC activation, oxidative stress and endothelial dysfunction. Endogenous ouabain is a putative target for the treatment of hypertension, and ROSTA may represent a novel therapeutic approach.
Assuntos
Androstanóis/farmacologia , Anti-Hipertensivos/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/fisiopatologia , Ouabaína/antagonistas & inibidores , Animais , Pressão Sanguínea/efeitos dos fármacos , Pressão Sanguínea/fisiologia , Ciclo-Oxigenase 2/metabolismo , Acetato de Desoxicorticosterona/toxicidade , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiopatologia , Humanos , Hipertensão/etiologia , Masculino , Artérias Mesentéricas/efeitos dos fármacos , Artérias Mesentéricas/fisiopatologia , NADPH Oxidases/metabolismo , Ouabaína/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Cloreto de Sódio na Dieta/toxicidade , ATPase Trocadora de Sódio-Potássio/metabolismo , Resistência Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Quinases da Família src/metabolismoRESUMO
Objetivo: El objetivo de este estudio fue analizar la incidencia de parálisis muscular residual producida por bloqueadores neuromusculares no despolarizantes en la Unidad de Cuidados Postanestésicos (UCPA)del Hospital Miguel Pérez Carreño, Caracas, Venezuela. Material y Métodos: Se incluyeron 246 pacientes en los que se midió la relación T4/T1 al momento del ingreso a la unidad, a los tres y a los cinco minutos. El criterio para considerar un paciente sin bloqueo residual fue una relación T4/T1 > 0,9. Además se monitorizó la saturación de oxígeno, variables demográficas, características de la cirugía y la anestesia, y uso o no de reversión. Resultados: El promedio de edad fue de 36,45 años, con un peso de 62,85 kg. La incidencia de parálisis residual en la UCPA fue 51,2 por ciento para el momento de llegada a la unidad, de 47,6 por ciento a los tres minutosy de 46,7 por ciento al quinto minuto, siendo los pacientes de mayor edad los más afectadas (p= 0,002). Cuando se comparó la utilización de reversión con la presencia de relajación residual no se encontró diferencia estadísticamente significativa (p = 0,516). Conclusión: La incidencia de parálisis muscular residual en la UCPA es alta en nuestro centro (51 por ciento), similar a lo que reporta la literatura a nivel mundial; los pacientes más afectados fueron los de mayor edad y el uso de reversión no excluyó la presencia de esta entidad.
Objective: The outcome of this study was to analyze the incidence of residual muscular paralysis produced by nondepolarizing neuromuscular blockers in the PostAnesthetic Care Unit (PACU) of the Doctor Miguel Pérez Carreño Hospital, Caracas, Venezuela. Methods: 246 patients were included. T4/T1 ratio was measured at the moment of arriving to the postoperative unit, 3 and 5 minutes later. Criteria for consideringno residual effects was a T4/T1 > 0,9. Moreover, oxygen saturation was monitored. Demographic variables,characteristics of surgery and anesthesia and the usage or not of reversion drugs were noted. Results: The average of age was 36,45 years, with an average weight of 62,85 kg. The incidence of residual muscularparalysis in the PACU was 51,2 percent at the time of arriving, and 47,6 percent and 46,7 percent at the 3rd and 5th minutes respectively, being the more aged patients the most affected (p = 0,002). When compared the usage ofreversion with the presence of residual muscular paralysis no difference statistically significant was found(p = 0,516). Conclusion: The incidence of residual muscular paralysis in PACU at our center was high (51 percent) and similar to the one reported in worldwide literature; the most affected were the more aged patients and the use of reversion did not exclude the presence of this entity.
Assuntos
Humanos , Masculino , Adolescente , Adulto , Feminino , Pessoa de Meia-Idade , Androstanóis/farmacologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Paralisia , Junção Neuromuscular , Fatores Etários , Período de Recuperação da Anestesia , Peso Corporal , Incidência , Oxigênio/sangue , Estudos Prospectivos , Fatores Sexuais , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVES: Lidocaine potentiates the effects of neuromuscular blockers and attenuates the hemodynamic response to orotracheal intubation. The objective of the present study was to test the effects of lidocaine on the latency of two different doses of rocuronium and on the hemodynamic response to intubation. METHODS: Eighty patients were distributed in 4 groups: Groups 1 and 2 received 0.6 mg.kg(-1) of rocuronium; patients in Group 2 also received 2 mg.kg(-1) of lidocaine before intubation. Patients in Groups 3 and 4 received 1.2 mg.kg(-1) of rocuronium; patients in Group 4 received additional 2 mg.kg(-1) of lidocaine. The latency of the neuromuscular blockade was measured by acceleromyography. Hemodynamic evaluation was performed at baseline, immediately before, and 1 minute after orotracheal intubation (OI). RESULTS: Statistically significant differences were not observed between the latency from 0.6 mg.kg(-1) and 1.2 mg.kg(-1) of rocuronium in patients who received lidocaine before induction and those who did not. The latency in patients who received 0.6 mg.kg(-1) of rocuronium with lidocaine was statistically similar to that of those who received 1.2 mg.kg(-1) rocuronium independently of whether lidocaine was administered or not. Patients who did not receive lidocaine before induction showed the same increases in systolic, diastolic, and mean arterial pressure and heart rate after OI, which was not observed in those patients who received lidocaine. CONCLUSIONS: Intravenous lidocaine before anesthetic induction was capable of attenuating the hemodynamic response associated to OI maneuvers, but it did not reduce the latency of the neuromuscular blockade produced by two different doses of rocuronium.
Assuntos
Androstanóis/administração & dosagem , Anestésicos Locais/administração & dosagem , Hemodinâmica/efeitos dos fármacos , Intubação Intratraqueal , Lidocaína/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Adulto , Androstanóis/farmacologia , Anestésicos Locais/farmacologia , Interações Medicamentosas , Feminino , Humanos , Injeções Intravenosas , Lidocaína/farmacologia , Masculino , Fármacos Neuromusculares não Despolarizantes/farmacologia , Tempo de Reação/efeitos dos fármacos , RocurônioRESUMO
PURPOSE: To evaluate in vitro lidocaine and racemic bupivacaine effects in neuromuscular transmission and in neuromuscular blockade produced by rocuronium. METHODS: Rats were distributed in 5 groups (n = 5) in agreement with the studied drugs: lidocaine, racemic bupivacaine, rocuronium, separately (Groups I, II, III); rocuronium in preparations exposed to local anesthetics (Groups IV, V). The concentrations used were: 20 microg/mL, 5 microg/mL and 4 microg/mL, for lidocaine, bupivacaine and rocuronium, respectively. It was evaluated: 1) amplitude of diaphragm muscle response to indirect stimulation, before and 60 minutes after separately addition of lidocaine, racemic bupivacaine and rocuronium and the association of local anesthetics - rocuronium; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP). RESULTS: Lidocaine and bupivacaine separately didn't alter the amplitude of muscle response and MP. In preparations previously exposed to lidocaine and racemic bupivacaine, the rocuronium blockade was significantly larger (90.10 +/- 9.15% and 100%, respectively), in relation to the produced by rocuronium separately (73.12 +/- 9.89%). Lidocaine caused an increase in the frequency of MEPP, being followed by blockade; racemic bupivacaine produced decrease being followed by blockade. CONCLUSIONS: Local anesthetics potentiated the blockade caused by rocuronium. The alterations of MEPP identify presynaptic action.
Assuntos
Androstanóis/farmacologia , Anestésicos Locais/farmacologia , Bloqueio Neuromuscular/métodos , Junção Neuromuscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Nervo Frênico/efeitos dos fármacos , Animais , Bupivacaína/farmacologia , Diafragma/inervação , Avaliação Pré-Clínica de Medicamentos , Estimulação Elétrica , Lidocaína/farmacologia , Masculino , Placa Motora/efeitos dos fármacos , Ratos , Ratos Wistar , Rocurônio , Estatísticas não ParamétricasRESUMO
PURPOSE: To evaluate in vitro lidocaine and racemic bupivacaine effects in neuromuscular transmission and in neuromuscular blockade produced by rocuronium. METHODS: Rats were distributed in 5 groups (n = 5) in agreement with the studied drugs: lidocaine, racemic bupivacaine, rocuronium, separately (Groups I, II, III); rocuronium in preparations exposed to local anesthetics (Groups IV, V). The concentrations used were: 20 µg/mL, 5 µg/mL and 4 µg/mL, for lidocaine, bupivacaine and rocuronium, respectively. It was evaluated: 1) amplitude of diaphragm muscle response to indirect stimulation, before and 60 minutes after separately addition of lidocaine, racemic bupivacaine and rocuronium and the association of local anesthetics - rocuronium; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP). RESULTS: Lidocaine and bupivacaine separately didn't alter the amplitude of muscle response and MP. In preparations previously exposed to lidocaine and racemic bupivacaine, the rocuronium blockade was significantly larger (90.10 ± 9.15 percent and 100 percent, respectively), in relation to the produced by rocuronium separately (73.12 ± 9.89 percent). Lidocaine caused an increase in the frequency of MEPP, being followed by blockade; racemic bupivacaine produced decrease being followed by blockade. CONCLUSIONS: Local anesthetics potentiated the blockade caused by rocuronium. The alterations of MEPP identify presynaptic action.
OBJETIVO: Avaliar in vitro os efeitos da lidocaína e bupivacaína racêmica na transmissão neuromuscular e no bloqueio neuromuscular produzido pelo rocurônio. MÉTODOS: Ratos foram distribuídos em 5 grupos (n = 5) de acordo com a droga estudada: lidocaina, bupivacaína racêmica, rocurônio, isoladamente (Grupos I, II, III); rocurõnio em preparações expostas aos anestésicos locais (Grupos IV, V). As concentrações utilizadas foram: 20 µg/mL, 5 µg/mL e 4 µg/mL, para lidocaína, bupivacaína e rocurônio, respectivamente. Avaliou-se: 1) amplitude das respostas do músculo diafragma à estimulação indireta, antes e 60 minutos após a adição da lidocaína, bupivacaína racêmica e rocurônio isoladamente e da associação anestésicos locais - rocurônio; 2) potenciais de membrana (PM) e potenciais de placa terminal em miniatura (PPTM). RESULTADOS: A lidocaína e a bupivacaína isoladamente não alteraram a amplitude das respostas musculares e os PM. Nas preparações previamente expostas a lidocaína e a bupivacaína racêmica, o bloqueio com o rocurônio foi significativamente maior (90,10 ± 9,15 por cento e 100 por cento, respectivamente), em relação ao produzido pelo rocurônio isoladamente (73,12 ± 9,89 por cento). A lidocaína causou aumento na freqüência dos PPTM, seguido de bloqueio; a bupivacaína racêmica produziu diminuição seguida de bloqueio. CONCLUSÕES: Os anestésicos locais potencializaram o bloqueio causado pelo rocurônio. As alterações do PPTM identificam ação pré-sináptica.
Assuntos
Animais , Masculino , Ratos , Androstanóis/farmacologia , Anestésicos Locais/farmacologia , Bloqueio Neuromuscular/métodos , Junção Neuromuscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Nervo Frênico/efeitos dos fármacos , Bupivacaína/farmacologia , Avaliação Pré-Clínica de Medicamentos , Diafragma/inervação , Estimulação Elétrica , Lidocaína/farmacologia , Placa Motora/efeitos dos fármacos , Ratos Wistar , Estatísticas não ParamétricasRESUMO
OBJECTIVE: To compare tracheal intubation conditions in morbidly obese patients 60 seconds after administration of succinylcholine or rocuronium doses based on real weight or ideal weight. METHOD: We evaluated patients with a body mass index (BMI) of 40 kg x m(-2) or more but no other indications of difficult-intubation risk. Induction was performed under fentanyl and propofol at doses calculated based on real weight. Patients were assigned to 1 of 4 groups for tracheal intubation. Group 1 received 1 mg of succinylcholine per kilogram of ideal weight, group 2 received 1 mg of succinylcholine per kilogram of real weight, group 3 received 0.6 mg of rocuronium per kilogram of ideal weight, and group 4 received 0.6 mg of rocuronium per kilogram of real weight. Tracheal intubation was performed 60 seconds later and intubation conditions were recorded using a clinical scoring system. RESULTS: Eighty patients with a mean BMI of 47.5 kg x m(-2) were enrolled. The difficult intubation rate was 3.75%. All patients were intubated. Laryngoscopy conditions and position and movement of vocal cords were similar in all 4 groups. Reaction to cuff inflation revealed intergroup differences; group 3 presented slight limb movements, diaphragm movement, and sustained cough for more than 10 seconds. CONCLUSION: These results suggest that administration of succinylcholine calculated based on real weight or ideal weight and rocuronium based on real weight can provide clinically acceptable conditions for tracheal intubation in morbidly obese patients with no other difficult-intubation criteria.
Assuntos
Androstanóis/farmacologia , Intubação Intratraqueal , Fármacos Neuromusculares Despolarizantes/farmacologia , Fármacos Neuromusculares não Despolarizantes/farmacologia , Obesidade Mórbida/cirurgia , Succinilcolina/farmacologia , Prega Vocal/efeitos dos fármacos , Adulto , Androstanóis/administração & dosagem , Peso Corporal , Tosse/induzido quimicamente , Diafragma/efeitos dos fármacos , Relação Dose-Resposta a Droga , Feminino , Humanos , Hipóxia/prevenção & controle , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Movimento/efeitos dos fármacos , Relaxamento Muscular/efeitos dos fármacos , Fármacos Neuromusculares Despolarizantes/administração & dosagem , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Aspiração Respiratória/prevenção & controle , Risco , Rocurônio , Succinilcolina/administração & dosagemRESUMO
Objetivo: Estudiar la precurarización de la succinilcolina utilizando d-tubocurarina y rocuronio introduciendo los métodos restrictivo, conceptos de velocidad de acción y recuperación y una nueva semiología para evaluar las fasciculaciones. Material y método: Se administraron succinilcolina (1 mg x Kg-1) (n =21) sola o precedida por rocuronio o d-tubocurarina (60 ó 50 ug x Kg-1) (n =21 c/u), determinándose: la fase inicial de comienzo hasta 80 por ciento de bloqueo, tiempo de comienzo, máximo efecto, duración clínica, tiempo de reversión espontánea entre 10 por ciento y 25 por ciento y 25 por ciento a 50 por ciento. Se calculó la velocidad de acción (inicial, final y global) como la relación tiempo/bloqueo fraccionado y la velocidad de recuperación. El método restrictivo fue empleado para el estudio del tiempo de comienzo, utilizando un rango restringido de bloqueo. Las fasciculaciones fueron evaluadas por su intensidad en seis regiones anatómicas por cuatro observadores imparciales e independientes y las medias de sus valoraciones utilizadas para analizarlas. Resultados: Aparentemente ambos desfasciculantes prolongan la fase inicial, tiempo de comienzo y velocidad de la succinilcolina, pero el método restrictivo únicamente lo confirmó para el tiempo de comienzo y la velocidad global. La velocidad inicial fue más rápida que la final. El rocuronio redujo el efecto y la duración clínica e incrementó la velocidad de recuperación de la succinilcolina. Las fasciculaciones fueron más frecuentes e intensas en el tronco y miembro superior izquierdo, pero los precurarizantes las redujeron tanto en intensidad como localización Discusión: La precurarización no modifica la fase inicial de comienzo, surgiendo la posibilidad de practicar una intubación temprana. Debido al acortamiento que provoca la precurarización con rocuronio se hace evidente la necesidad precoz de nuevas dosis de relajantes.
Objective: To study the precurarization of succinylcholine with d-tubocurarine and rocuronium, using the restrictive method, speed of action and recovery principles and a particular evaluation for fasciculations Material & Methods: Patients received succinylcholine (1 mg x Kg-1) (n =21) either alone or preceded by d-tubocurarine or rocuronium (60 ó 50 micron g x Kg-1) (n =21 e/a), and the following clinical measurements were made: earlyphase of onset time (up to 80 percent blockade), onset time, maximal block, clinical duration and recovery time between 10 percent and 25 percent and 25 percent to 50 percent. Speed of action (initial, final and global)as the ratio between time and fractional blockade and speed of recovery, were calculated. Restrictive method was used for the study of the entire onset time on patients included in a limited range of final block. Intensity of fasciculations was evaluated by four independent observers blind to the drugs used in six anatomical regions and their mean values used for analysis. Results: Apparently, precurarizing drugs prolonged initial phase, onset time and reduced speed for succinylcholine, but only onset time and global speed were confirmed by restrictive method. After rocuronium, maximal effect as well as clinical duration of succinylcholine werereduced and speed of recovery increased. Fasciculations were more frequent and intense at the trunk and left upper arm, but precurarization reduced both intensity and localization prevalence. Discussion: As lack of changes on the initial phase of onset time for succinylcholine inducedby precurarization was noticed, an early tracheal intubation could be contemplated. Due to reduction on clinical duration after rocuronium,new doses of muscle relaxants are sooner necessary. The present method for evaluation of fasciculations shows how far they are spread and how effective precurarization was, given rise to doubts on previous results.
Assuntos
Humanos , Masculino , Adulto , Feminino , Fármacos Neuromusculares não Despolarizantes/administração & dosagem , Androstanóis/administração & dosagem , Fasciculação/prevenção & controle , Succinilcolina/efeitos adversos , Tubocurarina/administração & dosagem , Fármacos Neuromusculares Despolarizantes/efeitos adversos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Androstanóis/farmacologia , Tempo de Reação , Tubocurarina/farmacologiaRESUMO
JUSTIFICATIVA E OBJETIVOS: Trata-se de um estudo experimental que investigou in vitro e in vivo o bloqueio neuromuscular produzido pelo rocurônio e atracúrio em ratos tratados com carbamazepina e determinou as concentrações de citocromo P450 e b5 redutase em microssomos hepáticos. MÉTODO: Ratos foram tratados por sete dias com carbamazepina (CBZ) - 40 mg.kg-1 pelo método de gavagem e sacrificados no oitavo dia sob anestesia com uretana. As preparações in vitro e in vivo foram montadas de acordo com as técnicas de Bulbring e de Leeuwin e Wolters, respectivamente. As concentrações e doses utilizadas dos bloqueadores nas preparações in vitro e in vivo foram, respectivamente, 20 µg.mL-1 e 0,5 mg.kg-1 para atracúrio (ATC); 4 µg.mL-1 e 0,6 mg.kg-1 para rocurônio (ROC). Cada protocolo teve um n = 5 e as respostas foram observadas por 60 minutos. Os efeitos do ATC e ROC foram avaliados nas preparações de ratos tratados (Cbz t) e comparados com os observados nas de ratos não-tratados (CBZst). As concentrações de citocromo P450 e b5 redutase foram determinadas em microssomos isolados de fígados de ratos tratados (CBZt) e comparadas com as obtidas em ratos não tratados (CBZst). RESULTADOS: A carbamazepina não alterou a amplitude das respostas musculares; in vitro e in vivo, não houve diferença entre o bloqueio neuromuscular produzido pelo atracúrio nas preparações CBZt versus CBZst; o bloqueio neuromuscular produzido pelo rocurônio nas preparações CBZt foi potencializado in vitro. A carbamazepina não alterou as concentrações de citocromo P450 e b5. CONCLUSÕES: O tratamento por sete dias com carbamazepina não influenciou no bloqueio produzido pelo atracúrio, e alterou in vitro os efeitos do rocurônio. O tempo de tratamento não foi suficiente para causar indução enzimática e diminuir a sensibilidade ao rocurônio.
BACKGROUND AND OBJECTIVES: This experimental study investigated the in vitro and in vivo neuromuscular blockade of rocuronium and atracurium in rats treated with carbamazepine and determined the concentration of cytochrome P450 and b5 reductase in hepatic microsomes. METHODS: Rats were treated with carbamazepine (CBZ) - 40 mg.kg-1 by gavage and sacrificed on the eighth day under anesthesia with urethane. In vitro and in vivo preparations followed the techniques of Bulbring and Leeuwin and Wolters, respectively. Concentrations and doses of the neuromuscular blockers used in in vitro and in vivo preparations were, respectively, 20 µg.mL-1 and 0.5 mg.kg-1 for atracurium (ATC); and 4 µg.kg-1 and 0.6 mg.kg-1 for rocuronium (ROC). Each protocol had an n = 5 and the response was observed for 60 minutes. The effects of ATC and ROC were evaluated in the preparations of rats treated with carbamazepine (CBZt) and compared to those of non-treated rats (CBZst). The concentration of cytochrome P450 and b5 reductase were determined in hepatic chromosomes of rats treated with carbamazepine (CBZt) and non-treated rats (CBZst). RESULTS: Carbamazepine did not change the amplitude of neuromuscular response; differences in the neuromuscular blockade produced by atracurium in CBZ1 preparations were not observed, in vitro or in vivo, when compared with CBZst; the neuromuscular blockade produced by rocuronium in CBZt preparations was potentiated in vitro. Carbamazepine did not change the concentrations of cytochrome P450 and b5. CONCLUSIONS: Seven-day treatment with carbamazepine did not change the neuromuscular blockade produce by atracurium, but altered the in vitro effects of rocuronium. The duration of the treatment was not enough to cause enzymatic induction and decrease the sensitivity to rocuronium.
JUSTIFICATIVA Y OBJETIVOS: Se trata de un estudio experimental que investigó in vitro e in vivo el bloqueo neuromuscular producido por el rocuronio y atracurio en ratones tratados con carbamazepina y determinó las concentraciones de citocromo P450 y b5 reductasis en microsomas hepáticos. MÉTODO: Ratones fueron tratados por siete días con carbamazepina (CBZ) - 40 mg.kg-1 a través de una sonda y sacrificados al octavo día bajo anestesia con uretana. Las preparaciones in vitro e in vivo fueron montadas de acuerdo con las técnicas de Bulbring y de Leeuwin y Wolters, respectivamente. Las concentraciones y dosis utilizadas de los bloqueadores en las preparaciones in vitro e in vivo fueron, respectivamente, 20 µg.mL-1 y 0,5 mg.kg-1 para atracurio (ATC); 4 µg.mL-1 y 0,6 mg.kg-1 para rocuronio (ROC). Cada protocolo tuvo un n = 5 y las respuestas fueron observadas por 60 minutos. Los efectos del ATC y ROC fueron evaluados en las preparaciones de ratones tratados (Cbz t) y comparados a los observados en los de ratones no tratados (CBZst). Las concentraciones de citocromo P450 y b5 reductasis fueron determinadas en microsomas aislados de hígados de ratones tratados (CBZt) y comparadas con las obtenidas en ratones no tratados (CBZst) RESULTADOS: La carbamazepina no alteró la amplitud de las respuestas musculares; in vitro y in vivo, no hubo diferencia entre el bloqueo neuromuscular producido por el atracurio en las preparaciones CBZt versus CBZst; el bloqueo neuromuscular producido por el Rocuronio en las preparaciones CBZt fue potenciado in vitro. La carbamazepina no alteró las concentraciones de citocromo P450 y b5. CONCLUSIONES: El tratamiento por siete días con carbamazepina, no influenció en el bloqueo producido por el atracurio, y alteró in vitro los efectos del rocuronio. El tiempo de tratamiento no fue suficiente para causar la inducción enzimática y disminuir la sensibilidad al rocuronio.
Assuntos
Animais , Ratos , Androstanóis/farmacologia , Atracúrio/farmacologia , Carbamazepina/administração & dosagem , Técnicas In Vitro , Bloqueio Nervoso , Fármacos Neuromusculares não Despolarizantes/farmacologia , Junção Neuromuscular/efeitos dos fármacos , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVES: This experimental study investigated the in vitro and in vivo neuromuscular blockade of rocuronium and atracurium in rats treated with carbamazepine and determined the concentration of cytochrome P450 and b5 reductase in hepatic microsomes. METHODS: Rats were treated with carbamazepine (CBZ)--40 mg x kg(-1) by gavage and sacrificed on the eighth day under anesthesia with urethane. In vitro and in vivo preparations followed the techniques of Bulbring and Leeuwin and Wolters, respectively. Concentrations and doses of the neuromuscular blockers used in in vitro and in vivo preparations were, respectively, 20 microg x mL(-1) and 0.5 mg x kg(-1) for atracurium (ATC); and 4 microg x kg(-1) and 0.6 mg x kg(-1) for rocuronium (ROC). Each protocol had an n = 5 and the response was observed for 60 minutes. The effects of ATC and ROC were evaluated in the preparations of rats treated with carbamazepine (CBZ(t)) and compared to those of non-treated rats (CBZ(st)). The concentration of cytochrome P450 and b5 reductase were determined in hepatic chromosomes of rats treated with carbamazepine (CBZ(t)) and non-treated rats (CBZ(st)). RESULTS: Carbamazepine did not change the amplitude of neuromuscular response; differences in the neuromuscular blockade produced by atracurium in CBZ1 preparations were not observed, in vitro or in vivo, when compared with CBZ(st); the neuromuscular blockade produced by rocuronium in CBZ(t) preparations was potentiated in vitro. Carbamazepine did not change the concentrations of cytochrome P450 and b5. CONCLUSIONS: Seven-day treatment with carbamazepine did not change the neuromuscular blockade produce by atracurium, but altered the in vitro effects of rocuronium. The duration of the treatment was not enough to cause enzymatic induction and decrease the sensitivity to rocuronium.