Samanta Cristina Antoniassi Fernandes

Phenobarbital influence on neuromuscular block produced by rocuronium in rats

PURPOSE To evaluate in vitro and in vivo neuromuscular blockade produced by rocuronium in rats treated with Phenobarbital and to determine cytochrome P450 and cytochrome b5 concentrations in hepatic microsomes. METHODS Thirty rats were included in the study and distributed into 6 groups of 5 animals each. Rats were treated for seven days with phenobarbital (20 mg/kg) and the following parameters were evaluated: 1) the amplitude of muscle response in the preparation of rats exposed to phenobarbital; 2) rocuronium effect on rat preparation exposed or not to phenobarbital; 3) concentrations of cytochrome P450 and cytochrome b5 in hepatic microsomes isolated from rats exposed or not to phenobarbital. The concentration and dose of rocuronium used in vitro and in vivo experiments were 4 microg/mL and 0,6 mg/kg, respectively. RESULTS Phenobarbital in vitro and in vivo did not alter the amplitude of muscle response. The neuromuscular blockade in vitro produced by rocuronium was significantly different (p=0.019) between exposed (20%) and not exposed (60%) rats; the blockade in vivo was significantly greater (p=0.0081) in treated rats (93.4%). The enzymatic concentrations were significantly greater in rats exposed to phenobarbital. CONCLUSIONS Phenobarbital alone did not compromise neuromuscular transmission. It produced enzymatic induction, and neuromuscular blockade in vivo produced by rocuronium was potentiated by phenobarbital.

Influence of lidocaine on the neuromuscular block produced by rocuronium: study in rat phrenic-diaphragmatic nerve preparation

BACKGROUND AND OBJECTIVES: The action mechanism of local anesthetics (LA) on neuromuscular junction motivated several studies. When administered at low doses, they do not interfere on neuromuscular transmission. But high doses may compromise neuromuscular transmission and increase the effects of neuromuscular blockers. The objective of this study was to evaluate lidocaine interaction with rocuronium on rat diaphragm through its influence on neuromuscular block degree. METHODS: Rats, weighing between 250 and 300 g, were used. Preparation was set according to the technique described by Bulbring. Groups were formed (n = 5) according to the drug being studied: lidocaine - 20 µg.mL-1 (Group I); rocuronium - 4 µg.mL-1 (Group II), and rocuronium - 4 µg.mL-1 with lidocaine - 20 µg.mL-1 (Group III). The following items were assessed: 1) the extent of diaphragm muscle responses to indirect stimulation, both before and 60 minutes after adding lidocaine and a neuromuscular blocker; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP); 3) the effectiveness of neostigmine, and 4) aminopyridine on neuromuscular blockage reversal. RESULTS: When administered separately, lidocaine did not alter the extent of muscular responses. With the previous use of lidocaine, rocuronium neuromuscular blockage was 82.8% ± 1.91%, with a significant difference (p = 0.0079) when compared to the group with isolated rocuronium (57.8% ± 1.9%). Blockage was both partially and fully reverted by neostigmine and 4-aminopyridine, respectively. Lidocaine did not alter membrane potential and caused an initial increase on MEPP, followed by a blockage. CONCLUSIONS: Lidocaine increases the neuromuscular blocking produced by rocuronium. MEPP modifications identify a presynaptic action. The complete antagonism of 4-aminopyridine indicates a presynaptic component. This idea is supported by the partial antagonism through neostigmine.BACKGROUND AND OBJECTIVES The action mechanism of local anesthetics (LA) on neuromuscular junction motivated several studies. When administered at low doses, they do not interfere on neuromuscular transmission. But high doses may compromise neuromuscular transmission and increase the effects of neuromuscular blockers. The objective of this study was to evaluate lidocaine interaction with rocuronium on rat diaphragm through its influence on neuromuscular block degree. METHODS Rats, weighing between 250 and 300 g, were used. Preparation was set according to the technique described by Bulbring. Groups were formed (n = 5) according to the drug being studied: lidocaine - 20 microg.mL-1 (Group I); rocuronium - 4 microg.mL-1 (Group II), and rocuronium - 4 microg.mL-1 with lidocaine - 20 microg.mL-1 (Group III). The following items were assessed: 1) the extent of diaphragm muscle responses to indirect stimulation, both before and 60 minutes after adding lidocaine and a neuromuscular blocker; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP); 3) the effectiveness of neostigmine, and 4) aminopyridine on neuromuscular blockage reversal. RESULTS When administered separately, lidocaine did not alter the extent of muscular responses. With the previous use of lidocaine, rocuronium neuromuscular blockage was 82.8% +/- 1.91%, with a significant difference (p = 0.0079) when compared to the group with isolated rocuronium (57.8% +/- 1.9%). Blockage was both partially and fully reverted by neostigmine and 4-aminopyridine, respectively. Lidocaine did not alter membrane potential and caused an initial increase on MEPP, followed by a blockage. CONCLUSIONS Lidocaine increases the neuromuscular blocking produced by rocuronium. MEPP modifications identify a presynaptic action. The complete antagonism of 4-aminopyridine indicates a presynaptic component. This idea is supported by the partial antagonism through neostigmine.

In vitro and in vivo neuromuscular effects of atracurium and rocuronium in rats treated with carbamazepine for seven days

JUSTIFICATIVA Y OBJETIVOS: Se trata de un estudio experimental que investigo in vitro e in vivo el bloqueo neuromuscular producido por el rocuronio y atracurio en ratones tratados con carbamazepina y determino las concentraciones de citocromo P450 y b5 reductasis en microsomas hepaticos. METODO: Ratones fueron tratados por siete dias con carbamazepina (CBZ) - 40 mg.kg-1 a traves de una sonda y sacrificados al octavo dia bajo anestesia con uretana. Las preparaciones in vitro e in vivo fueron montadas de acuerdo con las tecnicas 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 (Cbzt) 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 higados de ratones tratados (CBZt) y comparadas con las obtenidas en ratones no tratados (CBZst) RESULTADOS: La carbamazepina no altero 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 altero las concentraciones de citocromo P450 y b5. CONCLUSIONES: El tratamiento por siete dias con carbamazepina, no influencio en el bloqueo producido por el atracurio, y altero in vitro los efectos del rocuronio. El tiempo de tratamiento no fue suficiente para causar la induccion enzimatica y disminuir la sensibilidad al rocuronio.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.

Influence of nifedipine on the neuromuscular block produced by atracurium and cistracurium: study in rat phrenic-diaphragmatic nerve preparation

BACKGROUND AND OBJECTIVES Calcium channel blockers may interact with neuromuscular blockers, increasing its effects. Research studies about this interaction display controversial results. In some studies these drugs produced neuromuscular blockage, or contracture, or no effect at all was proved over skeletal neuromuscular response. This study assessed the nifedipine effects over muscular responses and its possible interaction with neuromuscular blockers in rat diaphragm. METHODS A number of 25 rats were used, weighing between 250 and 300 g and sacrificed under anesthesia with intraperitoneal pentobarbital (40 mg.kg-1). Preparation was mounted according to the technique described by Bulbring. Diaphragm was kept under tension, connected to an isometric transducer and subjected to an indirect stimulation of 0.1 Hz frequency. Diaphragm contractions were registered on a physiograph. In order to evaluate the effect of these drugs on neuromuscular transmission, they were added separately or associated to the preparation, on the following concentrations: nifedipine (4 microg.mL-1); atracurium (20 microg.mL-1); cistracurium (3 microg.mL-1). On phrenic-nerve preparation, the assessed items were: 1) the extent of diaphragm muscle response to indirect stimulation, before and 45 minutes after adding nifedipine and neuromuscular blockers separately and after the association of both drugs; 2) nifedipine effects on membrane potentials (MP) and miniature end-plate potentials (MEPP). RESULTS Employed separately, nifedipine did not alter the extent of muscular responses, but it did significantly increase the neuromuscular blocking activity of atracurium and cistracurium. Nifedipine did not alter the membrane potential and caused an initial increase on MEPP frequencies, followed by a blockage. CONCLUSIONS Nifedipine, on the employed concentration, increased the neuromuscular blockage produced by atracurium and cistracurium. Electrophysiological studies demonstrate the existence of presynaptic action and absence of depolarizing action over the muscle fiber.

Efeitos neuromusculares in vitro e in vivo do atracúrio e do rocurônio em ratos submetidos a tratamento de sete dias com carbamazepina

JUSTIFICATIVA Y OBJETIVOS: Se trata de un estudio experimental que investigo in vitro e in vivo el bloqueo neuromuscular producido por el rocuronio y atracurio en ratones tratados con carbamazepina y determino las concentraciones de citocromo P450 y b5 reductasis en microsomas hepaticos. METODO: Ratones fueron tratados por siete dias con carbamazepina (CBZ) - 40 mg.kg-1 a traves de una sonda y sacrificados al octavo dia bajo anestesia con uretana. Las preparaciones in vitro e in vivo fueron montadas de acuerdo con las tecnicas 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 (Cbzt) 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 higados de ratones tratados (CBZt) y comparadas con las obtenidas en ratones no tratados (CBZst) RESULTADOS: La carbamazepina no altero 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 altero las concentraciones de citocromo P450 y b5. CONCLUSIONES: El tratamiento por siete dias con carbamazepina, no influencio en el bloqueo producido por el atracurio, y altero in vitro los efectos del rocuronio. El tiempo de tratamiento no fue suficiente para causar la induccion enzimatica y disminuir la sensibilidad al rocuronio.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.

Influência do lítio no bloqueio neuromuscular produzido pelo atracúrio e pelo cisatracúrio: estudo em preparações nervo frênico-diafragma de rato

JUSTIFICATIVA Y OBJETIVOS: El litio, farmaco ampliamente utilizado en los disturbios bipolares, puede interactuar con los bloqueadores neuromusculares. Los mecanismos para explicar sus efectos en la transmision neuromuscular y en la interaccion con bloqueadores neuromusculares son controvertidos. El objetivo de este trabajo fue evaluar, en diafragma de raton, los efectos del litio sobre la respuesta muscular al estimulo indirecto y la posible interaccion con los bloqueadores neuromusculares. METODO: Se utilizaron ratones con peso entre 250 y 300 g, sacrificados bajo anestesia con uretana. La preparacion nervio frenico-diafragma se monto de acuerdo con la tecnica de Bulbring. El diafragma se mantuvo bajo tension, ligado a un transductor isometrico y sometido a la estimulacion indirecta de 0,1 Hz de frecuencia. Las contracciones del diafragma fueron registradas en un fisiografo. Del analisis de la amplitud de las respuestas musculares se evaluaron los efectos de los farmacos: litio (1,5 mg.mL-1); atracurio (20 µg.mL-1) y cisatracurio (3 µg.mL-1) empleados aisladamente; de la asociacion litio-bloqueadores neuromusculares; y del litio en el bloqueo neuromuscular producido por el atracurio (35 µg.mL-1) y cisatracurio (5 µg.mL-1). Los efectos se evaluaron antes y 45 minutos despues de la adicion de los farmacos. Tambien se estudiaron los efectos del litio en los potenciales de membrana (PM) y potenciales de placa terminal en miniatura (PPTM). RESULTADOS: El litio aisladamente no altero la amplitud de las respuestas musculares, pero si que redujo significativamente el bloqueo neuromuscular producido por el atracurio y el cisatracurio. No altero el PM y ocasiono un aumento inicial de la frecuencia de los PPTM. CONCLUSIONES: El litio empleado aisladamente no comprometio la transmision neuromuscular y aumento la resistencia al efecto del atracurio y del cisatracurio. No mostro accion sobre la fibra muscular, siendo que las alteraciones en los potenciales de placa terminal en miniatura mostraron una accion presinaptica.BACKGROUND AND OBJECTIVES Lithium is widely used for the treatment of bipolar disorders and can interact with neuromuscular blockers. There is a controversy about the mechanisms by which it affects neuromuscular transmission and its interaction with neuromuscular blockers. The objective of this study was to evaluate, on the rat diaphragm, the effects of lithium on the muscular response and indirect stimulation, and the possible interaction with neuromuscular blockers. METHODS Rats weighing between 250 and 300 g were sacrificed under urethane anesthesia. The phrenic nerve-diaphragm preparation was assembled according to the Bulbring technique. The diaphragm was kept under tension, connected to an isometric transducer, and submitted to indirect stimulation with a frequency of 0.1 Hz. The contractions of the diaphragm were registered on a physiograph. The analysis of the amplitude of the muscular responses evaluated: the effects of the isolated drugs: lithium (1.5 mg.mL-1); atracurium (20 microg.mL-1), and cisatracurium (3 microg.mL-1); the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 microg.mL-1) and cisatracurium (5 microg.mL-1). The effects were evaluated before and 45 minutes after the addition of the drugs. The effects of lithium on membrane potentials (MP) and miniature end-plate potentials (MEPP) were also evaluated. RESULTS Lithium by itself did not change the amplitude of the muscular responses, but it decreased significantly the neuromuscular blockade produced by atracurium and cisatracurium. It did not change MP and caused an initial increase in MEPP. CONCLUSIONS Lithium by itself did not compromise neuromuscular transmission and increased the resistance to the effects of atracurium and cisatracurium. It did not show any action on the muscle fiber, and the changes in miniature end-plate potentials indicated pre-synaptic action.

Influence of lithium on the neuromuscular blockade produced by atracurium and cisatracurium: study on rat phrenic nerve-diaphragm preparations

JUSTIFICATIVA Y OBJETIVOS: El litio, farmaco ampliamente utilizado en los disturbios bipolares, puede interactuar con los bloqueadores neuromusculares. Los mecanismos para explicar sus efectos en la transmision neuromuscular y en la interaccion con bloqueadores neuromusculares son controvertidos. El objetivo de este trabajo fue evaluar, en diafragma de raton, los efectos del litio sobre la respuesta muscular al estimulo indirecto y la posible interaccion con los bloqueadores neuromusculares. METODO: Se utilizaron ratones con peso entre 250 y 300 g, sacrificados bajo anestesia con uretana. La preparacion nervio frenico-diafragma se monto de acuerdo con la tecnica de Bulbring. El diafragma se mantuvo bajo tension, ligado a un transductor isometrico y sometido a la estimulacion indirecta de 0,1 Hz de frecuencia. Las contracciones del diafragma fueron registradas en un fisiografo. Del analisis de la amplitud de las respuestas musculares se evaluaron los efectos de los farmacos: litio (1,5 mg.mL-1); atracurio (20 µg.mL-1) y cisatracurio (3 µg.mL-1) empleados aisladamente; de la asociacion litio-bloqueadores neuromusculares; y del litio en el bloqueo neuromuscular producido por el atracurio (35 µg.mL-1) y cisatracurio (5 µg.mL-1). Los efectos se evaluaron antes y 45 minutos despues de la adicion de los farmacos. Tambien se estudiaron los efectos del litio en los potenciales de membrana (PM) y potenciales de placa terminal en miniatura (PPTM). RESULTADOS: El litio aisladamente no altero la amplitud de las respuestas musculares, pero si que redujo significativamente el bloqueo neuromuscular producido por el atracurio y el cisatracurio. No altero el PM y ocasiono un aumento inicial de la frecuencia de los PPTM. CONCLUSIONES: El litio empleado aisladamente no comprometio la transmision neuromuscular y aumento la resistencia al efecto del atracurio y del cisatracurio. No mostro accion sobre la fibra muscular, siendo que las alteraciones en los potenciales de placa terminal en miniatura mostraron una accion presinaptica.BACKGROUND AND OBJECTIVES Lithium is widely used for the treatment of bipolar disorders and can interact with neuromuscular blockers. There is a controversy about the mechanisms by which it affects neuromuscular transmission and its interaction with neuromuscular blockers. The objective of this study was to evaluate, on the rat diaphragm, the effects of lithium on the muscular response and indirect stimulation, and the possible interaction with neuromuscular blockers. METHODS Rats weighing between 250 and 300 g were sacrificed under urethane anesthesia. The phrenic nerve-diaphragm preparation was assembled according to the Bulbring technique. The diaphragm was kept under tension, connected to an isometric transducer, and submitted to indirect stimulation with a frequency of 0.1 Hz. The contractions of the diaphragm were registered on a physiograph. The analysis of the amplitude of the muscular responses evaluated: the effects of the isolated drugs: lithium (1.5 mg.mL-1); atracurium (20 microg.mL-1), and cisatracurium (3 microg.mL-1); the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 microg.mL-1) and cisatracurium (5 microg.mL-1). The effects were evaluated before and 45 minutes after the addition of the drugs. The effects of lithium on membrane potentials (MP) and miniature end-plate potentials (MEPP) were also evaluated. RESULTS Lithium by itself did not change the amplitude of the muscular responses, but it decreased significantly the neuromuscular blockade produced by atracurium and cisatracurium. It did not change MP and caused an initial increase in MEPP. CONCLUSIONS Lithium by itself did not compromise neuromuscular transmission and increased the resistance to the effects of atracurium and cisatracurium. It did not show any action on the muscle fiber, and the changes in miniature end-plate potentials indicated pre-synaptic action.

Efectos neuromusculares in vitro e in vivo del atracurio y del rocuronio en ratones sometidos a tratamiento de siete días con carbamazepina

JUSTIFICATIVA Y OBJETIVOS: Se trata de un estudio experimental que investigo in vitro e in vivo el bloqueo neuromuscular producido por el rocuronio y atracurio en ratones tratados con carbamazepina y determino las concentraciones de citocromo P450 y b5 reductasis en microsomas hepaticos. METODO: Ratones fueron tratados por siete dias con carbamazepina (CBZ) - 40 mg.kg-1 a traves de una sonda y sacrificados al octavo dia bajo anestesia con uretana. Las preparaciones in vitro e in vivo fueron montadas de acuerdo con las tecnicas 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 (Cbzt) 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 higados de ratones tratados (CBZt) y comparadas con las obtenidas en ratones no tratados (CBZst) RESULTADOS: La carbamazepina no altero 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 altero las concentraciones de citocromo P450 y b5. CONCLUSIONES: El tratamiento por siete dias con carbamazepina, no influencio en el bloqueo producido por el atracurio, y altero in vitro los efectos del rocuronio. El tiempo de tratamiento no fue suficiente para causar la induccion enzimatica y disminuir la sensibilidad al rocuronio.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.

Influencia del litio en el bloqueo neuromuscular producido por el atracurio y por el cisatracurio: estudio en preparo nervio frénico-diafragma del ratón

JUSTIFICATIVA Y OBJETIVOS: El litio, farmaco ampliamente utilizado en los disturbios bipolares, puede interactuar con los bloqueadores neuromusculares. Los mecanismos para explicar sus efectos en la transmision neuromuscular y en la interaccion con bloqueadores neuromusculares son controvertidos. El objetivo de este trabajo fue evaluar, en diafragma de raton, los efectos del litio sobre la respuesta muscular al estimulo indirecto y la posible interaccion con los bloqueadores neuromusculares. METODO: Se utilizaron ratones con peso entre 250 y 300 g, sacrificados bajo anestesia con uretana. La preparacion nervio frenico-diafragma se monto de acuerdo con la tecnica de Bulbring. El diafragma se mantuvo bajo tension, ligado a un transductor isometrico y sometido a la estimulacion indirecta de 0,1 Hz de frecuencia. Las contracciones del diafragma fueron registradas en un fisiografo. Del analisis de la amplitud de las respuestas musculares se evaluaron los efectos de los farmacos: litio (1,5 mg.mL-1); atracurio (20 µg.mL-1) y cisatracurio (3 µg.mL-1) empleados aisladamente; de la asociacion litio-bloqueadores neuromusculares; y del litio en el bloqueo neuromuscular producido por el atracurio (35 µg.mL-1) y cisatracurio (5 µg.mL-1). Los efectos se evaluaron antes y 45 minutos despues de la adicion de los farmacos. Tambien se estudiaron los efectos del litio en los potenciales de membrana (PM) y potenciales de placa terminal en miniatura (PPTM). RESULTADOS: El litio aisladamente no altero la amplitud de las respuestas musculares, pero si que redujo significativamente el bloqueo neuromuscular producido por el atracurio y el cisatracurio. No altero el PM y ocasiono un aumento inicial de la frecuencia de los PPTM. CONCLUSIONES: El litio empleado aisladamente no comprometio la transmision neuromuscular y aumento la resistencia al efecto del atracurio y del cisatracurio. No mostro accion sobre la fibra muscular, siendo que las alteraciones en los potenciales de placa terminal en miniatura mostraron una accion presinaptica.BACKGROUND AND OBJECTIVES Lithium is widely used for the treatment of bipolar disorders and can interact with neuromuscular blockers. There is a controversy about the mechanisms by which it affects neuromuscular transmission and its interaction with neuromuscular blockers. The objective of this study was to evaluate, on the rat diaphragm, the effects of lithium on the muscular response and indirect stimulation, and the possible interaction with neuromuscular blockers. METHODS Rats weighing between 250 and 300 g were sacrificed under urethane anesthesia. The phrenic nerve-diaphragm preparation was assembled according to the Bulbring technique. The diaphragm was kept under tension, connected to an isometric transducer, and submitted to indirect stimulation with a frequency of 0.1 Hz. The contractions of the diaphragm were registered on a physiograph. The analysis of the amplitude of the muscular responses evaluated: the effects of the isolated drugs: lithium (1.5 mg.mL-1); atracurium (20 microg.mL-1), and cisatracurium (3 microg.mL-1); the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 microg.mL-1) and cisatracurium (5 microg.mL-1). The effects were evaluated before and 45 minutes after the addition of the drugs. The effects of lithium on membrane potentials (MP) and miniature end-plate potentials (MEPP) were also evaluated. RESULTS Lithium by itself did not change the amplitude of the muscular responses, but it decreased significantly the neuromuscular blockade produced by atracurium and cisatracurium. It did not change MP and caused an initial increase in MEPP. CONCLUSIONS Lithium by itself did not compromise neuromuscular transmission and increased the resistance to the effects of atracurium and cisatracurium. It did not show any action on the muscle fiber, and the changes in miniature end-plate potentials indicated pre-synaptic action.

Influência da lidocaína no bloqueio neuromuscular produzido pelo rocurônio: estudo em preparação nervo frênico-diafragma de rato

BACKGROUND AND OBJECTIVES: The action mechanism of local anesthetics (LA) on neuromuscular junction motivated several studies. When administered at low doses, they do not interfere on neuromuscular transmission. But high doses may compromise neuromuscular transmission and increase the effects of neuromuscular blockers. The objective of this study was to evaluate lidocaine interaction with rocuronium on rat diaphragm through its influence on neuromuscular block degree. METHODS: Rats, weighing between 250 and 300 g, were used. Preparation was set according to the technique described by Bulbring. Groups were formed (n = 5) according to the drug being studied: lidocaine - 20 µg.mL-1 (Group I); rocuronium - 4 µg.mL-1 (Group II), and rocuronium - 4 µg.mL-1 with lidocaine - 20 µg.mL-1 (Group III). The following items were assessed: 1) the extent of diaphragm muscle responses to indirect stimulation, both before and 60 minutes after adding lidocaine and a neuromuscular blocker; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP); 3) the effectiveness of neostigmine, and 4) aminopyridine on neuromuscular blockage reversal. RESULTS: When administered separately, lidocaine did not alter the extent of muscular responses. With the previous use of lidocaine, rocuronium neuromuscular blockage was 82.8% ± 1.91%, with a significant difference (p = 0.0079) when compared to the group with isolated rocuronium (57.8% ± 1.9%). Blockage was both partially and fully reverted by neostigmine and 4-aminopyridine, respectively. Lidocaine did not alter membrane potential and caused an initial increase on MEPP, followed by a blockage. CONCLUSIONS: Lidocaine increases the neuromuscular blocking produced by rocuronium. MEPP modifications identify a presynaptic action. The complete antagonism of 4-aminopyridine indicates a presynaptic component. This idea is supported by the partial antagonism through neostigmine.BACKGROUND AND OBJECTIVES The action mechanism of local anesthetics (LA) on neuromuscular junction motivated several studies. When administered at low doses, they do not interfere on neuromuscular transmission. But high doses may compromise neuromuscular transmission and increase the effects of neuromuscular blockers. The objective of this study was to evaluate lidocaine interaction with rocuronium on rat diaphragm through its influence on neuromuscular block degree. METHODS Rats, weighing between 250 and 300 g, were used. Preparation was set according to the technique described by Bulbring. Groups were formed (n = 5) according to the drug being studied: lidocaine - 20 microg.mL-1 (Group I); rocuronium - 4 microg.mL-1 (Group II), and rocuronium - 4 microg.mL-1 with lidocaine - 20 microg.mL-1 (Group III). The following items were assessed: 1) the extent of diaphragm muscle responses to indirect stimulation, both before and 60 minutes after adding lidocaine and a neuromuscular blocker; 2) membrane potentials (MP) and miniature end-plate potentials (MEPP); 3) the effectiveness of neostigmine, and 4) aminopyridine on neuromuscular blockage reversal. RESULTS When administered separately, lidocaine did not alter the extent of muscular responses. With the previous use of lidocaine, rocuronium neuromuscular blockage was 82.8% +/- 1.91%, with a significant difference (p = 0.0079) when compared to the group with isolated rocuronium (57.8% +/- 1.9%). Blockage was both partially and fully reverted by neostigmine and 4-aminopyridine, respectively. Lidocaine did not alter membrane potential and caused an initial increase on MEPP, followed by a blockage. CONCLUSIONS Lidocaine increases the neuromuscular blocking produced by rocuronium. MEPP modifications identify a presynaptic action. The complete antagonism of 4-aminopyridine indicates a presynaptic component. This idea is supported by the partial antagonism through neostigmine.