RESUMO
INTRODUCTION: The association between Local Anesthetics (LAs) and Neuromuscular Blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose-dependent manner and may potentiate the effects of NMB drugs. OBJECTIVE: The aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium. METHODS: Male Wistar rats, weighing from 250 g to 300g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 µg.mL-1 (Group I); racemic bupivacaine 5 µg.mL-1 (Group II); atracurium 20 µg.mL-1 (Group III); atracurium 20 µg.mL-1 in a preparation previously exposed to lidocaine 20 µg.mL-1 and racemic bupivacaine 5 µg.mL-1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane Potentials (MP) and Miniature Endplate Potentials (MEPPs). RESULTS: Lidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive. CONCLUSIONS: Lidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.
Assuntos
Anestésicos Locais/farmacologia , Atracúrio/farmacologia , Bupivacaína/farmacologia , Lidocaína/farmacologia , Bloqueio Neuromuscular , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/fisiologia , Animais , Interações Medicamentosas , Masculino , Ratos , Ratos WistarRESUMO
Abstract Introduction: The association between local anesthetics (LA) and neuromuscular blocking (NMB) drugs in clinical practice, and the possibility of interaction between these drugs has been investigated. LAs act on neuromuscular transmission in a dose-dependent manner and may potentiate the effects of NMB drugs. Objective: The aim of this study was to evaluate, in an experimental model, the effect of lidocaine and racemic bupivacaine on neuromuscular transmission and the influence on neuromuscular blockade produced by atracurium. Methods: Male Wistar rats, weighing from 250 to 300 g were used. The preparation was set up based on a technique proposed by Bülbring. Groups were formed (n = 5) according to the drug studied: lidocaine 20 µg.mL−1 (Group I); racemic bupivacaine 5 µg.mL−1 (Group II); atracurium 20 µg.mL−1 (Group III); atracurium 20 µg.mL−1 in a preparation previously exposed to lidocaine 20 µg.mL−1 and racemic bupivacaine 5 µg.mL−1, Groups IV and V, respectively. The following parameters were assessed: 1) Amplitude of hemi diaphragmatic response to indirect stimulation before and 60 minutes after addition of the drugs; 2) Membrane potentials (MP) and miniature endplate potentials (MEPPs). Results: Lidocaine and racemic bupivacaine alone did not alter the amplitude of muscle response. With previous use of lidocaine and racemic bupivacaine, the neuromuscular blockade (%) induced by atracurium was 86.66 ± 12.48 and 100, respectively, with a significant difference (p = 0.003), in comparison to the blockade produced by atracurium alone (55.7 ± 11.22). These drugs did not alter membrane potential. Lidocaine initially increased the frequency of MEPPs, followed by blockade. With the use of bupivacaine, the blockade was progressive. Conclusions: Lidocaine and racemic bupivacaine had a presynaptic effect expressed by alterations in MEPPs, which may explain the interaction and potentiation of NMB produced by atracurium.
Resumo Introdução: A associação de anestésicos locais (AL) com bloqueadores neuromusculares (BNM) na prática clínica e a possibilidade de interação entre esses fármacos têm sido investigadas. Objetivo: Avaliar, em modelo experimental, o efeito da lidocaína e da bupivacaína racêmica na transmissão neuromuscular e sua influência no bloqueio neuromuscular produzido pelo atracúrio. Método: Ratos machos da linhagem Wistar, peso entre 250 e 300 g. A preparação foi feita de acordo com a técnica proposta por Bulbring. Grupos (n = 5) de acordo com o fármaco em estudo: lidocaína 20 µg.mL-1 (Grupo I); bupivacaína racêmica 5 µg.mL-1 (Grupo II); atracúrio 20 µg.mL-1 (Grupo III); atracúrio 20 µg.mL-1 em preparação previamente exposta a lidocaína 20 µg.mL-1 e bupivacaína racêmica 5 µg.mL-1, Grupos IV e V, respectivamente. Foram avaliados: 1) A amplitude das respostas do hemidiafragma à estimulação indireta antes e 60 minutos após a adição dos fármacos; 2) Os potenciais de membrana (PM) e os potenciais de placa terminal em miniatura (PPTM). Resultados: Os AL, isoladamente, não alteraram a amplitude das respostas musculares. Com o uso prévio dos AL, o bloqueio neuromuscular (%) do atracúrio foi 86,66 ± 12,48 e 100, respectivamente, com diferença significante (p= 0,003) em relação ao produzido pelo atracúrio isoladamente (55,7 ± 11,22). Não alteraram o PM. A lidocaína inicialmente aumentou a frequência dos PPTM, seguido de bloqueio; com a bupivacaína, o bloqueio foi progressivo. Conclusão: A lidocaína e a bupivacaína racêmica apresentaram efeito pré-sináptico expresso por alterações nos PPTM, podem justificar a potencialização do bloqueio neuromuscular produzido pelo atracúrio.
Assuntos
Animais , Masculino , Ratos , Atracúrio/farmacologia , Bupivacaína/farmacologia , Bloqueio Neuromuscular , Anestésicos Locais/farmacologia , Lidocaína/farmacologia , Junção Neuromuscular/efeitos dos fármacos , Junção Neuromuscular/fisiologia , Ratos Wistar , Interações MedicamentosasRESUMO
JUSTIFICATIVA E OBJETIVOS: Os efeitos farmacodinâmicos dos bloqueadores neuromusculares (BNM) podem ser influenciados por diferentes drogas, entre elas os hipnóticos. O objetivo deste estudo foi avaliar a influência do propofol e do etomidato sobre o bloqueio neuromuscular produzido pelo cisatracúrio. MÉTODO: Foram incluídos 60 pacientes, ASA I e II, submetidos a cirurgias eletivas sob anestesia geral, distribuídos aleatoriamente em dois grupos de acordo com o hipnótico empregado: GI (propofol) e GII (etomidato). As pacientes receberam midazolam (0,1 mg.kg-1) por via muscular como medicação pré-anestésica, a indução foi com propofol (2,5 mg.kg-1) ou etomidato (0,3 mg.kg-1) precedido de fentanil (250 µg) e seguido de cisatracúrio (0,1 mg.kg-1). Os pacientes foram ventilados com oxigênio a 100% até a obtenção de redução de 95% ou mais na amplitude da resposta do adutor do polegar, quando foi feita a laringoscopia e a intubação traqueal. A função neuromuscular foi monitorizada com aceleromiografia. Avaliaram-se o início de ação do cisatracúrio, as condições de intubação traqueal e as repercussões hemodinâmicas. RESULTADOS: Os tempos médios e os desvios padrão para o início de ação do cisatracúrio foram: GI (86,6 ± 14,3") e GII (116,9 ± 11,6"), com diferença significativa (p < 0,0001). As condições de intubação traqueal foram aceitáveis em 100% dos pacientes do GI e em 53,3% no GII (p < 0,0001). CONCLUSÕES: A instalação do bloqueio neuromuscular com o cisatracúrio foi mais rápida e as condições de intubação traqueal foram melhores nos pacientes que receberam propofol em relação ao grupo que recebeu etomidato, sem repercussões hemodinâmicas.
BACKGROUND AND OBJECTIVE: Different drugs, including hypnotics, may influence the pharmacodynamic effects of neuromuscular blockers (NMB). The aim of this study was to evaluate the influence of propofol and etomidate on cisatracurium-induced neuromuscular blockade. METHOD: We included 60 patients, ASA I and II, undergoing elective surgery under general anesthesia in the study and randomly allocated them into two groups, according to their hypnotic drug: GI (propofol) and GII (etomidate). Patients received intramuscular (IM) midazolam (0.1 mg.kg-1) as premedication and we performed induction with propofol (2.5 mg.kg-1) or etomidate (0.3 mg.kg-1), preceded by fentanyl (250 mg) and followed by cisatracurium (0.1 mg.kg-1). The patients were ventilated with 100% oxygen until obtaining a reduction of 95% or more in the adductor pollicis response amplitude, with subsequent laryngoscopy and tracheal intubation. Neuromuscular function was monitored by acceleromyograhpy. We evaluated the onset of action of cisatracurium, tracheal intubation conditions, and hemodynamic repercussions. RESULTS: The mean time and standard deviations of cisatracurium onset were: GI (86.6 ± 14.3 s) and GII (116.9 ± 11.6 s), with a significant difference (p < 0, 0001). Intubation conditions were acceptable in 100% of GI and 53.3% of GII patients (p < 0.0001). CONCLUSION: Induction of neuromuscular blockade with cisatracurium was faster, with better intubation conditions in patients receiving propofol compared to those receiving etomidate, without hemodynamic repercussions.
JUSTIFICATIVA Y OBJETIVOS: Los efectos farmacodinámicos de los bloqueantes neuromusculares (BNM) pueden estar influenciados por diferentes fármacos, entre ellos los hipnóticos. El objetivo de este estudio, fue evaluar la influencia del propofol y del etomidato sobre el bloqueo neuromuscular producido por el cisatracurio. MÉTODO: Se incluyeron en el estudio 60 pacientes, con ASA I y II, sometidos a cirugías electivas bajo anestesia general, distribuidos aleatoriamente en dos grupos de acuerdo con el hipnótico usado: GI (propofol) y GII (etomidato). Las pacientes recibieron midazolam (0,1 mg.kg-1) por vía muscular como medicación preanestésica, la inducción fue con propofol (2,5 mg.kg-1) o etomidato (0,3 mg.kg-1) precedido de fentanilo (250 µg) y seguido de cisatracurio (0,1 mg.kg-1). Los pacientes fueron ventilados con oxígeno al 100% hasta la obtención de la reducción de un 95% o más en la amplitud de la respuesta del aductor del pulgar cuando se hizo la laringoscopia y la intubación traqueal. La función neuromuscular fue monitorizada con aceleromiografía. Se evaluaron el inicio de acción del cisatracurio, las condiciones de intubación traqueal y las repercusiones hemodinámicas. RESULTADOS: Los tiempos promedios y las desviaciones estándar para el inicio de acción del cisatracurio fueron: GI (86,6 ± 14,3") y GII (116,9 ± 11,6"), con una diferencia significativa (p < 0,0001). Las condiciones de intubación traqueal fueron aceptables en un 100% de los pacientes del GI y en 53,3% en el GII (p < 0,0001). CONCLUSIONES: La instalación del bloqueo neuromuscular con el cisatracurio fue más rápida y las condiciones de intubación traqueal fueron mejores en los pacientes que recibieron propofol con relación al grupo que recibió etomidato, sin repercusiones hemodinámicas.
Assuntos
Adulto , Feminino , Humanos , Atracúrio/análogos & derivados , Etomidato/farmacologia , Hipnóticos e Sedativos/farmacologia , Bloqueio Neuromuscular , Bloqueadores Neuromusculares/farmacologia , Propofol/farmacologia , Atracúrio/farmacologia , Interações Medicamentosas , Miografia/métodosRESUMO
BACKGROUND AND OBJECTIVE: Different drugs, including hypnotics, may influence the pharmacodynamic effects of neuromuscular blockers (NMB). The aim of this study was to evaluate the influence of propofol and etomidate on cisatracurium-induced neuromuscular blockade. METHOD: We included 60 patients, ASA I and II, undergoing elective surgery under general anesthesia in the study and randomly allocated them into two groups, according to their hypnotic drug: GI (propofol) and GII (etomidate). Patients received intramuscular (IM) midazolam (0.1mg.kg(-1)) as premedication and we performed induction with propofol (2.5mg.kg(-1)) or etomidate (0.3mg.kg(1)), preceded by fentanyl (250mg) and followed by cisatracurium (0.1mg.kg(-1)). The patients were ventilated with 100% oxygen until obtaining a reduction of 95% or more in the adductor pollicis response amplitude, with subsequent laryngoscopy and tracheal intubation. Neuromuscular function was monitored by acceleromyograhpy. We evaluated the onset of action of cisatracurium, tracheal intubation conditions, and hemodynamic repercussions. RESULTS: The mean time and standard deviations of cisatracurium onset were: GI (86.6±14.3s) and GII (116.9±11.6s), with a significant difference (p<0, 0001). Intubation conditions were acceptable in 100% of GI and 53.3% of GII patients (p<0.0001). CONCLUSION: Induction of neuromuscular blockade with cisatracurium was faster, with better intubation conditions in patients receiving propofol compared to those receiving etomidate, without hemodynamic repercussions.
Assuntos
Atracúrio/análogos & derivados , Etomidato/farmacologia , Hipnóticos e Sedativos/farmacologia , Bloqueio Neuromuscular , Bloqueadores Neuromusculares/farmacologia , Propofol/farmacologia , Adulto , Atracúrio/farmacologia , Interações Medicamentosas , Feminino , Humanos , Miografia/métodosRESUMO
BACKGROUND AND OBJECTIVES: Since atracurium can cause hypotension in humans, the hemodynamic effects of atracurium and cisatracurium as well as the hemodynamic protection of diphenhydramine and cimetidine were investigated in rats. METHODS: 1) Wistar rats were anesthetized with sodium pentobarbital and prepared according to Brown et al. to evaluate different doses of atracurium and cisatracurium in the reduction of T4/T1 equal or greater than 95%. 2) Assessment of the hemodynamic changes caused by the intravenous administration of atracurium and cisatracurium by monitoring the blood pressure in the carotid artery and the electrocardiogram of rats. 3) Observation of the hemodynamic protection of prior treatment with the intravenous administration of diphenhydramine (2 mg.kg(-1)) and/or cimetidine (4 mg.kg(-1)). STATISTICAL ANALYSIS: Student t test and ANOVA. RESULTS: Doses of 1 mg.kg(-1) and 0.25 mg.kg(-1) of atracurium and cisatracurium respectively did not change the mean arterial pressure (MAP). Doses of 4 mg.kg(-1) of atracurium and cisatracurium decreased MAP to 62.8 +/- 4.5% and 82.5 +/- 2.3% respectively when compared to control levels. When the rats were pre-treated with diphenhydramine and cimetidine, diastolic pressure was reduced to 95.4% +/- 2.5%. With cimetidine, diastolic pressure was reduced to 82.7 +/- 8.4% when compared to the control group. The effects on systolic and diastolic blood pressure were reflected in the levels of MAP. CONCLUSIONS: The isolated administration of diphenhydramine and cimetidine did not prevent the reduction in mean arterial pressure induced by atracurium. However, the association of both drugs was able to prevent the hemodynamic effects of atracurium. The doses of cisatracurium used in this study did not cause a reduction in blood pressure significant enough to justify the use of the preventive measures used in the atracurium groups.
Assuntos
Atracúrio/análogos & derivados , Atracúrio/antagonistas & inibidores , Atracúrio/farmacologia , Cimetidina/farmacologia , Difenidramina/farmacologia , Hemodinâmica/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos H1/farmacologia , Antagonistas dos Receptores H2 da Histamina/farmacologia , Bloqueadores Neuromusculares/antagonistas & inibidores , Bloqueadores Neuromusculares/farmacologia , Fármacos Neuromusculares não Despolarizantes/antagonistas & inibidores , Fármacos Neuromusculares não Despolarizantes/farmacologia , Animais , Feminino , Masculino , Ratos , Ratos WistarRESUMO
PURPOSE: We investigated whether presynaptic facilitatory M1 and/or inhibitory M2 muscarinic receptors contributed to pancuronium- and cisatracurium-induced tetanic fade. METHODS: Phrenic nerve-diaphragm muscle preparations of rats were indirectly stimulated with tetanic frequency (75 +/- 3.3 Hz; mean +/- SD). Doses of pancuronium, cisatracurium, hexamethonium, and d-tubocurarine for producing approximately 25% fade were determined. The effects of pirenzepine and methoctramine, blockers of presynaptic M1 and M2 receptors, respectively, on the tetanic fade were investigated. RESULTS: The concentrations required for approximately 25% fade were 413 microM for hexamethonium (26.8 +/- 2.4% 4% fade), 55 nM for d-tubocurarine (28.7 +/- 2.55% fade), 0.32 microM for pancuronium (25.4 +/- 2.2% fade), and 0.32 microM for cisatracurium (24.7 +/- 0.8% fade). Pirenzepine or methoctramine alone did not produce the fade. Methoctramine, 1 microM, attenuated the fade induced by hexamethonium (to 16.0 +/- 2.5% fade), d-tubocurarine (to 6.0 +/- 1.6 fade), pancuronium (to 8.0 +/- 4.0% fade), and cisatracurium (to 11.0 +/- 3.3% fade). 10 nM pirenzepine attenuated only the fades produced by pancuronium (to 5.0 +/- 0.11% fade) and cisatracurium (to 13.3 +/- 5.3% fade). Cisatracurium (0.32 microM) showed antiacetylcholinesterase activity (in plasma, 14.2 +/- 1.6%; 6%; in erythrocyt 17.2 +/- 2.66%) similar to that of pancuronium (0.32 microM). The selective A1 receptor blocker, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; 2.5 nM), also attenuated the fades induced by pancuronium and cisatracurium. CONCLUSION: The tetanic fades produced by pancuronium and cisatracurium depend on the activation of presynaptic inhibitory M2 receptors; these agents also have anticholinesterase activities. The fades induced by these agents also depend on the activation of presynaptic inhibitory A1 receptors through the activation of stimulatory M1 receptors by acetylcholine.
Assuntos
Atracúrio/análogos & derivados , Contração Muscular/efeitos dos fármacos , Fármacos Neuromusculares não Despolarizantes/farmacologia , Pancurônio/farmacologia , Receptor A1 de Adenosina/efeitos dos fármacos , Receptor Muscarínico M1/efeitos dos fármacos , Receptor Muscarínico M2/efeitos dos fármacos , Animais , Atracúrio/farmacologia , Diaminas/farmacologia , Estimulação Elétrica , Hexametônio/farmacologia , Técnicas In Vitro , Masculino , Antagonistas Muscarínicos/farmacologia , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/inervação , Antagonistas Nicotínicos/farmacologia , Nervo Frênico/efeitos dos fármacos , Pirenzepina/farmacologia , Ratos , Ratos Wistar , Xantinas/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.
Assuntos
Androstanóis/farmacologia , Atracúrio/farmacologia , Carbamazepina/administração & dosagem , Bloqueio Nervoso , Fármacos Neuromusculares não Despolarizantes/farmacologia , Animais , Técnicas In Vitro , Junção Neuromuscular/efeitos dos fármacos , Ratos , Rocurônio , Fatores de TempoRESUMO
OBJECTIVE: The onset time of neuromuscular blocking drugs is partially determined by circulatory factors, including muscle blood flow and cardiac output. The aim of the present paper was to: 1) compare the haemodynamic effects of adding different doses of ephedrine to an induction dose of propofol and remifentanil. 2) onset time of cisatracurium. METHODS: Sixty patients were randomly allocated into three groups: G1 - 1% propofol; G2 - 1% propofol + 0.5 mg.ml-1 ephedrine and G3 - 1% propofol + 1.0 mg.ml-1 ephedrine. All patients received continuous infusion of remifentanil (0.5 mg.kg-1.min-1). The rate of propofol infusion was 180 ml.h-1 until loss of consciousness and a loading dose of cisatracurium (0.15 mg.kg-1) was then given. After induction of anesthesia, the ulnar nerve was stimulated supramaximally every 10s, and the evoked twitch response of the adductor pollicis was recorded by accelerometry. RESULTS: There was no statistical difference between groups with respect to age, weight, dose of propofol administered and onset time of cisatracurium. Heart rate, SpO2, systolic, diastolic and mean blood pressures were compared at 1 and 3 min post-induction. There were statistical differences in HR, SAP, DAP and MAP, without significant adverse clinical effects. CONCLUSIONS: There were no clinically important decreases in the hemodynamic parameters evaluated in the groups receiving ephedrine or not, and the onset time of cisatracurium was the same for all groups.
Assuntos
Adrenérgicos/uso terapêutico , Anestésicos Intravenosos/efeitos adversos , Atracúrio/análogos & derivados , Efedrina/uso terapêutico , Hipotensão/prevenção & controle , Bloqueadores Neuromusculares/farmacologia , Adolescente , Adulto , Anestesia Geral , Anestésicos Intravenosos/administração & dosagem , Atracúrio/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Feminino , Frequência Cardíaca/efeitos dos fármacos , Hemodinâmica/efeitos dos fármacos , Humanos , Hipotensão/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Piperidinas/administração & dosagem , Piperidinas/efeitos adversos , Propofol/administração & dosagem , Propofol/efeitos adversos , Remifentanil , Fatores de Tempo , Vasoconstritores/uso terapêuticoRESUMO
JUSTIFICATIVA E OBJETIVOS: O lítio, fármaco amplamente utilizado nos distúrbios bipolares, pode interagir com os bloqueadores neuromusculares. Os mecanismos para explicar os seus efeitos na transmissão neuromuscular e a interação com bloqueadores neuromusculares são controversos. O objetivo deste trabalho foi avaliar, em diafragma de rato, os efeitos do lítio sobre a resposta muscular à estimulação indireta e a possível interação com os bloqueadores neuromusculares. MÉTODO: Utilizaram-se ratos com peso entre 250g e 300g, sacrificados sob anestesia com uretana. A preparação nervo frênico-diafragma foi montada de acordo com a técnica descrita por Bulbring. O diafragma foi mantido sob tensão, ligado a um transdutor isométrico e submetido à estimulação indireta de 0,1 Hz de freqüência. As contrações do diafragma foram registradas em fisiógrafo. Da análise da amplitude das respostas musculares avaliaram-se: os efeitos dos fármacos: lítio (1,5 mg.mL-1); atracúrio (20 µg.mL-1) e cisatracúrio (3 µg.mL-1) empregados isoladamente; da associação lítio-bloqueadores neuromusculares; e do lítio no bloqueio neuromuscular produzido pelo atracúrio (35 µg.mL-1) e cisatracúrio (5 µg.mL-1). Os efeitos foram avaliados antes e 45 minutos após a adição dos fármacos. Também foram estudados os efeitos do lítio nos potenciais de membrana (PM) e potenciais de placa terminal em miniatura (PPTM). RESULTADOS: O lítio isoladamente não alterou a amplitude das respostas musculares, mas diminuiu significativamente o bloqueio neuromuscular produzido pelo atracúrio e cisatracúrio. Não alterou o PM e ocasionou aumento inicial da freqüência dos PPTM. CONCLUSÕES: O lítio empregado isoladamente não comprometeu a transmissão neuromuscular e aumentou a resistência ao efeito do atracúrio e cisatracúrio. Não mostrou ação sobre a fibra muscular, sendo que as alterações nos potenciais de placa terminal em miniatura evidenciaram ação pré-sináptica.
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 µg.mL-1), and cisatracurium (3 µg.mL-1); the lithium-neuromuscular blockers association; and the effects of lithium on the neuromuscular blockade produced by atracurium (35 µg.mL-1) and cisatracurium (5 µg.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.
JUSTIFICATIVA Y OBJETIVOS: El litio, fármaco ampliamente utilizado en los disturbios bipolares, puede interactuar con los bloqueadores neuromusculares. Los mecanismos para explicar sus efectos en la transmisión neuromuscular y en la interacción con bloqueadores neuromusculares son controvertidos. El objetivo de este trabajo fue evaluar, en diafragma de ratón, los efectos del litio sobre la respuesta muscular al estímulo indirecto y la posible interacción con los bloqueadores neuromusculares. MÉTODO: Se utilizaron ratones con peso entre 250 y 300 g, sacrificados bajo anestesia con uretana. La preparación nervio frénico-diafragma se montó de acuerdo con la técnica de Bulbring. El diafragma se mantuvo bajo tensión, ligado a un transductor isométrico y sometido a la estimulación indirecta de 0,1 Hz de frecuencia. Las contracciones del diafragma fueron registradas en un fisiógrafo. Del análisis de la amplitud de las respuestas musculares se evaluaron los efectos de los fármacos: litio (1,5 mg.mL-1); atracurio (20 µg.mL-1) y cisatracurio (3 µg.mL-1) empleados aisladamente; de la asociación 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 después de la adición de los fármacos. También 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 alteró la amplitud de las respuestas musculares, pero sí que redujo significativamente el bloqueo neuromuscular producido por el atracurio y el cisatracurio. No alteró el PM y ocasionó un aumento inicial de la frecuencia de los PPTM. CONCLUSIONES: El litio empleado aisladamente no comprometió la transmisión neuromuscular y aumentó la resistencia al efecto del atracurio y del cisatracurio. No mostró acción sobre la fibra muscular, siendo que las alteraciones en los potenciales...