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

Caroline Coutinho de Barcelos; Angélica de Fátima de Assunção Braga; Franklin Sarmento da Silva Braga; Gloria Braga Potério; Samanta Cristina Antoniassi Fernandes; Yoko Oshima Franco; Léa Rodrigues Simioni

doi:10.1590/S0034-70942008000200006

Scientific Article

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

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

Caroline Coutinho de Barcelos; Angélica de Fátima de Assunção Braga; Franklin Sarmento da Silva Braga; Gloria Braga Potério; Samanta Cristina Antoniassi Fernandes; Yoko Oshima Franco; Léa Rodrigues Simioni

http://dx.doi.org/10.1590/S0034-70942008000200006 Braz J Anesthesiol, vol.58, n2, p.137-151, 2008

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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.

Palavras-chave

ANIMAIS: ratos, ANTICONVULSIVANTE: carbamazepina, BLOQUEADORES NEUROMUSCULARES, adespolarizante

Abstract

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.

Keywords

ANIMALS, rats, ANTICONVULSANTS, carbamazepine, NEUROMUSCULAR BLOCKERS, non-depolarizing, NEUROMUSCULAR BLOCKERS, non-depolarizing

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

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

Caroline Coutinho de Barcelos; Angélica de Fátima de Assunção Braga; Franklin Sarmento da Silva Braga; Gloria Braga Potério; Samanta Cristina Antoniassi Fernandes; Yoko Oshima Franco; Léa Rodrigues Simioni

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