Efeitos neuromusculares do atracurio e do rocuronio em ratos pre-tratados com carbamazepina e fenobarbital : estudo in vitro e in vivo / Neuromuscular effects of atracurium and rocuronium in pre treated rats with carbamazepine and phenobarbital : study in vitro e in vivo

AUTOR(ES)
DATA DE PUBLICAÇÃO

2007

RESUMO

Atracurium (ATC) and rocuronium (ROC) are neuromuscular blockers of intermediate action. In this study, the neuromuscular effects had been investigated in vitro and in vivo in treated rats, by gavage (7d), with the anticonvulsantes (AC) carbamazepine (CBZ, 40 mg/kg) and phenobarbital (FB, 20 mg/kg) and sacrificed on the eight day, under anesthesia with urethane. The results had been compared with the control-condition (rats not treated AC). The chronic exposition the AC can determine the induction of microsomes enzyme for the responsible metabolization (oxidation) of drugs. For the control of this pharmacologic phenomenon the enzymatic concentrations of P450 and b5 cytochromes had been determined, in livers microsomes of rats treated with AC, and compared with the controls. The preparations in vitro and in vivo had been followed the Bulbring and Leeuwin and Wolters techniques, respectively. The in vitro and in vivo concentrations were 20 µg/ml and 0.5 mg/kg, respectively, for atracurium (ATC); and 4 µg/ml and 0.6 mg/kg for rocuronium (ROC). Each protocol presented n=5 and the answers were calculated during 60 minutes. The in vitro and in vivo results showed that treatment with carbamazepine reduced the extent of muscle response in about 30%. Under its validity, did not alter the extent of the muscle response block produced by atracurium and rocuronium possibly because the period of time of carbamazepine treatment was not enough to cause enzymatic induction. Regarding phenobarbital, the in vitro and in vivo results did not alter significant the extent of the muscle response block produced. Under its validity, reduced the ATC sensitivity the block neuromuscular in vitro produced. However, in vivo increased the neuromuscular block of both the blockers studied. These alterations observed in both the experimental models can have occured induction with the phenobarbital, as proven P450 (0,69 nmol/mg protein) and b5 (0,62 nmol/mg protein) of cytochrome concentration.

ASSUNTO(S)

drug interactions rocuronio rocuronium medicamentos - interações carbamazepina agentes não despolarizantes phenobarbital atracurio nondepolarizing agents carbamazepine atracurium anticonvulsants fenobarbital anticonvulsivantes

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