Brazilian Journal of Anesthesiology
https://bjan-sba.org/article/doi/10.1590/S0034-70942008000200006
Brazilian Journal of Anesthesiology
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
PDF Português
PDF English
Downloads: 0
Views: 1014

Resumo

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

Referencias

Martins RS, Martins ALC. Bloqueadores Neuromusculares. Anestesiologia: Princípios e Técnicas. 1997:308-331.

Miranda FG, Marín JS, Aränó JA. Neurofisiologia de la Union Neuromuscular. Relajantes Musculares em Anestesia y Terapia Intensiva. 2000:61-70.

Cardoso LSM, Martins CR, Tardelli MA. Efeitos da lidocaína por via venosa sobre a farmacodinâmica do rocurônio. Rev Bras Anestesiol. 2005;55:371-380.

Loyola YCS, Braga AFA, Potério GMB. Influência da lidocaína no bloqueio neuromuscular produzido pelo rocurônio: Estudo em preparação nervo frênico - diafragma de rato. Rev Bras Anestesiol. 2006;56:147-156.

Sousa SRS, Braga AFA, Potério GMB. Influência da nifedipina no bloqueio neuromuscular produzido pelo atracúrio e pelo cisatracúrio: Estudo em preparações nervo frênicodiafragma de rato. Rev Bras Anestesiol. 2006;56:157-167.

Haywood PT, Divekar N, Karalliedde LD. Concurrent medication and the neuromuscular junction. Eur J Anaesthesiol. 1999;16:77-91.

Spacek A, Kress HG. Drug interactions with muscle relaxants. Acta Anaesthesiol Scand. 1998;42(^s112):236-238.

Mei PA, Montenegro MA, Guerreiro MM. Pharmacovigilance in epileptic patients using antiepileptic drugs. Arq Neuropsiquiatr. 2006;64:198-201.

Rang HP, Dale MM, Ritter JM. Fármacos Antiepilépticos. Farmacologia. 2003:627-639.

Perucca E. An introduction to antiepileptic drugs. Epilepsia. 2005;46:31-37.

Beydoun S, Alarcón F, Mangat S. Long-term safety and tolerability of carbamazepine in painful diabetic neuropathy. Acta Neurol Scand. 2007;115:284-288.

Eisenberg E, River Y, Shifrin A. Antiepileptic drugs in the treatment of neuropathic pain. Drugs. 2007;67:1265-1289.

Alloul K, Whalley DG, Shutway F. Pharmacokinetic origin of carbamazepine-induced resistance to vecuronium neuromuscular blockade in anesthetized patients. Anesthesiology. 1996;84:330-339.

Nguyen A, Ramzan I. In vitro response of neuromuscular blockers after chronic carbamazepine treatment in rats. Pharmazie. 2000;55:957.

Richard A, Girard F, Girard DC. Cisatracurium-induced neuromuscular blockade is affected by chronic phenytoin or carbamazepine treatment in neurosurgical patients. Anesth Analg. 2005;100:538-544.

Tempelhoff R, Modica PA, Jellish WS. Resistance to atracurium-induced neuromuscular blockade in patients with intractable seizure disorders treated with anticonvulsants. Anesth Analg. 1990;71:665-669.

Spacek A, Neiger FX, Spiss CK. Atracurium-induced neuromuscular block is not affected by chronic anticonvulsant therapy with carbamazepine. Acta Anaesthesiol Scand. 1997;41:1308-1311.

Spacek A, Nickl S, Neiger FX. Augmentation of the rocuronium-induced neuromuscular block by the acutely administered phenytoin. Anesthesiology. 1999;90:1551-1555.

Spacek A, Neiger FX, Krenn CG. Rocuronium-induced neuromuscular block is affected by chronic carbamazepine therapy. Anesthesiology. 1999;90:109-112.

Kim JU, Lee YK, Lee YM. The effect of phenytoin on rocuronium-induced neuromuscular block in the rat phrenic nerve-hemidiaphragm preparation. J Neurosurg Anesthesiol. 2005;17:149-152.

Bulbring E. Observation on the isolated phyrenic nerve-diaphragm preparation of the rat. Br J Pharmacol. 1946;1:38-61.

Leeuwin RS, Wolters ECMJ. Effects of corticosteroids on the sciatic nerve-tibialis anterior muscle of rats treated with hemicholinium-3. Neurology. 1977;27:171-177.

Ostergaard D, Engbaek J, Viby-Mogensen J. Adverse reactions and interactions of the neuromuscular blocking drugs. Med Toxicol Adverse Drug Exp. 1989;4:351-368.

Anderson GD. A mechanistic approach to antiepileptic drug interactions. Ann Pharmacother. 1998;32:554-563.

Ornstein E, Matteo RS, Schwartz AE. The effect of phenytoin on the magnitude and duration of neuromuscular block following atracurium or vecuronium. Anesthesiology. 1987;67:191-196.

Ornstein E, Matteo RS, Weinstein JA. Accelerated recovery from doxacurium-induced neuromuscular blockade in patients receiving chronic anticonvulsant therapy. J Clin Anesth. 1991;3:108-111.

Whalley DG, Ebrahim Z. Influence of carbamazepine on the dose-response relationship of vecuronium. Br J Anaesth. 1994;72:125-126.

Norman J. Resistance to vecuronium. Anaesthesia. 1993;48:1068-1069.

Roth S, Ebrahim ZY. Resistance to pancuronium in patients receiving carbamazepine. Anesthesiology. 1987;66:691-693.

Jellish WS, Modica PA, Tempelhoff R. Accelerated recovery from pipecuronium in patients treated with chronic anticonvulsant therapy. J Clin Anesth. 1993;5:105-108.

Jellish WS, Thalji Z, Brundidge PK. Recovery from mivacurium-induced neuromuscular blockade is not affected by anticonvulsant therapy. J Neurosurg Anesthesiol. 1996;8:4-8.

Brodie MJ, Dichter MA. Antiepileptic drugs. N Engl J Med. 1996;334:168-175.

Alderdice MT, Trommer BA. Differential effects of the anticonvulsants phenobarbital, ethosuximide and carbamazepine on neuromuscular transmission. J Pharmacol Exp Ther. 1980;215:92-96.

Platt PR, Thackray NM. Phenytoin-induced resistance to vecuronium. Anaesth Intensive Care. 1993;21:185-191.

Hartman GS, Fiamengo SA, Riker WF Jr. Succinylcholine: mechanism of fasciculations and their prevention by d-tubocurarine or diphenylhydantoin. Anesthesiology. 1986;65:405-413.

Kohling R. Voltage-gated sodium channels in epilepsy. Epilepsia. 2002;43:1278-1295.

Stoelting RK, Hillier SC. Neuromuscular blocking drugs. Pharmacology & Physiology in Anesthetic Practice. 2006:208-250.

Norris FH Jr, Colella J, Mcfarlin D. Effect of diphenylhydantoin on neuromuscular synapse. Neurology. 1964;14:869-876.

Gray HS, Slater RM, Pollard BJ. The effect of acutely administered phenytoin on vecuronium-induced neuromuscular blockade. Anaesthesia. 1989;44:379-381.

Nguyen A, Ramzan I. Acute in vitro neuromuscular effects of carbamazepine and carbamazepine-10,11-epoxide. Anesth Analg. 1997;84:886-890.

Soriano SG, Sullivan LJ, Venkatakrishnan K. Pharmacokinetics and pharmacodynamics of vecuronium in children receiving phenytoin or carbamazepine for chronic anticonvulsant therapy. Br J Anaesth. 2001;86:223-229.

Ebrahim ZY, Bulkey R, Roth S. Carbamazepine therapy and neuromuscular blockade with atracurium or vecuronium. Anesth Analg. 1988;67:S55.

Fisher DM, Canfell PC, Fahey MR. Elimination of atracurium in humans: contribution of Hofmann elimination and ester hydrolysis versus organ-based elimination. Anesthesiology. 1986;65:6-12.

Loan PB, Connolly FM, Mirakhur RK. Neuromuscular effects of rocuronium in patients receiving beta-adrenoreceptor blocking, calcium entry blocking and anticonvulsant drugs. Br J Anaesth. 1997;78:90-91.

Kim CS, Arnold FJ, Itani MS. Decreased sensitivity to metocurine during long-term phenytoin therapy may be attributable to protein binding and acetylcholine receptor changes. Anesthesiology. 1992;77:500-506.

Kremer JM, Wilting J, Janssen LH. Drug binding to human alpha-1-acid glycoprotein in health and disease. Pharmacol Ver. 1988;40:1-47.

Martyn JA, Abernethy DR, Greenblatt DJ. Plasma protein binding of drugs after severe burn injury. Clin Pharmacol Ther. 1984;35:535-539.

Wood M. Plasma binding and limitation of drug access to site of action. Anesthesiology. 1991;75:721-723.

Hans P, Brichant JF, Pieron F. Elevated plasma alpha1-acid glycoprotein levels: lack of connection to resistance to vecuronium blockade induced by anticonvulsant therapy. J Neurosurg Anesthesiol. 1997;9:3-7.

Pirttiaho HI, Sotaniemi EA, Pelkonen RO. Hepatic blood flow and drug metabolism in patients on enzyme-inducing anticonvulsants. Eur J Clin Pharmacol. 1982;22:441-445.

5dd6c7600e8825ec4113f286 rba Articles
Links & Downloads
2352-2291 (Electrónico) 0104-0014 (Impreso)
Braz J Anesthesiol ©2024 Todos los derechos reservados.

Braz J Anesthesiol

Share this page
Page Sections