Influência da procainamida sobre o bloqueio neuromuscular produzido pelo rocurônio e investigação sobre o mecanismo de ação da procainamida na junção neuromuscular

Abstract

JUSTIFICATIVA E OBJETIVOS:A potencialização da procainamida sobre o bloqueio neuromuscular produzido pela d-tubocurarina já está comprovada, porém o mecanismo é controverso. O objetivo do estudo foi avaliar a influência da procainamida no bloqueio neuromuscular produzido pelo rocurônio e investigar os mecanismos desta interação. MÉTODO: Foram utilizados 15 ratos (250 a 300 g) em preparação descrita por Bülbring. Formaram-se os seguintes grupos (n = 5 cada): procainamida -20 µg.mL -1 (Grupo I); rocurônio -4 µg.mL -1 (Grupo II) e rocurônio -4 µg.mL -1 e procainamida -20 µg.mL -1 (Grupo III). Avaliaram-se: 1) a amplitude das contrações musculares sob estimulação indireta em cada grupo, antes e após a adição dos fármacos; 2) os potenciais de placa terminal em miniatura (PPTM); 3) a eficácia da 4-aminopiridina na reversão do bloqueio neuromuscular. O mecanismo da interação foi estudado em Biventer cervicis (n = 5) e diafragma de rato desnervado (n = 5), observando-se a influência da procainamida na resposta à acetilcolina antes e após a adição da procainamida. RESULTADOS: A procainamida isoladamente não alterou as respostas neuromusculares. O bloqueio produzido com o Grupo III foi de 68,6% ± 7,1%, com diferença significativa (p = 0,0067) em relação ao Grupo II (10,4% ± 4,5%), revertido pela 4-aminopiridina. A procainamida ocasionou aumento na freqüência dos PPTM, seguido de bloqueio revertido pela 4-aminopiridina. Em Biventer cervicis a procainamida aumentou a resposta à ação de contração da acetilcolina, resultado não observado com o diafragma desnervado. CONCLUSÕES: A procainamida potencializou o bloqueio produzido pelo rocurônio. As alterações observadas com PPTM e Biventer cervicis identificaram ação pré-sináptica. O antagonismo da 4-aminopiridina sobre o bloqueio dos PPTM sugeriu dessensibilização dos receptores pela procainamida. Unitermos: ANIMAL: rato; ANTIARRÍTMICOS: procainamida; BLO-QUEADORES NEUROMUSCULARES, Não-despolarizantes: rocurônio; DROGAS: interação. SUMMARYMartins TD, Loyola YCS, Braga AFA -Influence of Procainamide on the Neuromuscular Blockade Caused by Rocuronium and Investigation on the Mechanism of Action of Procainamide on the Neuromuscular Junction. BACKGROUND AND OBJECTIVES: It has already been proved that procainamide potentiates the neuromuscular blockade of d-tubocurarine; however, the mechanism of this potentiation is controversial. The aim of this study was to assess the influence of procainamide on the neuromuscular blockade produced by rocuronium and investigate the mechanisms of this interaction. METHODS: Fifteen rats (250 to 300 g) were used in the preparation described by Bülbring. They were divided in three groups (n = 5 each): procainamide -20 µg.mL -1 (Group I); rocuronium -4 µg.mL -1 (Group II); and rocuronium -4 µg.mL -1 and procainamide -20 µg.mL -1 (Group III). The following parameters were evaluated: 1) amplitude of muscle contractions under indirect stimulation, before and after the administration of the drugs; 2) miniature end plate potentials (MEPPs); and 3) the effic...

The influence of lidocaine and racemic bupivacaine on neuromuscular blockade produced by rocuronium: a study in rat phrenic nerve-diaphragm preparation

“…Besides the likeness to the receivers, this stereoisomerism is also factor that contributes to the cellular membranes fluidly 19 . The results of this study resemble each other to the experimental and clinical researches [2][3][7][8][9][11][12][16][17] that also demonstrated that local anesthetics employed separately for different routes, don't commit neuromuscular transmission, but they potentiate neuromuscular blockade produced for different neuromuscular blocking.…”

“…Clinical assays describe that local anesthetics by peridural route, routine used in association to general anesthesia, can interact and potentiate the effects of neuromuscular blocking agents [2][3]7,12 , interaction also observed in experimental studies 9,11 . However, although these effects have been experimentally demonstrated in isolated preparations and clinical assays, the influence in neuromuscular transmission and in neuromuscular blockade produced by competitive neuromuscular blocking agents it is still objective of little investigation 1-3, 6-9,11-12,14 .…”

“…There are evidences that pharmacokinetic and pharmacodynamic properties of neuromuscular blocking agents, drugs commonly used in general anesthesia, can be modified by factors as acid-basic state, temperature, monitoring, certain diseases (burns, superior and inferior motor neuron disease) and drugs administered by different routes [1][2][3][4][5][6][7][8][9][10][11][12][13] . Clinical assays describe that local anesthetics by peridural route, routine used in association to general anesthesia, can interact and potentiate the effects of neuromuscular blocking agents [2][3]7,12 , interaction also observed in experimental studies 9,11 .…”

Effect of 50% enantiomeric excess bupivacaine mixture combined with pancuronium on neuromuscular transmission in rat phrenic nerve-diaphragm preparation; a pilot study

“…The influence of local anaesthetics on these parameters may indicate a presynaptic action, consequently decreasing acetylcholine release or reducing the sensitivity of the postjunctional membrane to acetylcholine. [ 1 3 9 10 11 12 13 ] In our study, impaired neurotransmitter release was observed. This event was demonstrated by a progressive decrease in the frequency and amplitude of MEPPs.…”

“…Through postsynaptic action, binding to different specific acetylcholine sites may block acetylcholine-induced contractile response, temporarily occluding nicotinic receptor channels. [ 8 13 14 15 16 17 18 19 ]…”