Summary
In summation, the effect of three mycin antibiotics on pancuronium bromide-induced depression of neuromuscular transmission was studied, using a sciatic nerve tibialis anterior muscle preparation of anaesthetized dogs. Muscle twitch responses were recorded before and after administration of non-paralysing doses of the muscle relaxant and the test antibiotic.
It was inferred from the results that colymycin, gentamycin and kanamycin potentiated the neuromuscular blockade induced by pancuronium. Colymycin showed the least potency while kanamycin induced the most effective blockade. Calcium and neostigmine had limited effect in reversing the neuromuscular blockade due to gentamycin and kanamycin. The antibiotics are believed to depress neuromuscular transmission by depleting acetylcholine at the motor endplate, through inhibition of its release. With decreased calcium levels in the motor nerve terminal membranes, non-depolarizing muscle relaxants exert a similar effect. At the post-synaptic membrane the antibiotic desensitizes the receptors to acetylcholine, while the muscle relaxant acts by occupying the receptor.
The mode of action of the antibiotic and muscle relaxant at the presynaptic membrane is similar to that of magnesium ions. The resistance to reversal of the neuromuscular blockade by both calcium and neostigmine finds explanation in its multifocal nature.
Résumé
Nous avons étudié la synergie pharmacologique entre le pancuronium et trois antibiotiques en mycin (colymicine, gentamycine et kanamycine) en mesurant la transmission neuro-musculaire sur une préparation nerf sciatique-jambier antérieur de chien anesthésié. Les réponses du muscle à des stimulations non tétaniques ont été enregistrées avant et aprés administration de doses sub-liminaires ( non curarisantes ) de pancuronium et de l’antibiotique étudié.
Nous concluons de nos résultats que ces trois antibiotiques potentialisent le blocage neuro-musculaire du pancuronium. Cet effet était minime avec la colymycine mais tres puissant avec la kanamycine. Le calcium et la néostigmine ne renversent que médiocrement le blocage neuro-musculaire attribuable à la gentamycine et la kanamycine. On croit que ces antibiotiques exercent leur action bloquante en privant la plaque neuro-musculaire d’acétylcholine par inhibition de sa libération. II a deja été demontre que les relaxants non depolarisants, eux aussi, produisent un effet presynaptique similaire. Au niveau de la membrane post-synaptique, l’antibiotique reduit l’affinite des recepteurs a I’acétylcholine alors que le myo-resolutif pour sa part occupe d’emblee le site récepteur. Au niveau pre-synaptique la combinaison antibiotique et relaxant musculaire agit tout comme les ions magnesium, c’est-a-dire, en empêchant la libération d’acétylcholine. Ainsi le bloc neuro-musculairé cause par cette combinaison médicamenteuse est-il résistant à la néostigmine et au calcium en raison de la dualité de son origine, c’est-à-dire, qu’il est à la fois d’origine pré- et post-synaptique.
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Chinyanga, H.M., Stoyka, W.W. The effect of colymycin m, gentamycin and kanamycin on depression of neuromuscular transmission induced by pancuronium bromide. Canad. Anaesth. Soc. J. 21, 569–579 (1974). https://doi.org/10.1007/BF03006018
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DOI: https://doi.org/10.1007/BF03006018