RESUMEN
Phenytoin is a widely used anticonvulsant drug, the chronic administration of which maybe associated with several drug interactions. This study aims at testing the presence of an interaction between phenytoin and two of the newly used neuromuscular b lockers [NMBs], namely rocuronium and cisatracurium. 96 male albino rats were used, half of which were treated daily with oral phenytoin, 100 mg/Kg for four weeks, while the rest were given the vehicle and served as controls. Thirty six animals from each group were used for in vivo administration of three different doses of each tested neuromuscular blacker [0.5, 1.0 and 2.0 mg/Kg in case of rocuronium and 0.4, 0.8 and 1.6 mg/Kg in case of cisatracurium] and twelve were used to obtain phrenic nerve diaphragm preparations for evaluation of in vitro actions of different concentrations of the tested NMBs [0.25, 0.5 and 1.0 micro g/Kg in case of rocuronium and 0.5, 1.0 and 2.0 micro g/Kg in case of cisatracurium]. With both NMBs, there was a significantly shorter duration of paralysis and a significantly shorter recovery index following phenytoin treatment. This was true for all studied doses. The effect of all tested concentrations of rocuronium and cisatracurium on the response to phrenic nerve stimulation was significantly less in preparations obtained from phenytoin treated animals with an almost parallel rightward shift of concentration response curves. Results of this study suggest a dynamic background for the resistance commonly encountered with NMBs among patients on chronic phenytoin therapy. A kinetic type of interaction, however can not be excluded. It is thus recommended that more frequent or continuous monitoring should be considered in patients known to be on chronic anticonvulsant therapy even those receiving NMBs like cisatracurium, with a predominantly organ-independent elimination