Effect of Diltiazem on Pancuronium - and Vecuronium - induced Neuromuscular Blockade

Park, Jong Gwan; Song, Yoon Kang; Kim, Tae Yo; Choi, Bong Kyu

Abstract

The effects and interactions of pancuronium and vecuronium with diltiazem on the electri- cally-evoked twitch response, train-of-four and tetanic stimulation were studied in the isolated rat hemi-diaphragm preparation. Pancuronium(3 X 10(-7) -10(-5) M) and vecuronium(3 X 10(-6)-15 X 10(-6) M) decreased the electrically evoked(nerve stimulation, 0.1Hz, 0.5ms, 10V) twitch response, train-of-four and tetanus ratio in a dose-related fashion and pancuronium was more potent than vecuronium. The inhibitory effects of pancuronium and vecuronium were potentiated by pretreatment with 5 & 10 uM diltiazem, a Ca++-channel blocker, in which the concentration of diltiazem has no obvious effects on the twitch response itself. Furthermore, it is noteworth that the inhibitory effects of pancuronium and vecuronium were markedly potentiated by 150 uM hemicholinium pretreatment. In cases of the direct(muscle, 0.1 Hz, 5 ms, 10 V) stimulation, pancuronium and vecuronium decreased the electrically evoked twitch response dose dependently, but the amplitudes of inhibition were less than those in indirect(nerve) stimulation. The inhibitory effects were not affected by diltiazem pretreatment except low doses of vecuronium. On the basis of these findings, the result of the present study suggests that the muscle relaxation by pancuronium and vecuronium is mediated by pre- and post-junctional receptor blockade, and that diltiazem intensifies neuromuscular blockade produced by muscle relaxants. The potentiating effect of diltiazem may be due to blocking influx of calcium and/or release of acetylcholine from presynaptic nerve terminals.