| The Neuromuscular Blocking Effect of Mivacurium in Isolated Rat Phrenic-Hemidiaphragm with Long-term Phenytoin Pretreatment. |
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Tae Gan Ryu, Jong Sul Kim, Mi Kyeong Lee, Young Cheol Park, Sang Ho Lim, Young Seok Choi, Suk Min Yoon |
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| Abstract |
BACKGROUND
Long-term phenytoin therapy induces resistance to the neuromuscular blocking effects of metocurine, atracurium, doxacurium, and pipecuronium. This study examine neuromuscu-lar blocking effect and recovery of mivacurium in isolated rat phrenic-hemidiaphragm with two-weeks phenytoin pretreatment.
METHOD
After the administration of 14 days of phenytoin 40 mg/kg, administered intraperitoneally twice daily (n=10), ED90, antagonism of neostigmine and 4-aminopyridine on the electrically evoked twitch response and train-of-four (TOF) stimulation were compared to control groups in isolated rat phrenic-hemidiaphragm preparation.
RESULTS
ED90 was significantly greater in the phenytoin group than in the control group (319 +/- 39.5 g vs. 209.5 +/- 52.2 g, respectively). After the administration of neostigmine 0.75 M, the recovery of the single twitch and TOF ratio were significantly lesser in the phenytoin group than in the control group (single twitch; 19.6 +/- 6.6% vs.
69.2 +/- 9.4%, TOF ratio; 0.258 +/- 0.149 vs. 0.543 +/- 0.1, respectively). After the administration of 4-aminopyridine 40uM, the recovery of the single twitch and TOF ratio were no significant differrence between the phenytoin group and the control group (twitch; 118.1 +/- 25.3% vs. 122.6 +/- 24.8%, TOF ratio; 0.937 +/- 0.051 vs. 0.949 +/- 0.067, respectively).
CONCLUSION
Long-term phenytoin therapy induces resistance to the neuromuscular blocking effects of mivacurium. |
| Key Words:
Neuromuscular relaxants, mivacurium; Anticonvulsants, phenytoin; Interactions, drug |
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