Studies of Interaction between Hexamethonium and Lidocaine, alpha-Bungarotoxin or Decamethonium in Vitro.
10.4097/kjae.2001.40.5.645
- Author:
Jeong Seok LEE
1
;
Dae Geun JEON
;
Sung Yell KIM
;
Sae Jin CHOI
Author Information
1. Department of Anesthesiology, College of Medicine, Soon Chun Hyang University, Seoul, Korea.
- Publication Type:In Vitro ; Original Article
- Keywords:
Neuromuscular transmission: alpha-bungarotoxin;
decamethonium;
hexamethonium;
lidocaine
- MeSH:
Animals;
Bungarotoxins*;
Colon, Sigmoid;
Depression;
Hexamethonium*;
Lidocaine*;
Neuromuscular Blocking Agents;
Rats
- From:Korean Journal of Anesthesiology
2001;40(5):645-654
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
BACKGROUND: Interactions of neuromuscular blocking agents are antagonistic in a combination of depolarizing and nondepolarizing agents, additive in a combination of relative two compounds or synergistic in a combination of different two nondepolarizing agents. However, the interactions of neuromuscular blocking agents with a different site of action from each other have not been studied clearly. This study was designed to examine the interaction between hexamethonium and lidocaine, alpha-bungarotoxin or decamethonium with markedly different pre and postsynaptic sites of action. METHODS: Square wave, 0.1 Hz supramaximal stimuli or 2 Hz, 0.2 ms train of four (TOF) stimuli, was applied to the rat phrenic nerve-hemidiaphragm preparation, and the twitch height response was recorded mechanomyographically. The cumulative concentration effect and TOF ratio at each point of twitch depression after hexamethonium, lidocaine, alpha-bungarotoxin or decamethonium given were measured. The EC50 and EC95 of hexamethonium, lidocaine, alpha-bungarotoxin and decamethonium were calculated using an inhibitory sigmoid Emax model. In the experiment of each combination of two drugs, three points of the isobole for hexamethonium-lidocaine, hexamethonium-alpha-bungarotoxin and hexamethonium-decamethonium were established using ratios of 1 : 3, 1 : 1 and 3 : 1 of their EC50. Points on the line of theoretical additivity and 95% confidence intervals were calculated according to Tallarida et al. TOF ratios were observed at 75, 50 and 25% of the control twitch height value during each combination ratio of their EC50. RESULTS: Significant deviations of points on the isobole from the line of additivity to the left were found at all EC50 ratios of hexamethonium-lidocaine (P < 0.05 respectively), that to the right was found at all EC50 ratios of a hexamethonium-alpha-bungarotoxin and hexamethonium-decamethonium (P < 0.05 respectively). The magnitude of TOF fade depended upon the mixed ratios for their EC50. CONCLUSIONS: The interaction was found to be synergistic in the combination of hexamethonium- lidocaine, and antagonistic in the combination of hexamethonium-alpha-bungarotoxin and hexamethonium- decamethonium.
