Effects of Sulphadimidine on the Toxicity of Phenobarbital, Pentetrazole and Bemegride in Mice of Different Ages

Abstract

Simunek J., Eva Hegerov3, J. Jaros and E. Tkadlec: Effects of Sulphadimi4ine on the Toxicity of Phenobarbital, Pentetrazole and Bemegride in Mice of Different Ages. Acta vet. Br~o, 54,1985: 177-182. Acute toxicity of phenobarbital sodium salt and of injection solutions of bemegride and pentetrazole administered subcutaneously alone and after premedication with sulphadimidine sodium salt at 0.2 g/kg body mass was determined in conventionally read white mice of 12-16 and 22-27 g respectively, in body mass. The toxicity , of phenobarbital alone was higher for the younger mice, whereas that of the two analeptics of the central nervous system (CNS) was lower for the younger than for the older animals. Premedication with sulphadimidine increased the toxicity of all the drugs under study, having a particularly marked effect in the younger mice. Acute toxicity, phenobarbital, bemegride,pentetrazole, sulphadimidine premedication, mice, age-dependence.A previous study from our laboratory (Simunek et al. 1985) was concerned with the effects of sulphadimidine premedication on the acute toxicity of phenobarbital in cockerels of different ages. The impetus to the study was possible simultaneous action of the two pharmaceuticals in flocks where SedophenR, a drug containing phenobarbital, is used to tranquilize chickens and sulphadimidine is used therapeutically, e. g. to combat coccidiosis. Considering the differences in the response to drugs between birds and mammals, the present study was designed to investigate this possible interaction with regard to acute toxicity in white mice This time the experiments were extended to cover possible effects of sulphadimidine premedication on the acute toxicity of two central analeptics, pentetrazole and bemegride.No published data were available to us for direct comparison, particularly as regards the ontogenetic point of view. Nevertheless, it is well established that phenobarbital,like other barbiturates, plays a major role in changing the effects of concurrently administered drugs by affecting the enzyme systems of the body. Thus a number of clinically important interactions have been described. Kvetina and Fendrich (1978), e. g., mentioned the potentiation of the action of the CNS irihibitors; reduced effects of anticoagulants, corticosteroids (glucocorticoids) and riphampicine as a result of enzyme induction; reduced effects of griseofulvine as a result of both enzyme induction and reduced gastrointestinal absorption; and the observation that antacids reduce gastrointestinal absorption of orally administered phenobarbital. Krishna and Bonanomi (1974) described erihanced binding of chloramphenicol to macromolecules of various tissues of phenobarbital--premedicated rats. Dunajev et al., in a long-term experiment with rats given a phenobarbital solution (1g per 1) instead of drinking water, demonstrated the activation of hepatocyte enzymes.According to Skovsted et al. (1974) sulphonamides can prolong the action of other drugs presumably by retarding their metabolism in the ...