Enhanced Psychotropic Effect of Diazepam Due to Invivo Drug-Alcohol Interaction

Diazepam is a benzodiazepine derivative with hypnotic, anxyolitic, sedative, skeletal muscle relaxant, anticonvulsant, anti-tremor and amnestic activity. The inherent property of the drug is its metabolism in the liver by the cytochrome P (CYP) 450 enzyme system. The active metabolite of the drug is N-desmethyldiazepam which is N-demethylated by CYP3A4. N-desmethyl-diazepam is further metabolized to oxazepam. The intake of inhibitors or inducers of the CYP isozymes involved in the biotransformation of diazepam may alter plasma concentrations of this drug. In the present study, a case related to death under mysterious circumstances of a 50 year old man was examined. During the routine analysis the drug extracted from the biological fluids of the deceased showed the presence of N-desmethyldiazepam which is anactive metabolite of diazepam. Further, the biological sample of the deceased confirmed the presence of ethyl alcohol. Hence, it was analyzed that the ethanol ingestion may have enhanced the central nervous system effects of diazepam. Alcohol increases the absorption and raises the serum levels of diazepam. The cognitive deficits induced by diazepam may be increased in patients who chronically consume large amounts of alcohol. Diazepam has low potential for pharmaco-kinetic drug interactions.