In the case of benzodiazepines, barbiturates also increase the binding affinity of the benzodiazepine binding sites thus leading to an exaggerated effect of benzodiazepines.[3] This makes the predicting the effect of combinations difficult and the same dose of the same drugs will not always produce the same degree of sedation and respiratory depression as the previous experience.
Benzodiazepines increase the frequency of chloride channel opening while barbiturates increase the duration that the chloride pore remains open. If a normal pore opened once every 30 seconds to pass one chloride ion, a benzodiazepine may cause it to open once every ten seconds while a barbiturate may cause it to remain open until three ions have passed through. Separately, both of these increase the effect of the pore threefold, but together, the channel would allow three ions to pass every 10 seconds. This would exponentially increase the effect of the pore ninefold, greater than the sum of the two drugs effects.
