Barbiturates

Derivatives of barbituric acid, and the sedative class the benzodiazepines displaced. They modulate GABA-A positively at low exposure and open the chloride channel directly at higher exposure, without needing GABA to be present — which is the whole difference. A benzodiazepine can only amplify a signal already there, so it has a ceiling of its own; a barbiturate has none, and the interval between sedation, anaesthesia and respiratory arrest is far narrower for that reason. Flumazenil acts at a different site and does not reverse them.

Within the family, duration is the variable: thiopental is ultra-short and used to induce anaesthesia, phenobarbital is long and used as an anticonvulsant, and butalbital appears in combination headache tablets beside paracetamol, which brings its own hepatotoxicity. Phenobarbital is a strong enzyme inducer, lowering blood levels across much of this tree. Withdrawal after sustained use can produce seizures.