Barbiturates

Barbiturates are a class of drugs derived from barbituric acid that act as central nervous system depressants. Historically used as sedatives, hypnotics, anesthesia-inducing agents, and anticonvulsants, they have been largely supplanted for many indications by safer alternatives but remain in use in some medical contexts and in certain regions. Barbiturates can be categorized by duration of action into short-acting, intermediate-acting, and long-acting agents, with pentobarbital and secobarbital typically short-acting, phenobarbital long-acting, and others intermediate.

Their primary mechanism is modulation of the GABA-A receptor: they bind to distinct sites and increase the duration of chloride channel opening, enhancing inhibitory neurotransmission and producing sedation, hypnosis, and sometimes anesthesia. Because of high lipid solubility, they reach the brain rapidly after administration. Barbiturates induce hepatic enzymes, altering the metabolism of many other drugs and themselves, contributing to drug interactions and tolerance.

Clinical uses have included induction of anesthesia (e.g., thiopental), preoperative sedation, treatment of insomnia, and seizure control (notably phenobarbital). However, risks are significant: marked potential for tolerance, physical dependence, and withdrawal that can be severe or life-threatening; overdose can cause respiratory depression and coma, especially when combined with alcohol or other depressants. They have a narrow therapeutic index and must be used with caution and under supervision where permitted.

Today, benzodiazepines and newer agents have largely replaced barbiturates for most indications due to greater safety margins and lower abuse potential. Barbiturates remain in limited use in certain refractory seizures and specific anesthesia protocols, and some older formulations remain available in some jurisdictions.