Barbiturates

Barbital was introduced into medical practice in 1903, and phenobarbital, in 1912. Their rapid success led to the development of over 2,000 derivatives of barbituric acid, with dozens being used in medical practice. The only sedatives to precede the barbiturates were the bromides and chloral hydrate, both of which were in widespread use before the end of the 19th century.

The most commonly used barbiturates today are amobarbital (Amytal), butabarbital (Butisol), mephobarbital (Mebaral), pentobarbital (Nembutal), secobarbital (Seconal), and phenobarbital (Luminal). The first five have an intermediate duration of action, whereas the last, phenobarbital, has a long duration of action. Short-acting barbiturates are used as anesthetics, but not in outpatient medicine.

Barbiturates reversibly suppress the activity of all excitable tissue, with the CNS being particularly sensitive to these effects. Except for the antiepileptic effects of phenobarbital, there is a low therapeutic index for the sedative effects of the barbiturates, with general CNS depression being linked to the desired therapeutic effects. The amount of barbiturates that can cause a fatal overdose is well within the usual size of a single prescription. A common problem with the medical use of the barbiturates for both sedation and hypnosis is the rapid development of tolerance, with a common tendency of medical patients to raise the dose on chronic administration. The barbiturates affect the gamma-aminobutyric acid (GABA) system, producing both a cross-tolerance to other sedating drugs, including alcohol and the benzodiazepines, and a heightened risk of fatal overdose reactions (Charney et al., 2001).

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