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Barbiturates are still the most common class of antiepileptic drugs used in developing countries, but their use is declining due to the introduction of safer, less toxic sedative-hypnotics (e.g., benzodiazepines) and second-generation anticonvulsants.1 Status epilepticus,2 severe ethanol and sedative withdrawal syndromes,3-5 and toxicologic seizures6 are typically managed with benzodiazepines, but barbiturates have a useful role as second-line agents. They are still used in combination drugs (e.g., butalbital) and alone (e.g., secobarbital) for the treatment of tension and migraine headaches7-9 and for refractory intracranial hypertension from focal and diffuse brain injury.10
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Barbiturates are generally classified according to their duration of action, which is primarily dependent on lipid solubility and tissue distribution rather than the elimination half-life (Table 182-1).
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Barbiturates readily distribute throughout the body to most tissues, crossing the blood–brain barrier and placenta, and are excreted in breast milk. Fetal blood barbiturate concentrations closely reflect maternal plasma levels, creating the potential for fetal withdrawal syndrome. Most barbiturates are metabolized in the liver to inactive metabolites, primarily through routes involving the cytochrome P450 system. The elimination half-life of barbiturates can be greatly shortened in infants and children and very prolonged in the elderly and in patients with liver or renal disease. Chronic barbiturate use induces activity of the cytochrome P450 enzymes and may accelerate the metabolism of concurrently taken therapeutic drugs such as oral contraceptives, anticoagulants, and corticosteroids.
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Barbiturates’ main action is the depression of activity in the CNS and musculoskeletal system. In the CNS, this is accomplished by enhancing the action of the primary inhibitory neurotransmitter γ-aminobutyric acid at its receptor.11 When γ-aminobutyric acid binds to its chloride channel receptor, it causes it to open, resulting in a depolarization; the depolarization temporarily stabilizes the resting membrane potential and inhibits the firing of new action potentials. Barbiturates bind to the α subunit of the γ-aminobutyric acid receptor, causing an increase in the duration of opening of the cell membrane chloride channel; this results in prolonged depolarization and prolonged inactivity.
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