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Barbiturate toxicity has historically been associated with the highest risk of morbidity and mortality among all sedative-hypnotics. 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, such as 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 a second-line agent. They are still used in combination drugs (i.e., butalbital) and alone (i.e., secobarbital) for the treatment of tension and migraine headaches,7,8 although the efficacy of either is controversial.9 Barbiturates are used in the pharmacologic management of refractory intracranial hypertension from focal and diffuse brain injury, but evidence of improved outcomes has been modest.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 1).

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Table 1 Selected Properties of Commonly Used Barbiturates
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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.11 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 other therapeutic drugs, such as oral contraceptives, anticoagulants, and corticosteroids, when taken concurrently.

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Barbiturates' main ...

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