Glutethimide, USP. Glutethimide, 2-ethyl-2-phenyl-glutarimide (Doriden), is one of the most active nonbarbitu-rate hypnotics that is structurally similar to the barbiturates, especially phenobarbital. Because of glutethimide's low aqueous solubility, its dissolution and absorption from the GI track is somewhat erratic. Consistent with its high lipophilicity, it undergoes extensive oxidative metabolism in the liver with a half-life of approximately 10 hours. Glutethimide is used as a racemic mixture with the (+) enantiomer being primarily metabolized on the glutarimide ring and the ( —) enantiomer on the phenyl ring. The product of metabolic detoxification is excreted after conjugation with glucuronic acid at the hydroxyl group. The drug is an enzyme inducer. In the therapeutic dosage range, adverse effects tend to be infrequent. Toxic effects in overdose are as severe as, and possibly more troublesome than, those of the barbiturates.
The very simple alcohol ethanol has a long history of use as a sedative and hypnotic. Its modes of action were described under the anesthetic heading and are said to apply to other alcohols. It is widely used in self-medication as a sedative-hypnotic. Because this use has so many hazards, it is seldom a preferred agent medically.
Chapter 12 # Central Nervous System Depressants 455 CH3 q
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