Kaplan + Sadock's Synopsis of Psychiatry, 11e

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29.8 Barbiturates and Similarly Acting Drugs

Laboratory Interferences.  Meprobamate can interfere with the metyrapone, phentolamine, and urinary 17-hydroxy- corticosteroid tests. Dosing and Clinical Guidelines.  Meprobamate is avail- able in 200, 400, and 600 mg tablets; 200 and 400 mg extended- release capsules; and various combinations, for example, aspirin, 325 mg and 200 mg of meprobamate (Equagesic) for oral use. For adults, the usual dose is 400 to 800 mg twice daily. Elderly patients and children aged 6 to 12 years require half the adult dose. Chloral Hydrate Chloral hydrate is a hypnotic agent rarely used in psychiatry because numerous safer options, such as benzodiazepines, are available. Pharmacological Actions.  Chloral hydrate is well absorbed from the GI tract. The parent compound is metabo- lized within minutes by the liver to the active metabolite tri- chloroethanol, which has a half-life of 8 to 11 hours. A dose of chloral hydrate induces sleep in about 30 to 60 minutes and maintains sleep for 4 to 8 hours. It probably potentiates GABAergic neurotransmission, which suppresses neuronal excitability. Therapeutic Indications.  The major indication for chlo- ral hydrate is to induce sleep. It should be used for no more than 2 or 3 days because longer-term treatment is associated with an increased incidence and severity of adverse effects. Toler- ance develops to the hypnotic effects of chloral hydrate after 2 weeks of treatment. The benzodiazepines are superior to chlo- ral hydrate for all psychiatric uses. Precautions and Adverse Reactions.  Chloral hydrate has adverse effects on the CNS, GI system, and skin. High doses ( > 4 g) may be associated with stupor, confusion, ataxia, falls, or coma. The GI effects include nonspecific irritation, nausea, vomiting, flatulence, and an unpleasant taste. With long-term use and overdose, gastritis and gastric ulceration can develop. In addition to the development of tolerance, dependence on chloral hydrate can occur, with symptoms similar to those of alcohol dependence. With a lethal dose between 5,000 and 10,000 mg, chloral hydrate is a particularly poor choice for potentially sui- cidal persons. Drug Interactions.  Because of metabolic interference, chloral hydrate should be strictly avoided with alcohol, a noto- rious concoction known as a Mickey Finn. Chloral hydrate may displace warfarin (Coumadin) from plasma proteins and enhance anticoagulant activity; this combination should be avoided. Laboratory Interferences.  Chloral hydrate administra- tion can lead to false-positive results for urine glucose deter- minations that use cupric sulfate (e.g., Clinitest) but not in tests that use glucose oxidase (e.g., Clinistix and Tes-Tape). Chloral hydrate can also interfere with the determination of urinary cat- echolamines in 17-hydroxycorticosteroids.

half-lives range from 3.4 to 9.8 hours. The onset of action is 15 to 30 minutes.

Therapeutic Indications.  Paraldehyde is not indicated as an anxiolytic or a hypnotic and has little place in current psy- chopharmacology. Precautions and Adverse Reactions.  Paraldehyde fre- quently causes foul breath because of expired unmetabolized drug. It can inflame pulmonary capillaries and cause coughing. It can also cause local thrombophlebitis with IV use. Patients may experience nausea and vomiting with oral use. Overdose leads to metabolic acidosis and decreased renal output. There is risk of abuse among drug addicts. Drug Interactions.  Disulfiram (Antabuse) inhibits acetal- dehyde dehydrogenase and reduces metabolism of paraldehyde, leading to possible toxic concentration of paraldehyde. Paralde- hyde has addictive sedating effects in combination with other CNS depressants such as alcohol or benzodiazepines. Laboratory Interferences.  Paraldehyde can interfere with the metyrapone, phentolamine, and urinary 17-hydroxycortico- steroid tests. Dosing and Clinical Guidelines.  Paraldehyde is avail- able in 30-mL vials for oral, IV, or rectal use. For seizures in adults, up to 12 mL (diluted to a 10% solution) can be adminis- tered by gastric tube every 4 hours. For children, the oral dose is 0.3 mg/kg. Meprobamate Meprobamate, a carbamate, was introduced shortly before the benzodiazepines, specifically to treat anxiety. It is also used for muscle relaxant effects. PharmacologicActions.  Meprobamate is rapidly absorbed from the GI tract and from IM injections. It is metabolized pri- marily by the liver, and a small portion is excreted unchanged in urine. The plasma half-life is approximately 10 hours. Therapeutic Indications.  Meprobamate is indicated for short-term treatment of anxiety disorders. It has also been used as a hypnotic and is prescribed as a muscle relaxant. Precautions and Adverse Reactions.  Meprobamate can cause CNS depression and death in overdose and carries the risk of abuse by patients with drug or alcohol dependence. Abrupt cessation after long-term use can lead to withdrawal syndrome, including seizures and hallucinations. Meprobamate can exac- erbate acute intermittent porphyria. Other rare side effects include hypersensitivity reactions, wheezing, hives, paradoxical excitement, and leukopenia. It should not be used in patients with hepatic compromise. Drug Interactions.  Meprobamate has additive sedating effects in combination with other CNS depressants, such as alcohol, barbiturates, or benzodiazepines.