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INTRODUCTION

Sedative–hypnotic agents are used widely for the treatment of insomnia and anxiety. As a group, they are one of the most frequently prescribed medications. Barbiturates , benzodiazepines, antihistamines, skeletal muscle relaxants, antidepressants, and anticholinergic agents are discussed elsewhere in this book. This section and Table II–58 list some of the less commonly used hypnotic agents.

TABLE II–58.SEDATIVE–HYPNOTIC AGENTSa

MECHANISM OF TOXICITY

The exact mechanism of action and the pharmacokinetics (see also Table II–66) vary for each agent. The major toxic effect that causes serious poisoning or death is CNS depression resulting in coma, respiratory arrest, and pulmonary aspiration of gastric contents.

TOXIC DOSE

The toxic dose varies considerably between drugs and also depends largely on individual tolerance and the presence of other drugs, such as alcohol. For most of these drugs, ingestion of 3–5 times the usual hypnotic dose results in coma. However, co-ingestion of alcohol or other drugs may cause coma after smaller ingestions, whereas individuals who chronically use large doses of these drugs may tolerate much higher acute doses.

CLINICAL PRESENTATION

Overdose with many of these drugs may cause drowsiness, ataxia, nystagmus, stupor, coma, and respiratory arrest. Deep coma may result in absent reflexes, fixed pupils, and depressed or absent electroencephalographic (EEG) activity. Hypothermia is common. Most of these agents also slow gastric motility and decrease muscle tone. Hypotension with a large overdose is caused primarily by depression of cardiac contractility and, to a lesser extent, loss of venous tone.

  1. Chloral hydrate is metabolized to trichloroethanol, which also has CNS-depressant activity. In addition, trichloroethanol may sensitize the myocardium to the effects of catecholamines, resulting in cardiac arrhythmias.

  2. Buspirone may cause nausea, vomiting, drowsiness, and miosis. There have been no reported deaths.

  3. Glutethimide often produces mydriasis (dilated pupils) and other anticholinergic side effects, and patients may exhibit prolonged and cyclic or fluctuating coma. Glutethimide sometimes is taken in combination with codeine ("loads"), which may produce opioid effects.

  4. Meprobamate has ...

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