Acute Intoxication with Sedative–Hypnotics

Acute Intoxication with Sedative–Hypnotics

The acute toxicity of sedative–hypnotics consists of slurred speech, incoordination, ataxia, sustained nystagmus, impaired judgment and mood lability. When taken in large amounts sedative–hypnotics produce progressive respiratory depression and coma. The amount of respiratory depression produced by the benzodiazepines is much less than that produced by the barbiturates and other sedative–hypnotics. Consistent with its general approach, the DSM-IV-TR diagnosis of intoxication requires “clinically significant maladaptive behavioral or psychological changes” developing after drug use in addition to the signs and symptoms of acute toxicity.

Dependence

Sedative–hypnotics can produce tolerance and physiological dependence. Physiological dependence can be induced within several days with continuous infusion of anesthetic doses. Pa-tients who are taking barbiturates daily, for example, for a month or more above the upper therapeutic range listed in Table 44.1 should be presumed to be physically dependent and in need of medically managed detoxification.

Withdrawal Syndrome

The withdrawal syndrome arising from the discontinuation of short-acting sedative–hypnotics is similar to that from stopping or cutting down on the use of alcohol. Signs and symptoms of sedative–hypnotic withdrawal include anxiety, tremors, night-mares, insomnia, anorexia, nausea, vomiting, postural hypo-tension, seizures, delirium and hyperpyrexia. The syndrome is qualitatively similar for all sedative–hypnotics; however, the time course of symptoms depends on the particular drug. With short-acting sedative–hypnotics (e.g., pentobarbital, secobarbi-tal, meprobamate, oxazepam, alprazolam and triazolam), with-drawal symptoms typically begin 12 to 24 hours after the last dose and peak in intensity between 24 and 72 hours (symptoms may develop more slowly in patients with liver disease or in the elderly because of decreased drug metabolism). With long-acting drugs (e.g., phenobarbital, diazepam and chlordiazepox-ide), withdrawal symptoms peak on the fifth to eighth day. The withdrawal delirium may include confusion, visual and auditory hallucinations. The delirium generally follows a period of insom-nia. Some patients may have only delirium; others only seizures; and some may have both delirium and convulsions.

Iatrogenic Dependence

Patients treated for months to years with benzodiazepines and other sedative–hypnotics may become physically dependent on sedative–hypnotics. The possibility of physical dependence should be discussed with the patient and, in some cases, the pa-tient’s family. The distinction between physical dependence as a process of neuroadaptation and physical dependence as a com-ponent of a substance-use disorder should be explained in detail. Patients need to be advised against abruptly stopping the medica-tion because of the possibility of developing severe withdrawal symptoms, including seizures.