Sedative-Hypnotic Toxicity

Updated: Oct 11, 2019
  • Author: Jeffrey S Cooper, MD, FAAEM, FACEP; Chief Editor: Asim Tarabar, MD  more...
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Overview

Practice Essentials

Sedative-hypnotics are a group of drugs that cause central nervous system (CNS) depression. Benzodiazepines and barbiturates are the most commonly used agents in this class. Other agents include the nonbarbiturate nonbenzodiazepine sedative-hypnotics. Most cases of severe sedative-hypnotic poisoning are deliberate (suicidal). These agents are also commonly abused as recreational drugs.

Barbiturates include the following:

  • Ultrashort acting - Methohexital (Brevital) and thiopental (Pentothal)
  • Short and intermediate acting - Amobarbital (Amytal), pentobarbital (Nembutal), secobarbital (Seconal), butalbital (Fioricet, Fiorinal)
  • Long acting - Phenobarbital (Luminal)

Nonbarbiturates include the following:

  • Benzodiazepines
  • Carbamates - Meprobamate (Equanil, Miltown)
  • Chloral derivatives - Chloral hydrate (Noctec)
  • Ethchlorvynol (Placidyl)
  • Piperidines - Glutethimide (Doriden), methyprylon (Noludar)
  • Quinazolinone - Methaqualone (Quaalude)
  • Imidazopyridine - Zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta)
  • Antihistamines (over-the-counter sleep aids) - Diphenhydramine, doxylamine
  • Gamma-hydroxybutyrate (GHB) and its analog gamma-butyrolactone (GBL)

Mild toxicity resembles ethanol intoxication. Severe respiratory depression is more likely to occur when the sedative-hypnotic is ingested with other CNS depressants or alcohol. Death from sedative-hypnotics is caused by respiratory arrest. Treatment is supportive or designed to limit absorption or enhance elimination. 

For patient education information, see Drugs and MedicationsDrug Overdose and Poisoning, and Child-Proofing Basics.

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Pathophysiology

All the sedative-hypnotics are general CNS depressants. Most stimulate the activity of gamma-aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the CNS. Benzodiazepines, which are one of the most frequently prescribed medications in the world, enhance the effect of GABA at the GABAA receptor. [1, 2]

GHB is a sedative-hypnotic that is banned for sale to the public because of frequent abuse (eg, "date rape") and serious toxic adverse effects. GHB is a neuroinhibitory neurotransmitter or neuromodulator in the CNS. It also appears to increase GABAB receptor activity and dopamine levels in the CNS. It binds to GABAB receptors in the brain, inhibits noradrenaline release in the hypothalamus, and mediates the release of an opiatelike substance in the striatum. It produces a biphasic dopamine response, increasing release at high doses and inhibiting release at lower doses.

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Epidemiology

According to the 2017 Annual Report of the American Association of Poison Control Centers' National Poison Data System (AAPCC-NPDS), sedative/hypnotics/antipsychotics exposures as a class increased the most rapidly (4.91/year) over the last 17 years for cases showing more serious outcomes. It was the fourth most frequent exposure documented and the second most frequent exposure in adults aged 20 years or older. In 2017, there were with 53,419 single exposures resulting in 33 deaths. However, sedative/hypnotics/antipsychotics exposures were involved in 404 fatalies where more than one substance was present. This is the highest number of fatalities of any category. [3]  

 

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Prognosis

In 2017, over 60% of ingestions were suicide related. [3]  These drugs are also used to offset the stimulatory effects of other drugs of abuse (eg, amphetamines, hallucinogens). [4]  Because they are prescribed so commonly, benzodiazepines have the highest morbidity and mortality of the sedative-hypnotics and represent nearly half of reported exposures. [3]  Alprazolam (Xanax) is relatively more toxic than other benzodiazepines in overdose and accounted for the majority of benzodiazepine fatalities in the 2017 AAPCC-NPDS annual report. [3]  

Benzodiazepines are commonly misused by individuals with opioid dependence, with prevalence rates of 45–70% for patients in opioid maintenance treatment. [5] Concomitant benzodiazepine use is a known risk factor for fatal and non-fatal opioid overdose; benzodiazepine co-ingestion is involved in 40–80% of heroin- and methadone-related deaths, and in 80% or more of buprenorphine-related deaths. [6]

Death from sedative-hypnotics is caused by respiratory arrest. Some sedative-hypnotics may have teratogenic or mutagenic effects. Complications associated with mortality in patients requiring intubation include difficulties with intubation, shock, and evidence of gastric aspiration. [7]

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