Sedative-Hypnotic Toxicity

Updated: Dec 29, 2015
  • Author: Jeffrey S Cooper, MD, FAAEM, FACEP; Chief Editor: Asim Tarabar, MD  more...
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Overview

Background

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

  • 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

  • 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,d doxylamine
  • Gamma-hydroxybutyrate (GHB) and its analog gamma-butyrolactone (GBL)
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Pathophysiology

All the sedative-hypnotics are general CNS depressants. Most stimulate the activity of 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 the neurotransmitter gamma-aminobutyric acid (GABA) at the GABAA receptor. [1, 2]

GHB is a sedative-hypnotic that is banned for sale to the public because of frequent abuse and serious toxic adverse effects. GHB is a neuroinhibitory neurotransmitter or neuromodulator in the CNS. It also appears to increase GABA B receptor activity and dopamine levels in the CNS.

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Epidemiology

Frequency

United States

According to the 2014 Annual Report of the American Association of Poison Control Centers' National Poison Data System, 55,653 single exposures were documented for the sedative/hypnotics/antipsychotics drug category. Of these, 41 resulted in death. [3]

In 1998, a total of 70,982 sedative-hypnotic exposures were reported to US poison control centers, of which 2310 (3.2%) resulted in major toxicity and 89 (0.1%) resulted in death.

Mortality/Morbidity

Most of the serious ingestions are suicide-related. These drugs are also used with other drugs of abuse (eg, amphetamines, hallucinogens) to offset stimulatory effects. [4]

Because they are prescribed so commonly, benzodiazepines have the highest morbidity and mortality of the sedative-hypnotics.

Death from sedative-hypnotics is caused by respiratory arrest. Alprazolam (Xanax) is relatively more toxic than other benzodiazepines in overdose.

Chloral hydrate, barbiturates, and related sedatives had a much higher toxicity index (fatalities per prescriptions) than benzodiazepines, buspirone, zolpidem, and zopiclone in a study from the United Kingdom. [5]

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