Sedative-Hypnotic Toxicity
- Author: Jeffrey S Cooper, MD, FAAEM, FACEP; Chief Editor: Asim Tarabar, MD more...
Background
Sedative-hypnotics are a group of drugs that cause CNS depression. Benzodiazepines and barbiturates are the most commonly used agents in this class. Other agents include the nonbarbiturate nonbenzodiazepine sedative-hypnotics, such as buspirone, zolpidem, ethchlorvynol, glutethimide, chloral hydrate, meprobamate, methaqualone, methyprylon, carisoprodol, and gamma-hydroxybutyrate (GHB) and its analog gamma-butyrolactone (GBL). Most severe sedative-hypnotic poisonings 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), and butalbital (Fioricet, Fiorinal)
- Long acting - Phenobarbital (Luminal)
Nonbarbiturates
- Benzodiazepines
- Carbamates - Meprobamate (Miltown)
- Chloral derivatives - Chloral hydrate (Noctec)
- Ethchlorvynol (Placidyl)
- Piperidines - Glutethimide (Doriden) and methyprylon (Noludar)
- Quinazolinone - Methaqualone (Quaalude)
- Imidazopyridine - Zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta) and alpidem
- Antihistamines (over-the-counter sleep aids) - Diphenhydramine and doxylamine
- GHB- Gamma-hydroxybutyrate
Pathophysiology
All the sedative-hypnotics are general CNS depressants. Most stimulate the activity of GABA, the principal inhibitory neurotransmitter in the CNS. GHB is a sedative-hypnotic recently 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. Benzodiazepines are one of the most frequently prescribed medications in the world.
Epidemiology
Frequency
United States
According to the 2008 Annual Report of the American Association of Poison Control Centers' National Poison Data System, 67,617 single exposures were documented for the sedative/hypnotics/antipsychotics drug category. Of these, 21 resulted in death.[1]
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.
- 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.
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