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:
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Ultrashort acting - Methohexital (Brevital) and thiopental (Pentothal)
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Short and intermediate acting - Amobarbital (Amytal), pentobarbital (Nembutal), secobarbital (Seconal), butalbital (Fioricet, Fiorinal)
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Long acting - Phenobarbital (Luminal)
Nonbarbiturates include the following:
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Benzodiazepines
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Carbamates - Meprobamate (Equanil, Miltown)
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Chloral derivatives - Chloral hydrate (Noctec)
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Ethchlorvynol (Placidyl)
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Piperidines - Glutethimide (Doriden), methyprylon (Noludar)
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Quinazolinone - Methaqualone (Quaalude)
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Imidazopyridine - Zolpidem (Ambien), zaleplon (Sonata), eszopiclone (Lunesta)
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Antihistamines (over-the-counter sleep aids) - Diphenhydramine, doxylamine
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Gamma-hydroxybutyrate (GHB) and its analog gamma-butyrolactone (GBL)
New psychoactive substances (NPS) have become available as substitutes for controlled sedative-hypnotics. The European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) monitors 30 new benzodiazepines, over 80% of which were detected for the first time between 2014 and 2020. While many have been described in scientific publications or patent literature, they have never been approved for medical use and therefore remain uncontrolled by the international drug control system. [1]
Mild sedative-hypnotic toxicity resembles ethanol intoxication. Severe respiratory depression is more likely to occur when a 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 Medications, Drug Overdose, and Poison Proofing Your Home..
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. [2, 3]
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.
Epidemiology
According to the 2020 Annual Report of the American Association of Poison Control Centers' National Poison Data System (AAPCC-NPDS), sedative/hypnotics/antipsychotics exposures were the fifth most frequent exposure documented overall and the second most frequent exposure in adults aged 20 years or older. In 2020, the AAPCC-NPDS reported 47,042 single exposures resulting in 38 deaths. However, sedative/hypnotics/antipsychotics exposures were involved in 334 fatalities in where more than one substance was present, which was the highest number of fatalities of any category. [4]
Prognosis
In 2020, over 60% of ingestions were suicide related. [4] These drugs are also used to offset the stimulatory effects of other drugs of abuse (eg, amphetamines, hallucinogens). [5] Because they are prescribed so commonly, benzodiazepines have the highest morbidity and mortality of the sedative-hypnotics and represent nearly half of reported exposures. [4] Alprazolam (Xanax) is relatively more toxic than other benzodiazepines in overdose and accounted for the majority of benzodiazepine fatalities in the 2020 AAPCC-NPDS annual report. [4]
Benzodiazepines are commonly misused by individuals with opioid dependence, with prevalence rates of 45–70% for patients in opioid maintenance treatment. [6] 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. [7]
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. [8]
