The term sedative-hypnotic refers to any drug
designed to produce sedation and sleepiness. These drugs can be
divided into the benzodiazepines (see Chapter 177, Benzodiazepines) and nonbenzodiazepines (Table
Table 178-1 Nonbenzodiazepine
Sedatives |Favorite Table|Download (.pdf)
Table 178-1 Nonbenzodiazepine
|Name||Protein Binding (%)||Volume of Distribution (L/kg)||Plasma Half-Life|
|Chloral hydrate||35 for trichloroethanol||0.6||4 min for chloral hydrate and 6–10 h for trichloroethanol|
|Gamma hydroxyl butyric acid||0||0.4||0.3–1 h|
|Zopiclone and eszopiclone||45||1.3–1.6||3.5–6.5 h|
Sedatives were some of the first class of agents to be used in
modern medicine. Chloral hydrate, one of the oldest sedative-hypnotic
agents, was originally synthesized in 1832. The first death attributed
to this agent was reported in 1890.1 In the beginning
of the 20th century, the barbiturates barbital and phenobarbital
were introduced. As the toxicity of the barbiturate was recognized,
the search for newer, safer drugs began.
The emergency physician is likely to encounter these nonbenzodiazepine sedative
drugs as part of accidental or nonaccidental overdose, as well as
in patients presenting after an assault or trauma. In 2008, the
American Association of Poison Control Centers received reports
of 27,705 exposures to nonbenzodiazepine sedatives; 13,054 were
single drug exposures, and two deaths were reported.2
Three agents commonly used in the past have been removed from
the legal U.S. and Canadian markets: ethchlorvynol, glutethimide,
and methaqualone. In 1984, methaqualone was upgraded to a Schedule
I drug by the U.S. Food and Drug Administration and the remaining
U.S. manufacturer stopped production. In 1999, the U.S. manufacturers
stopped production and sale of ethchlorvynol and glutethimide. However,
unverified comments on the Internet suggest these drugs might be
available to North American customers from locations in Eastern
Europe, Africa, and Asia.
Many of these nonbenzodiazepines were developed and are marketed
for the treatment of insomnia. The sedative effect of other agents,
including antihistamines (e.g., diphenhydramine, doxylamine), antidepressants (e.g.,
amitriptyline, trazodone, and mirtazapine), and antipsychotics (e.g., quetiapine)
are also used to promote sleep.
Buspirone was originally approved by the U.S. Food and Drug Administration
for treatment of generalized anxiety in 1986.3 Other
off-label uses include treatment of depression and nicotine dependence.
Buspirone is a partial agonist at the serotonin-1A receptor and
an antagonist of the dopamine-D2 receptor.4 The
resultant effect on serotonin and dopamine neurotransmitter levels
is complex, depending on the concentration of the drug and specific
brain location. The reported noradrenergic effects are likely an
indirect effect of the serotoninergic effect of buspirone.
Buspirone has a complex mechanism of action, but its primary
effects are presumably due to suppression ...