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C H A P T E R

Sedative-Hypnotic Drugs

Anthony J. Trevor, PhD

C ASE STUD Y

At her annual physical examination, a 53-year-old middle not overweight, and she takes no prescription drugs. She
school teacher complains that she has been having difficulty drinks decaffeinated coffee but only one cup in the morning;
falling asleep, and after falling asleep, she awakens several however, she drinks as many as six cans per day of diet cola.
times during the night. These episodes now occur almost She drinks a glass of wine with her evening meal but does
nightly and are interfering with her ability to teach. She has not like stronger spirits. What other aspects of this patient’s
tried various over-the-counter sleep remedies, but they were history would you like to know? What therapeutic measures
of little help and she experienced “hangover” effects on the are appropriate for this patient? What drug, or drugs, (if any)
day following their use. Her general health is good, she is would you prescribe?

Assignment of a drug to the sedative-hypnotic class indicates relationship between the dose and the degree of CNS depression.
that it is able to cause sedation (with concomitant relief of Two examples of such dose-response relationships are shown in
anxiety) or to encourage sleep (hypnosis). Because there is Figure 22–1. The linear slope for drug A is typical of many of the
considerable chemical variation within the group, this drug older sedative-hypnotics, including the barbiturates and alcohols.
classification is based on clinical uses rather than on simi- With such drugs, an increase in dose higher than that needed for
larities in chemical structure. Anxiety states and sleep disorders hypnosis may lead to a state of general anesthesia. At still higher
are common problems, and sedative-hypnotics are widely doses, these sedative-hypnotics may depress respiratory and vaso-
prescribed drugs worldwide. motor centers in the medulla, leading to coma and death. Devia-
tions from a linear dose-response relationship, as shown for drug
B, require proportionately greater dosage increments to achieve
■ BASIC PHARMACOLOGY OF CNS depression more profound than hypnosis. This appears to be
SEDATIVE-HYPNOTICS the case for benzodiazepines and for certain newer hypnotics that
have a similar mechanism of action.

An effective sedative (anxiolytic) agent should reduce anxiety
and exert a calming effect. The degree of central nervous system CHEMICAL CLASSIFICATION
(CNS) depression caused by a sedative should be the minimum
consistent with therapeutic efficacy. A hypnotic drug should The benzodiazepines are widely used sedative-hypnotics. All of
produce drowsiness and encourage the onset and maintenance of the structures shown in Figure 22–2 are 1,4-benzodiazepines, and
a state of sleep. Hypnotic effects involve more pronounced depres- most contain a carboxamide group in the seven-membered het-
sion of the CNS than sedation, and this can be achieved with erocyclic ring structure. A substituent in the 7 position, such as a
many drugs in this class simply by increasing the dose. Graded halogen or a nitro group, is required for sedative-hypnotic activity.
dose-dependent depression of CNS function is a characteristic of The structures of triazolam and alprazolam include the addition of
most sedative-hypnotics. However, individual drugs differ in the a triazole ring at the 1,2-position.

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