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

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Assignment of a drug to the sedative-hypnotic class indicates that it is able to cause sedation (with concomitant relief of anxiety) or to encourage sleep. Because there is considerable chemical variation within the group, this drug classification is based on clinical uses rather than on similarities in chemical structure. Anxiety states and sleep disorders are common problems, and sedative-hypnotics are widely prescribed drugs worldwide.

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An effective sedative (anxiolytic) agent should reduce anxiety and exert a calming effect. The degree of central nervous system depression caused by a sedative should be the minimum consistent with therapeutic efficacy. A hypnotic drug should produce drowsiness and encourage the onset and maintenance of a state of sleep. Hypnotic effects involve more pronounced depression of the central nervous system than sedation, and this can be achieved with many drugs in this class simply by increasing the dose. Graded dose-dependent depression of central nervous system function is a characteristic of most sedative-hypnotics. However, individual drugs differ in the relationship between the dose and the degree of central nervous system depression. Two examples of such dose-response relationships are shown in Figure 22–1. The linear slope for drug A is typical of many of the older sedative-hypnotics, including the barbiturates and alcohols. With such drugs, an increase in dose higher than that needed for hypnosis may lead to a state of general anesthesia. At still higher doses, these sedative-hypnotics may depress respiratory and vasomotor centers in the medulla, leading to coma and death. Deviations from a linear dose-response relationship, as shown for drug B, require proportionately greater dosage increments to achieve central nervous system depression more profound than hypnosis. This appears to be the case for benzodiazepines and for certain newer hypnotics that have a similar mechanism of action.

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Figure 22–1
Graphic Jump Location

Dose-response curves for two hypothetical sedative-hypnotics.

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Chemical Classification

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The benzodiazepines are widely used sedative-hypnotics. All of the structures shown in Figure 22–2 are 1,4-benzodiazepines, and most ...

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