Assignment of a drug to the sedative-hypnotic class indicates
that its major therapeutic use is to cause sedation (with concomitant
relief of anxiety) or to encourage sleep. Because there is considerable
chemical variation within this 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. Drugs in this class include alcohols,
benzodiazepines, barbiturates, carbamates, and several newer hypnotics,
including eszopiclone, zaleplon, and zolpidem (Figure 13–1).
Drugs used as sedative-hypnotics. Benzodiazepine and
barbituratedrug classes are further subdivided into short-, intermediate-,
and long-acting groups depending on their respective half-lives.
An effective sedative (anxiolytic) agent should reduce anxiety
and exert a calming effect. The degree of central nervous system
(CNS) 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 CNS than sedation,
and this is achieved with most drugs in this class simply by increasing
the dose. Graded dose-dependent depression of CNS function is a
characteristic of sedative-hypnotics. However, individual drugs
differ in the relationship between the dose and the degree of CNS
depression. Two examples of such dose-response relationships are
shown in Figure 13–2. The linear slope for barbiturates
means an increase in dose above that needed for hypnosis may lead
to a state of general anesthesia. At still higher doses, these types
of sedative-hypnotics may depress respiratory and vasomotor centers
in the medulla, leading to coma and death. Deviation from a linear
dose-response relationship, as shown for benzodiazepine drugs, will
require much greater dosage increments in order to achieve CNS depression
more profound than hypnosis. This greater margin of safety for benzodiazepines
and the newer hypnotics (e.g., zolpidem) is an important reason
for their widespread use to treat anxiety states and sleep disorders.
Dose-response curves demonstrating the relationships
between dose of benzodiazepines and barbiturates and their CNS effects.
Benzodiazepines have a higher therapeutic index than barbiturates.
Lipid solubility plays a major role in determining the rate at
which a particular sedative-hypnotic enters the CNS. Most of the
sedative-hypnotic drugs are lipid soluble and are absorbed well
from the gastrointestinal tract, with good distribution to the brain.
This property is responsible for the rapid onset of CNS effects
of triazolam, thiopental (Chapter 15), and the newer hypnotics.
Oral absorption of triazolam and the
newer hypnotics is extremely rapid, and that of diazepam and
the active metabolite of clorazepate is more rapid than other commonly
used benzodiazepines. Clorazepate is
converted to its active form, desmethyldiazepam (nordiazepam),
by acid hydrolysis in the stomach. Most of the barbiturates and ...