Sleep-inducing agents benzodiazepine

Barbiturates and benzodiazepines enhance the actions of the inhibitory neurotransmitter, gamma-aminobutyric acid (Fig 3.6). Tables 3.8A, 3.8B and 3.8C compare barbiturates and benzodiazepines. Agents from both classes are effective sedative-hypnotics (sleep-inducing agents), antianxiety agents, and anticonvulsants (Table 3.9). Physicians prescribe benzodiazepines more often than barbiturates because they cause fewer side effects. 

Valerian is a mild sedative and sleep-inducing agent that has an effect similar to benzodiazepines. It has been called herbal valium. However, Valerian has an odor of dirty socks making it a very low risk for overdose. There have been no reports that frequent use of Valerian leads to habituation and addiction. 

Chloral hydrate and triclofos are of some use as hypnotics for children. However these compounds are largely superseded by the benzodiazepines and are not recommended other than for exceptional cases. Chloral hydrate has a low therapeutic index. These agents have an unpleasant taste and odor. The hypnotic effect has a rapid onset but a short duration. Tolerance appears to occur rapidly with a loss of sleep-inducing and sleep-maintaining effects after about 2 weeks. 

Benzodiazepines are used as daytime anxiolytics, sleep inducers, anesthetics, anticonvulsants (also known as antiseizure agents), and muscle relaxants they will be discussed in depth in Chapters 20 and 22. Examination of the basic pharmacodynamic properties of the benzodiazepines (defined as receptor-specific binding activity) show that the clinically useful benzodiazepines exhibit comparable sedative activity at therapeutically comparable doses (Fig. 19.1) (13). The use of a specific benzodiazepine as a hypnotic is based primarily on... 

The antianxiety effects of chlordiazepoxide (165) were described in 1960 and this compound was followed by diazepam (135). These two drugs have captured 75% of the market for sedatives in the USA. Other benzodiazepines used as antianxiety agents include oxazepam (166 R = H), a metabolite of diazepam that is better tolerated, lorazepam (166 R = Cl) and potassium clorazepate (167). Prazepam is the iV-cyclopropylmethyl analogue of diazepam. The benzodiazepines have other therapeutic applications, many being used for inducing sleep, diazepam and nitrazepam are anticonvulsants and flurazepam (168) is both an antianxiety agent and a potent hypnotic. Thieno- and pyrazolo-1,4-diazepinones isosteric with diazepam have similar pharmacological properties (B-81 Ml 10604). 

HYPNOTICS are agents that induce sleep. They are used mainly to treat short-term insomnia, for instance in shiftwork, to cope with Jet-lag or in sleep disturbances due to emotional problems or in serious illness. The best-known and most-used hypnotics in current use are the benzodiazepines - and this class of drug is also used, at a lower dose, as ANXIOLYTICS. Examples from the class that are of relatively long-lasting action and may cause drowsiness the next day include diazepam, flunitrazepam, flurazepam and nitrazepam. Examples with a shorter duration include loprazolam, lormetazepam and temazepam. All can cause drug dependence on continued usage. Examples of hypnotics that are now much less used include chloral hydrate, chlormethiazole and triclofos. The barbiturates (e.g. amylobarbitone) are now very little used, as they are prone to cause serious dependence and are dangerous in overdose. 

Despite their efficacy in a variety of pathologic anxiety syndromes, the benzodiazepines are not perfect anxiolytics. Such a hypothetical agent would selectively ameliorate anxiety without inducing other behavioral effects. Future efforts to enhance the efficacy of benzodiazepine anxiolytics may depend on a greater understanding of the heterogeneity of the GABAa receptor—for example, which specific clinical actions (anxiolytic, muscle relaxation, sleep facilitation) reside with which specific subunit composition. 

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