Sedative-hypnotic effects

The ultra-short-acting barbiturates include methohexital sodium (Brevi-tal) and thiopental sodium (Pentothal). These agents are used as anesthetics and are administered intravenously. Barbiturates with short-to-intermediate duration of action are used for their sedative-hypnotic effect in the treatment of anxiety. These medications include amobarbital (Amytal), butabarbital (Butisol), sodium pentobarbital (Nembutal), and secobarbital (Seconal). 

There are now indications for the interaction of progesterone metabolites with the Cl channel of the GABAa receptor (Fig. 52-7). The A-ring-reduced steroids, especially those with the 5a,3a configuration, are particularly active on the GABAa receptor [ 12]. By facilitating chloride-channel opening, these steroids produce anesthetic, anxiolytic and sedative-hypnotic effects (see Ch. 16). 

The development of tolerance is a major drawback to the use of benzodiazepines in the long-term treatment of insomnia. Whereas tolerance to the hypnotic effects of benzodiazepines permits them to be used without excessive sedation when treating anxiety disorders, this is counterproductive when attempting to treat insomnia. Patients often find themselves requiring higher doses to obtain the same sedative-hypnotic effect initially accomplished by lower doses. For this reason, careful consideration must be given before benzodiazepines are used to treat chronic insomnia. 

As already noted, there are drugs found among benzodiazepine derivatives that have expressed anxiolytic action and that lack or have poorly expressed sedative-hypnotic effects, which are called daytime tranquilizers. Medazepam, a representative of the daytime tranquilizers, is a drug that differs from diazepam only in the absence of a carbonyl group in the seven-membered azepine ring. 

All of the benzodiazepines will produce sedative-hypnotic effects of sufficient magnitude to induce sleep, provided that the dose is high enough. However, the aim in the treatment of sleep disorders is to induce sleep that is as close as possible to natural sleep so that the patient falls asleep quickly, sleeps through the night, and has sleep of sufficient quality to awake refreshed. 

Benzodiazepines listed here are indicated specifically as hypnotic agents and are not approved for other uses [antianxiety, anticonvulsant, and so forth]. Virtually all benzodiazepines have sedative-hypnotic effects, and other benzodiazepines may be administered to produce sedation or sleep, depending on the dosage and the patient. 

The mechanism of action of the benzodiazepines was discussed previously in this chapter. The antianxiety properties of these drugs involve a mechanism similar or identical to their sedative-hypnotic effects (i.e., potentiating GABAergic transmission).37 Benzo-... 

Antihistamines Provide sedative-hypnotic effects Diphenhydramine Hydroxyzine Oral 50 mg 20 to 30 minutes before surgery Oral 50-100 mg... 

Barbiturates (a class of drugs with more effective sedative-hypnotic effects) replace most use of sedative bromides. 

Barbiturates (a class of drugs with more effective sedative-hypnotic effects) replaced bromides in 1903. Depending on the dose, frequency, and duration of use, however, tolerance, physical dependence, and psychological dependence on barbiturates can occur relatively rapidly. With the development of tolerance, the margin of safety between the effective dose and the lethal dose becomes very narrow. That is, in order to obtain the same level of intoxication, the tolerant abuser may raise his or her dose to a level that can produce coma and death. 

Due to their high potential for abuse, most barbitu-rate-like substances have been replaced by newer, safer agents—such as the BZDs and non-BZD sedative-hypnotics—that exert a sedative-hypnotic effect. 

Flunitrazepam (Rohypnol), also known as roofies, is a benzodiazepine with physiological effects similar to diazepam (Valium), although it is about 10 times more potent. The drug produces sedative-hypnotic effects that include muscle relaxation and amnesia it can also produce physical and psychological dependence. It is illegal and not approved for use in the United States. 

Gamma-hydroxybutyrate (GHB), also called liquid ecstasy, is a clear, odorless, and tasteless liquid whose sedative-hypnotic effects are intensified by alcohol. It has been poured into the drink of an... 

Figure 2.1 Because of its sedative-hypnotic effects, Rohypnol is often considered the date rape drug of choice. Although it is similar to Valium, it is 10 times stronger. Some of the characteristics of Rohypnol are described here.

Inhibitory actions in sieep centers may provide sedative hypnotic effects... 

May enhance GABA inhibifory acfions fhat provide sedative hypnotic effects more selectively than other actions of GABA... 

Sedative-hypnotic effects The calming and sleep-inducing effects of some drugs (Chapter 13). 

The benzodiazepines are primarily administered for their sedative-hypnotic effects. Benzodiazepines are commonly used as anxiolytics, muscle relaxants, anticonvulsants, and to treat alcohol withdrawal, insomnia, and agitation. They are administered pre-operatively for their anterograde amnesia effects and are combined frequently with other medications for conscious sedation before procedures. They are also utilized as drugs of abuse. 

Anxiolytics treat anxiety and insomnia by providing a sedative-hypnotic effect, few side effects, and no risk of the overdose that is common to traditional sedative medications. Anxiolytics are prescribed when the patient is unable to perform activities of daily life. 

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