Sedative-Hypnotic and Antianxiety Agents

By producing sedation, many drugs will also decrease the level of anxiety in a patient. Of course, these anxiolytic properties often cause a decrease in the level of alertness in the individual. However, certain agents are available that can reduce anxiety without an overt sedative effect. Those medications that selectively produce antianxiety effects are discussed later in this chapter. 

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Special Consideration of Sedative-Hypnotic and Antianxiety Agents in Rehabilitation... 

It is not uncommon for heavy users of caffeine to also be taking a variety of other psychoactive medications, mostly of the CNS depressant variety. Sedative-hypnotics and antianxiety agents are used... 

Hj-Lorazepam, 3-hydroxy-1,4-benzodiazepine, 45, a sedative hypnotic and antianxiety agent, has been synthesized in a seven-step procedure presented in equation 12 for use as an internal standard in GC-MS-NICI-SIM (NICl-SIM = negative ion chemical ionization-selective ion monitoring) quantitative analysis of this drug in complex matrices encountered in forensic work and for study of its complex kinetics. The procedure involved selective trideuteriation, protection of the amino group and... 

Anxiolytics are compounds that act primarily to refleve the symptoms of anxiety although such agents can also be used as anticonvulsants, sedatives, hypnotics, and anesthetic agents (see Anesthetics). The principal class of anxiolytics, the BZs, shows dependence HabiUty (5) whereas newer agents such as buspkone [36505-84-7] and ritanserine [8705-43-2] produce antianxiety effects via central serotoninergic systems (6). 

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. 

Introduction - Although an effort has been made in this chapter to exclude depressants classified in other chapters as antipsychotic and antianxiety agents, certain benzodiazepines will be considered here because of the number of compounds in this series which have been found clinically to possess sedative-hypnotic and anticonvulsant activity. In most cases, compounds with more than preliminary pharmacological data or representatives of new structural types were selected for inclusion in this chapter. 

Sales for hypnotic—sedative agents ia the United States for 1993 were estimated to be 139,000,000. Anticonvulsant sales for 1993 were estimated at 525,000,000. U.S. sales of antianxiety agents including both the BZs and buspirone-hke agents for 1993 were estimated at 1,046,000,000. 

May have additive effects with alcohol and other CNS depressants (eg, hypnotics, sedatives, tranquilizers, antianxiety agents) use with caution. 

To achieve all the objectives, a combination of 2 or 3 drugs is used depending on the need. The commonly employed drugs are opioids, sedative-hypnotics, antianxiety agents, anti-cholinergics, neuroleptics and antiemetics. 

Treatment With Antianxiety and Sedative-Hypnotic Agents... 

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. 

Barbiturates are classified according to their duration of action (Figure 9.7). For example, thiopental [thye oh PEN tal], which acts within seconds and has a duration of action of about 30 minutes, is used in the intravenous induction of anesthesia. By contrast, phenobarbital [fee noe BAR bi tal], which has a duration of action greater than a day, is useful in the treatment of seizures (see p. 148). Pentobarbital [pen toe BAR bi tal], secobarbital [see koe BAR bi tal] and amobarbital [am oh BAR bi tal] are short-acting barbiturates, which are effective as sedative and hypnotic (but not antianxiety) agents. 

People who use BZs to calm their anxiety will frequently use alcohol and other sedatives interchangeably for the same purpose, either in combination or at different times. As they switch from drug to drug, they tend to find little or no difference in the antianxiety effect. This confirms that BZs have no specificity for anxiety in comparison to other sedative/ hypnotic agents. 

The introduction of chlordiazepoxide (Librium) into clinical medicine in 1961 ushered in the era of benzodiazepines. Most of the benzodiazepines that have reached the marketplace were selected for their effectiveness as antianxiety agents, not for their ability to depress CNS function. However, all benzodiazepines possess sedative-hypnotic properties to varying degrees these properties are extensively exploited clinically, especially to facilitate sleep and ease anxiety. Mainly because of their remarkably low capacity to lead to fatal suppression of key CNS functions, the benzodiazepines have displaced barbiturates as sedative-hypnotic agents. 

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). 

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