Sedative-hypnotic agents barbiturates

Barbituric acid is the parent of a group of compounds known as barbiturates The bar biturates are classified as sedative-hypnotic agents meaning that they decrease the responsiveness of the central nervous system and promote sleep Thousands of deriva lives of the parent ring system of barbituric acid have been tested for sedative-hypnotic activity the most useful are the 5 5 disubstituted derivatives... 

The following general discussion of the barbiturates refers to their use as sedative-hypnotic agents and as anticonvulsants. 

The utility of barbituric acid derivatives as sedative-hypnotic agents is discussed in more detail later in this chapter. Studies on the chemical simplification of these pyrimidinetrione derivatives led to the discovery that pyridinediones, or glutarimides,... 

The researchers Joseph von Mering and Emil Fischer, a student of von Baeyer, developed the first barbiturate drug to be marketed. Fischer produced 5.5-diethylbarbituric acid, a hypnotic (medication to help patients sleep) and sedative (medication to relax people with constant nervousness and anxiety). This sedative/hypnotic drug was known by the trade names Barbital, Veronal, and Dorminal. Barbital proved to be a more effective sedative/hypnotic agent and replaced the class of drugs, sedative bromides, which were used at the time.14... 

Barbiturates are still used as sedative/hypnotic agents (see Chapter 3), but they have been largely replaced by benzodiazepines for treatment of anxiety and insomnia (difficulty sleeping). Barbiturates are still used occasionally, but benzodiazepines have proven to be much safer and have less risk of accidental overdose. 

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. 

Sedative-hypnotic agents are some of the most widely prescribed and used drugs in the developed world. They are also frequently drugs of abuse. Sedative-hypnotics are used to promote sleep, as their name implies, and to reduce anxiety. Their overall effect is to act as CNS depressants. We will consider the two major classes of drugs in this category, the benzodiazepines and the barbiturates. For a detailed discussion of the pharmacology of these agents, see Chamey et al. (2006). 

The barbitmates are the other major group of sedative-hypnotic agents. Similar to the benzodiazepines, they are a group of chemically related drugs and there are many variations in properties, particularly onset of effects and duration of action. The most recognized effects of the barbiturates are centrally mediated and include sedation, hypnosis, decreased anxiety, and, at high doses, anesthetic properties. The mechanism of... 

The names of many barbiturates end in al (c.g., phenobar-bital), appearing to denote an aldehydic compound, because chloral hydrate was widely recognized as a sedative-hypnotic agent when the first barbiturates were introduced. Hence, the suffix was an effort to indicate a therapeutic, not a chemical, class. 

Sedative-hypnotic agents are widely used for the treatment of anxiety and insomnia. As a group they are one of the most frequently prescribed medications. Barbiturates (see p 124), benzodiazepines (p 130), antihistamines (p 96), skeletal muscle relax-ants (p 339), antidepressants (pp 88 and 90), and anticholinergic agents (p 84) are discussed eisewhere in this book. In this section (and Table 11-51) are listed some of the iess commoniy used hypnotic agents. 

Pharmacological Profiles of Anxiolytics and Sedative—Hypnotics. Historically, chemotherapy of anxiety and sleep disorders rehed on a wide variety of natural products such as opiates, alcohol, cannabis, and kawa pyrones. Use of various bromides and chloral derivatives ia these medical iadications enjoyed considerable popularity early ia the twentieth century. Upon the discovery of barbiturates, numerous synthetic compounds rapidly became available for the treatment of anxiety and insomnia. As of this writing barbiturates are ia use primarily as iajectable general anesthetics (qv) and as antiepileptics. These agents have been largely replaced as treatment for anxiety and sleep disorders. 

Benzodiazepiaes have largely replaced barbiturates and barbiturate-like agents for use as anxiolytics and sedative—hypnotics. Because benzodiazepiaes rarely produce levels of CNS depression that require therapeutic iatervention, the need for analeptics has decreased considerably. 

The pseudo-barbiturate , 2-methyl-3-o-tolylquinazolin-4(3H)-one (methaqualone, Revonal 1017) has an even wider spectrum of activities than do the barbiturates proper it appears to be quite widely used as- a sedative, hypnotic, anticonvulsant, antispasmodic and local anaesthetic agent (63MI21301, b-75MI21301>. 

Benzodiazepines and similar agents occupy a position of intermediate abuse potential, compared with most other sedative-hypnotics (Griffiths and Weerts 1997). Animal models of abuse habihty indicate that the reinforcing effects of benzodiazepines are less pronounced than are those of the barbiturates, opioids, and stimulants. Differences in abuse potential within the class have not been consistently demonstrated however, most chnicians agree that benzodiazepines with a rapid onset and short duration of action pose the greatest risk in susceptible individuals. 

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). 

Sedatives (also called hypnotics, sedative-hypnotics, minor tranquilizers, antianxiety agents) Secobarbital (barbiturate) Glutethimide (nonbarbiturate hypnotic) Diazepam (benzodiazepine antianxiety agent) Chloral hydrate (miscellaneous hypnotic) alcohol ( substance )... 

Barbiturates are referred to as sedative-hypnotics. These drugs will induce sleep which can lead to even deeper sedation (hypnosis) and can cause a fatal depression of the RAS affecting the respiratory system. The sleep which is encountered does not have the normal cycles of slow wave and rapid eye movement activity, so it is not always restful. However, these agents prove to be useful in anesthesia for both short and longer durations of time. Many of you may have been given thiopental prior to wisdom tooth extraction. Thiopental "wears off quickly and so the actual anesthetic for the time of the extraction is usually nitrous oxide. 

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