Nervous system drugs sedative-hypnotics

CENTRAL NERVOUS SYSTEM DRUGS Sedative-Hypnotics... 

Diazepam, better known as Valium, is a central nervous system (CNS) sedative/ hypnotic. As a sedative, it diminishes activity and excitement and thereby has a calming effect. Back in 1976, based on the number of new and refilled prescriptions processed, diazepam was the most prescribed drug in the United States. 

Keywords Acetylcholine Autonomic nervous system Cyclosporine Epinephrine General anesthetics Immunostimu-lating agents Immunosuppressive agents Mycophenolate mofetil Opioid drugs Sedative-hypnotic agents... 

Sedative-hypnotic. A drug that decreases responsiveness of the central nervous system to the point of promoting sleep. 

Herbai sedatives and anxioiytics are a diverse group of plant drugs that commonly act as depressants of the central nervous system (CNS) (table 6.1). Pharmaceutical CNS depressants are used as anxiolytics, anti-epiieptics, sedatives, sleep-inducers (sedatives or hypnotics), general anesthetics, and recreationai drugs (e.g., ethanol) (table 6.2). CNS... 

Most anxiolytic and sedative-hypnotic drugs produce dose-dependent depression of central nervous system function. The ideal anxiolytic drug should calm the patient without causing too much daytime sedation and drowsiness and without producing physical or psycho-... 

Buspirone is as effective as the benzodiazepines in the treatment of general anxiety. However, the full anxiolytic effect of buspirone takes several weeks to develop, whereas the anxiolytic effect of the benzodiazepines is maximal after a few days of therapy. In therapeutic doses, buspirone has little or no sedative effect and lacks the muscle relaxant and anticonvulsant properties of the benzodiazepines. In addition, buspirone does not potentiate the central nervous system depression caused by sedative-hypnotic drugs or by alcohol, and it does not prevent the symptoms associated with benzodiazepine withdrawal. 

During the early twentieth century the barbiturates were used in children and adolescents for their sedative and hypnotic effects however, their safety profile and propensity to cause physical dependence led scientists in search of safer anxiolytics. The development of animal models of behavioral disorders facilitated the formulation of drugs with more specific central nervous system (CNS) effects. In 1959, chlordiazepoxide (Librium) was the first benzodiazepine (BZ) to receive a patent. It entered the market in 1960, followed by diazepam (Valium) in 1963. Today, over 35 BZs have been formulated and over 10 are available in the United States (Ballenger, 1995 Hobbs et ah, 1996). 

In very old patients and in patients with severe liver disease, the elimination half-lives of these drugs are often increased significantly. In such cases, multiple normal doses of these sedative-hypnotics can result in excessive central nervous system effects. 

Tolerance—decreased responsiveness to a drug following repeated exposure—is a common feature of sedative-hypnotic use. It may result in the need for an increase in the dose required to maintain symptomatic improvement or to promote sleep. It is important to recognize that partial cross-tolerance occurs between the sedative-hypnotics described here and also with ethanol (see Chapter 23)—a feature of some clinical importance, as explained below. The mechanisms responsible for tolerance to sedative-hypnotics are not well understood. An increase in the rate of drug metabolism (metabolic tolerance) may be partly responsible in the case of chronic administration of barbiturates, but changes in responsiveness of the central nervous system (pharmacodynamic tolerance) are of greater importance for most sedative-hypnotics. In the case of benzodiazepines, the development of tolerance in animals has been associated with down-regulation of brain benzodiazepine receptors. Tolerance has been reported to occur with the extended use of zolpidem. Minimal tolerance was observed with the use of zaleplon over a 5-week period and eszopiclone over a 6-month period. 

An understanding of common mechanisms of death due to poisoning can help prepare the care-giver to treat patients effectively. Many toxins depress the central nervous system (CNS), resulting in obtundation or coma. Comatose patients frequently lose their airway protective reflexes and their respiratory drive. Thus, they may die as a result of airway obstruction by the flaccid tongue, aspiration of gastric contents into the tracheobronchial tree, or respiratory arrest. These are the most common causes of death due to overdoses of narcotics and sedative-hypnotic drugs (eg, barbiturates and alcohol). 

Barbiturates are among the drugs classified as central nervous system (CNS) depressants. These drugs depress or slow down the activity of nerves that control emotions and bodily functions such as breathing. Barbiturates are prescribed as a sedative that calms the patient or as a hypnotic that helps a person sleep. Other uses include epilepsy treatment and anesthesia before surgery. 

Other classes of drugs not included in Figure 22-3 that may exert sedative effects include most antipsychotic and many antidepressant drugs and certain antihistaminic agents (eg, hydroxyzine, promethazine). As discussed in other chapters, these agents differ from conventional sedative-hypnotics in both their effects and their major therapeutic uses. Since they commonly exert marked effects on the peripheral autonomic nervous system, they are sometimes referred to as "sedative-autonomic" drugs. Certain antihistaminics with sedative effects are available in over-the-counter sleep aids. Their autonomic properties and their long durations of action can result in adverse effects. 

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