Anxiolytics and hypnotics

The popularity of BDZs arose from their apparently tow toxicity, but it is now realized that chronic BDZ treatment may cause cognitive 

Many anIidepressanCs (c.g. araitriplyline) are also anxiolytic and do not cau.se dependence. Buspirone is a non-sedative anxiolytic that acts ill 5HT synapses. P-Klockers can be useful in anxiety where auto-(lumic sympujins predominate (e.g. tremor, tachycardia, sweating). 

Different BDZs arc marketed a,s hypnotics (top left) and anxiolytics (top right i. it is mainly the duration of action that deiennines the choice of drug. Many RDZ.s are metabolized in the liver to active inctabRliles. which may have longer elimination half-lives (r,, ) iliun the parent drug. For example, dia/epam (r, j = 20-80 hours) has an active N-desmcthyl metabolite that has an elimination half-life of up to 200 hours. 

Flumaxenil is acompetiiive BDZ antagonist that has a short duration of action and is given intravenously. It can be used to revasc the sedative effects of BDZs in anaesthesia, intensive care, diagnostic procedures and in uvetdoses. 

Barbiturates are fur more depressant than BDZs. because at higher doses they increase the Cl conductance directly and decrease the sensitivity of the neurtmal pustsynupiic membrane to excitatory transmillers. 

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Beginning in the 1960s, ben2odia2epiae anxiolytics and hypnotics rapidly became the standard prescription dmg treatment. In the 1980s, buspkone [36505-84-7] (3), which acts as a partial agonist at the serotonin [50-67-9] (5-hydroxytryptamine, 5-HT) type lA receptor, was approved as treatment for generali2ed anxiety. More recently, selective serotonin reuptake inhibitors (SSRIs) have been approved for therapy of panic disorder and obsessive—compulsive behavior. 

Chouinard, G., Lefko-Singh, K., and Teboul, E. (1999) Metabolism of anxiolytics and hypnotics benzodiazepines, buspirone, zopli-cone, and zolpidem. Cell Mol Neurobiol 19 533—552. 

In this chapter, we discuss the pharmacology of medications that are classified as anxiolytic, sedative, or hypnotic—primarily the benzodiazepines, buspirone, zolpidem, eszopiclone, and zale-plon. Subsequently, we present diagnosis-specific treatment guidelines (outlined in Table 3-1). The commonly used anxiolytics and hypnotics, together with their usual doses, are shown in Table 3-2. Many antidepressant medications are also effective in the treatment of anxiety disorders. The pharmacology of antidepressants is discussed in Chapter 2 their clinical use in anxiety disorders is addressed in the diagnosis-specific sections later in this chapter. 

TABLE 3-2. Commonly used anxiolytic and hypnotic medications ... 

Some 25 anxiolytics and hypnotics are marketed at present the best known of these are listed in Table 1.10. Here, again., there are striking differences between the doses of these products, which can be explained m the same way as for antipsychotics. The benzodiazepine derivatives and related compounds show few qualitative differences nevertheless, the time effect features, i.e. the timing of onset of action and peak action as well as duration of action, mean that it is sensible to use different products for different purposes. 

The problems of withdrawal of anxiolytics and hypnotics have been described in innumerable publications (reviews by Owen and Tyrer, 1983 Griffiths and Sannerud, 1987). Schopf (1985) produced a compilation of the... 

Because there is a great demand for anxiolytic and hypnotic substances and because the use of benzodiazepines should, in the opinion of many, be restricted,... 

There are hundreds of published studies on the effects of benzodiazepine anxiolytics and hypnotics on ptr/ermam-e parameters m healthy subjects, and it is generally recognized that these drugs cause a dose-related reduction m most... 

Benzodiazepine anxiolytics and hypnotics lead to a decrease in alpha and an increase in beta activity in pharmaco-EEG trials. With regard to theta and delta activities, the results of different studies vary. Buspirone at the usual therapeutic doses induces no or only a very weak EEG effect (Greenblatt et al., 1994) and is thus differentiated from the benzodiazepine anxiolytics. 

More recently, non-BZD anxiolytics, such as buspirone, and nonbarbiturate, non-BZD hypnotics, such as zolpidem and zaleplon, have been developed. The more recent anxiolytics and hypnotics offer equal efficacy, fewer serious adverse effects, and less risk of a fatal consequence due to accidental or intentional overdose. Unfortunately, these compounds have not entirely eliminated the hazards of tolerance, dependency, and withdrawal syndromes, although they do have a lower abuse potential than their predecessors. 

In addition to buspirone and the non-barbituate, non-BZP hypnotics, selective serotonin reuptake inhibitors (SSRIs), venlafaxine, and other new antidepressants all represent attempts to achieve anxiolytic and hypnotic effects seen with the BZDs, while avoiding their unwanted properties. 

Long-term users account for the bulk of anxiolytic (and hypnotic) BZDs sold in the United States (and probably worldwide). 

The number of long-term users of anxiolytic (and hypnotic users) has increased in recent years, even though the efficacy of long-term use has not been established (30). 

A BZD s pharmacokinetics may play a role in the occurrence, in part accounting for the increase in its incidence after the advent of short-acting BZD anxiolytics and hypnotics (e.g., lorazepam, alprazolam, and triazolam). 

Table 10.1 Pharmacokinetic properties of some anxiolytic and hypnotic drugs...

Most of the minor tranquilizers in the BZD exhibit similar clinical effects they differ primarily in their duration of action and in the dosage required to achieve the same effect. The BZDs are classified as short- (triazolam [Halcion]), intermediate- (alprazolam [Xanax] and lorazepam [Ativan]), and long-acting (chlordiazepoxide [Librium] and diazepam [Valium]). Of the various BZDs available in the United States in 2002, those primarily prescribed as anxiolytics and hypnotics include the intermediate- and long-acting variety. 

Psychotropic drugs Major tranquillisers, anxiolytics and hypnotics, tricyclic antidepressants, selective serotonin reuptake inhibitors ... 

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