Sedative-hypnotic agents benzodiazepines

Taper off antipsychotics, benzodiazepines or sedative-hypnotic agents if possible... 

Extensive sleep studies have been conducted with a variety of sedative-hypnotic drugs, and all of these drugs appear to alter the normal distribution of rapid eye movement (REM) and non-REM sleep. Most of the older sedative-hypnotic agents markedly depress REM sleep. In contrast, when the benzodiazepines are used in appropriate doses, they depress REM sleep to a much smaller extent. As with treatment of anxiety, the choice... 

The newer sedative-hypnotics that are not benzodiazepines are rapidly becoming the first-line treatment for insomnia. These agents not only have pharmacodynamic advantages over benzodiazepines in terms of their mechanism of action, but perhaps more importantly, pharmacokinetic advantages as well. Three nonbenzodiazepine sedative-hypnotic agents that are now available are zaleplon (a pyrazolopyrimidine), zopiclone (a cyclopyrrolone not available in the United States), and zolpidem (an imidazopyridine) (Figs. 8—28-8—30 Table 8—4). 

The nonbenzodiazepine sedative-hypnotics zaleplon, zolpidem, and zopiclone are replacing benzodiazepine sedative-hypnotics as first-line treatments for insomnia. Some antidepressants, such as sedating tricyclic antidepressants and trazodone, are also used as sedative-hypnotic agents for the treatment of insomnia. 

Although they have been used for over 30 years, benzodiazepines are still widely prescribed in the treatment of anxiety disorders and other medical conditions. These drugs are classified as sedative-hypnotic agents, which depress or slow down the body. In the past 15 years, the development of the newer selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression and anxiety have pushed benzodiazepines aside as the first treatment choice because the SSRIs as a class of drugs have not yet been found to be addictive. 

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. 

Alprazolam, 269, a popular sedative/hypnotic agent and benzodiazepine receptor agonist, has been labelled257 with 11C in metabolically stable position in reaction of the amidrazone, 7-chloro-5-phenyl-3//-l,4-benzodiazepine-2-yl hydrazone, 270, with 1-[ Cjacetyl chloride followed by pyrolysis of the resulting 1-acetylhydrazone 271. Compound 269 has been obtained in 43-65% yield during 40-55 min at specific activity 0.93-2.18 Ci /miol-1, and used for metabolism and tissue distribution studies257 (equation 107). 

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. 

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

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... 

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. 

Section II Benzodiazepines Sedative-Hypnotic Agents Peter Wald MD, MPH... 

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. 

In subjects with sedative-hypnotic dependence who underwent detoxification in an addictions treatment unit, a significant association was not found between abstinence rate and either gender or psychiatric status (Charney et al. 2000). Patients dependent on benzodiazepines reported decreased anxiety during follow-up, even though their use of these agents had decreased. 

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 )... 

Specific factors to consider are both psychiatric and physical contraindications. For example, bupropion is contraindicated in a depressed patient with a history of seizures due to the increased risk of recurrence while on this agent. Conversely, it may be an appropriate choice for a bipolar disorder with intermittent depressive episodes that is otherwise under good control with standard mood stabilizers. This consideration is based on the limited data suggesting that bupropion is less likely to induce a manic switch in comparison with standard heterocyclic antidepressants. Another example is the avoidance of benzodiazepines for the treatment of panic disorder in a patient with a history of alcohol or sedative-hypnotic abuse due to the increased risk of misuse or dependency. In this situation, a selective serotonin reuptake inhibitor (SSRI) may be more appropriate. 

---