Benzodiazepines general discussion

A benzodiazepine withdrawal syndrome has been described in some patients discontinuing therapy (Table 2). Although potentially serious, it is generally mild and self-limiting (up to 6 weeks), but may accompany or provoke a recurrence of anxiety symptoms and cause great concern to the patient. As with any other treatment, the risks and benefits of benzodiazepine therapy should be carefully assessed and discussed with the patient. Monotherapy will not be first-line treatment for the majority of patients, but benzodiazepines offer a valuable option that should not be discounted. 

Before 1980, the term anxiety neurosis was used to describe a syndrome that included both chronic generalized anxiety and panic attacks. GAD and panic were first listed as discrete diagnoses in the DSM-III, in part because of observed differences in their response to available drug treatments (i.e., the former to benzodiazepines, the latter to antidepressants for a more detailed discussion of panic disorder, see Chapter 13). 

We have discussed how various antidepressants, especially venlafaxine XR, are being used increasingly for the treatment of generalized anxiety disorder. Buspirone remains a first-line generalized anxiolytic for chronic anxiety, and benzodiazepines are used largely for short-term treatment of intermittent anxiety symptoms. 

High-potency benzodiazepines (alprazolam, clonazepam) generally are more effective in panic disorder than low-potency benzodiazepines (diazepam, lorazepam, etc.). Although less research has been done on the low-potency benzodiazepines, it is generally accepted that they frequently result in sedation prior to adequately relieving panic attacks. The reader is referred to the discussion of benzodiazepines in Chapter 8 for a detailed overview of mechanism of action. A critique of the issues of benzodiazepine dependence and appropriate use is given in Chapter 13-... 

Partial agonists at benzodiazepine receptors As discussed for general anxiolytic agents in Chapter 8, the partial benzodiazepine agonists could be a theoretical advance over the marketed benzodiazepines. Partial agonists should have the same efficacy as full agonists but less potential for sedation, dependence, and withdrawal effects. 

The focus of this section will be the prevention of sleep loss through the use of sleep-promoting medications. Choice of sleep medications will not be considered, as others have thoroughly discussed this issue (6). Short-acting benzodiazepine receptor agonists are generally the type of medication recommended for the treatment of transient insomnia and chronic primary insomnia, and as adjunctive therapy for secondary chronic insomnias. 

For details of the chemistry and SARs of the benzodiazepines. see the discussion of anxiolytic-.sedative-hypnotic drugs. Among the present clinically useful drugs, the structural features associated with anticonvulsant activity arc identical with those as.sociatcd with anxiolytic-scda-tive-hypnutic activity. - Animal models predict that benzodiazepines are modestly effective against generalized tonic-clonic and partial seizures and very highly active... 

The barbiturates can produce all degrees of depression of the CNS, ranging from mild sedation to general anesthesia. The use of barbiturates for general anesthesia is discussed in Chapter 13. Certain barbiturates, particularly those containing a 5-phenyl substituent (e.g., phenobarbital and mephobarbitaU have selective anticonvulsant activity (see Chapter 19). The antianxiety properties of the barbiturates are inferior to those exerted by the benzodiazepines. 

The client diagnosed with a general anxiety disorder is prescribed alprazolam (Xanax), a benzodiazepine. Which information should the clinic nurse discuss with the client ... 

In this chapter, the general outline used for 1,4-diazepines in Comprehensive Heterocyclic Chemistry, First Edition (CHEC-I) <84CHEC-I(7)593> is followed but with an expanded section on theoretical methods, experimental structural methods and thermodynamic aspects. The format of CHEC-I is followed in discussing synthetic methods and the examples are drawn mainly from the literature since 1982. The reactions of the 1,4-diazepines are presented in the following order fully unsaturated monocyclic systems first, then dihydro, tetrahydro, and hexahydro systems followed by the benzodiazepines again in the same order of unsaturation in the seven-membered ring. 

The scarcity of structural studies of benzodiazepines and benzothiazepines is because of the difficulty encoimtered in the cycfization of these seven-membered heterocycles. In general, cycfization of linear precursors is in principle, an excellent route to heterocycles. However, for cycloheptane rings, this reaction is disfavored by entropic and enthalpic factors besides trans annular interactions [105,106]. Hence, these heterocycles are usually obtained in good yield only when configurational and/or conformational constraints facilitate intramolecular cycfization. These facts kindle further interest in the study of their conformational featines. Here, the structural details of a few diazepines, benzodiazepines, and benzothiazepines are discussed. Benzodiazepines involve the fusion of benzene rings with diazepine rings, whereas... 

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