Benzodiazepines hypnotic

Zolpidem, chemically unrelated to benzodiazepines or barbiturates, acts selectively at the y-aminobutyric acidA (GABAA)-receptor and has minimal anxiolytic and no muscle relaxant or anticonvulsant effects. It is comparable in effectiveness to benzodiazepine hypnotics, and it has little effect on sleep stages. Its duration is approximately 6 to 8 hours, and it is metabolized to inactive metabolites. Common side effects are drowsiness, amnesia, dizziness, headache, and GI complaints. Rebound effects when discontinued and tolerance with prolonged use are minimal, but theoretical concerns about abuse exist. It appears to have minimal effects on next-day psychomotor performance. The usual dose is 10 mg (5 mg in the elderly or those with liver impairment), which can be increased up to 20 mg nightly. Cases of psychotic reactions and sleep-eating have been reported. 

The pharmacokinetic properties of benzodiazepine hypnotics are summarized in Table 72-4. 

With the exception of temazepam, which is eliminated by conjugation, all benzodiazepine hypnotics are metabolized by microsomal oxidation followed by glucuronide conjugation. 

Miki A, Tatsuno M, Katagi M, Nishikawa M, Tsuchihashi H. 2002. Simultaneous determination of eleven benzodiazepine hypnotics and eleven relevant metabolites in urine by column-switching liquid chromatography-mass spectrometry. J Anal Toxicol 26 87. 

Sedation is an intermediate degree of CNS depression, while hypnosis is a degree of CNS depression similar to natural sleep. From the chemical point of view, soporific, sedative, and hypnotic drugs are classified as barbiturates, benzodiazepine hypnotics, and so on. Except for a few rare exceptions, any one of these compounds can be used for acquiring a sedative effect or state of sleep. Presently, the less toxic benzodiazepines are edging out the class of barbiturates more and more because of the possibility of chronic dependence associated with the use of barbiturates. Drugs of both classes are primarily CNS depressants, and a few of their effects, if not all, are evidently linked to action on the GABA-receptor complex. 

Flurazepam (Dalmane) This benzodiazepine hypnotic has an extremely long half-life in elderly patients (often days), producing prolonged sedation and increasing the incidence of falls and fracture. Medium- or short-acting benzodiazepines are preferable. High... 

U.S. Food and Drug Administration for the treatment of insomnia, almost all benzodiazepines may be used for this purpose. Benzodiazepines are most clearly valuable as hypnotics in the hospital setting, where high levels of sensory stimulation, pain, and acute stress may interfere with sleep. The safe, effective, and time-limited use of benzodiazepine hypnotics may, in fact, prevent chronic sleep difficulties (NIMH/NIH Consensus Development Conference Statement 1985). Benzodiazepines are also used to treat akathisia and catatonia and as adjuncts in the treatment of acute mania. 

Zolpidem is a non-benzodiazepine hypnotic of the imidazopyridine class. It is a GABA receptor agonist selective for omega-1 receptor subunit. 

Hajak G, Muller WE, Wittchen HU, Pittrow HU Kirch W (2003). Abuse and dependence potential for the non-benzodiazepine hypnotics Zolpidem and zopiclone a review of case reports and epidemiological data. Addiction, 98, 1371-8... 

TABLE 12-12. Miscellaneous adverse effects reported with benzodiazepine hypnotics... 

Gelenberg AJ, ed. The use of benzodiazepine hypnotics a scientific examination of the clinical controversy. J Clin Psychiatry 1992 53(suppl) 1-87. 

Greenblatt DJ. Benzodiazepine hypnotics sorting the pharmacokinetic facts. J Clin Psychiatry 1991 52(suppl 9) 4-10. 

Kales A, Soldatos CR, Vela-Bueno A. Clinical comparison of benzodiazepine hypnotics with short and long elimination of half-lives. In Smith DE, Wesson DR, eds. The benzodiazepines. 

Kales A, Bixler EO, Vela-Bueno A, et al. Comparison of short and long half-life benzodiazepine hypnotics triazolam and quazepam. Clin Pharmacol Ther 1986 40 378-386. 

DeClerck A, Smits M. Zolpidem, a valuable alternative to benzodiazepine hypnotics for chronic insomnia. J Int Med Res 1999 27 253-263. 

Elie R, Ruther E, Farr I, et al. Sleep latency is shortened during 4 weeks of treatment with zaleplon, a novel benzodiazepine hypnotic. Zaleplon Clinical Study Group. J Clin Psychiatry 1999 60 536-544. 

Bixler EO, Kales A, Brubaker BH, et al. Adverse reactions to benzodiazepine hypnotics spontaneous reporting systems. Pharmacology 1987 35 286-300. 

The abuse of benzodiazepine hypnotics (for example, Temazepam, Triazolam) by injection of the crushed tablets is of increasing concern, and these drugs can be used to lace supplies of street heroin and consequently they have a black market value. General prescribing habits need to be maintained to ensure some control of the abuse. 

Sanger DJ The pharmacology and mechanism of action of new generation, non-benzodiazepine hypnotic agents. CNS Drugs 2004 18(Suppl 1) 9. 

Pharmacokinetics differ significantly among the most widely used benzodiazepine hypnotics, with some such as triazolam (Fig. 8—31) having rapid onset and short... 

The benzodiazepine hypnotics midazolam, triazolam, and brotizolam, together with zopiclone, eszopiclone, zolpidem, and zaleplon are short-acting derivatives. The benzodiazepines flunitrazepam and temazepam are intermediate-acting hypnotics,... 

In summary, based on the available evidence, a reduction in the initial dose of benzodiazepine hypnotics, zopiclone, zolpidem, zaleplon, and presumably eszopiclone, is recommended in elderly patients and patients with hepatic or renal impairment. 

Evaluation of the effect of hypnotic drugs on sleep induction and maintenance in patients with chronic primary insomnia is based on sleep laboratory studies and subjective data from clinical trials. The sleep induced by benzodiazepine hypnotics, including midazolam, triazolam, temazepam, flunitrazepam, quazepam, and flu-razepam, is characterized by shortened sleep-onset latency, decreased number of... 

---