Sedative-hypnotic agents pharmacokinetics

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). 

A wide difference in milligram potency exists between the benzodiazepine compounds however, when dosage adjnstments are made, all agents share similar anxiolytic and sedative-hypnotic activity. The variations in lipid solubility between componnds inflnence the pharmacokinetic properties of benzodiazepines. Different pharmacokinetic and pharmacodynamic properties can assist the clinician in choosing an appropriate anxiolytic (Table 69-9). After a single dose, the onset, intensity, and duration of pharmacological effects are important factors to consider when using benzodiazepines for the short-term, intermittent, or as-needed treatment of anxiety. 

The decision to use these agents should be made with considerable caution, and only after possible underlying causes of the patient s symptoms have been explored and treated appropriately. Although surveys indicate that BZDs are frequently prescribed for elderly patients, the NIH Consensus Development Conference stated that the efficacy and safety of sedatives and hypnotics have not been established for older people, nor has the extent to which they contribute to or alleviate sleep problems (302, 305, 306). Saizman (307) has pointed out that relatively few research studies, most of which are seriously flawed, have examined the therapeutic effect of these agents in elderly patients. Thus, recommendations for the use of BZDs in elderly patients are derived almost exclusively from studies of young adult patients, studies of pharmacokinetics and toxicity in elderly patients, and clinical and anecdotal experience. 

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