A guide to benzodiazepine selection. Part I: Pharmacological aspects.
Since absorption rates, volumes of distribution and elimination rates differ greatly among the benzodiazepine derivatives, each benzodiazepine has a unique plasma concentration curve. Although the time to peak plasma levels provides a rough guide, it is not equivalent to the time to clinical onset of effect. Two half-lives can be described: the alpha half-life, the rate of decline in plasma concentrations due to the process of drug redistribution from the central to the peripheral compartment, and the beta half-life, the rate of decline due to the process of drug elimination due to metabolism. The frequent classification of benzodiazepines into long, intermediate, and short-"acting" categories based on their terminal beta half-lives is unfounded; the duration of action is much more dependent on the alpha half-life. Benzodiazepines with short beta half-lives are commonly thought to be preferable because they accumulate less. However, with repeated use, sedation and cognitive neuromotor impairment usually diminish progressively despite stable or even rising benzodiazepine plasma concentrations, whereas anxiolytic effects generally persist over time.
Teboul
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Department of Psychiatry, McGill University, Montreal, Quebec.
Chouinard
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D014151:Anti-Anxiety Agents / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001008:Anxiety Disorders / Q000097:blood / Q000188:drug therapy*; D001569:Benzodiazepines; D001921:Brain / Q000187:drug effects*; D018118:Chloride Channels; D006801:Humans; D008565:Membrane Proteins / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D007319:Sleep Initiation and Maintenance Disorders / Q000097:blood / Q000188:drug therapy*; D009435:Synaptic Transmission / Q000187:drug effects
D014151:Anti-Anxiety Agents; D018118:Chloride Channels; D008565:Membrane Proteins; D011963:Receptors, GABA-A; D001569:Benzodiazepines