Determinants of pharmacologic effects and toxicity of benzodiazepine hypnotics: role of lipophilicity and plasma elimination rates.

Clinical issues related to recognition of depression in elderly patients are reviewed and a systematic approach to diagnostic and treatment decision making is provided to assist the clinician when confronted with this often complex and challenging patient population.

Abstract

A recent consensus statement from the American Psychiatric Association emphasized that plasma elimination half-life should not be confused with duration of action and labeled use of short half-life, high-potency benzodiazepines as a risk factor for chronic toxicity, cognitive impairment, true physiologic dependence, and discontinuance symptoms. Instead, other factors such as lipid solubility (lipophilicity), brain clearance rate, redistribution rate, receptor kinetics, and tolerance are currently thought to be additional important determinants of the pharmacodynamic profile of benzodiazepines. In in vitro experiments, quazepam and its first metabolite, 2-oxoquazepam, were found to have high lipophilicity, a finding that could have important clinical implications.