Recent advances in the clinical pharmacology of benzodiazepines part I: Pharmacokinetics

Abstract

Tranquillizers, and specifically benzodiazepines (BZD), have become one of the most widely used group of drugs in the world; some have suggested too widely used. Interest in these drugs is still extremely high, both from the scientific and sociological point of view. This is best documented by the fact that the present review is based on more than 700 articles published between 1981 and 1984 covering various aspects of clinical pharmacology. Pharmacokinetic studies dealing with absorption, metabolism and elimination after acute and chronic administration demonstrate that the onset and duration of action of BZD after single oral doses depend largely on absorption rate and the rate and extent of distribution. The rate and extent of accumulation during multiple dosage depend on the elimination half-life and clearance. A framework is proposed for classification of BZD according to the elimination half-life. Various factors -such as age, sex, disease state and drug interactioninfluence the pharmacokinetic properties of BZD. Pharmacodynamic studies are mostly concerned with effects of the drug on the central nervous system (CNS), as well as on behaviour and neuroendocrine functions. The former include computer-assisted quantitative analyses of the scalp-recorded wake electroencephalogram (EEG), based on which it seems possible to determine if, how, when and at what dose a newly developed compound affects the human brain. Sleep investigations are now concerned not only with the effect of the drug on the all-night sleep, but also on the quality of awakening and early morning behaviour as well as with residual effects during daytime, affecting mnestic and cognitive functions, psychomotor performance (specifically in regard to driving ability), as well as mood and affectivity. Finally, for almost a decade increasing concern has been expressed about the widespread use of tranquillizers in society. Scientific evidence concering this issue will be reviewed so that an appropriate medical decision may be reached for the treatment of the individual patients after consideration of the beneficial effects as well as undesirable side-effects.

Insomnia in Generalized Anxiety Disorder: Polysomnographic, Psychometric and Clinical Investigations before, during and after Therapy with a Long- versus a Short-Half-Life Benzodiazepine (Quazepam versus Triazolam)

“…Last but not least, our sleep architecture data in GAD patients are of interest for interpreting clinical and phar macological phase 1 data obtained in normal subjects after application of anxiolytic sedatives, which generally increase sleep stage 2 and a tendency to decrease sleep stage 3 + 4 [ 19,23], Thus, tranquillizers induce in normal subjects changes opposite to the ones seen in GAD patients, as compared with controls, thereby normalizing sleep architecture. This is at variance with statements that anxiolytics and hypnotics disturb sleep patterns, because they induce the aforementioned changes in normal volun 87 teers.…”

Drug effect on EEG connectivity assessed by linear and nonlinear couplings

“…The effect of different drug classes on the spectral variables of univariate EEG time series is already known. Benzodiazepines, for example, basically decrease α 1 power and increase β power (defined from 7.5 to 10.5 Hz and from 13 to 35 Hz, respectively) [Barbanoj et al,1994; Saletu and Pakesch,1987]. However, interactions between brain locations remain unclear.…”

Reducción de artefactos en señales electroencefalográficas mediante nuevas técnicas de filtrado automático basadas en separación ciega de fuentes.

“…The effect of different drug classes on the spectral variables of univariate EEG time series is already known. Benzodiazepines, for example, basically decrease a 1 power and increase b power (defined from 7.5 to 10.5 Hz and from 13 to 35 Hz, respectively) [Barbanoj et al, 1994;Saletu and Pakesch, 1987]. However, interactions between brain locations remain unclear.…”