Benzodiazepine Kinetics: Implications for Therapeutics and Pharmacogeriatrics

Greenblatt, David J.; Divoll, Marcia; Abernethy, Darrell R.; Ochs, Hermann R.; Shader, Richard I.

doi:10.3109/03602538308991391

Cited by 100 publications

(38 citation statements)

References 59 publications

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“…This process procedes at a faster rate than does the oxidative mechanism by which diazepam and chlordiazepoxide are metabolized (Greenblatt 1981). The elimination half-life of lorazepam in humans (15 h, range = 8-25 h) has been characterized as intermediate, as has that of oxazepam, compared to those of chlordiazepoxide and diazepam, which have been characterized as slow (Greenblatt 1981 ;Greenblatt et al 1983). Thus, although there are differences between lorazepam and other benzodiazepines, there does not yet seem to be a variable unique to lorazepam that might be relevant to the question at hand.…”

Section: Discussionmentioning

confidence: 99%

Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Ator

Griffiths

1989

Psychopharmacology

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In drug discrimination studies benzodiazepine-trained animals have typically responded on the drug lever when tested with barbiturates. In a recent study, greater specificity appeared to be shown when lorazepam was used as a training drug. The generality and limits of this finding were explored in the present set of experiments. The asymmetrical cross-generalization found in lorazepam- and pentobarbital-trained baboons was replicated in rats and was shown not to be a function of either lorazepam (0.1., 0.32, or 1.0 mg/kg) or pentobarbital (10 or 25 mg/kg) training dose (i.e., pentobarbital-trained rats responded on the drug lever in tests with lorazepam, but lorazepam-trained rats did not show comparable pentobarbital generalization). In the next experiment, groups of rats were trained to discriminate chlordiazepoxide (10 mg/kg), triazolam (0.1 mg/kg), or diazepam (1.0 mg/kg). Generalization to both lorazepam and pentobarbital was shown by these rats. Finally after daily pentobarbital administration, lorazepam-trained rats made a sufficient number of responses after high pentobarbital doses to permit extension of the range of pentobarbital doses tested. Pentobarbital generalization increased, but still did not occur in all rats and was unreliable in successive tests in the same rats. These results suggest less homogeneity in the discriminative stimulus effects of "depressant drugs" than generally has been recognized.

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Section: Discussionmentioning

confidence: 99%

Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Ator

Griffiths

1989

Psychopharmacology

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“…They have anxiolytic, sedative-hypnotic, anticonvulsant, and muscle-relaxant properties [14] and act mainly by reinforcing inhibitory effects on the GABA-A receptor [15]. Diazepam has an elimination half-life of >24 h [14] and is metabolized in the liver [16]. …”

Section: Introductionmentioning

confidence: 99%

Comparison of Clomethiazole and Diazepam in the Treatment of Alcohol Withdrawal Syndrome in Clinical Practice

2017

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Background: The objective of this retrospective study was to compare the effectivity and tolerability of diazepam and clomethiazole in the treatment of alcohol withdrawal syndrome (AWS) in a large clinical sample. Methods: The data of 566 patients admitted to an intensive care psychiatric unit in Germany (2010-2014) were evaluated. The course of withdrawal was analyzed on a matched sample (n = 152) consisting of a diazepam group (n = 76) and a clomethiazole group (n = 76). Medical assessment was based on a standardized point-based symptom rating scale called AESB (Alkoholentzugssymptom-Bogen), a German modified version of the Revised Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA-Ar). Results: Although the mean daily symptom reduction did not differ significantly, patients treated with clomethiazole were treated significantly shorter and needed less concomitant antipsychotic medication. Numbers of complications and adverse events did not show significant differences. Conclusion: Both clomethiazole and diazepam were effective and equally safe in the treatment of AWS. Clomethiazole provided a faster withdrawal and required less concomitant antipsychotic medication and therefore might be the more favorable option for patients and physicians. Taken into account the methodological limitations of the study (retrospective design, secondary matching, missing randomization, use of clomethiazole as drug of first choice), further studies are needed to confirm this result.

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“…[1][2][3][4][5][6] However, in the elderly, the safety of benzodiazepines is less clear because of their impaired metabolic elimination and increased sensitivity. [7][8][9][10][11][12][13][14] An estimated 10.9 million (6.2%) of U.S. adults purchased or obtained benzodiazepines in 1987, and of those aged 65 years and older (elderly), 11.3% to 13.7% reported taking a benzodiazepine in the previous year. 15,16 In 1988, individuals over 60 constituted approximately 20% of the U.S. population, yet received 49% of all prescriptions for benzodiazepines.…”

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confidence: 99%

Correlates and prevalence of benzodiazepine use in community-dwelling elderly

Schulz²,

et al. 1998

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OBJECTIVE:To describe the prevalence of benzodiazepine use, sociodemographic and physical health factors associated with use, dosages taken, and directions for use among individuals aged 65 years and older. DESIGN:Cross-sectional analysis of baseline data from the community-based, prospective observational Cardiovascular Health Study. PATIENTS/PARTICIPANTS:Medicare eligibility lists from four U.S. communities were used to recruit a representative sample of 5,201 community-dwelling elderly, of which 5,181 participants met all study criteria. MEASUREMENTS AND MAIN RESULTS:Among participants, 511 (9.9%) were taking at least one benzodiazepine, primarily anxiolytics (73%). Benzodiazepines were often prescribed to be taken pro re nata (PRN "as needed"), and 36.5% of prescriptions with instructions to be taken regularly were taken at a dose lower than prescribed. Reported over-the-counter (OTC) sleep aid medication use was 39.2% in benzodiazepine users and 3.3% in nonusers. In a multivariate logistic model, the significant independent correlates of benzodiazepine use were being white (odds ratio [

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Benzodiazepine Kinetics: Implications for Therapeutics and Pharmacogeriatrics

Cited by 100 publications

References 59 publications

Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Differential generalization to pentobarbital in rats trained to discriminate lorazepam, chlordiazepoxide, diazepam, or triazolam

Comparison of Clomethiazole and Diazepam in the Treatment of Alcohol Withdrawal Syndrome in Clinical Practice

Correlates and prevalence of benzodiazepine use in community-dwelling elderly

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