Relationship between diazepam dose, plasma level, age, and central nervous system depression

Reidenberg, Marcus M.; Levy, Micha; Warner, Howard; Coutinho, Claude B.; Schwartz, Morton A.; Yu, George T.; Cheripko, Joyce A.

doi:10.1002/cpt1978234371

Cited by 191 publications

(38 citation statements)

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“…In addition to looking at renal function, I showed that age was an independent variable affecting doseresponse (Reidenberg et al, 1978). Because by the early 1970s much was known about why individuals differed in their responses to drugs, I organized an American College of Physicians postgraduate course, "Individualization of Drug Therapy," subsequently published as a book (Reidenberg, 1974).…”

Section: Introductionmentioning

confidence: 99%

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

Reidenberg¹

2011

The Journal of Pharmacology and Experimental Therapeutics

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Most reviews of drug withdrawal effects focus on drugs of potential abuse such as opioids, benzodiazepines, etc. Abrupt discontinuation of many other drugs used in medicine cause withdrawal syndromes, some of which can be fatal. Discontinuation of a number of cardiovascular drugs can increase risk of cardiovascular events above that of people not taking these drugs. These include ␤-adrenergic receptor antagonists, aspirin, HMG-CoA reductase inhibitors (statins), and heparin. Rebound hypertension occurs after abrupt cessation of many antihypertensive drugs. The possibility of discontinuation syndromes has usually been neglected until adverse clinical events force them to be noticed. Attention to the possibility of drug discontinuation effects is an important part of drug safety evaluation.

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Section: Introductionmentioning

confidence: 99%

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

Reidenberg¹

2011

The Journal of Pharmacology and Experimental Therapeutics

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“…Studies with parenteral diazepam (Giles et al, 1978;Reidenberg et al, 1978;Cook et al, 1984) and oral nitrazepam (Castleden et al, 1977) have provided evidence that responsiveness may be enhanced in the elderly, independently of changes in plasma concentration. We have therefore undertaken a controlled study of the response to single oral doses of diazepam in young and elderly healthy volunteers, with concurrent measurement of plasma concentrations and estimation of protein binding, in order to evaluate further the role of pharmacodynamic factors in the reported increased 'sensitivity'.…”

Section: Introductionmentioning

confidence: 99%

Responsiveness to oral diazepam in the elderly: relationship to total and free plasma concentrations.

Swift¹,

Ewen²,

Clarke³

et al. 1985

Brit J Clinical Pharma

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1 The immediate and residual response to single doses of oral diazepam 10 mg was measured in 11 young and 12 elderly healthy volunteers using postural sway, digit symbol substitution scores and subjective ratings. 2 The effect on postural sway was markedly accentuated in the older volunteers, but the difference between groups in the effect on the other measures used did not achieve significance. 3 The corresponding plasma total diazepam concentrations were lower in the older subjects beyond 0.5 h post dose and the concentrations of plasma desmethyldiazepam did not differ between the groups. 4 Diazepam plasma protein binding was significantly reduced in the elderly subjects, but the plasma free (unbound) diazepam concentrations did not exceed those in the young group. 5 There was poor correlation between the responses measured and the concentrations of either total diazepam, desmethyldiazepam or free diazepam. 6 The results suggest the occurrence of a non-uniform effect of age on different aspects of benzodiazepine response, and that where an accentuated effect occurs the mechanisms are substantially pharmacodynamic.

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“…Previous reports have shown that the elderly exhibit increased sensitivity to the sedative eŠects of the benzodiazepines. 26,27) Elderly subjects require lower doses and lower plasma diazepam concentrations than younger patients to achieve the same degree of sedative eŠect. 26) Aging leads to an increase in pharmacological eŠects in humans and rats.…”

Section: Discussionmentioning

confidence: 99%

“…26,27) Elderly subjects require lower doses and lower plasma diazepam concentrations than younger patients to achieve the same degree of sedative eŠect. 26) Aging leads to an increase in pharmacological eŠects in humans and rats. [28][29][30] To identify the independent variables that best predicted DSST score diŠerences, we performed a multiple regression analysis for age, plasma albumin level, and plasma diazepam concentration 30 min after intravenous administration.…”

Section: Discussionmentioning

confidence: 99%

Impairment State of Cognitive Performance and the Affecting Factors in Outpatients Following Gastrointestinal Endoscopy after Single-dose Diazepam

et al. 2005

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Diazepam is commonly used as premedicant for endoscopic procedures. Wide interindividual diŠerences have been observed in the residual cognitive eŠects of the drug after gastrointestinal endoscopy. Our aim was to clarify the major factors, including pharmacokinetic factors, contributing to this wide variation in residual cognitive eŠect after gastrointestinal endoscopy in the study. Sixty-one outpatients undergoing gastrointestinal endoscopy participated in the study. Cognitive eŠects were evaluated in the diazepam group (n＝52) by the digit symbol substitution test (DSST) twice before and 30 min after an intravenous administration of 5 mg diazepam; in the intervening time gastrointestinal endoscopy was performed. Plasma concentrations of diazepam were determined by HPLC. The control group (n＝9) was tested by DSST in the same manner. The cognitive eŠects according to the change in DSST score was signiˆcantly decline in the diazepam group compared with the control group (by 0.2 versus -4.6; P＝0.014). This prospective study conrmed that cognition was signiˆcantly impaired after gastrointestinal endoscopy by premedication to subjects with 5 mg diazepam. There were very wide variations in change in DSST score. However we could not identify the independent variables that best predicted DSST score diŠerence in a multiple regression analysis for age, plasma albumin level, and plasma diazepam concentration 30 min after intravenous administration. We should pay attention to patients' individual states in cognitive performance following gastrointestinal endoscopy after single-dose diazepam.

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Relationship between diazepam dose, plasma level, age, and central nervous system depression

Cited by 191 publications

References 1 publication

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

Drug Discontinuation Effects Are Part of the Pharmacology of a Drug

Responsiveness to oral diazepam in the elderly: relationship to total and free plasma concentrations.

Impairment State of Cognitive Performance and the Affecting Factors in Outpatients Following Gastrointestinal Endoscopy after Single-dose Diazepam

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