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Title: Pharmacodynamics and pharmacokinetics of centrally acting depressants in man
Author: Fagan, Denise
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1992
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A 'steady-state' constant plasma concentration paradigm was used to assess: a) whether rapid acute tolerance to the central nervous system effects occurred following administration of three centrally acting drugs and, b) the profiles of psychomotor impairments obtained under these constant conditions. The issue of differential test sensitivites at steady-state was also addressed. The drugs used were chlormethiazole, ethanol and nitrous oxide. These were administered by the intravenous, oral and inhalation routes respectively. Central nervous system effects were assessed using a battery of standard and new psychological tests and subjective measures which were first assessed for reliability. In terms of cognitive and psychomotor performance, there was no evidence of acute tolerance to chlormethiazole or to ethanol at steady-state. There was, however, evidence of acute tolerance to some peripheral effects of chlormethiazole, and to some of the subjective effects of nitrous oxide. The patterns of effects were consistent with the view that the drugs had broadly the same profile of effect on the tests used, but at different points on the same basic dose response curve of impairment. The exception was critical flicker frequency which was less affected than expected with chlormethiazole (a hypnotic) and nitrous oxide. The nitrous oxide data suggested that some of the dose-response curves for different processes may cross over. Thus body sway which was substantially impaired with all three drugs, was one of the least sensitive tests at the lower concentrations of nitrous oxide. Tapping, on the other hand, was sensitive at the lower concentrations, but the magnitude of impairment was smaller than for other tests at the higher concentrations.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available