ABSTRACT
Eight young women taking oral contraceptives and 10 young men each received three different doses of diazepam, 0.07, 0.14, and 0.28 mg/kg. The women also received each dose both on days 10 and 28 of an oral contraceptive cycle. Performance based on both a psychomotor and cognitive-encoding task was significantly impaired after a 0.28-mg/kg dose of diazepam in women taking oral contraceptives and in men. In general, however, impairment in performance was less on day 10 than on day 28 of the oral contraceptive cycle. The onset of behavioral impairment was also slower on cycle day 10 than on day 28; peak impairment was reached at 20 min after dosing for men and women on day 28, but at 60 min for women on day 10. The cycle phase effects are potentially dangerous because of their unexpected nature. Individuals may obtain an expectation of intoxication based on the 21-day OC period yet experience capriciously greater acute impairment during their 7-day menstrual pause.
Subject(s)
Contraceptives, Oral/pharmacology , Diazepam/poisoning , Psychomotor Disorders/chemically induced , Adult , Cognition/drug effects , Double-Blind Method , Female , Humans , Male , Menstruation , Psychomotor Performance/drug effectsABSTRACT
Acute tolerance, defined as a decreasing drug effect relative to drug-plasma levels (DPL) over a period of minutes to a few hours, is pronounced following single doses of diazepam or pentobarbital. Both of these lipid-soluble drugs produce an early peak behavioral impairment and subsequent rapid recovery component that is followed by a much slower blood-drug rise time. These pronounced early peak effects were not shared by alcohol, and contribute significantly to the lack of correlation between impairment and DPL.
Subject(s)
Anti-Anxiety Agents/pharmacology , Adult , Anti-Anxiety Agents/blood , Automobile Driving , Diazepam/pharmacology , Drug Tolerance , Ethanol/pharmacology , Humans , Male , Pentobarbital/pharmacology , Psychomotor Performance/drug effects , Time FactorsABSTRACT
Single doses of diazepam induced peak impairment of performance on cognitive and psychomotor tasks early (20 min after ingestion), when blood levels had reached less than two thirds of their eventual plateau. Alcohol did not have this effect. Early peak impairment and the acute tolerance that follows it contribute greatly to the lack of correlation between diazepam plasma level and performance impairment.
Subject(s)
Cognition/drug effects , Diazepam/adverse effects , Ethanol/adverse effects , Adult , Diazepam/blood , Ethanol/blood , Humans , Psychomotor Disorders/chemically induced , Time FactorsABSTRACT
Examination of the effect of three doses of pentobarbital on the comparative performance of a complex psychomotor task with two simple neuromotor tasks, i. e., standing steady and pendulum eye tracking, revealed a high correlation. These simple tasks could be used as measures of intoxication since they do not require extensive training. Examination of the complex task impairment blood level ratio revealed that impairment relative to blood level was much greater in the absorption phase. This changing ratio underscores the point that blood levels alone are not an adequate estimate of intoxication.
