It was recently reported that cycloheximide, an inhibitor of protein synthesis, induces tyrosine transaminase in the liver of adrenalectomized rats. We have been unable to confirm this effect in the anesthetized animal and our data show that cycloheximide inhibits the induction caused by hydrocortisone in adrenalectomized rats or by stress in intact rats.

Adrenalectomy↗

PubMedDate not supplied

Dose-related effects of ethanol on visual sustained attention and event-related potentials.

The effects of acute ethanol intoxication on visual sustained attention were investigated in male social drinkers. Four doses ranging from 0 (placebo) to 1.05 g/kg lean body weight, with periodic maintenance dosing of 0.12 g/kg, were given in separate sessions. The task required subjects to monitor a series of blurred digits presented singly at a rate of one per sec and to respond to occasional (p = 0.25) target digits with a speeded button press. Detection performance deteriorated as a function of both dose and time on task. In addition, the factors of dose and time on task interacted to produce a more rapid performance decrement under the higher doses. Early event-related potential (ERP) components (N1 and P2) were not greatly affected, suggesting that the performance decrement reflects central rather than peripheral factors. Later components related to cognitive appraisal processes (N2, P3), in contrast, varied in both amplitude and latency. Ethanol yielded dose-related delays in N2 and P3 latencies, which paralleled reaction time increases. The amplitude of N2 also decreased over time on task, and P3 amplitude decreased both as a function of dose and time on task. ERP and performance data were interpreted as demonstrating an adverse effect of ethanol on central processing capacity.

Adult↗

PubMedDate not supplied

Effects of ethanol on drug and metabolite pharmacokinetics.

Pharmacokinetic interactions of ethanol with other drugs, including its effects upon drug metabolite disposition, are reviewed in terms of clearance concepts. This approach is particularly useful in understanding the mechanisms of ethanol-drug interactions, i.e. in separating the effects of ethanol upon drug clearance, volume of distribution and plasma protein binding. The application of clearance concepts provides the basis for understanding the qualitative differences in ethanol interactions with low and high hepatic extraction ratio drugs. The effects of short and long term ethanol consumption upon different types of drug metabolism (oxidative, acetylation and glucuronidation) have been considered. Long term ethanol consumption may increase the clearance of a drug by induction of oxidative metabolism whereas short term consumption may decrease the clearance of such a drug. Clearance by N-acetylation appears to be increased in the presence of ethanol, and clearance by conjugation to glucuronic acid is decreased for some drugs by single-dose consumption of ethanol.

Analgesics↗

PubMedDate not supplied

Analysis of parent drug-metabolite relationship in the presence of an inducer. Application to the carbamazepine-clobazam interaction in normal man.

An increase in drug metabolic clearance results in a decrease in concentration of parent drug but the effect on concentration of metabolite has been unclear. The effect of increases in the clearance of parent drug and/or metabolite upon the metabolite concentration, metabolite-to-parent drug concentration ratio, and fraction metabolized is described theoretically. It is shown that several combinations of increases in specific clearances can lead to qualitatively similar effects on steady state concentration of metabolite. The effect of increases in metabolic clearances of the clobazam-norclobazam system caused by carbamazepine treatment was studied in normal volunteers. The steady state concentration of metabolite (norclobazam) increased 1.4-fold and the ratio of metabolite to parent drug increased 4-fold. These effects of carbamazepine on clobazam-norclobazam pharmacokinetics could be a result of five theoretical cases. It is concluded that at least the formation clearance of norclobazam was increased. Carbamazepine treatment caused at least a 4-fold increase in the N-demethylation clearance of clobazam. It was also deduced that, in the baseline state, no more than 70% of the clobazam dose was metabolized to norclobazam, even though the norclobazam concentration was more than twice the clobazam concentration.

Adult↗