A SIMPLIFIED APPROACH TO THE EFFECT KINETICS OF ATRACURIUM

The combination of the Hill equation, which describes the concentration—effectrelation, with the monoexponential function for the terminaldecline of plasma concentration, yields a compound time constant,. This constant is a combination of the terminal elimination half-life () and the exponent (s) of the Hill equation and maybe used to describe the time course of recovery from neuromuscularblock. The constant may be estimated by non-linear curve fittingto f, the effect expressed as fraction of maximal effect, orby linear regression of the logit function of f. The methodswere validated using plasma concentration and effect data fromseven patients administered atracurium. The two methods utilizingeffect data alone yielded values of 4.2 (0.7) min and 4.3 (0.5)min (mean (SEM)), respectively, for compared with 4.1 (0.6) min when the constant was calculatedusing plasma concentration data for and curve fitting to the concentration—effect data todetermine s. These methods offer and objective measure of therate of recovery and a means of testing if redistribution orelimination is the primary process in the termination of drugeffect.     

EXPERIMENTAL COMPARISON OF EXTRADUPAL AND I.M. MORPHINE

Morphine sulphate 3 or 4 mg was administered to the extraduralspace in five volunteers. Morphine 10 or 15 mg i.m. was givenas control. Extradural administration resulted in an increaseof pain threshold in the legs but not in the forehead. Therewas no significant depression of carbon dioxide response ordeterioration of co-ordination or short-term memory. I.mn. morphinecaused an increase in forehead pain threshold, depression ofthe carbon dioxide response and some deterioration of cerebralfunction. Extradural morphine caused urinary retention in fourand inability to ejaculate in three of the subjects. The principalsite of action of extradural morphine appears to be regional,at spinal cord level, but it appears that autonomic functionas well as pain perception can be affected.