The pharmacodynamics of the neuromuscular blocking drug gallamine were investigated in 10 surgical patients using a constant-rate infusion regimen, and results are compared to those for d-tubocurarine (dTc). Gallamine effect (paralysis)-time data gathered during and following the infusion were fitted to a pharmacodynamic effect model, while paralysis-plasma concentration data gathered during (onset) and following (offset) the infusion were fitted separately to a nonlinear form of the Hill equation. The effect model was most appropriate in characterizing the combined (on and off infusion) effect data. While there was also an excellent characterization of onset and offset data with the Hill equation, the two effect-concentration curves were not superimposable. The mean (+/- S.D.) plasma concentration of gallamine at 50 per cent paralysis during onset of action (Cp50(onset) 8.0 +/- 1.8 micrograms/ml) or that predicted to exist at steady state using the effect model (Cp50(ss) 5.4 +/- 1.4 micrograms/ml). Cp50(offset) and Cp50(ss) did not differ significantly, and there was no significant difference in the power factor (lambda) estimates for the various model fits. Comparison of the pharmacodynamic parameters for gallamine and dTc using the effect model revealed no significant differences in keo, t1/2(keo), and lambda estimates. However, Cp50(ss) for gallamine (5.4 +/- 1.4 micrograms/ml) was nine times higher than that for dTc (0.61 +/- 0.15 micrograms/ml) in absolute terms and seven times higher when compared on a molar basis.

Aged↗

PubMedDate not supplied

Tertiary educational assessment with mean individual level knowledge.

It is proposed that Tertiary Educational Assessment should be made using a Curve-Unifying Paradigm with its Scientific And Ultra-Conservative Experiment Ratio. Central Ranking Evaluation And Marking was used to process examination results, generating the Mean Individual Level Knowledge for the group. The concept of MILK grew from the need to encourage the average examination candidate and with it came the need for a Judgmental Understanding Goal. The results of some candidates required further handling by the addition of Student's Universal Grade Averaging Regimen.

Educational Measurement↗

PubMedDate not supplied

Clinical pharmacokinetics of the non-depolarising muscle relaxants.

Muscle relaxants are of great benefit to the anaesthetist as adjuncts to anaesthesia. These drugs are used to facilitate endotracheal intubation and to reduce muscle tone during surgery, and may also find application in assisting ventilator care in the intensive care situation. The pharmacological effect of the relaxants may be readily assessed by the anaesthetist by means of a variety of techniques to quantify muscular activity in response to electrical stimulation. A number of factors may modify the effects of the muscle relaxants including anaesthetic agents, hypothermia, patient age and disease status and a variety of drugs. The disposition kinetics of the muscle relaxants have been well characterised although information on protein binding and placental transfer is somewhat scanty. A common characteristic of their pharmacokinetics is multicompartmental behaviour. Clearance of the relaxants ranges from total elimination by the kidneys (gallamine) to substantial hepatic clearance (fazadinium), and thus their clearance may be adversely affected by renal or hepatic disease. Dosage regimens have been designed using knowledge of the disposition kinetics of the relaxants to provide for continuous adequate relaxation during prolonged surgical procedures. With the use of sophisticated pharmacokinetic and pharmacodynamic models good relationships have been demonstrated between plasma concentrations of the relaxants throughout the entire range of relaxant response.

Adolescent↗