thiopental and Kidney-Diseases

We have previously reported that brain sensitivity to thiopental with respect to electroencephalogram (EEG) is enhanced in uranyl acetate pretreated renal dysfunction rats. The results were attributed to pharmacodynamic factors. In this study, in vivo EEG and in vitro binding studies for gamma-aminobutyric acid (GABA)-benzodiazepine receptor complex were performed to investigate the mechanism of the enhanced effect of thiopental. The receptor binding properties in the brain membrane from normal and renal dysfunction rats were examined using [3H]tertbutylbicycloorthobenzoate (TBOB), [3H]flunitrazepam and [3H]muscimol. The effect of plasma dialysate from normal (ND) and renal dysfunction rats (RDD) on the thiopental induced EEG and receptor binding were also examined to confirm the role of endogenous compounds. The intrinsic receptor binding characteristics of various sites and their allosteric interaction with thiopental was similar in membrane preparations from normal and renal dysfunction rats. However, RDD, when compared to ND, enhanced the EEG induced by thiopental. At the receptor level, RDD significantly enhanced the thiopental induced inhibition of TBOB. No difference was found between the influence of ND and RDD on the interaction between thiopental and flunitrazepam or muscimol binding. These results showed that the thiopental induced allosteric inhibition of TBOB binding was potentiated by some endogenous compounds in RDD and suggests that this action might be the mechanism, at least in part, for the increased sensitivity of thiopental in renal dysfunction rats.

Topics: Animals; Dialysis; Drug Evaluation, Preclinical; Electroencephalography; Flunitrazepam; GABA Modulators; Kidney Diseases; Male; Membranes; Muscimol; Plasma; Rats; Rats, Wistar; Receptors, GABA-A; Reference Values; Thiopental

Binding of thiopental to proteins in plasma from healthy, cirrhotic, and uremic subjects was studied using equilibrium dialysis. In plasma from healthy volunteers 28.0 plus or minus 0.9 per cent of thiopental was unbound. In plasma from patients with hepatic disease 53.0 plus or minus 2.1 per cent was unbound, while in patients with renal disease 55.7 plus or minus 1.5 per cent remained unbound. The decreased binding in uremia could not be explained completely by competitive displacement by nitrogenous end products or by hypoalbuminemia, although hypoalbuminemia may account for the decreased binding in cirrhotic patients.

Topics: Binding, Competitive; Blood Proteins; Blood Urea Nitrogen; Creatinine; Dialysis; Humans; In Vitro Techniques; Kidney Diseases; Liver Cirrhosis; Protein Binding; Renal Dialysis; Serum Albumin; Spectrophotometry; Thiopental; Uremia

Topics: Abruptio Placentae; Anesthesia; Anesthesia, General; Blood Circulation; Blood Pressure; Blood Pressure Determination; Catheterization; Cesarean Section; Female; Humans; Kidney Diseases; Pregnancy; Pregnancy Complications, Cardiovascular; Succinylcholine; Thiopental; Varicose Veins; Vena Cava, Inferior; Venae Cavae