Pharmacodynamics of non-depolarizing muscle relaxants in rat model with chronic renal failure

Abstract

The pharmacodynamics of non-depolarizing muscle relaxants in chronic renal failure (CRF) was examined in a rat model made by removing three-fourths of the right kidney and total of left kidney. Single dose response curves in the CRF group and control for pancuronium and vecuronium were obtained respectively to investigate the pharmacodynamics of these drugs in CRF. Single dose response curves for both drugs in CRF were significantly shifted to the right compared to those in the control. This means that more non-depolarizing neuro-muscular blocking agents are needed in CRF to obtain the same neuro-muscular block as in the control. The factors changing the pharmacodynamics in CRF are hyperpotassemia, hypercalemia, large distribution volume, metabolic acidosis and possible accumulations of methyl guanidine and guanidine. This study suggested that more non-depolarizing muscle relaxants are necessary in CRF in the initial dose because of the resistance in pharmacodynamics and less in the maintenance dose because of the accumulation in pharmacokinetics.