General Principles and Methods of Evaluation of Neuromuscular Blocking Agents in Anesthesiology

Abstract

There is considerable species variation in the pharmacodynamic effects (Paton and Zaimis 1949; Foldes 1954) and pharmacokinetics (Agostin 1976) of neuromuscular (NM) blocking agents (NMBA). Because of this, the information obtained in animal experiments on the potency, onset, and duration of the NM effect of NMBA and on their side effect liability and disposition has only limited relevance to the effects of these compounds in humans. Thus, for example, pancuronium (Pavulon) is about five and ten times more potent than tubocurarine (Tc) in humans (Baird and Reid 1967) and cats (buckett et al. 1968), respectively, but about five times less potent than Tc in rats (Chaudhry and Foldes 1981). Vecuronium (Org-NC-45, Norcuron) is more potent than pancuronium in humans (Crul and Booij 1980) and dogs (Marshall et al. 1980), but less potent than pancuronium in rats, cats, and rhesus monkeys (Marshall et al. 1980). To predict the effects of NMBA in the clinical setting, it is necessary to investigate their pharmacodynamics and pharmacokinetics, with accepted pharmacologic methods, in humans. Preliminary observations should be carried out in conscious human subjects. These should be followed by more comprehensive studies in anesthetized volunteers and/or patients.