Clinical Pharmacokinetics of Neuromuscular Blocking Drugs

Abstract

Neuromuscular blocking agents provide muscle relaxation for a great variety of surgical procedures with light planes of general anaesthesia. Besides having a significant impact in the development of anaesthesia and surgery, these agents continue to play an important role as pharmacological tools in the elucidation of the physiological and pharmacological regulation of neuromuscular transmission and the morphofunctional organisation of the neuromuscular junction. In the daily practice of anaesthesia, muscle relaxants are considered to be safe drugs with predictable, straightforward pharmacological actions. However, the use of relaxants constitutes a deliberate encroachment on respiration, one of the most important physiological mechanisms. The pharmacokinetic behaviour of this class of agents is little influenced by age or anaesthetic agents; however, hepatic or renal disease may profoundly alter their excretion pattern, resulting in prolonged duration of neuromuscular blockade. Biotransformation plays an important role in the total elimination of recently introduced compounds. Consequently, knowledge of the disposition pharmacokinetics, excretion and biotransformation of this class of drugs is indispensable for their rational choice for various surgical procedures. In this review, the known pharmacokinetics of standard compounds (introduced before 1980) are briefly summarised and new information generated by the development of vecuronium, rocuronium, pipecuronium (steroidal agents) and atracurium, mivacurium, doxacurium (benzylisoquinolinium esters) is discussed in more detail.

Influence of acute normovolemic hemodilution on the potency and time course of action of rocuronium in rabbits

“…After ANH, the volume of distribution of rocuronium had increased, plasma clearance was reduced, and distribution and clearance half-life had decreased [8]. The effects of muscle relaxants such as rocuronium are determined by the distribution periods rather than the clear periods [21]; therefore, we expected that reducing plasma concentration by increasing the volume of distribution would decrease the duration of rocuronium. These findings are inconsistent in the current study, but on the other hand, they are consistent with previous results [6][7][8].…”

Adverse Effects of Nondepolarising Neuromuscular Blocking Agents

“…Alcuronium and gallamine are also eliminated predomiDrug Safety 10 (6) 1994 nantly by the kidney (Collins 1993), both having dramatically prolonged t\l2 in the presence of renal failure (Agoston et al 1992).…”

Pharmacokinetic Optimisation of General Anaesthesia in Pregnancy

“…For continuation of neuromuscular block, drugs with rapid elimination such as vecuronium (Dailey et al 1984) and atracurium (Flynn et al 1984;Shearer et al 1991) are more attractive than older drugs which are eliminated more slowly (Agoston et al 1992). At caesarean section, clearance of vecuronium was greater (Dailey et al 1984) and onset of action was faster, but the duration of action was prolonged (Baraka et al 1992) compared with that in nonpregnant women.…”

“…The duration of action of vecuronium was also prolonged in post-67 partum patients and may be a result of an increased dosage relative to nonpregnant bodyweight or decreased metabolism (Khuenl-Brady et al 1991). Atracurium is metabolised by spontaneous degradation and the duration of action is unaltered by disease states (Agoston et al 1992) and is not prolonged in postpartum patients (Khuenl-Brady et al 1991). Offset of action with atracurium is rapid because it is metabolised even at the neuromuscular junction and it has less fade during offset of block than vecuronium (Fletcher et al 1992).…”