Pancuronium concentrations

The plasma concentrations of d-tubocurarine and pancuronium are increased in patients with impaired liver functions because liver disease interferes with the metabolism of pancuronium. 

In a suicide case due to the intravenous administration of pancuronium bromide, postmortem concentrations were blood 1.6 pg/ml, urine 1.5 pg/ ml thiopentone and thioridazine were also detected (A. Poklis and E. G. Melanson, J. analyt. Toxicol., 1980, 4, 275-280). 

Miller RD, Way WL, Dolan WM, Stevens WC, Eger El 2nd. The dependence of pancuronium- and d-tubocurarine-induced neuromuscular blockades on alveolar concentrations of halothane and forane. Anesthesiology 1972 37(6) 573-81. 

Cardiovascular adverse effects are minimal with pancuronium. Ganglion blockade does not occur. Shght dose-dependent rises in heart rate, blood pressure, and cardiac output are common (5), but are often masked by the actions of other co-administered agents, such as fentanyl or halothane, which cause bradycardia or hypotension. These adverse effects of pancuronium are thus often beneficial and can be deliberately harnessed. Several mechanisms contribute vagal blockade via selective blockade of cardiac muscarinic receptors (6), release of noradrenaline from adrenergic nerve endings (7), increased blood catecholamine concentrations (8), inhibition of neuronal catecholamine reuptake (9-11), and direct effects on myocardial contractility (12). These have been reviewed (13-15). 

Pancuronium is relatively contraindicated, particularly in combination with halothane, in patients who may have raised catecholamine concentrations, or who are receiving drugs with sympathomimetic effects. Severe hypertension together with tachycardia can occur when pancuronium is given to a patient with a pheochromocytoma (34,35). 

AminophyUme facilitates neuromuscular transmission, perhaps by increasing neurotransmitter release, through raising cyclic AMP concentrations at the neuromuscular junction via phosphodiesterase inhibition (37). This would account for the antagonism of pancuronium-induced blockade that has been reported in the presence of very high serum concentrations of theophylline (38). 

Fahey MR, Sessler DI, Cannon JE, Brady K, Stoen R, Miller RD. Atracurium, vecuronium, and pancuronium do not alter the minimum alveolar concentration of halothane in humans. Anesthesiology 1989 71(l) 53-6. 

The matemofetal transfer or rocuronium, as indicated by a fetaFmatemal plasma concentration ratio of 0.16, is between that of vecuronium and pancuronium (32). When rocuronium was used for cesarean section, no adverse effects on the fetus were observed (32). With regard to the duration of rocuronium-induced paralysis and the relatively high incidence of failed intubations in obstetric patients, however, it was agreed that rocuronium should be considered for rapid-sequence intubation for cesarean section only if suxamethonium is contraindicated (33-35). 

Antagonism to pancuronium has been found with theophylline concentrations in excess of the recommended target range (SEDA-5, 4). 

In liver disease, increased amounts of D-tubocurarine may be reqnired. In the past it has been suggested that this could be due to reduced synthesis of acetylcholinesterase, or to increased concentrations of gammaglobulins binding the relaxant (14), although this is disputed (15). Similar kinetic mechanisms to those suggested for pancuronium may be involved, but there are no studies on D-tubocurarine. In primary liver cancer in children, resistance to D-tubocurarine (and alcuronium) has been reported (SEDA-13,104) (16). 

Doxapram, used as a respiratory stimulant, increased partial D-tubocurarine and pancuronium neuromuscular blockade when used in high concentrations in rats (SEDA-14, 113) (65). There have been no reports in man so far. 

There is placental transfer of vecuronium, but no effects have been detected in the newborn (the feto-maternal concentration ratio is about 10% less than for pancuronium (31). Postpartum, vecuronium has been reported to have an appreciably longer duration of action (SEDA-13, 105) (32,33) when given in a dose of 0.1 mg/kg. 

The ciclosporin interaction may be partly due to the vehicle used in intravenous preparations. One idea is that Cremophor, a surfactant which has been used as a solvent for the ciclosporin, may increase the effective concentration of pancuronium at the neuromuscular junction. Both compounds have been observed in animal studies to increase vecuronium blockade, and Cremophor has also been seen to decrease the onset time... 

All NMBDs inhibit histamine-A/-methyl-transferase (HMT), the primary catabolic enzyme for histamine in humans (see Fig. 3.6). Inhibition is competitive with respect to the methyl donor and noncompetitive with respect to histamine. Six different NMBDs, alcuronium, pancuronium, d-mbocurarine, gallamine, succinylcholine, and decamethonium, inhibited enzyme activity in the concentration range 10 -10 M with alcuronium being the most potent inhibitor ( 50=2 x 10" M)... 

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