A Pharmacodynamic Model for Pancuronium

Hull, C.J.; Beem, H.B.H. van; McLeod, K. R.; Sibbald, A.; Watson, M. J.

doi:10.1093/bja/50.11.1113

Cited by 188 publications

(80 citation statements)

References 11 publications

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“…The pharmacokinetic data for pancuronium obtained by Hull et al 13 were applied to the conditions of the present study and calculations of predicted pancuronium concentration at the neuromuscular junction were performed on an IBM personal computer. These calculations demonstrated that the concentration of pancuronium sufficient to produce paralysis did occur earlier after divided dose administration.…”

Section: Discussionmentioning

confidence: 99%

Accelerated onset of pancuronium with divided doses

Doherty

Breen

Donati

et al. 1985

Can. Anaesth. Soc. J.

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To determine the consequences of administering neuromuscular relaxants in divided doses, pancuronium was given either in a single dose, 0.07 mg.kg -I, or One of the aims in the search for new neuromuscular blocking drugs (NMBDs) is a non-depolarizing relaxant with a rapid onset of action. The goal remains elusive despite the introduction of the shorter-acting NMBDs, atracurium and vecuronium, in the U.S.A. and Europe. In equipotent doses, these agents have a similar onset of action as d-tubocurarine and pancuronium. ~,2Small doses of non-depolarizing relaxants modify the action of succinylcholine given later 3 and, recently, it has been observed that such "precurarization" accelerates the onset of subsequent doses of the same drug. Reductions of approximately 25 per cent have been observed in man after divided doses of alcuronium 4 or atracurium.5 Also, intubation can be performed more rapidly when a bolus dose of pancuronium is preceded by a small "priming" dose of metocurine. 6The present study was designed to determine whether the onset of action and duration of effect of pencuronium were modified by its administration in divided doses. MethodsWith appropriate institutional approval, 52 patients undergoing elective general surgical and orthopaedic procedures were studied. All were ASA physical status class I or II and were not known to suffer from renal, hepatic or neuromuscular disease. None had electrolyte abnormalities nor was any taking medication known to interfere with neuromuscular transmission.Premcdication, with meperidine (1 mg'kg-I), and atropine (0.4-0.6 rag), was given 60-90 minutes before surgery. Anaesthesia was induced with thiopentone (3-5 mg'kg-~), and maintained with nitrous oxide (70 per cent) in oxygen and halothane (0.5-1 per cent inspired). Patients were allowed to breathe spontaneously until the onset of neuromuscular blockade when ventilation was assisted. When full paralysis had been obtained the tracheas were intubated and their lungs were ventilated to maintain noruaocapnia, 7 which was checked, in most patients, by measuring end-tidal CO2 concentration (Hewlett Packard capnograph). Blood pressure and electrocardiogram were recorded.Neuromuscular transmission was monitored according to the method of Ali et al. 8 The ulnar nerve was stimulated supramaximally with subcutaneous electrodes at the elbow. Four square wave impulses of 0.2 ms duration and 2 Hz frequency were administered every 12 seconds using a Grass $48 stimulator and SIU5 isolation unit. The hand and forearm were immobilized in a splint. The force of contraction of the adductor pollicis muscle was measured with a Grass FT10 force displacement transducer and the response recorded on a Grass Polygraph pen and ink recorder. The skin temperature over the thumb was measured and maintained CAN ANAESTH SOC J 1985 / 32; I /ppl-4

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Section: Discussionmentioning

confidence: 99%

Accelerated onset of pancuronium with divided doses

Doherty

Breen

Donati

et al. 1985

Can. Anaesth. Soc. J.

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“…This signifies that it is necessary to use a variable infusion rate K(t) to maintain the concentration in the therapeutic margin. However, the drug concentrations are not an adequate basis for therapeutic decision when the plasma is not the site of drug effect (5,6). The The curves of Figure 5 demonstrate the influence ofthe administration time.…”

Section: Discussionmentioning

confidence: 99%

Chemical substance kinetics in the case of chronobiological variations of elimination rate

Merabet-Atmani¹,

Aliguechi-Bouhadja²,

Redouane³

et al. 1999

Eur. J. Drug Metab. Pharmacokinet.

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“…The effect of the opioid was assumed to relate to C e at a theoretical effect compartment. [20][21][22] Equilibration between this effect compartment and the plasma compartment was assumed to follow a first-order transfer process with a rate constant k e0 . Thus, the time course of C e , C e (t), is described by…”

Section: Methodsmentioning

confidence: 99%

Relevance of frequent μ-opioid receptor polymorphisms for opioid activity in healthy volunteers

Lötsch

Geißlinger

2006

Pharmacogenomics J

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Polymorphisms in the m-opioid receptor gene (OPRM1) are primary candidate sources of clinical variability in opioid therapy. Apart from the 118A4G single nucleotide polymorphism, nothing is known about the role of OPRM1 mutations in opioid therapy. The influence of the OPRM1 mutations on opioid pharmacodynamics was assessed in pooled data from 31 healthy volunteers obtained in previous studies with available plasma concentrations and pupil diameters after intravenous administration of morphine or morphine-6-glucuronide (M6G). A total of 24 candidate ORPM1 mutations were screened for and those found at an allelic frequency of at least 5% in the 31 subjects were analyzed for functional consequences, using population pharmacokinetic-pharmacodynamic modeling of the miotic effects of the opioids as a reliable and sensitive surrogate parameter of the central nervous opioid effects. Polymorphisms at an allelic frequency of X5% (n ¼ 310) were 118A4G in exon 1 (11.5%), the IVS2-31G4A (8.9%) and IVS2-691C4G (44.5%) SNPs in intron 2. The 118A4G SNP significantly increased the values of EC 50 by a factor of more than 2 (nonmutated: EC 50,morphine ¼ 30 nmol/l, EC 50,M6G ¼ 750 nmol/l, 118G carriers: EC 50,morphine ¼ 66 nmol/l, EC 50,M6G ¼ 1650 nmol/l), whereas the IVS2-691C4G SNP had no effect. Based on morphine and M6G, the present analysis encourages focusing on the 118A4G SNP when investigating the role of OPRM1 mutations for the activity of opioid analgesics. Other OPRM1 mutations are probably less important either owing to low allelic frequency or due to poor indications for functional consequences. This applies to opioid potency in the context of opioid therapy but not to pain processing or substance addiction, in which opioid receptors are involved but other or additional OPRM1 mutations may be important.

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A Pharmacodynamic Model for Pancuronium

Cited by 188 publications

References 11 publications

Accelerated onset of pancuronium with divided doses

Accelerated onset of pancuronium with divided doses

Chemical substance kinetics in the case of chronobiological variations of elimination rate

Relevance of frequent μ-opioid receptor polymorphisms for opioid activity in healthy volunteers

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