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Anesthesiology Jan 1998Pancuronium has sympathomimetic actions but does not change or lowers systemic blood pressure in some studies of anesthetized humans and dogs. The present study was done...
BACKGROUND
Pancuronium has sympathomimetic actions but does not change or lowers systemic blood pressure in some studies of anesthetized humans and dogs. The present study was done to determine the actions and mechanisms of action of pancuronium on coronary and renal arteries other than those as a sympathomimetic agent.
METHODS
Helical strips of coronary and renal arteries from mongrel dogs were suspended in oxygenated, warmed Ringer-Locke solution, and changes in the isometric tension were recorded. In some strips, transmural electrical stimulation (5 Hz for 40 s) was applied to activate perivascular adrenergic nerves.
RESULTS
Pancuronium (10[-7] to 10[-5] M) caused dose-dependent relaxation in coronary and renal arteries contracted with prostaglandin (PG) F2alpha, whereas no significant response was induced with vecuronium. The relaxation was endothelium independent and abolished by indomethacin or tranylcypromine, a PGI2 synthase inhibitor. Transmural electrical stimulation caused coronary arterial relaxation, which was augmented by pancuronium and vecuronium. Desipramine also increased the response, and additional potentiation of the response was not elicited by pancuronium and vecuronium. In renal arteries, electrical stimulation caused contraction, which was also augmented by pancuronium and vecuronium. With desipramine treatment, these muscle relaxants did not potentiate the response. Endothelium-dependent coronary arterial relaxation caused by bradykinin was not affected by pancuronium.
CONCLUSIONS
Pancuronium-induced relaxations in canine coronary and renal arteries appear to be mediated by PGI2 released from subendothelial tissues. Potentiations by pancuronium and vecuronium of the response to adrenergic nerve stimulation are expected to be due to an inhibition of the norepinephrine uptake but not to facilitated release of the amine.
Topics: Animals; Coronary Vessels; Dogs; Dose-Response Relationship, Drug; Electric Stimulation; Endothelium, Vascular; Epoprostenol; Female; Indomethacin; Male; Neuromuscular Nondepolarizing Agents; Pancuronium; Renal Artery; Vasodilation; Vecuronium Bromide
PubMed: 9447869
DOI: 10.1097/00000542-199801000-00024 -
Anesthesiology Jun 1985Dose-response relationships for a 1:4 weight ratio-mixture of pancuronium and metocurine were studied during inhalational anesthesia with halothane and isoflurane in... (Comparative Study)
Comparative Study
Dose-response relationships for a 1:4 weight ratio-mixture of pancuronium and metocurine were studied during inhalational anesthesia with halothane and isoflurane in patients with and without renal failure. The time for recovery from 10 to 20% of control thumb twitch tension also was determined. In subjects with normal renal function, relaxant doses required for 95% twitch height suppression (ED95) were 50% of those predicted by simple addition of effects when used with a balanced anesthetic technique, 37% of predicted when used with 1.3 MAC halothane, and 25% of predicted when used with 1.3 MAC isoflurane (P less than 0.05). In subjects with renal failure, ED95 values for the combination were 40% of predicted when used with 1.2 MAC halothane and 45% of predicted when used with 1.2 MAC isoflurane (NS). For relaxants used singly in renal failure, pancuronium alone was slightly enhanced by 1.2 MAC halothane (85% of predicted), while 1.1 MAC isoflurane reduced the ED95 to 57% of predicted (P less than 0.05). Similar results were obtained for metocurine alone when used in renal failure (77 and 58% of predicted when used with halothane and isoflurane, respectively) (NS). Predicted values are published results for balanced anesthesia in normals. Recovery times were prolonged twofold in renal failure (P less than 0.05). Thus, the combination of pancuronium and metocurine is synergistic to the same degree in normals and in renal failure patients, but the total blockade produced by the combination is enhanced by halothane and isoflurane only in normals.
Topics: Adult; Dose-Response Relationship, Drug; Drug Synergism; Female; Halothane; Humans; Isoflurane; Kidney Failure, Chronic; Male; Methyl Ethers; Middle Aged; Pancuronium; Tubocurarine
PubMed: 4003796
DOI: 10.1097/00000542-198506000-00010 -
Anesthesiology Jun 1988To assess the interaction between verapamil and fentanyl-pancuronium, dogs were chronically instrumented to measure heart rate; PR interval; aortic, left ventricular,...
To assess the interaction between verapamil and fentanyl-pancuronium, dogs were chronically instrumented to measure heart rate; PR interval; aortic, left ventricular, and left atrial pressures; and coronary, carotid, and renal blood flows. The effect of fentanyl citrate infusion on single-dose verapamil pharmacokinetics was examined in six animals. The effects of verapamil infusion (3 micrograms.kg-1.min-1 and 6 micrograms.kg-1.min-1) were examined in the conscious state and during fentanyl infusion plus pancuronium on two separate occasions in nine dogs. In addition, the effects of fentanyl citrate (500 micrograms.kg-1 followed by 1.5 micrograms.kg-1.min-1) were examined over 1 h of infusion. Fentanyl infusion did not affect single-dose verapamil pharmacokinetics. In the conscious animals, verapamil increased heart rate and PR interval, and slightly decreased LV dP/dt. Fentanyl combined with pancuronium increased mean arterial pressure and LV dP/dt. During fentanyl infusion, verapamil decreased mean arterial pressure and LV dP/dt, increased PR interval, and did not change heart rate. The hemodynamic effects of fentanyl infusion were steady over 1 h. In contrast to the inhalational anesthetics, which alter verapamil pharmacokinetics and have mainly additive effects with verapamil on left ventricular contractility, cardiac conduction, and regional blood flows, fentanyl-pancuronium had no effect on verapamil pharmacokinetics and minimal effect on verapamil pharmacodynamics in healthy dogs.
Topics: Animals; Dogs; Drug Interactions; Fentanyl; Hemodynamics; Pancuronium; Verapamil
PubMed: 3377234
DOI: 10.1097/00000542-198806000-00007 -
Anesthesiology Jul 1981ORG NC45, a neuromuscular blocking agent not producing tachycardia, was examined first, to establish the kinetics of the anatagonism it produces, and second, to test the... (Comparative Study)
Comparative Study
ORG NC45, a neuromuscular blocking agent not producing tachycardia, was examined first, to establish the kinetics of the anatagonism it produces, and second, to test the hypothesis that the tachycardia seen with pancuronium and gallamine reflects an action on vagal postganglionic nerve endings. The action of ORG NC45 was studied on end-plate depolarization and neuromuscular transmission in the guinea pig lumbrical muscle. Also, the effect of ORG NC45 on the response of the cardiac pacemaker to carbachol and on the response of the pacemaker to pre- and postganglionic vagal stimulation was examined in isolated guinea pig atria. ORG NC45 was a potent neuromuscular blocking agent (twice as potent as pancuronium) in this species and showed typical competitive kinetics with a dissociation constant of 0.0103 micro M. However, ORG NC45 affected the atrial system only at very high concentrations and did not affect release of transmitter from vagal nerve terminals. These results thus confirm the hypothesis that presence or absence of vagolytic action goes hand-in-hand with tachycardia or its absence clinically.
Topics: Animals; Carbachol; Guinea Pigs; Heart Atria; Heart Conduction System; Heart Rate; Motor Endplate; Neuromuscular Blocking Agents; Neuromuscular Junction; Pancuronium; Receptors, Muscarinic; Synaptic Transmission; Vagus Nerve; Vecuronium Bromide
PubMed: 6113793
DOI: 10.1097/00000542-198107000-00005 -
Anesthesiology Jul 1981
Topics: Atracurium; Cardiovascular System; Drug Evaluation; Humans; Isoquinolines; Neuromuscular Blocking Agents; Pancuronium; Quinolinium Compounds; Vecuronium Bromide
PubMed: 6113792
DOI: 10.1097/00000542-198107000-00001 -
Anesthesiology Apr 2006
Topics: Androstanols; Anesthesia; Animals; Humans; Neostigmine; Neuromuscular Blockade; Neuromuscular Nondepolarizing Agents; Pancuronium; Rocuronium; Sugammadex; gamma-Cyclodextrins
PubMed: 16571954
DOI: 10.1097/00000542-200604000-00003 -
British Journal of Pharmacology Nov 1983The actions of pancuronium, a selective antagonist of acetylcholine (ACh) at nicotinic cholinoceptors at motor endplates, and hexamethonium, a selective antagonist of...
The actions of pancuronium, a selective antagonist of acetylcholine (ACh) at nicotinic cholinoceptors at motor endplates, and hexamethonium, a selective antagonist of ACh at nicotinic cholinoceptors in autonomic ganglia, have been studied in rat phrenic nerve diaphragm preparations. The effects on paraoxon-induced twitch potentiation and antidromic firing (ADF) in the phrenic nerve, were compared with the effects on normal twitch tension and intracellularly recorded miniature endplate potentials (m.e.p.ps) and endplate potentials (e.p.ps.) In preparations exposed to paraoxon, pancuronium was found to be approximately 10 times more effective in reducing the potentiated component of the twitch than the component which corresponded to the pre-paraoxon twitch. A similar result was obtained with hexamethonium. Pancuronium and hexamethonium, in concentrations which reduced paraoxon-induced twitch potentiation but had no effect on the twitch tension of preparations not treated with paraoxon, reduced paraoxon-induced ADF. The lowest concentrations of pancuronium and hexamethonium required for this also reduced the amplitude of m.e.p.ps and e.p.ps. Dithiothreitol, a disulphide bond reducing agent which reduces the affinity of ACh for nicotinic cholinoceptors, enhanced the potency of pancuronium 2 to 3 fold. The same also applied for hexamethonium. It is concluded that the experiments failed to provide evidence for an action of ACh on prejunctional nicotinic cholinoceptors of the ganglionic-type being involved in the initiation by paraoxon of twitch potentiation and ADF. Furthermore, the results obtained can be explained by pancuronium and hexamethonium reducing the action of ACh at the postjunctional membrane.
Topics: Animals; Hexamethonium Compounds; In Vitro Techniques; Male; Membrane Potentials; Motor Endplate; Neuromuscular Junction; Pancuronium; Paraoxon; Rats; Rats, Inbred Strains
PubMed: 6640203
DOI: 10.1111/j.1476-5381.1983.tb10720.x -
Anesthesiology Aug 1979To establish whether the plasma concentration of pancuronium reflects magnitude of neuromuscular blockade, the authors determined times of recovery from neuromuscular...
To establish whether the plasma concentration of pancuronium reflects magnitude of neuromuscular blockade, the authors determined times of recovery from neuromuscular blockade and associated plasma concentrations following equipotent doses of pancuronium using three methods of pancuronium administration: the isolated-arm technique in conscious volunteers (n = 4), and the bolus intravenous injection (n = 7) and continuous-infusion methods (n = 3) in anesthetized patients. Although maximum depressions of twitch tension were similar (85 +/- 11,91 +/- 6, and 92 +/- 4 per cent, respectively) with the three techniques, times to recovery from neuromuscular blockade differed significantly, being 10 +/- 2 min with the isolated-arm technique, 23 +/- 7 min with the bolus-injection technique, and 46 +/- 5 min with the continuous-infusion method. The plasma concentration of pancuronium necessary for neuromuscular blockade was least with the isolated-arm technique and greatest with continuous infusion. At 25 and 75 per cent recovery, mean plasma concentrations were 0.07 +/- 0.01 and 0.04 +/- 0.01 microgram/ml in the isolated arm; 0.13 +/- 0.04 and 0.09 +/- 0.02 microgram/ml after bolus injection, and 0.20 +/- 0.04 and 0.11 microgram/ml during continuous infusion, respectively. It is concluded that the relationship between plasma concentration of pancuronium and magnitude of neuromuscular blockade depends on the method of pancuronium administration.
Topics: Humans; Injections; Injections, Intravenous; Neuromuscular Junction; Pancuronium; Receptors, Drug; Ulnar Nerve
PubMed: 453611
DOI: 10.1097/00000542-197908000-00005 -
Anesthesiology Oct 1988Using the isolated perfused rat liver preparation, the disappearance from the perfusate and the excretion in the bile of vecuronium bromide and pancuronium bromide and... (Comparative Study)
Comparative Study
Using the isolated perfused rat liver preparation, the disappearance from the perfusate and the excretion in the bile of vecuronium bromide and pancuronium bromide and their metabolites were followed for 2 h after the addition of 1 mg of either drug to the perfusate. In addition, the rate of change of the hepatic content of these two compounds was calculated by serially subtracting the amount of the compound and the metabolites in the bile and in the perfusate from the dose of drug added to the perfusate. It was found that, whereas the concentration of pancuronium in the perfusate declined slowly and monoexponentially, vercuronium concentration in the perfusate declined rapidly in a biexponential manner. No metabolites of either drug were detected in the perfusate. Approximately 40% of the injected dose of vecuronium was excreted in the bile as unchanged vecuronium and another 30% as the 3-hydroxy metabolite. No other metabolites of vecuronium were found in the bile. In total only about 7% of pancuronium (unchanged) was collected in the bile by the end of the experiment. It is concluded that, in comparison to pancuronium, the rat liver takes up large amounts of vecuronium rapidly, half of which is eliminated as unchanged vecuronium and half as the 3-hydroxy derivative. A small amount of vecuronium or its 3-hydroxy metabolite is returned to the perfusate from the liver. Some possible mechanisms underlying these differences are discussed.
Topics: Animals; Bile; In Vitro Techniques; Liver; Male; Pancuronium; Perfusion; Rats; Rats, Inbred Strains; Vecuronium Bromide
PubMed: 2902816
DOI: 10.1097/00000542-198810000-00007 -
The Journal of Emergency Medicine 1996Neuromuscular blocking agents (NMBAs) are utilized frequently in the emergency department (ED). We begin with a brief history of neuromuscular blockade, then review the... (Review)
Review
Neuromuscular blocking agents (NMBAs) are utilized frequently in the emergency department (ED). We begin with a brief history of neuromuscular blockade, then review the indications and guidelines for its use in the emergency department setting. The relevant agents will be discussed focusing on dosage, side effects, and adverse reactions. Special attention will be paid to succinylcholine, the drug most commonly employed in the ED setting, followed by a summary of the nondepolarizing agents currently available, in particular the four shorter-acting agents that are most appropriate for administration in the ED.
Topics: Androstanols; Atracurium; Drug Utilization; Emergency Service, Hospital; Humans; Isoquinolines; Mivacurium; Neuromuscular Depolarizing Agents; Neuromuscular Nondepolarizing Agents; Pancuronium; Rocuronium; Succinylcholine; Vecuronium Bromide
PubMed: 8740751
DOI: 10.1016/0736-4679(95)02105-1