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Pharmacy World and Science

, Volume 19, Issue 1, pp 13–34 | Cite as

Part 2: Pharmacology of neuromuscular blocking agents

  • L.H.D.J. Booij
Article

Abstract

Clinically, neuromuscular blockade is induced with either depolarizing or non‐depolarizing relaxants. Suxamethonium is the only depolarizing relaxant still in use. It is hydrolysed in the plasma by pseudo‐cholinesterase (plasma cholinesterase). In some patients and in particular diseases the plasma cholinesterase activity is low and hence the effect of suxamethonium prolonged. Suxamethonium is characterized by side‐effects such as myalgia, fasciculations and increase in intraocular, intracranial and intragastric pressure. More serious adverse reactions are masseter muscle spasm and potassium release, in patients with some neuromuscular diseases and increase in extrajunctional acetylcholine receptors. As non‐depolarizing muscle relaxants benzylisoquinolines and steroidal compounds are mainly used. Each relaxant has its own pharmacological characteristics. The effect of most relaxants depends on liver and renal function because the pharmacokinetic behaviour is strongly dependent on these organs. Also, acid‐base balance disturbances, change in temperature, and neurological diseases have an effect on the profile of the relaxants. A number of drugs (anaesthetics, antibiotics, antiepileptics, etc.) have an effect on neuromuscular transmission, and thus interact with the relaxants. Some non-depolarizing relaxants cause histamine release and cardiovascular effects.

Aminosteroids Benzylisoquinolines Cardiovascular effects Depolarizing relaxants Drug interactions Histamine release Muscle relaxants Non-depolarizing relaxants Effect of hepatic diseases Effect of renal diseases Neuromuscular diseases 

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References

  1. 1.
    Katz RL. Neuromuscular effects of d-tubocurarine, edrophonium and neostigmine in man. Anesthesiology 1967;28: 327–36.Google Scholar
  2. 2.
    Ritter DM, Rettke SR, Ilstrup DM, Burritt MF. Effect of plasma cholinesterase activity on the duration of action of succinylcholine in patients with genotypically normal enzyme. Anesth Analg 1988;67:1123–6.Google Scholar
  3. 3.
    VanLinthout LEH, van Egmond J, De Boo T, Lerou JGC, Wevers RA, Booij LHDJ. Factors affecting magnitude and time course of neuromuscular block produced by suxame-thonium. Br J Anaesth 1992;69:29–35.Google Scholar
  4. 4.
    Schulte-Sasse U, Eberlein HJ, Kirch EM, Schlittenhardt W, Schmücker, Underwood D. Has the routine use of Succinylcholine come to an end after forty years? Anaesth Intensivemed 1993;34:230–4.Google Scholar
  5. 5.
    Zahl K, Apfelbaum JL. Muscle pain occurs after outpatient laparoscopy despite the substitution of vecuronium for suc-cinylcholine. Anesthesiology 1989;70:408–11.Google Scholar
  6. 6.
    Trépanier CA, Brousseau C, Lacerte L. Myalgia in outpatient surgery: comparison of atracurium and succinylcholine. Can J Anaesth 1988;35:255–9.Google Scholar
  7. 7.
    Erkola O. Effects of precurarisation on suxamethonium-induced postoperative myalgia during the first trimester of pregnancy. Acta Anaesthesiol.Scand. 1990;34:63–76.Google Scholar
  8. 8.
    Pace NL. Prevention of succinylcholine myalgias: A meta-analysis. Anesth Analg 1990;70:477–83.Google Scholar
  9. 9.
    McLouglin C, Elliott P, McCarthy G, Mirakhur RK. Muscle pains and biochemical changes following suxamethonium administration after six pretreatment regimes. Anaesthesia 1992;47:202–6.Google Scholar
  10. 10.
    Warner LO, Brener DL, Davidson PJ, Rogers GL, Beach TP. Effects of lidocaine, succinylcholine, and tracheal intubation on intraocular pressure in children anaesthetized with halo-thane-nitrous oxide. Anesth Analg 1989;69:687–90.Google Scholar
  11. 11.
    Libonati MM, Leahy JJ, Ellison N. The use of succinylcholine in open eye surgery. Anesthesiology 1985;62:637–40.Google Scholar
  12. 12.
    Kelly RE, Dinner M, Turner LS, Haik B, Abramson DH, Daines P. Succinylcholine increased intraocular pressure in the human eye with the extraocular muscles detached. Anesthesiology 1993;79:948–52.Google Scholar
  13. 13.
    Smith G, Dalling R, Williams TIR. Gastro-oesophageal pres-sure gradient changes produces by induction of anaesthesia and suxamethonium. Br J Anaesth 1978;50:1137–43.Google Scholar
  14. 14.
    Minton MD, Grosslight K, Stirt JA, Bedford RF. Increases in intracranial pressure from succinylcholine: prevention by prior nondepolarising blockade. Anesthesiology 1986;65: 165–9.Google Scholar
  15. 15.
    Kovarik WD, Mayberg TS, Lam AL, Mathisen TL, Winn HR. Succinylcholine does not change intracranial pressure, cere-bral blood flow velocity, or the electroencephalogram in patients with neurologic injury. Anesth Analg 1994;78:469–73.Google Scholar
  16. 16.
    Artru AA. Muscle relaxation with succinylcholine or vecuro-nium does not alter the rate of CSF production or resistance to reabsorption of CSF in dogs. Anesthesiology 1988;68: 392–6.Google Scholar
  17. 17.
    Thiagarajah S, Sophie S, Lear E, Azar I, Frost EAM. Effect of suxamethonium on the ICP of cats with and without thio-pentone pretreatment. Br J Anaesth. 1988;60:157–60.Google Scholar
  18. 18.
    Smith CE, Donati F, Bevan DR. Effects of succinylcholine at the masseter and adductor pollicis muscle in adults. Anesth Analg 1989;69:159–62.Google Scholar
  19. 19.
    VanderSpek AFL, Reynolda PI, Fang WB, Ashton-Miller JA, Stohles CS, Schork MA. Changes in resistance to mouth opening induced by depolarizing and non-depolarizing neuromuscular relaxants. Br J Anaesth 1990;64:21–7.Google Scholar
  20. 20.
    O'Flynn RP, Shutack JG, Rosenberg H, Fletcher JE. Masseter muscle rigidity and malignant hyperthermia susceptibility in pediatric patients. Anesthesiology 1994;80:1228–33.Google Scholar
  21. 21.
    Manninen PH, Makendran B, Gelb AW, Merchant RN. Succinylcholine does not increase serum potassium levels in patients with acutely ruptured cerebral aneurysms. Anesth Analg 1990;70:172–5.Google Scholar
  22. 22.
    Koller ME, Breivik H, Grieder P, Jones DJ, Smith RB. Synergistic effect of acidosis and succinyl-induced hyperka-lemia in spinal cord transected rats. Acta Anaesthesiol Scand 1984;28:87–90.Google Scholar
  23. 23.
    Schwartz DE, Kelly B, Caldwell JE, Carlisle AS, Cohen NH. Succinylcholine-induced hyperkalemic arrest in a patient with severe metabolic acidosis and exsanguinating hemor-rhage. Anesth Analg 1992;75:291–3.Google Scholar
  24. 24.
    Brown TCK, Bell B. Electromyographic responses to small doses of suxamethonium in children after burns. Br J Anaesth 1987;59:1017–21.Google Scholar
  25. 25.
    Viby-Mogensen J, Hanel HK, Hansen E, Sorensen B, Graae J. Serum cholinesterase activity in burned patients. I. Biochemical findings. Acta Anaesthesiol Scand 1975;19: 159–79.Google Scholar
  26. 26.
    Gronert GA, Theye RA. Pathophysiology of hyperkalemia produced by succinylcholine. Anesthesiology 1975;43:89–99.Google Scholar
  27. 27.
    Martin J, Goldhill DR, Goudsouzian NG. Clinical pharmacol-ogy of muscle relaxants in patients with burns. J Clin Pharmacol 1986;26:680–5.Google Scholar
  28. 28.
    Rosenberg H, Gronert GA. Intractable cardiac arrest in chil-dren given succinylcholine. Anesthesiology 1992;77:1054.Google Scholar
  29. 29.
    Marell RC, Berman JM, Royster RI, Petrozza PH, Kelly JS, Colonna DM. Revised label regarding use of succinylcholine in children and adolescents: I. Anesthesiology 1994;80:242.Google Scholar
  30. 30.
    Badgwell JM, Hall SC, Lockhart C. Revised label regarding use of succinylcholine in children and adolescents: II. Anesthesiology 1994;80:243.Google Scholar
  31. 31.
    Lerman J, Berdock JE, Bissonnette B, Braude BM, Cox P, Crawford MW, Creighton RE, Dodgson BG, Fear DW, Gerus LR et al. Succinylcholine warning. Can J Anaesth 1993;41:165.Google Scholar
  32. 32.
    Katz L, Wright C, Harter J, Zung M, Scally D, Spyker D. In reply. Anesthesiology 1994;80:243–4.Google Scholar
  33. 33.
    Kent RS. In reply. Anesthesiology 1994;80:244–5.Google Scholar
  34. 34.
    Rosenberg H, Gronert GA. Intractable cardiac arrest in chil - dren given succinylcholine. Anesthesiology 1992;77:1054.Google Scholar
  35. 35.
    Sorensen M, Engbaek J, Viby-Mogensen J, Guldager H, Jensen FM. Bradycardia and cardiac asystole following a sin-gle injection of suxamethonium. Acta Anaesthesiol Scand 1984;28:232–5.Google Scholar
  36. 36.
    Nigrovic V, McCullough LS, Watskol A, Levin JA, Martin JT. Succinylcholine-induced increases in plasma catecholamine levels in humans. Anesth Analg 1983;62:627–32.Google Scholar
  37. 37.
    Oshita S, Denda S, Fujiwara Y, Takeshida H, Kosaka F. Pretreatment with d-tubocurarine, vecuronium, and pancu-ronium attenuates succinylcholine-induced increases in plas-ma norepinephrine concentrations in humans. Anesth Analg 1991;72:84–8.Google Scholar
  38. 38.
    Yasuda I, Hirano T, Amaha K, Fudeta H, Obara S. Chronotropic effects of succinylcholine and succinylmo-nocholine on sinoatrial node. Anesthesiology 1982;57:289–92.Google Scholar
  39. 39.
    Leiman BC, Katz J, Butler BD. Mechanisms of succinylcho-line-induced arrhythmias in hypoxic or hypoxic-hypercarbic dogs. Anesth Anal 1987;66:1292–7.Google Scholar
  40. 40.
    Bowman WC. Prejunctional and postjunctional cholinocep-tors at the neuromuscular junction. Anesth Analg 1980;59:935–43.Google Scholar
  41. 41.
    Greenawalt III, JW. Succinylcholine-induced hyperkalemia 8 weeks after a brief paraplegic episode. Anesth Analg 1992;75:294–5.Google Scholar
  42. 42.
    Orndahl G, Sternberg K. Myotonic human musculature: stimulation with depolarizing agents. Mechanical registra-tion of the effect of succinylcholine, succinylmonocholine, and decamethonium. Acta Med.Scand. 1962;172:3 (suppl.389):3–29.Google Scholar
  43. 43.
    Baraka A, Baroody M, Yazbeck V. Repeated doses of suxame-thonium in the myasthenic patient. Anaesthesia 1993;48:782–4.Google Scholar
  44. 44.
    Eisenkraft JB, Book WJ, Mann SM, Papatestas AE, Hubbard M. Resistance to succinylcholine in myasthenia gravis: a dose response study. Anesthesiology 1988;69:760–3.Google Scholar
  45. 45.
    Wainwright AP, Brodrick PM. Suxamethonium in myasthenia gravis. Anaesthesia 1987;42:950–7.Google Scholar
  46. 46.
    Vanlinthout LEH, Robertson EN, Booij LHDJ. Response to suxamethonium during propofol-fentanyl-N2O/O2 anaesthesia in a patient with active myasthenia gravis receiv-ing chronic anticholinesterase therapy. Anaesthesia 1994;49:509–11.Google Scholar
  47. 47.
    Baraka A. Suxamethonium block in the myasthenic patient. Correlation with plasma cholinesterase. Anaesthesia 1992;47:217–19.Google Scholar
  48. 48.
    Whittaker M, Britten JJ. Phenotyping of individuals sensitive to suxamethonium. Br J Anaesth 1987;59:1052–5.Google Scholar
  49. 49.
    Robertson GS. Serum cholinesterase deficiency I. Disease and inheritance. Br J Anaesth 1966;38:355–60.Google Scholar
  50. 50.
    Robertson GS. Serum cholinesterase deficiency II pregnancy. Br J Anaesth 1966;38:361–4.Google Scholar
  51. 51.
    Robson N, Robertson I, Whittaker. Plasma cholinesterase changes in the puerperium. Anaesthesia 1986;41:243–9.Google Scholar
  52. 52.
    Matsuki A, Oyama T. Effects of extracorporeal circulation on plasma cholinesterase activity in man. Agressologie 1981;22:79–81.Google Scholar
  53. 53.
    Shearer ES, Russel GN. The effect of cardiopulmonary bypass on cholinesterase activity. Anaesthesia 1993;48:293–6.Google Scholar
  54. 54.
    Whittaker M. Plasma cholinesterase variants and the anaesthetist. Anaesthesia 1980;35:174–97.Google Scholar
  55. 55.
    Maddineni VR, Mirakhur RK, McCoy EP. Plasma cholineste-rase activity in elderly and young patients. Br J Anaesth 1994;72:497.Google Scholar
  56. 56.
    McCoy EP, Mirakhur RK. Comparison of the effect of neo-stigmine and edrophonium on the duration of action of sux-amethonium. Acta Anaesthesiol Scand 1995;39:744–7.Google Scholar
  57. 57.
    Shanks CA, Somogyi AA, Triggs EJ. Dose-response and plas-ma concentration-response relationship of pancuronium in man. Anesthesiology 1979;51:111–18.Google Scholar
  58. 58.
    Agoston S, Feldman SA, Miller RD. Plasma concentrations of pancuronium and neuromuscular blockade after injection into isolated arm, bolus injection, and continuous infusion. Anesthesiology 1979;51:119–22.Google Scholar
  59. 59.
    Wintersteiner O, Dutcher JD. Curare alkaloids from Chondodendron tomentosum. Science 1943;97:467–70.Google Scholar
  60. 60.
    Matteo RS, Nishitateno K, Pua EK, Spector S. Pharmacokinetics of d-tubocurarine in man: effect of an osmotic diuretic on urinary excretion. Anesthesiology 1980;52:335–8.Google Scholar
  61. 61.
    Amaki Y, Waud BE, Waud DR. Atracurium-receptor kinetics: simple behavior from a mixture. Anesth Analg 1985;64:777–80.Google Scholar
  62. 62.
    Stenlake JB, Waigh RD, Dewar GH, Dhar NC, Hughes R, Chapple DJ, et al. Biodegradable neuromuscular blocking agents. Part 6: Stereochemical studies on atracurium and related polyalkylene diesters. Eur J Med Chem 1984;19: 441–50.Google Scholar
  63. 63.
    Tsui D, Graham GG, Torda TA. The pharmacokinetics of atra-curium isomers in vitro and in humans. Anesthesiology 1987;67:722–8.Google Scholar
  64. 64.
    Robertson EN, Booij LHDJ, Fragen RJ, Crul JF. A clinical com-parison of atracurium and vecuronium (Org NC45). Br J Anaesth 1983;55:125–30.Google Scholar
  65. 65.
    Griffiths RB, Hunter JM, Jones RM. Atracurium infusions in patients with renal failure on an ITU. Anaesthesia 1986;41:375–81.Google Scholar
  66. 66.
    Hosking MP, Lennon RL, Gronert GA. Combined H1 and H2 receptor blockade attenuates the cardiovascular effects of high dose atracurium for rapid sequence endotracheal intu-bation. Anesth Analg 1988;67:1089–92.Google Scholar
  67. 67.
    Hughes R, Chapple DJ. The pharmacology of atracurium: a new competitive neuromuscular blocking agent. Br J Anaesth 1981;53:31–44.Google Scholar
  68. 68.
    Stenlake JB, Waigh RD, Dewar GH. Biodegradable neuro-muscular blocking agents part 4: atracurium besylate and related polyalkylene di-esters. Europ J Med Chem 1981;16: 515–24.Google Scholar
  69. 69.
    Kent AP, Parker CJR, Hunter JM. Pharmacokinetics of atracu-rium and laudanosine in the elderly. Br J Anaesth 1989; 63:661–6.Google Scholar
  70. 70.
    Nigrovic V, Banoub M. Pharmacokinetic modelling of a par-ent drug and its metabolite. Atracurium and laudanosine. Clin Pharmacokinet 1992;22:396–408.Google Scholar
  71. 71.
    Diefenbach C, Abel M, Buzello W. Greater neuromuscular blocking potency of atracurium during hypothermic than during normothermic cardiopulmonary bypass. Anesth Analg 1992;75:675–8.Google Scholar
  72. 72.
    Meretoja OA, Taivaninen T, Wirtavuori K. Pharmacodynamic effects of 51W89, an isomer of atracurium, in children under halothane anaesthesia. Br J Anaesth 1995;74:6–11.Google Scholar
  73. 73.
    Belmont MR, Lien CA, Quessy S, Abou-Donia MM, Abalos A, Eppich L, Savarese JJ. The clinical neuromuscular pharmacol-ogy of 51W89 in patients receiving nitrous oxide/opi-oid/ barbiturate anesthesia. Anesthesiology 1995;82:1139–45.Google Scholar
  74. 74.
    Littlejohn IH, Abhay K, El Sayed A, Broohead CJ, Duvaldestin P, Flynn PJ. Intubating conditions following 1R CIS 1'R CIS atracurium (51W89). Anaesthesia 1995;50:499–502.Google Scholar
  75. 75.
    Lien CA, Belmont MR, Abalos A, Eppich L, Quessy S, Abou-Donia MM, Savarese JJ. The cardiovascular effects and hista-mine-releasing properties of 51W89 in patients receiving nitrous oxide/opioid/barbiturate anesthesia. Anesthesiology 1995;82:1131–8.Google Scholar
  76. 76.
    Konstadt SN, Reich DL, Stanley III TE, DePerio M, Chuey C, Schwartzbach C, Abou-Donia M. A two-center comparison of the cardiovascular effects of cisatracurium (Nimbex TM) and vecuronium in patients with coronary artery disease. Anesth Analg 1995;81:1010–14.Google Scholar
  77. 77.
    Eastwood NB, Boyd AH, Parker CJR, Hunter JM: Pharmacokinetics of 1R-cis-1'cisatracurium besylate (51W89) and plasma laudanosine concentrations in health and chronic renal failure. Br J Anaesth 1995;75:431–5.Google Scholar
  78. 78.
    Boyd AH, Eastwood NB, Parker CJR, Hunter JM: Pharmacodynamics of the 1R cis-1'R cisisomer of atracurium (51W89) in health and chronic renal failure. Br J Anaesth 1995;74:400–4.Google Scholar
  79. 79.
    Savarese JJ, Ali HH, Basta SJ, Embree PB, Scott RPF, Sunder N, Weakly JN, Wasila WB, El-Sayad HA. The clinical neuromus-cular pharmacology of Mivacurium chloride (BW B1090U). Anesthesiology 1988;68:723–32.Google Scholar
  80. 80.
    Maehr RB, Belmont MR, Wray DL, Savarese JJ, Wastila WB. Autonomic and neuromuscular effects of mivacurium and isomer in cats. Anesthesiology 1991;75:A772.Google Scholar
  81. 81.
    Head-Rapson AG, Devlin JC, Parker CJR, Hunter JM. Pharmacokinetics and pharmacodynamics of the three iso-ers of mivacurium in health, in end-stage renal failure and in patients with impaired renal function. Br J Anaesth 1995;75:31–6.Google Scholar
  82. 82.
    Stoops CM, Curtis CA, Kovach DA, McCammon RL, Stoelting RK, Warren TM, Miller D, Bopp SK, Jugovic DJ, Abou-Donia MM. Hemodynamic effects of Mivacurium chloride administered to patients during oxygen-sufentanil anesthesia for coronary artery bypass grafting or valve replacement. Anesth Analg 1989;68:333–9.Google Scholar
  83. 83.
    Stoops CM, Curtis CA, Kovach DA, McCammon RL, Stoelting RK, Warren TM, Miller D, Bopp SK, Jugovic DJ, Abou-Donia MM. Hemodynamic effects of Mivacurium chloride administered to patients during oxygen-sufentanil anesthesia for coronary artery bypass grafting or valve replacement. Anesth Analg 1989;68:333–9.Google Scholar
  84. 84.
    Savarese JJ, Ali HH, Basta SJ, Scott RPF, Embree PB, Wastila WB, Abou-Donia MM, Gelb C. The cardiovascular effects of mivacurium chloride (BW B1090U) in patients receiving nitrous oxide-opiate-barbiturate anesthesia. Anesthesiology 1989;70:386–94.Google Scholar
  85. 85.
    Goldhill DR, Whitehead JP, Emmott RS, Griffith AP, Bracey BJ, Flynn PJ. Neuromuscular and clinical effects of mivacurium chloride in healthy adult patients during nitrous oxide-enflu-rane anaesthesia. Br J Anaesth 1991;67:289–95.Google Scholar
  86. 86.
    Naguib M, Abdulatif M, Selim M, Al-Ghamdi A. Dose-response studies of the interaction between mivacurium and suxamethonium. Br J Anaesth 1995;74:26–30.Google Scholar
  87. 87.
    Goudsouzian NG, Alifirmoff JK, Eberly C, Smeets R, Griswold J, Miller V, McNulty BF, Savarese JJ. Neuromuscular and car-diovascular effects of mivacurium in children. Anesthesio-logy 1989;70:237–42.Google Scholar
  88. 88.
    Cook DR, Stiller RL, Weakly JN, Chakravorti S, Brandom BW, Wlech RM. In vitro metabolism of Mivacurium chloride (BW B1090U) and succinylcholine. Anesth Analg 1989;68:452–6.Google Scholar
  89. 89.
    Ostergaard D, Jensen FS, Jensen E, Viby-Mogensen J. Influence of plasma cholinesterase activity on recovery from mivacurium-induced neuromuscular blockade. Acta Anaes-thesiol Scand 1989;33 suppl. 191:164.Google Scholar
  90. 90.
    Ostergaard D, Janden E, Jensen FS, Viby-Mogensen J. The duration of action of mivacurium induced neuromuscular block in patients homozygous for the atypical plasma choli-nesterase gene. Anesthesiology 1991;75:A774.Google Scholar
  91. 91.
    Ostergaard D, Jensen FS, Jensen E, Skovgaard LT, Viby-Mogensen J. Influence of plasma cholinesterase activity on recovery from mivacurium-induced neuromuscular block-ade in phenotypically normal patients. Acta Anaesthesiol Scand 1992;36:702–6.Google Scholar
  92. 92.
    Goudsouzian NG, d'Hollander AA, Viby-Mogensen J. Prolonged neuromuscular block from mivacurium in two patients with cholinesterase deficiency. Anesth Analg 1993;77:183–5.Google Scholar
  93. 93.
    Maddineni VR, Mirakhur RK. Prolonged neuromuscular block following mivacurium. Anesthesiology 1993;71:227–31.Google Scholar
  94. 94.
    Sockalingam I, Green DW. Mivacurium-induced prolonged neuromuscular block. Br J Anaesth 1995;74:234–6.Google Scholar
  95. 95.
    Fox MW, Hunt PCW. Prolonged neuromuscular block asso-ciated with mivacurium. Br J Anaesth 1995;74:237–8.Google Scholar
  96. 96.
    Diefenbach C, Abel M, Rump AFE, Grond S, Korb H, Buzello W. Changes in plasma cholinesterase activity and mivacuri-um neuromuscular block in response to normothermic car-diopulmonary bypass. Anesth Analg 1995;80:1088–91.Google Scholar
  97. 97.
    Petersen RS, Bailey PL, Kalameghan R, Ashwood ER. Prolonged neuromuscular block after mivacurium. Anesth Analg 1993;76:194–6.Google Scholar
  98. 98.
    Hart PS, Wright PC, Brown R, Lau M, Sharma ML, Miller RD, Gruenke L, Fisher DM. Edrophonium increases mivacurium concentrations during constant mivacurium infusion, and large doses minimally antagonize paralysis. Anesthesiology 1995;82:912–18.Google Scholar
  99. 99.
    Abdulatif M. Recovery characteristics after early administra-tion of anticholinesterases during intensive mivacurium-induced neuromuscular block. Br J Anaesth 1995;74:20–5.Google Scholar
  100. 100.
    Mangar D, Kirchhoff GT, Rose PL, Castellano FC. Prolonged neuromuscular block after mivacurium in a patient with end-stage renal disease. Anesth Analg 1993;76:866–7.Google Scholar
  101. 101.
    Naguib M, El-Grammal M, Daoud W, Ammar A, Moukhtar H, Turkistani A. Human plasma cholinesterase for antago-nism of prolonged mivacurium-induced neuromuscular blockade. Anesthesiology 1995;82:1288–92.Google Scholar
  102. 102.
    Petersen RS, Bailey PL, Kalameghan R, Ashwood ER. Prolonged neuromuscular block after mivacurium. Anesth Analg 1993;76:194–6.Google Scholar
  103. 103.
    Robertson WS, Shaikh J, Purdie DW. Mivacurium sensitivity in a patient heterozygous for the atypical and silent genes for plasma cholinesterase. Ann Clin Biochem 1995;32:431–3.Google Scholar
  104. 104.
    Goudsouzian NG, Alifinoff JK, Eberly C, Smeets R, Grisvold J, Miller V, McNully BF, Savarese JJ. Neuromuscular and cardio-vascular effects of mivacurium in children. Anesthesiology 1989;70:237–42.Google Scholar
  105. 105.
    Shanks CA, Fragen RJ, Pemberton D, Katz JA, Rizner ME. Mivacurium induced neuromuscular blockade following sin-gle bolus doses and with continuous infusion during either balanced or enflurane anesthesia. Anesthesiology 1989;71: 362–6.Google Scholar
  106. 106.
    Caldwell JE, Kitts JB, Heier T, Fahey MR, Lynam DP, Miller RD. The dose-response relationship of mivacurium chloride in humans during nitrous oxide-fentanyl or nitrous oxide-enflurane anesthesia. Anesthesiology 1989;70:31–5.Google Scholar
  107. 107.
    Maddineni VR, Cooper R, Stanley JC, Mirakhur RK, Clarke RSJ. Clinical evaluation of doxacurium chloride. Anaesthesia 1992;47:554–7.Google Scholar
  108. 108.
    Murray DJ, Mehta MP, Choi WW, Forbes RB, Sokoll MD, Gergis SD, Rudd GD, Abou-Donia MM. The neuromuscular blocking and cardiovascular effects of Doxacurium chloride in patients receiving nitrous oxide narcotic anesthesia. Anesthesiology 69;1988:472–7.Google Scholar
  109. 109.
    Basta SJ, Savarese JJ, Ali HH, Embree PB, Schwartz AF, Rudd GD, Wastila WB. Clinical pharmacology of Doxacurium chlo-ride. Anesthesiology 69;1988:478–86.Google Scholar
  110. 110.
    Lennon RL, Hosking MP, Houck PC, Rose SH, Wedel DJ, Gibson BE, Ascher JA, Rudd GD. Doxacurium chloride for neuromuscular blockade before tracheal intubation and sur-gery during nitrous oxide-oxygen-narcotic-enflurane anes-thesia. Anesth Analg 1989;68:225–60.Google Scholar
  111. 111.
    Schmith VD, Fiedler-Kelly J, Abou-Donia M, Huffman CS, Grasela TH, Jr. Population pharmacodynamics of doxacuri-um. Clin Pharmacol Ther 1992;52:528–36.Google Scholar
  112. 112.
    Stoops CM, Curtis CA, Kovach DA, McCammon RL, Stoelting RK, Warren TM, Miller D, Abou-Donia MM. Hemodynamic effects of Doxacurium chloride in patients receiving oxygen sufentanil anesthesia for coronary artery bypass grafting or valve replacement. Anesthesiology 1988;69:365–70.Google Scholar
  113. 113.
    Emmott RS, Bracey DJ, Goldhill DR, Yate PM, Flynn PJ. Cardiovascular effects of doxacurium, pancuronium, and vecuronium in anaesthetised patients presenting for coro-nary artery bypass surgery. Br J Anaesth 1990;65:480–6.Google Scholar
  114. 114.
    Cashman JN, Luke J, Jones RM. Neuromuscular block with doxacurium (BE A938U) in patients with normal or absent renal function. Br J Anaesth 1990;64:186–92.Google Scholar
  115. 115.
    Cook DR, Freeman JA, Lai AA, Robertson KA, Kang Y, Stiller RL, Aggarwal S, Abou-Donia MM, Welch RM. Pharmacokinetics and pharmacodynamics of doxacurium in normal patients and those with hepatic or renal failure. Anesth Analg 1991;72:145–50.Google Scholar
  116. 116.
    Reich DL. Transient systemic hypotension and cutaneous flushing in response to doxacurium chloride. Anesthesiology 1989;71:783–5.Google Scholar
  117. 117.
    Katz JA, Fragen RJ, Shanks CA, Dunn K, McNulty B, Rudd GD. Dose-response relationships of doxacurium chloride in humans during anesthesia with nitrous oxide and fentanyl, enflurane, isoflurane, or halothane. Anesthesiology 1989;70: 432–6.Google Scholar
  118. 118.
    Goudsouzian NG, Alifimoff JK, Liu LMP, Foster VJ, McNulty BF, Savarese JJ. Neuromuscular and cardiovascular effects of doxacurium in children anaesthetized with halothane. Br J Anaesth 1989;62:263–8.Google Scholar
  119. 119.
    Sarner JB, Brandom BW, Cook DR, Dong ML, Horn MC, Woelfel SK, Davis PJ, Rudd GD, Foster VJ, McNulty BF. Clinical pharmacology of doxacurium chloride (BW 938U) in children. Anesth Analg 1988;67:303–6.Google Scholar
  120. 120.
    Scott RPF, Norman J. Doxacurium chloride: A preliminary clinical trial. Br J Anaesth 1989;62:373–7.Google Scholar
  121. 121.
    Hughes R. Evaluation of the neuromuscular blocking proper-ties and side-effects of the two new isoquinolinium bisquar-ternary compounds (BW 252C64 and BW 403C65). Br J Anaesth 1972;44:27–42.Google Scholar
  122. 122.
    Fiamengo SA, Savarese JJ, Chiscolm D, Lien C, Wastila WB. Pharmacology of BW954U. Anesthesiology 1990;73:A863.Google Scholar
  123. 123.
    Huu-Lainé FK, Pingo-Scognamiglio W. Activité curarisante du dichlorure de ?b-2???bistrimethylammonium ?a-prégnane (malouétine) et de ses stéréoisomères. Arch Int Pharmacodyn Thér 1964;147:209–19.Google Scholar
  124. 124.
    Bucket WR, Hewet CL, Savage DS. Pancuronium bromide and other steroidal neuromuscular blocking agents contain-ing acetylcholine fragments. J Med Chem 1973;16:1116–24.Google Scholar
  125. 125.
    Durant NN, Marshall IG, Savage DS, Nelson DJ, Sleigh T, Carlyle IC. The neuromuscular and autonomic blocking activities of pancuronium, Org. NC45, and other pancuroni-um analogues, in the cat. J Pharm Pharmacol 1979;31:83–7.Google Scholar
  126. 126.
    Marshall IG, Agoston S, Booij LHDJ, Durant NN, Foldes FF. Comparison of the cardiovascular actions of Org.NC45 with those produced by other non-depolarizing neuromuscular blocking agents in experimental animals. Br J Anaesth 1980;52:21S–32S.Google Scholar
  127. 127.
    Naguib M, Samarkandi AH, Bakhamees HS, Magboul MA, El-Bakry AK. Comparative potency of steroidal neuromuscu-lar blocking drugs and isobolographic analysis of the inter-action between rocuronium and other aminosteroids. Br J Anaesth 1995;75:37–42.Google Scholar
  128. 128.
    Krieg N, Crul JF, Booij LHDJ. Relative potency of Org NC45, pancuronium, alcuronium and tubocurarine in anaesthe-tized man. Br J Anaesth 1980;52:783–8.Google Scholar
  129. 129.
    Miller RD, Agoston S, Booij LHDJ, Kersten UW, Crul JF, Ham J. The comparative potency and pharmacokinetics of pancuro-nium and its metabolites in anesthetized man. J Pharmacol Exp Ther 1978;207;539–43.Google Scholar
  130. 130.
    Bergin AM, Clarke TA, Matthews TG. Problems with pancu-ronium in the neonatal intensive care unit. Irish Med J 1988;81:39–40.Google Scholar
  131. 131.
    Fahey MR, Morris RB, Miller RD, Nguyen TL, Upton RA. Pharmacokinetics of Org NC45 (Norcuron) in patients with and without renal failure. Br J Anaesth 1981;53:1049–53.Google Scholar
  132. 132.
    Bencinin AF, Scaf AHJ, Sohn YJ, Meistelman C, Lienhart A, Kersten UW, Schwarz S, Agoston S. Disposition and urinary excretion of vecuronium bromide in anesthetized patients with normal renal function or renal failure.Anesth Analg 1986;65:245–51.Google Scholar
  133. 133.
    Wright PMC, Hart P, Lau M, Sharma ML, Gruenke L, Fisher DM. Cumulative characteristics of atracurium and vecuroni-um. Anesthesiology 1994;81:59–68.Google Scholar
  134. 134.
    Caldwell JE, Szenohradszky J, Segredo V, Wright PMC, McLoughlin C, Sharma ML, Gruenke LD, Fisher DM, Miller RD. The pharmacodynamics and pharmacokinetics of the metabolite 3-desacetylvecuronium (Org 7268) and its par-ent compound, vecuronium, in human volunteers. J Pharmacol Exp Ther 1994;270:1216–22.Google Scholar
  135. 135.
    Stanley JC, Mirakhur RJ. Comparative potency of pipecuroni-um bromide and pancuronium bromide. Br J Anaesth 1989;63:754–5.Google Scholar
  136. 136.
    Fitzal S, Ilias W, Kalina K, Schwarz S, Foldes FF, Steinbereithner K, Neuromuskulare und kardiovaskulare Effekte von Duador, einem neuen kurz wirksamen nicht depolarisierenden Muskelrelaxans. Anaesthesist 1982;32: 674–9.Google Scholar
  137. 137.
    Dubois MY, Fleming NW, Lea DE. Effects of succinylcholine on the pharmacodynamics of pipecuronium and pancuroni-um. Anesth Analg 1991;72:364–8.Google Scholar
  138. 138.
    Caldwell JE, Castagnoli KP, Canfell PC, Fahey MR, Lynam DP, Fisher DM, Miller RD. Pipecuronium and pancuronium: comparison of pharmacokinetics and duration of action. Br J Anaesth 1988;61:693–7.Google Scholar
  139. 139.
    Pittet JF, Tassonyi E, Morel DR, Gemperle G, Richter M, Rouge JC. Pipecuronium-induced neuromuscular blockade during nitrous oxide-fentanyl, isoflurane, and halothane anesthesia in adults and children. Anesthesiology 1989;71:210–13.Google Scholar
  140. 140.
    Abdulatif M, Naguib M. Neostigmine and edrophonium for reversal of pipecuronium neuromuscular blockade. Can J Anaesth 1991;38:159–63.Google Scholar
  141. 141.
    Stanley JC, Carson IW, Gibson FM, McMurray TJ, Elliott P, Lyons SM, Mirakhur RK. Comparison of the haemodynamic effects of pipecuronium and pancuronium during fentanyl anaesthesia. Acta Anaesthesiol Scand 1991;35:262–6.Google Scholar
  142. 142.
    Tassonyi E, Neidhart P, Pittet JF, Morel DR, Gemperle M. Cardiovascular effects of pipecuronium and pancuronium in patients undergoing coronary artery bypass grafting. Anesthesiology 1988;69:793–6.Google Scholar
  143. 143.
    Barankay A. Circulatory effects of pipecuronium bromide during anaesthesia of patients with severe valvular and ischaemic heart disease. Drug Res 1980;30:386–9.Google Scholar
  144. 144.
    Wierda JMKH, Karliczek GF, Vandenbrom RHG, Pinto I, Kersten, Kleef UW, Meyer DK, et al. Pharmacokinetics and cardiovascular dynamics of pipecuronium bromide during coronary artery surgery. Can J Anaesth 1990;37:183–91.Google Scholar
  145. 145.
    Wierda JMKH, Szenohradszky J, de Wit APM, Zentai G, Agoston S, Kakas M, Kleef UW, Meyer DK. The pharmacoki-netics, urinary and biliary excretion of pipecuronium bro-mide (Arduan). Eur J Anaesthesiol 1991;8:451–7.Google Scholar
  146. 146.
    Lapreye G, Dubois M, Lea D, Kataria B, Tram D. Effects of 3 intubating doses of Org 9426 in humans. Anesthesiology 1990;73:A906.Google Scholar
  147. 147.
    Foldes FF, Nagashima H, Nguyen HD, Schiller WS, Mason MM, Ohta Y. The neuromuscular effects of Org 9426 in patients receiving balanced anesthesia. Anesthesiology 1991;75:191–5.Google Scholar
  148. 148.
    Cooper R, Mirakhur RK, Clarke RSJ, Boules ZS. Comparison of intubating conditions after administration of Org 9426 (rocuronium) and suxamethonium. Br J Anaesth 1992;69:269–73.Google Scholar
  149. 149.
    Huizenga ACT, Vandenbrom RHG, Wierda JMKH, Hommes FDM, Hennis PJ. Intubating conditions and onset of neuro-muscular block of rocuronium (ORG 9426);a comparison with suxamethonium. Acta Anaesthesiol Scand 1992;36:463–8.Google Scholar
  150. 150.
    Pühringer FK, Khuenl-Brady K, Koller J, Mitterschiffthaler G. Evaluation of the endotracheal intubating conditions of roc-uranium (ORG 9426) and succinylcholine in outpatient sur-gery. Anesth Analg 1992;75:37–40.Google Scholar
  151. 151.
    Wierda JMKH, de Wit APM, Kuizinga K, Agoston S. Clinical observations on the neuromuscular blocking action of Org 9426, a new steroidal non-depolarizing agent. Br J Anaesth 1990;64:521–3.Google Scholar
  152. 152.
    Davis GK, Sziam F, Lowdon JD, Levy JH. Evaluation of hista-mine release following Org 9426 administration using a new radioimmunoassay. Anesthesiology 1991;75:A818.Google Scholar
  153. 153.
    McCoy EP, Maddineni VR, Elliot P, Mirakhur RK, Caroon IW, Cooper RA. Haemodynamic effects of rocuronium during fentanyl anaesthesia: comparison with vecuronium. Can J Anaesth 1993;408:703–8.Google Scholar
  154. 154.
    Quil TJ, Begin M, Glass PSA, Ginsberg B, Gorback MS. Clinical responses to Org 9426 during isoflurane anesthesia. Anesth Analg 1991;72:203–6.Google Scholar
  155. 155.
    Dubois M, Kataria B, Lea D, Lapeyre G. Neuromuscular effects of Org 9426 in humans during general anesthesia with and without enflurane. Anesth Analg 1991;72:S57.Google Scholar
  156. 156.
    Cooper RA, Mirakhur RK, Maddineni VR. Neuromuscular effects of rocuronium bromide (Org 9426) during fentanyl and halothane anaesthesia. Anaesthesia 1993;48:103–5.Google Scholar
  157. 157.
    Naguib M, Abdulatif M, Al-Ghamdi A. Dose-response rela-tionships for edrophonium and neostigmine antagonism of rocuronium bromide (ORG 9426)-included neuromuscular blockade. Anesthesiology 1993;79:739–45.Google Scholar
  158. 158.
    Wierda JMKH, Kleef UW, Lambalk LM, Kloppenburg WD, Agoston S. The pharmacodynamics and pharmacokinetics of Org 9426, a new non-depolarizing neuromuscular block-ing agent, in patients anaesthetized with nitrous oxide, hal-othane and fentanyl. Can J Anaesth 1991;38:430–5.Google Scholar
  159. 159.
    Khuenl-Brady K. Castagnoli KP, Canfell C, Caldwell JE, Agoston S, Miller RD. The neuromuscular blocking effect and pharmacokinetics of Org 9426 and Org 9616 in the cat. Anesthesiology 1990;72:669–74.Google Scholar
  160. 160.
    Szenohradszky J, Fisher DM, Segredo V, Caldwell JE, Bragg P, Sharma ML. Pharmacokinetics of rocuronium bromide (Or g 9426) in patients with normal renal function or patients undergoing cadaver renal transplantation. Anesthesiology 1992;77:899–904.Google Scholar
  161. 161.
    Cooper R, Mirakhur RK, Clarke RSJ, Boules ZS. Comparison of intubating conditions after administration of Org 9426 (rocuronium) and suxamethonium. Br J Anaesth 1992;69: 269–73.Google Scholar
  162. 162.
    Pühringer FK, Khuenl-Brady K, Koller J, Mitterschiffthaler G. Evaluation of the endotracheal intubating conditions of roc-uranium (Org 9426) and succinylcholine in outpatient sur-gery. Anesth Analg 1992;75:37–40.Google Scholar
  163. 163.
    Cason B, Baker DG, Hickey RF, Miller RD, Agoston S. Cardiovascular and neuromuscular effects of three steroidal neuromuscular blocking drugs in dogs (Org 9616, Org 9426, Org 9991). Anesth Analg 1990;70:382–8.Google Scholar
  164. 164.
    Baird WLM. Initial studies in man with a new myoneural blocking agent (Org 6368). Br J Anaesth 1974;46:658–61.Google Scholar
  165. 165.
    Booij LHDJ, Crul JF, van der Pol F. Cardiovascular and neuro-muscular blocking effects of four new muscle relaxants in anaesthetized Beagle dogs. Eur J Anaesthesiol 1988;6:70.Google Scholar
  166. 166.
    Muir AW, Houston J, Marshall RJ, Bowman WC, Marshall IG. A comparison of the neuromuscular blocking and autonom-ic effects of two new short-acting muscle relaxants with those of succinylcholine in the anesthetized cat and pig. Anesthesiology 1989;70:533–40.Google Scholar
  167. 167.
    Gilly H, Hirtschl MM, Steinbereithner K. Pharmacodynamics of Org 8764, atracurium and vecuronium: a comparison of vocal cord, diaphragm and tibial muscle relaxation. Anesthesiology 1988;69:A481.Google Scholar
  168. 168.
    Muir AW, Anderson K, Marshall RJ, Booij LHDJ, Crul JF, Prior C, Bowman WC, Marshall IG. The effects of a 16-N-homopi-peridino analogue of vecuronium on neuromuscular trans-mission in anaesthetized cats, pigs, dogs and monkeys, and in isolated preparations. Acta Anaesthesiol Scand 1991;35:85–90.Google Scholar
  169. 169.
    van den Broek L, Wierda JMKH, Prosst JH, Hommes FDM, Agoston S. Clinical pharmacology of Org 7617, a short act-ing non-depolarizing neuromuscular blocking agent. Eur J Clin Pharmacol 1994;46:225–9.Google Scholar
  170. 170.
    Wierda JMKH, Beaufort AM, Kleef UW, Smeulers NJ, Agoston S. Preliminary investigations of the clinical pharmacology of three short-acting non-depolarizing neuromuscular block-ing agents, Org 9453, Org 9489 and Org 9487. Can J Anaesth 1994;41:213–20.Google Scholar
  171. 171.
    van den Broek L, Lambalk LM, Richardson FJ, Wierda JMKH. Dose-response relation, neuromuscular blocking action, intubation conditions, and cardiovascular effects of Org 9273, a new neuromuscular blocking agent. Anesth Analg 1991;72:811–16.Google Scholar
  172. 172.
    Wierda JMKH, Proost JH: Structure-pharmacodynamic-phar-macokinetic relationships of steroidal neuromuscular block-ing agents. Eur J Anaesth 1995;12(suppl.11):45–54.Google Scholar
  173. 173.
    Bowman WC, Rodger IW, Houston J, Marshall IG, McIndewar I. Structure-action relationships among some deacetoxy analogues of pancuronium and vecuronium in the anesthetized cat. Anesthesiology 1988;89:57–62.Google Scholar
  174. 174.
    Wierda JMKH, van den Broek L, Proost JH, Verbaan BW, Hennis PJ. Time course of action and endotracheal intubat-ing conditions of Org 9487, a new short-acting steroidal muscle relaxant. Anesth Analg 1993;77:579–84.Google Scholar
  175. 175.
    van den Broek L, Wierda JMKH, Smeulers NJ, Proost JH. Pharmacodynamics and pharmacokinetics of an infusion of Org 9487, a new short-acting steroidal neuromuscular blocking agent. Br J Anaesth 1994;73:331–5.Google Scholar
  176. 176.
    Gandiha A, Marshall IG, Paul D, Rodger IW, Scott W, Singh H. Some actions of chandonium iodide, a new short-acting muscle relaxant, in anesthetized cats and on isolated muscle preparations. Clin Exp Pharmacol Physiol 1975;2:150–70.Google Scholar
  177. 177.
    Suri YV. Chandonium iodide - New non-depolarizing muscle relaxant. In: Suri YV, Singh D eds. Anesthesiology - clinical pharmacology. Vani Educational Books New Delhi, 1984, pp.28–35. ISBN 0-7069-2559-9.Google Scholar
  178. 178.
    Marshall IG, Paul D, Singh H. The neuromuscular and other blocking actions of 4,17a-Diomethyl-4,17a-Diaza-d-homo-???androstane dimethiodide (HS-342) in the anaesthetized cat. Eur J Pharm 1973;22:129–34.Google Scholar
  179. 179.
    Fitzal S, Ilias W, Kalina K, Schwarz S, Foldes FF, Steinbereithner K. Neuromuskuläre Effekte von Duador @, einem neuen kurz wirksamen nicht depolarisierenden Muskelrelaxans. Anaesthesist 1982;31:674–9.Google Scholar
  180. 180.
    Walker J, Shanks CA, Triggs EJ. Clinical pharmacokinetics of alcuronium chloride in man. Eur J Clin Pharmacol 1990;17:449–57.Google Scholar
  181. 181.
    Ramzan MI, Triggs EJ, Shanks CA. Pharmacokinetic studies in man with gallamine triethiodide. I. Single and multiple clini-cal doses. Eur J Clin Pharamacol 1980;17:135–43.Google Scholar
  182. 182.
    Ramzan MI, Shanks CA, Triggs EJ. Gallamine disposition in surgical patients with chronic renal failure. Br J Clin Pharmacol 1981;12:141–7.Google Scholar
  183. 183.
    Savarese JJ, Ginsberg S, Lee CM, Kitz RJ. The pharmacology of new short-acting nondepolarizing ester neuromuscular blocking agents: clinical implications. Anesth Analg 1973; 52:982–8.Google Scholar
  184. 184.
    Savarese JJ, Antonio RP, Ginsberg S. Potential clinical uses of short-acting nondepolarizing neuromuscular-blocking agents as predicted from animal experiments. Anesth Analg 1974;54:669–78.Google Scholar
  185. 185.
    Savarese JJ, Wastila WB. Pharmacology of BW985U: A short acting nondepolarizing neuromuscular blocking agent. Anesthesiology 1979;51:S277.Google Scholar
  186. 186.
    Savarese JJ, Wastila WB. BW444U: an intermediate-duration nondepolarizing blocking agent with significant lack of car-diovascular and autonomic effect. Anesthesiology 1979;51:S279.Google Scholar
  187. 187.
    Wastila WB, Savarese JJ. Autonomic/neuromuscular dose-ratios and hemodynamic effects of BW785U), a short-acting nondepolarizing ester neuromuscular blocking agent. Anesthesiology 51;1979:S278.Google Scholar
  188. 188.
    Savarese JJ, Ali HH, Basta SJ, Ramsey FM, Rosow CE, Lebowitz PW, Lineberry CG, Cloutier G. Clinical neuromus-cular harmacology of BW785U, an ultra-short-acting non-depolarizing ester neuromuscular blocking agent. Anesthesiology 1980;53:S274.Google Scholar
  189. 189.
    Savarese JJ, Basta SJ, Ali HH, Sunder N, Gionfriddo M, Goudsouzian NG, Lineberry CG. Clinical neuromuscular pharmacology of BW444U. Anesthesiology 1981;55:A197.Google Scholar
  190. 190.
    Rosow CE, Basta SJ, Savarese JJ, Ali HH, Kniffen KJ, Moss J. BW785U: correlation of cardiovascular effects with increases in plasma histamine. Anesthesiology 1980;53:S271.Google Scholar
  191. 191.
    Basta SJ, Moss J, Savarese JJ, Ali HH, Sunder N, Gionfriddo M, Lineberry CG. Cardiovascular effects of BW444U: correla-tion with plasma histamine levels. Anesthesiology 1981;55:A198.Google Scholar
  192. 192.
    Stenlake JB, Dhar NC, Maehr RB, Scharver J, Wastila WB, Midgley JH. Neuromuscular blocking agents. Approaches to short-acting compounds 2. Bis-thiazolium salts. Eur J Med Chem 1993;28:415–18.Google Scholar
  193. 193.
    Foldes FF, Chaudhry IA, Barakat T, Flores CA, Kinjo M, Bikkhazi GB, Nagashima H. Species variation in the site and mechanism of the neuromuscular effects of diadonium in rodents. Anesth Analg 1989;68:638–44.Google Scholar
  194. 194.
    Mitenko PA, Ogilvie RI (1972) Rapidly achieved plasma con-centration plateaus, with observations on theophylline kinetics. Clin Pharmacol Ther 13:329–35.Google Scholar
  195. 195.
    Somogyi AA, Shanks CA, Triggs EJ (1977a) Disposition kinet-ics of pancuronium bromide in patients with total biliary obstruction. Br J Anaesth 49:1103–8.Google Scholar
  196. 196.
    Argov Z, Mastaglia FL. Disorders of neuromuscular transmis-sion caused by drugs. N Engl J Med 1979;301:409–13.Google Scholar
  197. 197.
    Garrett ER. Pharmacokinetics and clearances related to renal processes. Int J Clin PharmacolBiopharm. 1978;16:155–72.Google Scholar
  198. 198.
    Agoston S, Vermeer GA, Kersten UW, A preliminary investi-gation of the renal and hepatic elimination of gallamine tri-ethiodide in man. Br J Anaesth 1978;50:345–51.Google Scholar
  199. 199.
    Miller RD, Matteo RD, Benet LZ, Sohn YJ. The pharmacoki-netics of d-tubocurarine in man with and without renal fail-ure. J Pharmacol Exp Ther 1977;12:23–9.Google Scholar
  200. 200.
    Philips BJ, Hunter JM. Use of mivacurium chloride by con-stant infusion in the anephric patient. Br J Anaesth 1992;68:492–8.Google Scholar
  201. 201.
    Mangar D, Kirchhoff GT, Rose PL, Castellano FC. Prolonged neuromuscular block after mivacurium in a patient with end-stage renal disease. Anesth Analg 1993;76:866–7.Google Scholar
  202. 202.
    Cooper RA, maddineni VR, Mirakhur RK, Wierda JMKH, Brady M, Fitzpatrick KTJ. Time course of neuromuscular effects and pharmacokinetics of rocuronium bromide (Org 9426) during isoflurane anaesthesia in patients with and without renal failure. Br J Anaesth 1993;71:222–6.Google Scholar
  203. 203.
    Caldwell JE, Canfell PC, Castagnolie KP, Lynam DP, Fahey MR, Fisher DM, Miller RD. The influence of renal failure on the pharmacokinetics and duration of action of pipecuroni-um bromide in patients anaesthetized with halothane and nitrous oxide. Anesthesiology 1989;70:7–12.Google Scholar
  204. 204.
    Westra P, Keulemans GTP, Houwertjes MC, Hardonk MJ, Meijer DKF. Mechanisms underlying the prolonged duration of action of muscle relaxants caused by extrahepatic choles-tasis. Br J Anaesth 1981;53:217–27.Google Scholar
  205. 205.
    Wilkinson GR, Shand DG. A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975;18:377–90.Google Scholar
  206. 206.
    Khalil M, D'Honneur G, Duvaldestin P, Slavov V, De Hys C, Gomeni R. Pharmacokinetics and pharmacodynamics of roc-uranium in patients with cirrhosis. Anesthesiology 1994;80:1241–7.Google Scholar
  207. 207.
    Magorian T, Wood P, Caldwell J, Fisher D, Segredo V, Szenohradszky J, Sharma M, Gruenke L, Miller R. The phar-macokinetics and neuromuscular effects of rocuronium bro-mide patients with liver disease. Anesth Analg 1995;80:754–9.Google Scholar
  208. 208.
    Ono K, Nagano O, Ohta Y, Kosaka F. Neuromuscular effects of respiratory and metabolic acid-base changes in vitro with and without non-depolarizing muscle relaxants. Anesthesio-logy 1990;73:710–16.Google Scholar
  209. 209.
    Aziz L, Ono K, Ohta Y, Morita K, Hirakawa M. The effect of CO 2-induced acid-base changes on the potencies of muscle relaxants and antagonism of neuromuscular block by neo-stigmine in rat in vitro. Anesth Analg 1994;78:322–7.Google Scholar
  210. 210.
    Buzello W, Pollmaecher T, Schluermann D, Urbanyi B. The Influence of hypothermic cardiopulmonary bypass on neu-romuscular transmission in the absence of muscle relaxants. Anesthesiology 1986;64:279–81.Google Scholar
  211. 211.
    Buzello W, Schluermann D, Schindler M, Spillner G. Hypothermic cardiopulmonary bypass and neuromuscular blockade by pancuronium and vecuronium. Anesthesiology 1985;62:201–4.Google Scholar
  212. 212.
    Miller RD, Agoston S, van der Pol F, Booij LHDJ, Crul JF, Ham J. Hypothermia and the pharmacokinetics and pharmacody-namics of pancuronium in the cat. J Pharmacol Exp Ther 1978;207:532–8.Google Scholar
  213. 213.
    Buzello W, Schluermann D, Pollmaecher T, Spillner G. Unequal effects of cardiopulmonary bypass-induced hypo-thermia on neuromuscular blockade from constant infusion of alcuronium, d-tubocurarine, pancuronium, and vecuroni-um. Anesthesiology 1987;66:842–6.Google Scholar
  214. 214.
    Denny NM, Kneeshaw JD. Vecuronium and atracurium infu-sions during hypothermic cardiopulmonary bypass. Anesthesia 1986;41:919–22.Google Scholar
  215. 215.
    Heier T, Caldwell JE, Sessler DI, Kitts JB, Miller RD. The rela-tionship between adductor pollicis twitch tension and core, skin, and muscle temperature during nitrous oxide isoflu-rane anesthesia in humans. Anesthesiology 1989;71:381–4.Google Scholar
  216. 216.
    Heier T, Caldwell JE, Sessler DI, Miller RD. The effect of local surface and central cooling on adductor pollicis twitch ten-sion during nitrous oxide/isoflurane and nitrous oxide/fenta-nyl anesthesia in humans. Anesthesiology 1990;72:807–11.Google Scholar
  217. 217.
    Heier T, Caldwell JE, Sessler DI, Miller RD. Mild hypothermia increases duration of action and spontaneous recovery of vecuronium blockade during nitrous oxide-isoflurane anes-thesia in humans. Anesthesiology 1991;74:815–19.Google Scholar
  218. 218.
    Heier T, Caldwell JE, Eriksson LI, Sessler DI, Miller RD. The effect of hypothermia on adductor pollicis twitch tension during continuous infusion of vecuronium in isoflurane-anesthetized humans. Anest Analg 1994;78:312–17.Google Scholar
  219. 219.
    Smith RB, Grenvik A. Cardiac arrest following succinylcho-line in patients with central nervous system injuries. Anesthesiology 1970;33:558–60.Google Scholar
  220. 220.
    Cooperman LH, Strobel GE Jr., Kennell EM. Massive hyperka-lemia after administration of succinylcholine. Anesthesiology 1979;32:161–4.Google Scholar
  221. 221.
    Cowgill DB, Mostello LA, Shapiro HM. Encephalitis and a hyperkalemic response to succinylcholine. Anesthesiology 1974;40:409–11.Google Scholar
  222. 222.
    Stevenson PH, Birch AA. Succinylcholine-induced hyperkale-mia in a patient with a closed head injury Anesthesiology 1979;51:89–90.Google Scholar
  223. 223.
    Iwatsuki N, Kuroda N, Amaha K, Iwatsuki K. Succinylcholine induced hyperkalemia in patients with ruptured cerebral aneurysm. Anesthesiology 1980;53:64–7.Google Scholar
  224. 224.
    Feldman JM. Cardiac arrest after succinylcholine administra-tion in a pregnant patient recovering from Guillain-Barré syndrome. Anesthesiology 1990;72:942–4.Google Scholar
  225. 225.
    Gronert GA, Lambert EH, Theye RA. The response of dener-vated skeletal muscle to succinylcholine. Anesthesiology 1973;39:13–22.Google Scholar
  226. 226.
    Moorthy SS, Hilgenberg JC. Resistance to non-depolarizing muscle relaxants in paretic upper extremities of patients with residual hemiplegia. Anesth Analg 1980;59:624–7.Google Scholar
  227. 227.
    Shayevitz JR, Matteo RS. Decreased sensitivity tometocurine in patients with upper motorneuron disease. Anest Analg 1985;64:767–72.Google Scholar
  228. 228.
    Gronert GA, Theye RA. Effect of succinylcholine on skeletal muscle with immobilization atrophy. Anesthesiology 1974;40:268–71.Google Scholar
  229. 229.
    Fiacchino F, Gemma M, Bricchi M, Giombini S, Regi B. Sensitivity to curare in patients with upper and lower motor neurone dysfunction. Anaesthesia 1991;46:980–2.Google Scholar
  230. 230.
    Rosenbaum KJ, Neigh JL, Strobel GE. Sensitivity to non-depolarizing muscle relaxants in amyotrophic lateral sclero-sis: report of two cases. Anesthesiology 1971;35:638–41.Google Scholar
  231. 231.
    Stone WA, Beach TP, Hamelberg W. Succinylcholine-danger in the spinal-cord-injured patient. Anesthesiology 1970;32:168–9.Google Scholar
  232. 232.
    Tobgey RE. Paraplegia, succinylcholine and cardiac arrest. Anesthesiology 1970;32:359–64.Google Scholar
  233. 233.
    Hogue Jr CW, Itani MS, Martyn JAJ. Resistance to d-tubocu-rarine in lower motor neuron injury is related to increased acetylcholine receptors at the neuromuscular junction. Anesthesiology 1990;73:703–9.Google Scholar
  234. 234.
    Greenawalt III, JW. Succinylcholine-induced hyperkalemia 8 weeks after a brief paraplegic episode. Anesth Analg 1992;75:294–5.Google Scholar
  235. 235.
    Orndahl G, Sternberg K. Myotonic human musculature: stimulation with depolarizing agents. Mechanical registra-tion of the effect of succinylcholine, succinylmonocholine, and decamethonium. Acta Med Scand 1962;172:3 (suppl.389):3–29.Google Scholar
  236. 236.
    Azar I. The response of patients with neuromuscular disor-ders to muscle relaxants: a review. Anesthesiology 1984; 61:173–87.Google Scholar
  237. 237.
    Weintraub MI, Megahed MS, Smith BH. Myotonic-like syn-drome in multiple sclerosis. NY State J Med 1970;70:677–9.Google Scholar
  238. 238.
    Takamori M, Takahashi M, Yasukawa Y, Iwasa K, Nemoto Y, Suenga A, Nagataki S, Nakamura T. Antibodies to recombi-nant synapototagmin and calcium channel subtypes in Lambert-Eaton myasthenic syndrome. J Neurol Sci 1995; 133:95–101.Google Scholar
  239. 239.
    Tempelhoff R, Modica PA, Jellish WS, Spitznagel EL. Resistance to atracurium-induced neuromuscular blockade in patients with intractable seizure disorders treated with anticonvulsants. Anesth Analg 1990;71:665–7.Google Scholar
  240. 240.
    Lambert JJ, Durant NN, Henderson EG. Drug-induced mod-ifications of ionic conductance at the neuromuscular junc-tion. Ann Rev Pharmacol Toxicol 1983;23:505–39.Google Scholar
  241. 241.
    Gage PW, Hamill OP. Effects of anesthetics on ion channels in synapses. Int Rev Physiol 1981;25:1–45.Google Scholar
  242. 242.
    Bufler J, Pichlmeier R, Schneck HJ, Hussman H, Franke C. Block of nicotinic acetylcholine-activated channels of cul-tured mouse myotubes by isoflurane. Neuroscie Letters 1994;168;135–8.Google Scholar
  243. 243.
    Dilger JP, Brett RS, Mody HI. Effects of isoflurane on acetyl-choline receptor channels. 2. Currents elicited by rapid per-fusion of acetylcholine. Mol Pharmacol 1993;44:1056–63.Google Scholar
  244. 244.
    Liu YI, Dilger JP, Vidal AM. Effects of alcohols and volatile anesthetics on the activation of nicotinic acetylcholine receptor channels. Mol Pharmacol 1994;45:1235–41.Google Scholar
  245. 245.
    Taivainen T, Meretoja OA. The neuromuscular blocking effects of vecuronium during sevoflurane, halothane and balanced anaesthesia in children. Anaesthesia 1995;50: 1046–9.Google Scholar
  246. 246.
    Caldwell JE, Magorian T, Lynam DP, Segredo V, Eger II EI, Miller RD. Desflurane versus isoflurane: dose-response rela-tionships of pancuronium and succinylcholine. Anesthesio-logy 1990;73:A860.Google Scholar
  247. 247.
    Witkowski TA, Azad SS, Bartkowski RR, Epstein RH, Marr A, Lessin J. Desflurane (I-653) potentiation of pancuronium bromide: a comparison with isoflurane. Anesthesiology 1990;73:A903.Google Scholar
  248. 248.
    Smiley RM, Ornstein E, Mathews D, Matteo RS. A compari-son of the effects of desflurane and isoflurane on the action of atracurium in man. Anesthesiology 1990;A882.Google Scholar
  249. 249.
    Swen J, Gencarelli PJ, Koot HWJ. Vecuronium infusion dose requirements during fentanyl and halothane anesthesia in humans. Anesth Analg 1985;64:411–14.Google Scholar
  250. 250.
    Torda TA, Gage PW. Postsynaptic effect of I.V. anaesthetic agents at the neuromuscular junction. Br J Anaesth 1977;49: 771–6.Google Scholar
  251. 251.
    Wachtel RE, Wegrynowicz ES. Kinetics of nicotinic acetylcho-line ion channels in the presence of intravenous anaesthetics and induction agents. Br J Pharmacol 1992;106:623–7.Google Scholar
  252. 252.
    Charlesworth P, Richards CD. Anaesthetic modulations of nicotinic ion channel kinetics in bovine chromaffin cells. Br J Pharmacol 1995;114:909–17.Google Scholar
  253. 253.
    Booij LHDJ, Miller RD, Crul JF. Neostigmine and 4-aminopy-ridine antagonism of lincomycin-pancuronium neuromus-cular blockade in man. Anesth Analg 1978;57:316–21.Google Scholar
  254. 254.
    Sokoll MD, Gergis SD. Antibiotics and neuromuscular func-tion. Anesthesiology 1981;55:148–59.Google Scholar
  255. 255.
    Singh YN, Marshall IG, Harvey AL. Pre-and postjunctional blocking effects of aminoglycosides, polymyxin, tetracyclin and lincosamide antibiotics. Br J Anaesth 1982;54:1295–1305.Google Scholar
  256. 256.
    Fiekers JF. Neuromuscular block produced by polymyxin B-interaction with endplate ion channels. Eur J Pharmacol 1981;70:77–81.Google Scholar
  257. 257.
    Singh YN, Marshall IG, Harvey AL. Depression of transmitter release and postjunctional sensitivity during neuromuscular block produced by antibiotics. Br J Anaesth 1979;51:1027–33.Google Scholar
  258. 258.
    Singh YN, Marshall IG, Harvey AL. Some effects of the ami-noglycoside antibiotic amikacin on neuromuscular and autonomic transmission. Br J Anaesth 1978;50:109–17.Google Scholar
  259. 259.
    Wright JM, Collier B. The site of the neuromuscular block produced by polymyxin B and rolitetracycline. Can J Physiol Pharmacol 1976;54:926–36.Google Scholar
  260. 260.
    Wright JM, Collier B. Characterization of the neuromuscular block produced by clindamycin and lincomycin. Can J Physiol Pharmacol 1976;56:937–44.Google Scholar
  261. 261.
    Booij LHDJ, Miller RD, Crul JF. Neostigmine and 4-aminopy-ridine antagonism of lincomycin-pancuronium neuromus-cular blockade in man. Anesth Analg 1978;57:316–21.Google Scholar
  262. 262.
    Kornfeld P, Horowitz SH, Genkins G, Papatestas AE. Myasthenia gravis unmasked by antiarrhythmic agents. Mount Sinai J Med 1976;43:10–14.Google Scholar
  263. 263.
    Stoelting RK. Serum cholinesterase activity following pancu-ronium and antagonism with neostigmine or pyridostig-mine. Anesthesiology 1976;45:674–8.Google Scholar
  264. 264.
    Rautoma P, Erkola O, Meretoja OA. Synergism between miv-acurium and pancuronium in adults. Acta Anaesthesiol Scand 1995;39:733–7.Google Scholar
  265. 265.
    Waud BE, Waud DR. Quantitative examination of the inter-action of competitive neuromuscular blocking agents on the indirectly elicited twitch. Anesthesiology 1984;61:420–7.Google Scholar
  266. 266.
    Naguib M, Samarkandi AH, Bakhamees HS, Magboul MA, El-Bakry AK. Comparative potency of steroidal neuromuscu - lar blocking drugs and isobolographic analysis of the inter-action between rocuronium and other aminosteroids. BJA 1995;75:37–42.Google Scholar
  267. 267.
    Camp CE, Tessen J, Adenwala J, Joyce TH, 3rd. Vecuronium and prolonged neuromuscular block in postpartum patients. Anesthesiology 1987;67:1006–8.Google Scholar
  268. 268.
    Hawkins JL, Adenwala J, Camp C, Joyce III Th. The effect of H 2-receptor antagonist premedication on the duration of vecuronium-induced neuromuscular blockade in postpar-tum patients. Anesthesiology 1989;71:175–7.Google Scholar
  269. 269.
    Kroeker KA, Beattie WS, Yang H. Neuromuscular blockade in the setting of chronic nicotinic exposure. Anesthesiology 1994;81:A1120.Google Scholar
  270. 270.
    Teiriä H, Rautoma P, Yli-Hankala A. Effect of smoking on dose requirements for vecuronium. Br J Anaesth 1996;75:154–5.Google Scholar
  271. 271.
    Lambert JJ, Durant NN, Handerson EG. Drug-induced mod-ification of ionic conductance at the neuromuscular junc-tion. Ann Rev Pharmacol Toxicol 1983;23:505–39.Google Scholar
  272. 272.
    Wali FA. Interactions of nifedipine and diltiazem with muscle relaxants and reversal of neuromuscular blockade with edro-phonium and neostigmine. J Pharmacol (Paris) 1986;17: 244–53.Google Scholar
  273. 273.
    Doll DC, Rosenberg H. Antagonism of neuromuscular block-ade by theophylline. Anesth Analg 1979;58:139–40.Google Scholar
  274. 274.
    Ramanathan J, Sibai BM, Pillai R, Angel JJ. Neuromuscular transmission studies in preecclamptic women receiving magnesium sulfate. Am J Obstet Gynecol 1988;158:40–6.Google Scholar
  275. 275.
    Crosby E, Robblee JA. Cyclosporine-pancuronium interac-tion in a patient with a renal allograft. Can J Anaesth 1988;35:300–2.Google Scholar
  276. 276.
    Hickey DR, Sangwan S, Bevan JC. Phenytoin-induced resis-tance to pancuronium. Anaesthesia 1988;43:757–9.Google Scholar
  277. 277.
    Loflin MJ. Interaction of pancuronium and corticosteroids. Anesthesiology 1977;47:471–2.Google Scholar
  278. 278.
    Reddy P, Guzman A, Robalino J, Shevde K. Resistance to muscle relaxants in a patient receiving prolonged testoste-rone therapy. Anesthesiology 1989;70:871–3.Google Scholar
  279. 279.
    Parr SM, Robinson BJ, Rees D, Galletly DC. Interaction between betamethasone and vecuronium. Br J Anaesth 1991;67:447–51.Google Scholar
  280. 280.
    Parr SM, Galletly DC, Robinson BJ. Betamethasone induced resistance to vecuronium: a potential problem in neurosur-gery? Anesth Intens Care 1991;19:103–5.Google Scholar
  281. 281.
    Vervloet D. Allergy to muscle relaxants and related com-pounds. Clin Allergy 1985;15:501–8.Google Scholar
  282. 282.
    Shorten GD. Postoperative residual curarisation: incidence, aetiology and associated morbidity. Anaesth Int Care 1993;21:782–9.Google Scholar
  283. 283.
    Clarke RSJ, Mirakhur RK. Adverse effects of muscle relaxants. Adv Drug React Toxicol Rev 1994;13:23–41.Google Scholar
  284. 284.
    Bowman WC. Non-relaxant properties of neuromuscular blocking drugs. Br J Anaesth 1982;54:147–60.Google Scholar
  285. 285.
    Clayton D. Asystole associated with vecuronium. Br J Anaesth 1986;58:937.Google Scholar
  286. 286.
    Starr NH, Sethna DH, Estafanous FG. Bradycardia and asy-stole following the rapid administration of sufentanil with vecuronium. Anesthesiology 1986;64:521–3.Google Scholar
  287. 287.
    Cozanitis DA, Erkola O. A clinical study into the possible intrinsic bradycardic activity of vecuronium. Anaesthesia 1989;44:648–50.Google Scholar
  288. 288.
    Wierda JMKH, Maestrone E, Bencini AF, Boyer A, Rashkovsky OM, Lip H, Karliczek R, Ket JM, Agoston S. Haemodynamic effects of vecuronium. Br J Anaesth 1989;62:194–8.Google Scholar
  289. 289.
    Bergin AM, Clarke TA, Matthews TG. Problems with pancu-ronium in the neonatal intensive care unit. Irish Med J 1988;81:39–40.Google Scholar
  290. 290.
    Kinjo M, Nagashima H, Vizi ES. Effect of atracurium and lau-danosine on the release of 3H-noradrenaline. Br J Anaesth 1989;62:683–90.Google Scholar
  291. 291.
    Robertson EN, Hull JM, Verbeek AM, Booij LHDJ. A compari-son of rocuronium and vecuronium, the pharmacodynam-ics, cardiovascular and intra-ocular effects. Eur J Anaesthesiol 1994;9:116–21.Google Scholar
  292. 292.
    McCoy EP, Maddenini VR, Elliot P, Mirakhur RK, Caroon IW, Cooper RA. Haemodynamic effects of rocuronium during fentanyl anaesthesia: comparison with vecuronium. Can J Anesth 1993;408:703–8.Google Scholar
  293. 293.
    Pedersen T, Eliasen K, Henriksen E. A prospective study of risk factors and cardiopulmonary complications associated with anaesthesia and surgery: risk indicators of cardiopul-monary morbidity. Acta Anaesthesiol Scand 1990;34:144–55.Google Scholar
  294. 294.
    Zelcer J, Wells DG. Anaesthetic-related recovery room com-plications. Anaesth Intens Care 1987;15:168–74.Google Scholar
  295. 295.
    Basta SJ. Modulation of histamine release by neuromuscular blocking drugs. Curr Opin Anaesthesiol 1992;5:572–6.Google Scholar
  296. 296.
    Booij LHDJ, Krieg NN, Crul JF. Intradermal histamine releas-ing effect caused by Org-NC 45. A comparison with pancu - ronium, metocurine and d-tubocurarine. Acta Anaesthesiol Scand 1980;24:393–4.Google Scholar
  297. 297.
    Levy JH, Adelson D, Walker B. Wheal and flare responses to muscle relaxants in humans. Agents and Actions 1991;34: 302–8.Google Scholar
  298. 298.
    Vervloet D, Arnaud A, Senft M, Dor P, Bongrand P, Charpin C, Alazia M. Leucocyte histamine release to suxamethonium in patients with adverse reactions to muscle relaxants. J Allergy Clin Immunol 1985;75:338–42.Google Scholar
  299. 299.
    Levy DH, Davis GK, Duggan J, Szlam F. Determination of the hemodynamics and histamine release of rocuronium (Org 9426) when administered in increased doses under N 2 O/O 2-sufentanil anesthesia. Anesth Analg 1994;78:318–21.Google Scholar
  300. 300.
    Moss J, Rosow CE. Histamine release by narcotics and mus-cle relaxants in humans. Anesthesiology 1983;59:330–9.Google Scholar
  301. 301.
    Watkins J. Second report from an anaesthetic reactions advi-sory service. Anaesthesia 1989;44:157–9.Google Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • L.H.D.J. Booij
    • 1
  1. 1.Department of AnaesthesiologyCatholic University NijmegenNijmegenThe Netherlands

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