Skip to main content
SpringerLink
Log in

Adverse Effects of Opioid Agonists and Agonist-Antagonists in Anaesthesia

  • Review Article
  • Drug Experience
  • Published:
Drug Safety Aims and scope Submit manuscript

Abstract

The traditional view of opioids held that the individual opioid agonists shared the same mechanism of action, differing only in their potency and pharmacokinetic properties. However, recent advances in opioid receptor pharmacology have made this view obsolete. Distinguishing features of the synthetic opioid agonists are related, at least in part, to variation in affinity and intrinsic efficacy at multiple opioid receptors.

Respiratory depression is the opioid adverse effect most feared by an aesthesiologists. Specific κ-receptor agonists produce analgesia with little or no respiratory depression. There are a number of commercially available κ-receptor partial agonist drugs, the so-called agonist-antagonist or nalorphine-like opioids, which appear to have a limited effect on breathing.

Within the series of fentanyl analogues there are differences in behaviour towards particular opioid receptors and there is evidence for subtle differences in respiratory depressant effects.

Pethidine (meperidine) causes histamine release and myocardial depression, while the fentanyl analogues do not. Pethidine has atropine-like effects on heart rate, while fentanyl analogues reduce heart rate by a vagomimetic action. Severe bradycardia or even asystole is possible with fentanyl analogues, especially in conjunction with the vagal stimulating effects of laryngoscopy.

Fentanyl analogues often produce minor reductions in blood pressure, and occasionally severe hypotension by centrally mediated reduction in systemic vascular resistance. Muscle rigidity and myoclonic movement occurs frequently during induction of anaesthesia with larger doses of opioids. Fentanyl and alfentanil have been reported to produce localised temporal lobe electrical seizure activity in patients with complex partial epilepsy.

There are probably fewer biliary effects with agonist-antagonist opioids than the agonist opioids. The mechanism of adverse effects after spinal administration is distinctly different for morphine, which is very water soluble, compared with more lipid-soluble opioids. The systemic absorption of morphine after intrathecal or epidural administration is very slow, resulting in long duration of analgesia and low plasma concentrations, while lipid-soluble opioids are rapidly absorbed into the circulation and redistributed to the brain.

The serotonin syndrome may result from coadministration of pethidine, dextromethorphan, pentazocine or tramadol with monoamine oxidase inhibitors (MAOIs) or selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs). There are clinically important interactions between opioids and hypnosedatives, resulting in synergistic effects on sedation, breathing and blood pressure.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Hayashi Y, Maze M. Drags affecting adrenoceptors: alpha-2 agonists. In: Bowdle T, Horita A, Kharasch E, editors. The phannacologic basis of anesthesiology. New York: Churchill Livingstone, 1994: 607–779

    Google Scholar 

  2. Bowersox SS, Gadbois T, Singh T, et al. Selective N-type neuronal voltage-sensitive calcium channel blocker, SNX-11, produces spinal antinociception in rat models of acute, persistent and neuropathic pain. J Pharmacol Exp Ther 1996; 279: 1243–9

    CAS  PubMed  Google Scholar 

  3. Pasternak GW. Basic pharmacology of opioids. In: Bowdle T, Horita A, Kharasch E, editors. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone, 1994: 19–36

    Google Scholar 

  4. Pasternak GW, Standifer KM. Mapping of opioid receptors using antisense oligodeoxynucleotides: correlating their molecular biology and pharmacology. Trends Pharmacol Sci 1995; 16: 344–50

    Article  CAS  PubMed  Google Scholar 

  5. Rossi GC, Pan Y-X, Brown GP, et al. Antisense mapping the MOR-1 opioid receptor: evidence for alternative splicing and a novel morphine-6beta-glucuronide receptor. FEBS Lett 1995; 369: 192–6

    Article  CAS  PubMed  Google Scholar 

  6. Rossi GC, Brown GP, Leventhal L, et al. Novel receptor mechanisms for heroin and morphine-6beta-glucuronide analgesia. Neurosci Lett 1996; 216: 1–4

    Article  CAS  PubMed  Google Scholar 

  7. Henderson G, McKnight AT. The orphan opioid receptor and its endogenous ligand-nociceptin/orphanin FQ. Trends Pharmacol Sci 1997; 18: 293–300

    Article  CAS  PubMed  Google Scholar 

  8. Stein C. Peripheral mechanisms of opioid analgesia. Anesth Analg 1993; 76: 182–91

    Article  CAS  PubMed  Google Scholar 

  9. Kolesnikov YA, Jain S, Wilson R, et al. Peripheral morphine analgesia: synergy with central sites and a target of morphine tolerance. J Pharmacol Exp Ther 1996; 279: 502–6

    CAS  PubMed  Google Scholar 

  10. Khoury GF, Chen ACN, Garland DE, et al. Intraarticular morphine, bupivacaine, and morphine/bupivacaine for pain control after knee videoarthroscopy. Anesthesiology 1992; 77: 263–6

    Article  CAS  PubMed  Google Scholar 

  11. Dobreni K, Makman MH, Stefano GB. Occurrence of the opiate alkaloid-sensitive mu3 receptor in mammalian microglia, astrocytes and Kupffer cells. Brain Res 1995; 686: 239–48

    Article  Google Scholar 

  12. Stefano GB, Scharrer B. Endogenous morphine and related opiates, a new class of chemical messengers. Adv Neuroimmunol 1994; 4: 57–67

    Article  CAS  PubMed  Google Scholar 

  13. Kodaira H, Spector S. Transformation of thebaine to oripavine, codeine, and morphine by rat liver, kidney, and brain microsomes. Proc Natl Acad Sci USA 1988; 85: 1267–71

    Article  CAS  PubMed  Google Scholar 

  14. Stefano GB, Digenis A, Spector S, et al. Opiate-like substances in an invertebrate, an opiate receptor on invertebrate and human immunocytes, and a role in immunosuppression. Proc Natl Acad Sci USA 1993; 90: 11099–103

    Article  CAS  PubMed  Google Scholar 

  15. Freye E, Hartung E, Schenk GK. Bremazocine: an opiate that induces sedation and analgesia without respiratory depression. Anesth Analg 1983; 62: 483–8

    Article  CAS  PubMed  Google Scholar 

  16. Castillo R, Kissin I, Bradley E. Selective kappa opioid agonist for spinal analgesia without the risk of respiratory depression. Anesth Analg 1986; 65: 350–4

    Article  CAS  PubMed  Google Scholar 

  17. Millan MJ. Kappa-opioid receptors and analgesia. Trends Pharmacol Sci 1990; 11: 70–6

    Article  CAS  PubMed  Google Scholar 

  18. Bowdle TA, Nelson WL. Partial agonist, mixed agonist-antagonist, and antagonist opioids. In: Bowdle T, Horita A, Kharasch E, editors. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone, 1994

    Google Scholar 

  19. Keats AS, Telford T. Studies of analgesic drugs X. Respiratory effects of narcotic antagonists. J Pharmacol Exp Ther 1966; 112: 126–32

    Google Scholar 

  20. Romagnoli A, Keats AS. Ceiling effect for respiratory depression by nalbuphine. Clin Pharmacol Ther 1980; 27: 478–85

    Article  CAS  PubMed  Google Scholar 

  21. Romagnoli A, Keats AS. Ceiling respiratory depression by dezocine. Clin Pharmacol Ther 1984; 35: 367–73

    Article  CAS  PubMed  Google Scholar 

  22. Gal TJ, Di Fazio CA. Ventilatory and analgesic effects of dezocine in humans. Anesthesiology 1984; 61: 716–22

    Article  CAS  PubMed  Google Scholar 

  23. Nagashima H, Karamanian A, Malovany R, et al. Respiratory and circulatory effects of intravenous butorphanol and morphine. Clin Pharmacol Ther 1976; 19: 738–45

    CAS  PubMed  Google Scholar 

  24. Zucker JR, Neuenfeldt T, Freund PR. Respiratory effects of nalbuphine and butorphanol in anesthetized patients. Anesth Analg 1987; 66: 879–81

    Article  CAS  PubMed  Google Scholar 

  25. Pick CG, Peter Y, Schreiber S, et al. Pharmacological characterization of buprenorphine, a mixed agonist-antagonist with kappa3 analgesia. Brain Res 1997; 744: 41–6

    Article  CAS  PubMed  Google Scholar 

  26. Dum JE, Herz A. In vivo receptor binding of the opiate partial agonist, buprenorphine, correlated with its agonistic and antagonistic actions. Br J Pharmacol 1981; 74: 627–33

    Article  CAS  PubMed  Google Scholar 

  27. Orwin JM. The effect of doxapram on buprenorphine induced respiratory depression. Acta Anaesthsiol Belg 1977; 2: 93–105

    Google Scholar 

  28. Gal TJ. Naloxone reversal of buprenorphine-induced respiratory depression. Clin Pharmacol Ther 1989; 45: 66–71

    Article  CAS  PubMed  Google Scholar 

  29. Rovati GE, Nicosia S. Lower efficacy: interaction with an inhibitory receptor or partial agonism? Trends Pharmacol Sci 1994; 15: 140–1

    Article  CAS  PubMed  Google Scholar 

  30. Pedersen JE, Chraemmer-Jorgensen B, Schmidt JF, et al. Naloxone — a strong analgesic in combination with high-dose buprenorphine? Br J Anaesth 1985; 57: 1045–6

    Article  CAS  PubMed  Google Scholar 

  31. Hoskin PJ, Hanks GW. Opioid agonist-antagonist drugs in acute and chronic pain states. Drugs 1991; 41: 326–44

    Article  CAS  PubMed  Google Scholar 

  32. Yeadon M, Kitchen I. Comparative binding of mu and delta selective ligands in whole brain and pons/medulla homogenates from rat: affinity profiles of fentanyl derivatives. Neuropharmacology 1988; 27: 345–8

    Article  CAS  PubMed  Google Scholar 

  33. Clark NJ, Meuleman T, Liu W, et al. Comparison of sufentanil-N20 and fentanyl-N20 in patients without cardiac disease undergoing general surgery. Anesthesiology 1987; 66: 130–5

    Article  CAS  PubMed  Google Scholar 

  34. Bailey PL, Streisand JB, East KA, et al. Differences in magnitude and duration of opioid-induced respiratory depression and analgesia with fentanyl and sufentanil. Anesth Analg 1990; 70: 8–15

    Article  CAS  PubMed  Google Scholar 

  35. Yeadon M, Kitchen I. Multiple opioid receptors mediate the respiratory depressant effects of fentanyl-like drugs in the rat. Gen Pharmacol 1990; 21: 655–64

    Article  CAS  PubMed  Google Scholar 

  36. Jones JG. The respiratory effects of meptazinol. Postgrad Med J 1983; 59(Suppl. 1): 72–7

    PubMed  Google Scholar 

  37. Seitz W, Lubbe N, Fritz K, et al. Effects of tramadol on respiratory CO2 response and mouth occlusion pressure. Anaesthesist 1985; 34: 241–6

    CAS  PubMed  Google Scholar 

  38. Vickers MD, O’Flaherty D, Szekely SM, et al. Tramadol: pain relief by an opioid without depression of respiration. Anaesthesia 1992: 291-6

  39. Houmes RM, Voets MA, Verkaaik A, et al. Efficacy and safety of tramadol versus morphine for moderate and severe post-operative pain with special regard to respiratory depression. Anesth Analg 1992; 74: 510–4

    Article  CAS  PubMed  Google Scholar 

  40. Hughes J, Kosterlitz AW, Smith TW. The distribution of methionine-enkephalin and leucine-enkephalin in the brain and peripheral tissues. Br J Pharmacol 1977; 61: 639–47

    Article  CAS  PubMed  Google Scholar 

  41. Sapru HN, Willette RN, Krieger AJ. Stimulation of pulmonary J receptors by an enkephalin-analog. J Pharmacol Exp Ther 1981; 217: 228–34

    CAS  PubMed  Google Scholar 

  42. Ohtani M, Kotaki H, Nishitateno K, et al. Kinetics of respiratory depression in rats induced by buprenorphine and its metabolite, norbuprenorphine. J Pharmacol Exp Ther 1997; 281: 428–33

    CAS  PubMed  Google Scholar 

  43. Flacke JW, Flacke WE, Bloor BC, et al. Histamine release by four narcotics: a double-blind study in humans. Anesth Analg 1987; 66: 723–30

    Article  CAS  PubMed  Google Scholar 

  44. Freye E. Cardiovascular effects of high dosages of fentanyl, meperidine, and naloxone in dogs. Anesth Analg 1974; 53: 40–7

    Article  CAS  PubMed  Google Scholar 

  45. Hall RI, Murphy MR, Szlam F, et al. Dezocine-MAC reduction and evidence for myocardial depression in the presence of enflurane. Anesth Analg 1987; 66: 1169–74

    CAS  PubMed  Google Scholar 

  46. Buffington CW. Hemodynamic determinants of ischemic myocardial dysfunction in the presence of coronary stenosis in dogs. Anesthesiology 1985; 63: 651–62

    Article  CAS  PubMed  Google Scholar 

  47. Jaffe JH, Martin WR. Narcotic analgesics and antagonists. In: Goodman L, Gilman A, Koelle G, editors. The pharmacological basis of therapeutics. 5th ed. New York: MacMillan, 1975: 245–83

    Google Scholar 

  48. Flacke JW, Davis LJ, Flacke WE, et al. Effects of fentanyl and diazepam in dogs deprived of autonomic tone. Anesth Analg 1985; 64: 1053–9

    CAS  PubMed  Google Scholar 

  49. Flacke JW, Flacke WE, Bloor BC, et al. Effects of fentanyl, naloxone and clonidine on hemodynamics and plasma catecholamine levels in dogs. Anesth Analg 1983; 62: 305–13

    Article  CAS  PubMed  Google Scholar 

  50. Tomicheck RC, Rosow CE, Philbin DM, et al. Diazepam-fentanyl interaction-hemodynamic and hormonal effects in coronary artery surgery. Anesth Analg 1983; 62: 881–4

    Article  CAS  PubMed  Google Scholar 

  51. Thomson IR, Putnins CL, Friesen RM. Hyperdynamic cardio-vascular responses to anesthetic induction with high-dose fentanyl. Anesth Analg 1986; 65: 91–5

    Article  CAS  PubMed  Google Scholar 

  52. Janssen PAJ. The past, present and future of opioid analgesics in anesthesia. In: Estafanous F, ed. Opioids in anesthesia II. Boston: Butterworth-Heinemann, 1991: xvi

    Google Scholar 

  53. Benthuysen JL, Smith NT, Sanford TJ, et al. Physiology of alfentanil-induced rigidity. Anesthesiology 1986; 64: 440–6

    Article  CAS  PubMed  Google Scholar 

  54. Weinger MB, Segal IS, Maze M. Dexmedetomidine, acting through central alpha-2 adrenoceptors, prevents opiate-induced muscle rigidity in the rat. Anesthesiology 1989; 71: 242–9

    Article  CAS  PubMed  Google Scholar 

  55. Weinger MB, Chen D-Y, Lin T, et al. A role for CNS alpha-2 adrenergic receptors in opiate-induced muscle rigidity in the rat. Brain Res 1995; 669: 10–8

    Article  CAS  PubMed  Google Scholar 

  56. Vankova ME, Weinger MB, Chen D-Y, et al. Role of central mu, delta-1, and kappa-1 opioid receptors in opioid-induced muscle rigidity in the rat. Anesthesiology 1996; 85: 574–83

    Article  CAS  PubMed  Google Scholar 

  57. Weinger MB, Cline EJ, Smith NT, et al. Localization of brain-stem sites which mediate alfentanil-induced muscle rigidity in the rat. Pharmacol Biochem Behav 1988; 29: 573–80

    Article  CAS  PubMed  Google Scholar 

  58. Bowdle TA, Rook GA. Postoperative myoclonus and rigidity after anesthesia with opioids. Anesth Analg 1994; 78: 783–6

    Article  CAS  PubMed  Google Scholar 

  59. Smith NT, Benthuysen JL, Bickford RG, et al. Seizures during opioid anesthetic induction - are they opioid-induced rigidity? Anesthesiology 1989; 71: 852–62

    Article  CAS  PubMed  Google Scholar 

  60. Bowdle TA. Myoclonus following sufentanil without EEG seizure activity. Anesthesiology 1987; 67: 593–5

    CAS  Google Scholar 

  61. Tempelhoff R, Modica PA, Bernardo KL, et al. Fentanyl-induced electrocorticographic seizures in patients with complex partial epilepsy. J Neurosurg 1992; 77: 201–8

    Article  CAS  PubMed  Google Scholar 

  62. Cascino GD, So EL, Sharbrough FW, et al. Alfentanil-induced epileptiform activity in patients with partial epilepsy. J Clin Neurophysiol 1993; 10: 520–5

    Article  CAS  PubMed  Google Scholar 

  63. Armstrong PJ, Bersten A. Normeperidine toxicity. Anesth Analg 1986; 65: 536–8

    Article  CAS  PubMed  Google Scholar 

  64. Milde LN, Milde JH, Gallagher WJ. Effects of sufentanil on cerebral circulation and metabolism in dogs. Anesth Analg 1990; 70: 138–46

    Article  CAS  PubMed  Google Scholar 

  65. Artru AA. Effects of fentanyl, sufentanil, and alfentanil on epileptiform EEG activity, cerebral blood flow, and intracranial pressure. In: Hines R, Bowdle TA, editors. Anesthesiology clinics of North America annual of anesthetic pharmacology. Philadelphia: WB Saunders, 1997: 117–54

    Google Scholar 

  66. Wahl M. Effects of enkephalins, morphine and naloxone on pial arteries during perivascular microapplication. J Cereb Blood Flow Metab 1985; 5: 451–7

    Article  CAS  PubMed  Google Scholar 

  67. Radnay PA, Brodman E, Mankikar D, et al. The effect of equianalgesic doses of fentanyl, morphine, meperidine and pentazocine on common bile duct pressure. Anaesthesist 1980; 29: 26–9

    CAS  PubMed  Google Scholar 

  68. Jones RM, Detmer M, Hill AB, et al. Incidence of choledocho-duodenal sphincter spasm during fentanyl-supplemented anesthesia. Anesth Analg 1981; 60: 638–40

    CAS  PubMed  Google Scholar 

  69. Radnay PA, Duncalf D, Novakovic M, et al. Common bile duct pressure changes after fentanyl, morphine, meperidine, butor-phanol, and naloxone. Anesth Analg 1984; 63: 441–4

    Article  CAS  PubMed  Google Scholar 

  70. McCammon RL, Stoelting RK, Madura JA. Effects of butor-phanol, nalbuphine, and fentanyl on intrabiliary tract dynamics. Anesth Analg 1984; 63: 139–42

    Article  CAS  PubMed  Google Scholar 

  71. Economou G, Ward-McQuaid JN. A cross-over comparison of the effect of morphine, pethidine, pentazocine, and phenazocine on biliary pressure. Gut 1971; 12: 218–21

    Article  CAS  PubMed  Google Scholar 

  72. Staritz M, Poralla T, Manns M, et al. Effect of modern analgesic drugs (tramadol, pentazocine, and buprenorphine) on the bile duct sphincter in man. Gut 1986; 27: 567–9

    Article  CAS  PubMed  Google Scholar 

  73. Watcha M, White PF. Postoperative nausea and vomiting: its etiology, treatment and prevention. Anesthesiology 1992; 77: 162–84

    Article  CAS  PubMed  Google Scholar 

  74. Costello DJ, Borison HL. Naloxone antagonizes narcotic self-blockade of emesis in the cat. J Pharmacol Exp Ther 1977; 203: 222–30

    CAS  PubMed  Google Scholar 

  75. Longnecker DE, Grazis P, Eggers GWN. Naloxone antagonism of morphine induced respiratory depression. Anesth Analg 1973; 52: 447–52

    CAS  PubMed  Google Scholar 

  76. Yaksh TL, Collins JG. Studies in animals should precede human use of spinally administered drugs. Anesthesiology 1989; 70: 4–6

    Article  CAS  PubMed  Google Scholar 

  77. Sandler AN. Clinical pharmacology and applications of spinal opioids. In: Bowdle TA, Horita A, Kharasch ED, editors. The pharmacologic basis of anesthesiology. New York: Churchill Livingstone, 1994: 149–78

    Google Scholar 

  78. Sjostrom S, Tamsen A, Persson MP, et al. Pharmacokinetics of intrathecal morphine and meperidine in humans. Anesthesiology 1987; 67: 889–95

    Article  CAS  PubMed  Google Scholar 

  79. Loper KA, Ready B, Downey M, et al. Epidural and intravenous fentanyl infusions are clinically equivalent after knee surgery. Anesth Analg 1990; 70: 72–5

    Article  CAS  PubMed  Google Scholar 

  80. Camann WR, Loferski BL, Fanciullo GJ, et al. Does epidur administration of butorphanol offer any clinical advantage over the intravenous route? Anesthesiology 1992; 76: 216–20

    Article  CAS  PubMed  Google Scholar 

  81. Chaney M. Side effects of intrathecal and epidural opioids. Can J Anaesth 1995: 891-903

  82. Sandler AN, Stringer D, Panos L, et al. A randomized, double-blind comparison of lumbar epidural and intravenous fentanyl infusions for post-thoracotomy pain relief: analgesic, pharmacokinetic and respiratory effects. Anesthesiology 1992; 77: 626–34

    Article  CAS  PubMed  Google Scholar 

  83. James CF. Recurrence of herpes simplex virus blepharitis after cesarean section and epidural morphine. Anesth Analg 1996; 82: 1094–6

    CAS  PubMed  Google Scholar 

  84. Kavee EH, Ramanathan S. The hypothermic action of epidural and subarachnoid morphine in parturients. Region Anesth 1991; 16: 325–8

    CAS  Google Scholar 

  85. Sevarino FB, Johnson MD, Lema MJ, et al. The effect of epidural sufentanil on shivering and body temperature in the parturient. Anesth Analg 1989; 68: 530–3

    Article  CAS  PubMed  Google Scholar 

  86. Bodner RA, Lynch T, Lewis L, et al. Serotonin syndrome. Neurology 1995; 45: 219–23

    Article  CAS  PubMed  Google Scholar 

  87. Kam PCA, Chang GWM. Selective serotonin reuptake inhibitors: Pharmacology and clinical implications in anaesthesia and critical care medicine. Anaesthesia 1997; 52: 982–8

    Article  CAS  PubMed  Google Scholar 

  88. Mitchell RS. Fatal toxic encephalitis occurring during iproniazid therapy in pulmonary tuberculosis. Ann Intern Med 1955; 42: 417–24

    CAS  PubMed  Google Scholar 

  89. Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705–13

    CAS  PubMed  Google Scholar 

  90. Rivers N, Homer B. Possible lethal interaction between Nardil and dextromethorphan. Can Med Assoc J 1970; 103: 85

    CAS  PubMed  Google Scholar 

  91. Hansen TE, Dieter K, Keepers GA. Interaction of fluoxetine and pentazocine. Am J Psychiatry 1990; 147: 949–50

    CAS  PubMed  Google Scholar 

  92. Sinatra RS, Scramcik JL. Tramadol: its use in pain management. In: Hines R, Bowdle TA, editors. Anesthesiology clinics of North America annual of anesthetic pharmacology. Philadelphia: WB Saunders, 1998: 53–69

    Google Scholar 

  93. Amrein R, Guntert TW, Dingemanse J, et al. Interaction of moclobemide with concomitantly administered medication: evidence from pharmacological and clinical studies. Psycho-pharmacology 1992; 106: S24–31

    CAS  Google Scholar 

  94. Sternberg TL. All monoamine oxidase inhibitors are not equal. Anesth Analg 1997; 84: 938

    CAS  PubMed  Google Scholar 

  95. Lee CR, McTavish D, Sorkin EM. Tramadol: a preliminary review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in acute and chronic pain states. Drugs 1993; 313-340

  96. Raffa RB, Friderichs E, Reimann W, et al. Opioid and nonopioid components independently contribute to the mechanism of action of tramadol, an ‘atypical’ opioid analgesic. J Pharmacol Exp Ther 1992; 260: 275–85

    CAS  PubMed  Google Scholar 

  97. Bowdle TA, Ward RJ. Induction of anesthesia with small doses of sufentanil or fentanyl: dose versus EEG response, speed of onset and thiopental requirement. Anesthesiology 1989; 70: 26–30

    Article  CAS  PubMed  Google Scholar 

  98. Vinik HR. Intravenous anaesthetic drug interactions: practical applications. Eur J Anaesthesiol 1995; 12 Suppl. 12: 13–9

    CAS  Google Scholar 

  99. Vinik HR, Bradley EL, Kissin I. Midazolam-alfentanil synergism for anesthetic induction in patients. Anesth Analg 1989; 69: 213–7

    Article  CAS  PubMed  Google Scholar 

  100. Bailey PL, Pace NL, Ashburn MA, et al. Frequent hypoxemia and apnea after sedation with midazolam and fentanyl. Anesthesiology 1990; 73: 826–30

    Article  CAS  PubMed  Google Scholar 

  101. Jeal W, Benfield P. Transdermal fentanyl: a review of its pharmacological properties and therapeutic efficacy in pain control. Drugs 1997; 53: 109–38

    Article  CAS  PubMed  Google Scholar 

  102. Bowdle TA, Galer BS. Agonist-antagonist and partial agonist opioids: pharmacologic mechanisms and clinical application in the treatment of headache. Headache Q 1993; 4: 322–36

    Google Scholar 

  103. Preston KL, Sullivan JT, Testa M, et al. Psychopharmacology and abuse potential of transnasal butorphanol. Drug Alcohol Depend 1994; 35: 159–67

    Article  CAS  PubMed  Google Scholar 

  104. Rosow CE, Connors PM, Hennessy D, et al. Bioavailability of nasal butorphanol. Anesthesiology 1996; 85: A314

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Anaesthesiology, University of Washington, Box 356540, Room RR 444, Seattle, Washington, 98195, USA

    T. Andrew Bowdle

Authors
  1. T. Andrew Bowdle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. Andrew Bowdle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Andrew Bowdle, T. Adverse Effects of Opioid Agonists and Agonist-Antagonists in Anaesthesia. Drug-Safety 19, 173–189 (1998). https://doi.org/10.2165/00002018-199819030-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199819030-00002

Keywords

Search

Navigation