Systemic and Local Distribution of Opioids After Spinal Administration: Implications for their Clinical Use

  • Lars L. Gustafsson
Part of the Current Management of Pain book series (CUMP, volume 6)

Abstract

Spinal opioid analgesia may be achieved either by epidural or intrathecal administration. The analgesic effect is exerted through the binding of drugs to opioid receptors in the dorsal horn of the spinal cord [1, 2]. The fraction of the dose that reaches the intended site of action in the spinal cord is lower with epidural than with intrathecal administration because of the high blood flow and pronounced distribution into the systemic circulation in the first case. Similar therapeutic and toxic effects can be present irrespective of the route of administration when equipotent doses are given.

Keywords

Catheter Depression Morphine Fentanyl Dura 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Yaksh TL, Noueihed R. 1985. The physiology and pharmacology of spinal opiates. Ann Rev Pharmacol Toxicol 25:433–462.CrossRefGoogle Scholar
  2. 2.
    Yaksh TL. 1981. Spinal opiate analgesia: Characteristics and principles of action. Pain 11: 293–346.PubMedCrossRefGoogle Scholar
  3. 3.
    Max MB, Inturrisi CE, Kaiko RF, Grabinski PY, Li CH, Foley KM. 1985. Epidural and intrathecal opiates: Cerebrospinal fluid and plasma profiles in patients with chronic cancer pain. Clin Pharmacol Ther 38:631–641.PubMedCrossRefGoogle Scholar
  4. 4.
    Gustafsson LL. 1985. Spinal opiate analgesia: Clinical and experimental aspects. Thesis, Karolinska Institute, Stockholm.Google Scholar
  5. 5.
    Chauvin M, Salbaing J, Perrin D, Levron JC, Viars P. 1985. Clinical assessment and plasma pharmacokinetcs associated with intramuscular or extradural alfentanil. Br J Anaesth 57: 886–891.PubMedCrossRefGoogle Scholar
  6. 6.
    Bilsbach P, Roily G, Tampubolon O. 1985. Efficacy of the extradural administration of lofentanil, buprenorphine or saline in the management of postoperative pain. A double-blind study. Br J Anaesth 57:943–948.CrossRefGoogle Scholar
  7. 7.
    Cousins MJ, Mather LE. 1984. Intrathecal and epidural administration of opioids. Anesthesiology 61:276–310.PubMedCrossRefGoogle Scholar
  8. 8.
    Gustafsson LL, Post C. 1986. The degree of analgesia correlates to spinal morphine concentrations after intrathecal administration in rats. Acta Pharmacol Toxicol 58:243–248.CrossRefGoogle Scholar
  9. 9.
    Yaksh TL, Rudy TA 1977. Studies on the direct spinal action of narcotics in the production of analgesia in rat. J Pharmacol Ther 202:411–428.Google Scholar
  10. 10.
    Yaksh TL, Noueihed R, Durant PAC. 1986. Studies of the pharmacology and pathology of intrathecally administered 4-anilinopiperidine analogues and morphine in the rat and cat. Anesthesiology 64:54–66.PubMedCrossRefGoogle Scholar
  11. 11.
    Bryant RM, Olley JE, Tyers MB. 1983. Antinociceptive actions of morphine and buprenorphine given intrathecally in the conscious rat. Br J Pharmacol 78:659–663.PubMedGoogle Scholar
  12. 12.
    Yaksh TL, Reedy SVR. 1981. Studies in the primate on the analgetic effects associated with intrathecal opiates, alfa-adrenergic agonists and baclofen. Anesthesiology 54:451–467.PubMedCrossRefGoogle Scholar
  13. 13.
    Durant PAC, Yaksh TL. 1986. Epidural injections of bupivacaine, morphine, fentanyl, lofentanil, and DADL in chronically implanted rats: A pharmacologic and pathologic study. Anesthesiology 64:43–53.PubMedCrossRefGoogle Scholar
  14. 14.
    Colpaert FC, Leysen JE, Michiels M, van den Hoogen RHWM. 1986. Epidural and intravenous sufentanil in the rat: Analgesia, opiate receptor binding, and drug concentrations in plasma and brain. Anesthesiology 65:41–49.PubMedCrossRefGoogle Scholar
  15. 15.
    Rodan BA, Cohen FL, Bean WJ, Martyack SN. 1985. Fibrous mass complicating epidural morphine infusion. Neurosurgery 16:68–70.PubMedCrossRefGoogle Scholar
  16. 16.
    Durant PAC, Yaksh TL. 1986. Distribution in cerebrospinal fluid, blood, and lymph of epidurally injected morphine and insulin in dogs. Anesth Analg 65:583–592.PubMedCrossRefGoogle Scholar
  17. 17.
    Tucker GT, Mather LE. 1975. Pharmacokinetics of local anaesthetic agents. Br J Anaesth 47:213–224.PubMedCrossRefGoogle Scholar
  18. 18.
    Herz A, Teschemacher HJ. 1971. Activities and sites of antinociceptive action of morphine-like analgesics and kinetics of distribution following intravenous, intracerebral and intraventricular application. In Herper WJ, Simmonds AB (eds): Advances in Drug Research and Therapy, Vol. 6. New York: Academic Press, pp. 79–119.Google Scholar
  19. 19.
    Gustafsson LL, Post C, Edvardsen B, Ramsay CH. 1985. Distribution of morphine and meperidine after intrathecal administration in rat and mouse. Anesthesiology 63:483–489.PubMedCrossRefGoogle Scholar
  20. 20.
    Gustafsson LL, Hartvig P, Bergström K, Lundqvist H. Lindberg BS, Långström B, Svärd H, Rane A, Tamsen A. 1989. Distribution of C-labelled morphine and pethidine after spinal administration to Rhesus monkey. Acta Anaesthesiol Scand 33:105–111.PubMedCrossRefGoogle Scholar
  21. 21.
    Nordberg G, Hedner T, Mellstrand T, Dahlström B. 1983. Pharmacokinetic aspects of epidural morphine analgesia. Anesthesiology 58:545–551.PubMedCrossRefGoogle Scholar
  22. 22.
    Nordberg G. 1986. Epidural versus intrathecal route of opioid administration. Int Anesthesiol Clin 24:93–111.PubMedCrossRefGoogle Scholar
  23. 23.
    Watson J, Moore A, McQuay H, Teddy P, Baldwin D, Allen M, Bullingham R. 1984. Plasma morphine concentrations and analgesic effects of lumbar epidural morphine and heroin. Anesth Analg 63:629–634.PubMedCrossRefGoogle Scholar
  24. 24.
    Tamsen A, Sjöström S, Hartvig P, Persson P, Gabrielsson J, Paalzow L. 1983. CSF and plasma kinetics of morphine and meperidine administration. Anesthesiology 59:A196.Google Scholar
  25. 25.
    Nordberg G, Hedner T, Mellstrand T, Dahlström B. 1984. Pharmacokinetic aspects of intrathecal morphine analgesia. Anesthesiology 60:448–454.PubMedCrossRefGoogle Scholar
  26. 26.
    Chauvin M, Samii K, Schermann JM, Sandouk P, Bourdon R, Viars P. 1982. Plasma pharmacokinetics of morphine after i.m., extradural, and intrathecal administration. Br J Anaesth 54:843–847.PubMedCrossRefGoogle Scholar
  27. 27.
    Glynn CJ, Mather LE, Cousins MJ, Graham JR, Wilson PR, 1981. Peridural meperidine in humans: Analgetic response, pharmacokinetics and transmission into CSF. Anesthesiology 55:520–526.PubMedCrossRefGoogle Scholar
  28. 28.
    Gustafsson LL, Grell AM, Garle M, Rane A, Schildt B. 1984. Kinetics of morphine in cerebrospinal fluid after epidural administration. Acta Anaesthesiol Scand 28:535–539.PubMedCrossRefGoogle Scholar
  29. 29.
    Yeung JC, Rudy TA. 1980. Multiplicative interactions between narcotic agonisms expressed at spinal and supraspinal sites of antinociceptive action as revealed by concurrent intrathecal and intracerebroventricular injections of morphine. J Pharmacol Exp Ther 215:633–642.PubMedGoogle Scholar
  30. 30.
    Gustafsson LL, Friberg-Nielsen S, Garle M, Mohall A, Rane A, Schildt B, Symreng T. 1982. Epidural and parenteral morphine: Kinetics and effects in postoperative pain in a controlled clinical study. Br J Anaesth 544:1167–1174.CrossRefGoogle Scholar
  31. 31.
    Bromage PR, Camporesi E, Chestnut D. 1980. Epidural narcotics for postoperative analgesia. Anesth Analg 59:473–480.PubMedCrossRefGoogle Scholar
  32. 32.
    Baraka A, Noueihe R, Haij S. 1981. Intrathecal injection of morphine for obstetric analgesia. Anesthesiology 54:136–140.PubMedCrossRefGoogle Scholar
  33. 33.
    Rawal N, Wattwil M. 1984. Respiratory depression after epidural morphine — an experimental and clinical study. Anesth Analg 63:8–14.PubMedGoogle Scholar
  34. 34.
    Bromage PR, Comporesi EM, Durant PAC, Nielsen CH. 1982. Rostral spread of epidural morphine. Anesthesiology 56:431–436.PubMedCrossRefGoogle Scholar
  35. 35.
    Bromage PR, Comporesi EM, Durant PAC, Nielsen CH. 1982. Nonrespiratory side effects of epidural morphine. Anesth Analg 61:490–495.PubMedGoogle Scholar
  36. 36.
    Gustafsson LL, Johannisson J, Garle M. 1986. Extradural and parenteral pethidine as analgesia after total hip replacement: Effects and kinetics. A controlled clinical study. Eur J Clin Pharmacol 29:529–534.PubMedCrossRefGoogle Scholar
  37. 37.
    Torda TA, Pybus DA. 1982. Comparison of four narcotic analgesics for epidural analgesia. Br J Anaesth 54:291–295.PubMedCrossRefGoogle Scholar
  38. 38.
    Rutter DV, Shewes DG, Morgan M. 1981. Extradural opioids for postoperative analgesia. A double-blind comparison of pethidine, fentanyl and morphine. Br J Anaesth 915–920.Google Scholar

Copyright information

© Kluwer Academic Publishers 1990

Authors and Affiliations

  • Lars L. Gustafsson

There are no affiliations available

Personalised recommendations