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Contribution to variability in response to opioids

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Abstract

Opioids are the oldest and most effective agents for the short- and long-term control of severe pain, particularly chronic cancer pain palliation. However, morphine and other opioids display wide variations in pharmacological efficacy and tolerability, and a significant number of patients are unable to achieve adequately controlled pain at doses that do not produce intolerable adverse effects. This article reviews factors that affect the efficacy and tolerability of opioid analgesics and clinical strategies for successful pain mangement.

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References

  1. World Health Organization (1996) Cancer pain relief: with a guide to opioid availability. World Health Organization, Geneva

    Google Scholar 

  2. Reid C, Davies A (2004) The World Health Organization three-step analgesic ladder comes of age. Palliat Med 18:175–176

    Article  PubMed  Google Scholar 

  3. Jadad AR, Browman GP (1995) The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA 274:1870–1873

    CAS  PubMed  Google Scholar 

  4. Expert Working Group of the European Association for Palliative Care (1996) Morphine in cancer pain: modes of administration. BMJ 312:823–826

    Google Scholar 

  5. Hanks GW, Hoskin PJ, Aherne GW, Turner P, Poulain P (1987) Explanation for potency of repeated oral doses of morphine? Lancet 2:723–725

    Article  Google Scholar 

  6. Hoskin PJ, Hanks GW, Aherne GW, Chapman D, Littleton P, Filshie J (1989) The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers. Br J Clin Pharmacol 27:499–505

    Google Scholar 

  7. Glare PA, Walsh TD (1991) Clinical pharmacokinetics of morphine. Ther Drug Monit 13:1–23

    Google Scholar 

  8. Poyhia R, Vainio A, Kalso E (1993) A review of oxycodone’s clinical pharmacokinetics and pharmacodynamics. J Pain Symptom Manage 8:63–67

    Article  Google Scholar 

  9. Leow KP, Smith MT, Williams B, Cramond T (1992) Single-dose and steady-state pharmacokinetics and pharmacodynamics of oxycodone in patients with cancer. Clin Pharmacol Ther 52:487–495

    Google Scholar 

  10. Ma MK, Woo MH, McLeod HL (2002) Genetic basis of drug metabolism. Am J Health Syst Pharm 59:2061–2069

    Google Scholar 

  11. Wu D, Kang YS, Bickel U, Pardridge WM (1997) Blood-brain barrier permeability to morphine-6-glucuronide is markedly reduced compared with morphine. Drug Metab Dispos 25:768–771

    Google Scholar 

  12. Shimomura K, Kamata O, Ueki S, Ida S, Oguri K (1971) Analgesic effect of morphine glucuronides. Tohoku J Exp Med 105:45–52

    Google Scholar 

  13. Penson RT, Joel SP, Bakhshi K, Clark SJ, Langford RM, Slevin ML (2000) Randomized placebo-controlled trial of the activity of the morphine glucuronides. Clin Pharmacol Ther 68:667–676

    Article  Google Scholar 

  14. Osborne RJ, Joel SP, Slevin ML (1986) Morphine intoxication in renal failure: the role of morphine-6-glucuronide. Br Med J (Clin Res Ed) 292:1548–1549

    Google Scholar 

  15. Portenoy RK, Foley KM, Stulman J, Khan E, Adelhardt J, Layman M, Cerbone DF, Inturrisi CE (1991) Plasma morphine and morphine-6-glucuronide during chronic morphine therapy for cancer pain: plasma profiles, steady-state concentrations and the consequences of renal failure. Pain 47:13–19

    Article  Google Scholar 

  16. Hagen NA, Foley KM, Cerbone DJ, Portenoy RK, Inturrisi CE (1991) Chronic nausea and morphine-6-glucuronide. J Pain Symptom Manage 6:125–128

    Article  Google Scholar 

  17. Pasternak GW (2001) The pharmacology of mu analgesics: from patients to genes. Neuroscientist 7:220–231

    Google Scholar 

  18. Lotsch J, Skarke C, Grosch S, Darimont J, Schmidt H, Geisslinger G (2002) The polymorphism A118G of the human mu-opioid receptor gene decreases the pupil constrictory effect of morphine-6-glucuronide but not that of morphine. Pharmacogenetics 12:3–9

    Article  Google Scholar 

  19. Hollt V (2002) A polymorphism (A118G) in the mu-opioid receptor gene affects the response to morphine-6-glucuronide in humans. Pharmacogenetics 12:1–2

    Google Scholar 

  20. Bartlett SE, Smith MT (1995) The apparent affinity of morphine-3-glucuronide at mu1-opioid receptors results from morphine contamination: demonstration using HPLC and radioligand binding. Life Sci 57:609–615

    Article  Google Scholar 

  21. Bartlett SE, Dodd PR, Smith MT (1994) Pharmacology of morphine and morphine-3-glucuronide at opioid, excitatory amino acid, GABA and glycine binding sites. Pharmacol Toxicol 75:73–81

    Google Scholar 

  22. Beaver WT, Wallenstein SL, Houde RW, Rogers A (1977) Comparisons of the analgesic effects of oral and intramuscular oxymorphone and of intramuscular oxymorphone and morphine in patients with cancer. J Clin Pharmacol 17:186–198

    Google Scholar 

  23. Heiskanen T, Olkkola KT, Kalso E (1998) Effects of blocking CYP2D6 on the pharmacokinetics and pharmacodynamics of oxycodone. Clin Pharmacol Ther 64:603–611

    Google Scholar 

  24. Poyhia R, Seppala T, Olkkola KT, Kalso E (1992) The pharmacokinetics and metabolism of oxycodone after intramuscular and oral administration to healthy subjects. Br J Clin Pharmacol 33:617–621

    Google Scholar 

  25. Kirvela M, Lindgren L, Seppala T, Olkkola KT (1996) The pharmacokinetics of oxycodone in uremic patients undergoing renal transplantation. J Clin Anesth 8:13–18

    Article  Google Scholar 

  26. Otton SV, Wu D, Joffe RT, Cheung SW, Sellers EM (1993) Inhibition by fluoxetine of cytochrome P450 2D6 activity. Clin Pharmacol Ther 53:401–409

    Google Scholar 

  27. Zheng M, McErlane KM, Ong MC (2002) Hydromorphone metabolites: isolation and identification from pooled urine samples of a cancer patient. Xenobiotica 32:427–439

    Article  Google Scholar 

  28. Wright AW, Mather LE, Smith MT (2001) Hydromorphone-3-glucuronide: a more potent neuro-excitant than its structural analogue, morphine-3-glucuronide. Life Sci 69:409–420

    Article  Google Scholar 

  29. Lee MA, Leng ME, Tiernan EJ (2001) Retrospective study of the use of hydromorphone in palliative care patients with normal and abnormal urea and creatinine. Palliat Med 15:26–34

    Article  Google Scholar 

  30. McClain DA, Hug CC (1980) Intravenous fentanyl kinetics. Clin Pharmacol Ther 28:106–114

    CAS  PubMed  Google Scholar 

  31. Mather LE (1983) Clinical pharmacokinetics of fentanyl and its newer derivatives. Clin Pharmacokinet 8:422–446

    CAS  PubMed  Google Scholar 

  32. Inturrisi CE, Verebely K (1972) Disposition of methadone in man after a single oral dose. Clin Pharmacol Ther 18:923–930

    CAS  PubMed  Google Scholar 

  33. Pohland A, Boaz HE, Sullivan HR (1971) Synthesis and identification of metabolites resulting from the biotransformation of d,1-methadone in man and in the rat. J Med Chem 14:194–197

    CAS  PubMed  Google Scholar 

  34. Ripamonti C, Groff L, Brunelli C, Polastri D, Stavrakis A, De Conno F (1988) Switching from morphine to oral methadone in treating cancer pain: what is the equianalgesic dose ratio? J Clin Oncol 16:3216–3221

    Google Scholar 

  35. Cherny N, Ripamonti C, Pereira J, Davis C, Fallon M, McQuay H, Mercadante S, Pasternak G, Ventafridda V (2001) Strategies to manage the adverse effects of oral morphine: an evidence-based report. J Clin Oncol 19:2542–2554

    Google Scholar 

  36. Mercadante S (1999) Opioid rotation for cancer pain: rationale and clinical aspects. Cancer 86:1856–1866

    Article  Google Scholar 

  37. Gaveriaux-Ruff C, Kieffer BL (1999) Opioid receptors: gene structure and function. In: Stein C (ed) Opioids in pain control: basic and clinical aspects. Cambridge University Press, Cambridge, pp 1–20

  38. Knapp RJ, Porreca F, Burks TF, Yamamura HI (1989) Mediation of analgesia by multiple opioid receptors. In: Hill CS, Fields WS (eds) Advances in pain research and therapy. Raven Press, New York, pp 247–289

  39. de Stoutz ND, Bruera E, Suarez-Almazor M (1995) Opioid rotation for toxicity reduction in terminal cancer patients. J Pain Symptom Manage 10:378–384

    Google Scholar 

  40. Hawley P, Forbes K, Hanks GW (1998) Opioids, confusion and opioid rotation. Palliat Med 12:63–64

    Google Scholar 

  41. Massie MJ, Holland J, Glass E (1983) Delirium in terminally ill cancer patients. Am J Psychiatry 140:1048–1050

    Google Scholar 

  42. Dickenson AH (1994) Neurophysiology of opioid poorly responsive pain. Cancer Surv 21:5–16

    CAS  PubMed  Google Scholar 

  43. Yashpal K, Fisher K, Chabot JG, Coderre TJ (2001) Differential effects of NMDA and group I mGluR antagonists on both nociception and spinal cord protein kinase C translocation in the formalin test and a model of neuropathic pain in rats. Pain 94:17–29

    Article  Google Scholar 

  44. Trujillo KA (2002) The neurobiology of opiate tolerance, dependence and sensitization: mechanisms of NMDA receptor-dependent synaptic plasticity. Neurotox Res 4:373–391

    Article  CAS  PubMed  Google Scholar 

  45. Bell R, Eccleston C, Kalso E (2003) Ketamine as an adjuvant to opioids for cancer pain. Cochrane Library

  46. Hanks GW, Twycross RG (1984) Pain, the physiological antagonist of opioid analgesics. Lancet 1:1477–1478

    Article  Google Scholar 

  47. Colpaert FC, Niemegeers CJ, Janssen PA (1978) Nociceptive stimulation prevents development of tolerance to narcotic analgesia. Eur J Pharmacol 49:335–336

    Article  Google Scholar 

  48. Borgbjerg FM, Nielsen K, Franks J (1996) Experimental pain stimulates respiration and attenuates morphine-induced respiratory depression: a controlled study in human volunteers. Pain 64:123–128

    Article  Google Scholar 

  49. Hanks GW, Twycross RG, Lloyd JW (1981) Unexpected complication of successful nerve block: morphine induced respiratory depression following removal of severe pain. Anaesthesia 36:37–39

    CAS  PubMed  Google Scholar 

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Acknowledgement

This review was supported by Endo Pharmaceuticals, Chadds Ford, Pennsylvania, with editorial assistance provided by Accel Medical Education, New York, NY.

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Authors and Affiliations

  1. Department of Palliative Medicine, Bristol Haematology and Oncology Centre, University of Bristol, Horfield Road, Bristol, BS2 8ED, UK

    Geoffrey W. Hanks & Colette Reid

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  1. Geoffrey W. Hanks
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  2. Colette Reid
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Correspondence to Geoffrey W. Hanks.

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Hanks, G.W., Reid, C. Contribution to variability in response to opioids. Support Care Cancer 13, 145–152 (2005). https://doi.org/10.1007/s00520-004-0730-2

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  • DOI: https://doi.org/10.1007/s00520-004-0730-2

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