Prakt. lékáren. 2022; 18(1): 48-52 | DOI: 10.36290/lek.2022.007

Dual opioid analgesia

Jan Juřica
Farmakologický ústav LF, Masarykova univerzita, Brno
Farmakologický ústav LF, Ústav farmakologie a toxikologie FaF, Masarykova univerzita, Brno
Masarykův onkologický ústav, Brno

Current opioid analgesics are agonists or partial agonists of the opioid receptors μ, λ, δ, and ORL1 (MOPr, DOPr, KOPr, and NOPr.) The combination of agonists and partial agonists or two full agonists with different receptor affinities should theoretically reduce the potential of maximal analgesic effect. However, in clinical practice, these combinations are particularly effective in increasing analgesic efficacy, better tolerability, better control of pain intensity during the day, and delaying tolerance to the analgesic effect. The article provides an overview of the current state of knowledge about dual opioid analgesia and pharmacological arguments supporting the rationality of these combinations. Nevertheless, it should be emphasized that the combination of opioids is not recommended practice but rather an alternative approach in the case of failure of the standard treatment accordingly to the current clinical guidelines

Keywords: opioid receptors, pain management, opioids, dual opioid analgesia.

Published: March 14, 2022  Show citation

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Juřica J. Dual opioid analgesia. Praktické lékárenství. 2022;18(1):48-52. doi: 10.36290/lek.2022.007.
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References

  1. Vader K, Bostick G, Carlesso L, Hunter J, Mesaroli G, Perreault K, Tousignant­‑Laflamme Y, Tupper S, Walton D, Wideman T, Miller J. The Revised IASP Definition of Pain and Accompanying Notes: Considerations for the Physiotherapy Profession. Physiotherapy Canada. 2021;73(2):103-106. DOI 10.3138/ptc-2020-0124-gee Go to original source... Go to PubMed...
  2. Kiss I. Modrá kniha České onkologické společnosti. Brno: Masarykův onkologický ústav, 2021.
  3. Zelcer S, Kolesnikov Y, Kovalyshyn I, Pasternak DA, Pasternak GW. Selective potentiation of opioid analgesia by nonsteroidal anti­‑inflammatory drugs. Brain Res. 2005;1040(1-2):151-156. DOI 10.1016/j.brainres.2005. 01. 070. Go to original source... Go to PubMed...
  4. Shimoyama N, Shimoyama M, Inturrisi CE, Elliott KJ. Ketamine attenuates and reverses morphine tolerance in rodents. Anesthesiology. 1996;85(6):1357-1366. DOI 10.1097/00000542-199612000-00017. Go to original source... Go to PubMed...
  5. Mion G, Villevieille T. Ketamine pharmacology: an update (pharmacodynamics and molecular aspects, recent findings). CNS Neurosci Ther. 2013;19(6):370-380. DOI 10.1111/cns.12099. Go to original source... Go to PubMed...
  6. Lilius TO, Jokinen V, Neuvonen MS, Niemi M, Kalso EA, Rauhala PV. Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat. Br J Pharmacol. 2015;172(11):2799-2813. DOI 10.1111/bph.12974. Go to original source... Go to PubMed...
  7. Petrenko AB, Yamakura T, Baba H, Shimoji K. The role of N­‑methyl­‑D-aspartate (NMDA) receptors in pain: a review. Anesth Analg. 2003;97(4):1108-1116. DOI 10.1213/01.ane.0000081061.12235.55. Go to original source... Go to PubMed...
  8. Frymoyer AR, Rowbotham MC, Petersen KL. Placebo­‑controlled comparison of a morphine/dextromethorphan combination with morphine on experimental pain and hyperalgesia in healthy volunteers. J Pain. 2007;8(1):19-25. DOI 10.1016/j.jpain.2006. 05. 010. Go to original source... Go to PubMed...
  9. Vargas­‑Schaffer G. Is the WHO analgesic ladder still valid? Twenty­‑four years of experience. Canadian Family Physician. 2021;56(6):514-517.
  10. Jadad AR, Browman GP. The WHO analgesic ladder for cancer pain management. Stepping up the quality of its evaluation. JAMA. 1995;274(23):1870-1873. Go to original source... Go to PubMed...
  11. Ventafridda V, Tamburini M, Caraceni A, De Conno F, Naldi F. A validation study of the WHO method for cancer pain relief. Cancer. 1987;59(4):850-856. DOI 10.1002/1097-0142(19870215)59:43. 0. co;2-1 Go to original source... Go to PubMed...
  12. (2018) WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents; 2018.
  13. Cuomo A, Bimonte S, Forte C, Botti G, Cascella M. Multimodal approaches and tailored therapies for pain management: the trolley analgesic model. Journal of Pain Research. 2019;12:711-714 DOI 10.2147/JPR.S178910. Go to original source... Go to PubMed...
  14. Harris D. Management of pain in advanced disease. British Medical Bulletin 2014;110(1):117-128. DOI 10.1093/bmb/ldu010. Go to original source... Go to PubMed...
  15. Maltoni M, Scarpi E, Modonesi C, Passardi A, Calpona S, Turriziani A, Speranza R, Tassinari D, Magnani P, Saccani D, Montanari L, Roudnas B, Amadori D.A validation study of the WHO analgesic ladder: a two­‑step vs three­‑step strategy. Supportive Care in Cancer. 2005;13 (11):888-894. DOI 10.1007/s00520-005-0807-6. Go to original source... Go to PubMed...
  16. Chou R, Fanciullo G, Fine P, Adler J, Ballantyne J, Davies P, Donovan M, Fishbain D, Foley K, Fudin J, Gilson A, Kelter A, Mauskop A, O'Connor P, Passik S, Pasternak G, Portenoy R, Rich B, Roberts R, Todd K, Miaskowski C, O APSAAPM, O APSAAPM. Clinical Guidelines for the Use of Chronic Opioid Therapy in Chronic Noncancer Pain. Journal of Pain. 2009;10(2):113-130. DOI 10.1016/j.jpain.2008. 10. 008. Go to original source... Go to PubMed...
  17. Mercadante S. Efficacy and safety of dual opioid therapy. Expert Opin Drug Saf. 2014;13 (11): 1433-1436. DOI 10.1517/14740338.2014.966077. Go to original source... Go to PubMed...
  18. Webster L. Efficacy and safety of dual­‑opioid therapy in acute pain. Pain Med. 2012;13 Suppl 1: S12-20. DOI 10.1111/j.1526-4637.2012.01330.x. Go to original source... Go to PubMed...
  19. Fallon MT, Laird BJ. A systematic review of combination step III opioid therapy in cancer pain: an EPCRC opioid guideline project. Palliat Med. 2011;25(5):597-603. DOI 10.1177/0269216310392101. Go to original source... Go to PubMed...
  20. Brzeziński K. Opioid combination. Case report. Contemporary Oncology. 2011;15(6):409-411. DOI 10.5114/wo.2011.26449 Go to original source...
  21. Di Lorenzo L, Foti C, Forte AM, Palmieri E, Formisano R, Vatakencherry A, Pappagallo M. The addition of tramadol as a second opioid may improve pain relief in severe osteoarthritis: a prospective study. Pain Pract. 2010;10 (6):540-547. DOI 10.1111/j.1533-2500.2010.00384.x. Go to original source... Go to PubMed...
  22. Marinangeli F, Ciccozzi A, Aloisio L, Colangeli A, Paladini A, Bajocco C, Coaccioli S, Varrassi G. Improved cancer pain treatment using combined fentanyl­‑TTS and tramadol. Pain Pract. 2007;7 (4):307-312. DOI 10.1111/j.1533-2500.2007.00155.x. Go to original source... Go to PubMed...
  23. Mercadante S, Villari P, Ferrera P, Casuccio A. Addition of a second opioid may improve opioid response in cancer pain: preliminary data. Support Care Cancer. 2004;12 (11): 762-766. DOI 10.1007/s00520-004-0650-1. Go to original source... Go to PubMed...
  24. Yeh YC, Lin TF, Chang HC, Chan WS, Wang YP, Lin CJ, Sun WZ. Combination of low­‑dose nalbuphine and morphine in patient­‑controlled analgesia decreases incidence of opioid­‑related side effects. J Formos Med Assoc. 2009;108(7):548-553. DOI 10.1016/S0929-6646(09)60372-7. Go to original source... Go to PubMed...
  25. Yoshitake A, Yamamoto T, Susaki S, Abe E. Opioid combination of transdermal fentanyl and oral oxycodone for pain in a patient with giant­‑cell tumor of the sacrum. Masui. 2014;63(2):199-202. Go to PubMed...
  26. Kim HJ, Kim YS, Park SH. Opioid rotation versus combination for cancer patients with chronic uncontrolled pain: a randomized study. BMC Palliat Care. 2015;14:41. DOI 10.1186/s12904-015-0038-7. Go to original source... Go to PubMed...
  27. Mercadante S. Opioid combination: rationale and possible clinical applications. Ann Palliat Med. 2013;2 (4):189-196. DOI 10.3978/j.issn.2224-5820.2013. 09. 04. Go to original source... Go to PubMed...
  28. Waldhoer M, Bartlett SE, Whistler JL. Opioid receptors. Annu Rev Biochem. 2004;73: 953-990. DOI 10.1146/annurev.biochem.73.011303.073940. Go to original source... Go to PubMed...
  29. Corbett AD, Henderson G, McKnight AT, Paterson SJ. 75 years of opioid research: the exciting but vain quest for the Holy Grail. Br J Pharmacol. 2006;147 Suppl 1: S153-162. DOI 10.1038/sj.bjp.0706435. Go to original source... Go to PubMed...
  30. Mansour A, Khachaturian H, Lewis ME, Akil H, Watson SJ. Anatomy of CNS opioid receptors. Trends Neurosci. 1998;11(7):308-314. DOI 10.1016/0166-2236(88)90093-8. Go to original source... Go to PubMed...
  31. Rickli A, Liakoni E, Hoener MC, Liechti ME.Opioid­‑induced inhibition of the human 5-HT and noradrenaline transporters in vitro: link to clinical reports of serotonin syndrome. Br J Pharmacol. 2018;175 (3):532-543. DOI 10.1111/bph.14105. Go to original source... Go to PubMed...
  32. Francescangeli J, Karamchandani K, Powell M, Bonavia A. The Serotonin Syndrome: From Molecular Mechanisms to Clinical Practice. Int J Mol Sci. 2019;20 (9). DOI 10.3390/ijms20092288. Go to original source... Go to PubMed...
  33. Boyer EW (2021) Serotonin syndrome (serotonin toxicity). In: ed. UpToDate, Post TW (Ed), UpToDate, Waltham, MA.
  34. Heiskanen T, Kalso E. Controlled­‑release oxycodone and morphine in cancer related pain. Pain. 1997;73(1):37-45. DOI 10.1016/s0304-3959(97)00072-9. Go to original source... Go to PubMed...
  35. Lauretti GR, Oliveira GM, Pereira NL. Comparison of sustained­‑release morphine with sustained­‑release oxycodone in advanced cancer patients. Br J Cancer. 2003;89 (11): 2027-2030. DOI 10.1038/sj.bjc.6601365. Go to original source... Go to PubMed...
  36. Schmidt­‑Hansen M, Bennett MI, Arnold S, Bromham N, Hilgart JS. Efficacy, tolerability and acceptability of oxycodone for cancer­‑related pain in adults: an updated Cochrane systematic review. BMJ Support Palliat Care. 2018;8(2):117-128. DOI 10.1136/bmjspcare-2017-001457. Go to original source... Go to PubMed...
  37. Ibrahim AS, Aly MG, Thabet ME, Abdelaziz MR. Effect of adding nalbuphine to intrathecal bupivacaine with morphine on postoperative nausea and vomiting and pruritus after elective cesarean delivery: a randomized double blinded study. Minerva Anestesiol. 2019;85(3):255-262. DOI 10.23736/S0375-9393. 18. 12751-9. Go to original source... Go to PubMed...
  38. McPherson J, Rivero G, Baptist M, Llorente J, Al­‑Sabah S, Krasel C, Dewey WL, Bailey CP, Rosethorne EM, Charlton SJ, Henderson G, Kelly E. μ­‑opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization. Mol Pharmacol. 2010;78(4):756-766. DOI 10.1124/mol.110.066613. Go to original source... Go to PubMed...
  39. Gudin J, Fudin J. A Narrative Pharmacological Review of Buprenorphine: A Unique Opioid for the Treatment of Chronic Pain. Pain Ther. 2020;9(1):41-54. DOI 10.1007/s40122-019-00143-6. Go to original source... Go to PubMed...
  40. Whistler JL. Examining the role of mu opioid receptor endocytosis in the beneficial and side­‑effects of prolonged opioid use: from a symposium on new concepts in mu­‑opioid pharmacology. Drug Alcohol Depend. 2012;121(3):189-204. DOI 10.1016/j.drugalcdep.2011. 10. 031. Go to original source...
  41. Mercadante S. Opioid combination for cancer pain. Br J Cancer. 2004;90 (10): 2049. DOI 10.1038/sj.bjc.6601806. Go to original source... Go to PubMed...
  42. Quillinan N, Lau EK, Virk M, von Zastrow M, Williams JT. Recovery from mu­‑opioid receptor desensitization after chronic treatment with morphine and methadone. J Neurosci. 2011;3 (12): 4434-4443. DOI 10.1523/JNEUROSCI.4874-10.2011. Go to original source... Go to PubMed...
  43. Hashimoto T, Saito Y, Yamada K, Hara N, Kirihara Y, Tsuchiya M. Enhancement of morphine analgesic effect with induction of mu­‑opioid receptor endocytosis in rats. Anesthesiology. 2006;105 (3): 574-580. DOI 10.1097/00000542-200609000-00023. Go to original source... Go to PubMed...
  44. Enquist J, Ferwerda M, Milan­‑Lobo L, Whistler JL. Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice. J Pharmacol Exp Ther. 2012;340(2): 386-392. DOI 10.1124/jpet.111.187583. Go to original source... Go to PubMed...
  45. Darcq E, Kieffer BL. Opioid receptors: drivers to addiction? Nat Rev Neurosci. 2018;19 (8):499-514. DOI 10.1038/s41583-018-0028-x. Go to original source... Go to PubMed...
  46. Wang YH, Sun JF, Tao YM, Chi ZQ, Liu JG. The role of kappa­‑opioid receptor activation in mediating antinociception and addiction. Acta Pharmacol Sin. 2010;31(9):1065-1070. DOI 10.1038/aps.2010.138. Go to original source... Go to PubMed...
  47. Cuitavi J, Hipólito L, Canals M. The Life Cycle of the Mu­‑Opioid Receptor. Trends Biochem Sci. 2021;46(4):315-328. DOI 10.1016/j.tibs.2020. 10. 002. Go to original source... Go to PubMed...
  48. Wang S. Historical Review: Opiate Addiction and Opioid Receptors. Cell Transplant. 2019;28 (3): 233-238. DOI 10.1177/0963689718811060. Go to original source... Go to PubMed...
  49. Narita M, Funada M, Suzuki T. Regulations of opioid dependence by opioid receptor types. Pharmacol Ther. 2001;89(1):1-15. DOI 10.1016/s0163-7258(00)00099-1. Go to original source... Go to PubMed...
  50. McDonald J, Lambert D. Opioid receptors. Bja Education. 2015;15 (5):219-224. DOI 10.1093/bjaceaccp/mku041. Go to original source...
  51. Thomsen AB, Becker N, Eriksen J. Opioid rotation in chronic non­‑malignant pain patients. A retrospective study. Acta Anaesthesiol Scand. 1999;43 (9): 918-923. DOI 10.1034/j.1399-6576.1999.430909.x. Go to original source... Go to PubMed...
  52. Ding H, Kiguchi N, Yasuda D, Daga PR, Polgar WE, Lu JJ, Czoty PW, Kishioka S, Zaveri NT, Ko MC. A bifunctional nociceptin and mu opioid receptor agonist is analgesic without opioid side effects in nonhuman primates. Sci Transl Med. 2018;10 (456). DOI 10.1126/scitranslmed.aar3483. Go to original source... Go to PubMed...
  53. Kiguchi N, Ding H, Kishioka S, Ko MC. Nociceptin/Orphanin FQ Peptide Receptor­‑Related Ligands as Novel Analgesics. Curr Top Med Chem. 2020;20 (31):2878-2888. DOI 10.2174/1568026620666200508082615. Go to original source... Go to PubMed...
  54. Shinjo T, Okada M. The opioid combination of transdermal fentanyl and sustained release morphine for refractory cancer pain--a case report. Gan To Kagaku Ryoho. 2005;32 (12):1997-2000.
  55. Richards P, Riff D, Kelen R, Stern W, Team MS. Analgesic and adverse effects of a fixed­‑ratio morphine­‑oxycodone combination (MoxDuo) in the treatment of postoperative pain. J Opioid Manag. 2011;7 (3):217-228. DOI 10.5055/jom.2011.0064. Go to original source... Go to PubMed...
  56. Vora KS, Shah VR, Patel B, Parikh GP, Butala BP. Postoperative analgesia with epidural opioids after cesarean section: Comparison of sufentanil, morphine and sufentanil­‑morphine combination. J Anaesthesiol Clin Pharmacol. 2012;28 (4):491-495. DOI 10.4103/0970-9185.101935 Go to original source... Go to PubMed...




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