Review article. Opioid analgesics: Does potency matter?

Authors

  • Steven D. Passik, PhD
  • Lynn Webster, MD

DOI:

https://doi.org/10.5055/jom.2014.0214

Keywords:

opioids, potency, pharmacokinetics, abuse, analgesia, titration, safety

Abstract

Prescription opioid analgesics with a wide range of potencies are currently used for the treatment of chronic pain. Yet understanding the clinical relevance and therapeutic consequences of opioid potency remains ill defined. Both patients and clinicians alike have misperceptions about opioid potency, expecting that lesspotent opioids will be less effective or fearing that more-potent opioids are more dangerous or more likely to be abused. In this review, common myths about the potency of opioid analgesics will be discussed. Clinicians should understand that pharmacologic potency per se does not necessarily imply more effective analgesia or higher abuse liability. Published dose conversion tables may not accurately calculate the dose for effective and safe rotation from one opioid to another in patients receiving long-term opioid therapy because they are based on limited data that may not apply to chronic pain. Differences in pharmacologic potency are largely accounted for by the actual doses prescribed, according to individualized patient need. Factors for achieving effective analgesia and reducing the risks involved with opioid use include careful medication selection based on patient characteristics, appropriate dosing titration and opioid rotation practices, knowledge of product formulation characteristics (eg, extended release, immediate release, and tamper-resistant features), and an awareness of differences in opioid pharmacokinetics and metabolism. Clinicians should remain vigilant in monitoring patients on any opioid medication, regardless of classification along the opioid potency continuum.

Author Biographies

Steven D. Passik, PhD

Director of Clinical Addiction Research & Education, Millennium Laboratories, Inc., San Diego, California.

Lynn Webster, MD

Chief Medical Director, CRI Lifetree Research, Salt Lake City, Utah.

 

References

Knotkova H, Fine PG, Portenoy RK: Opioid rotation: The science and the limitations of the equianalgesic dose table. J Pain Symptom Manage. 2009; 38(3): 426-439. DOI: https://doi.org/10.1016/j.jpainsymman.2009.06.001

McPherson ML: Demystifying Opioid Conversion Calculations: A Guide to Effective Dosing. Bethesda, MD: American Society of Health System Pharmacists, 2010.

Waldman SA: Does potency predict clinical efficacy? Illustration through an antihistamine model. Ann Allergy Asthma Immunol. 2002; 89(1): 7-11. DOI: https://doi.org/10.1016/S1081-1206(10)61904-7

Blumenthal DK, Garrison JC: Pharmacodynamics: Molecular mechanisms of drug action. In Brunton LL, Chabner BA, Knollmann BC (eds.): Goodman and Gilman's The Pharmacological Basis of Therapeutics. New York, NY: McGraw-Hill, 2011: 41-72.

von Zastrow M, Bourne HR: Drug receptors and pharmacodynamics. In Katzung B, Masters S, Trevor A (eds.): Basic and Clinical Pharmacology. New York, NY: McGraw-Hill, 2009: 15-36.

Volpe DA, McMahon Tobin GA, Mellon RD, et al..: Uniform assessment and ranking of opioid mu receptor binding constants for selected opioid drugs. Regul Toxicol Pharmacol. 2011; 59(3): 385-390. DOI: https://doi.org/10.1016/j.yrtph.2010.12.007

Bostrom E, Hammarlund-Udenaes M, Simonsson US: Bloodbrain barrier transport helps to explain discrepancies in in vivo potency between oxycodone and morphine. Anesthesiology. 2008; 108(3): 495-505. DOI: https://doi.org/10.1097/ALN.0b013e318164cf9e

Zuurmond WW, Meert TF, Noorduin H: Partial versus full agonists for opioid-mediated analgesia—Focus on fentanyl and buprenorphine. Acta Anaesthesiol Belg. 2002; 53(3): 193-201.

Rozenfeld R, Devi LA: Receptor heterodimerization leads to a switch in signaling: Beta-arrestin2-mediated ERK activation by mu-delta opioid receptor heterodimers. FASEB J. 2007; 21(10): 2455-2465. DOI: https://doi.org/10.1096/fj.06-7793com

Kenakin T: Allosteric drugs and seven transmembrane receptors. Curr Top Med Chem. 2013; 13(1): 5-13. DOI: https://doi.org/10.2174/1568026611313010003

Kelly E: Ligand bias at the mu-opioid receptor. Biochem Soc Trans. 2013; 41(1): 218-224. DOI: https://doi.org/10.1042/BST20120331

Pasternak GW: Insights into mu opioid pharmacology the role of mu opioid receptor subtypes. Life Sci. 2001; 68(19-20): 2213-2219. DOI: https://doi.org/10.1016/S0024-3205(01)01008-6

Rajagopal S: Quantifying biased agonism: Understanding the links between affinity and efficacy. Nat Rev Drug Discov. 2013; 12(6): 483. DOI: https://doi.org/10.1038/nrd3954-c1

Sánchez-Blázquez P, Gómez-Serranillos P, Garzón J: Agonists determine the pattern of G-protein activation in muopioid receptor-mediated supraspinal analgesia. Brain Res Bull. 2001; 54(2): 229-235. DOI: https://doi.org/10.1016/S0361-9230(00)00448-2

Andresen T, Upton RN, Foster DJ, et al..: Pharmacokinetic/ pharmacodynamic relationships of transdermal buprenorphine and fentanyl in experimental human pain models. Basic Clin Pharmacol Toxicol. 2011; 108(4): 274-284. DOI: https://doi.org/10.1111/j.1742-7843.2010.00649.x

Carson S, Thakurta S, Low A, et al..: Drug Class Review: Long-Acting Opioid Analgesics. Portland, OR: Oregon Health and Science University, July 2011. Available at http://www.ncbi.nlm.nih.gov/books/NBK62335/pdf/TOC.pdf. Accessed May 9, 2014.

Chou R, Fanciullo GJ, Fine PG, et al..: Clinical guidelines for the use of chronic opioid therapy in chronic noncancer pain. J Pain. 2009; 10(2): 113-130. DOI: https://doi.org/10.1016/j.jpain.2008.10.008

Allan L, Hays H, Jensen NH, et al..: Randomised crossover trial of transdermal fentanyl and sustained release oral morphine for treating chronic non-cancer pain. BMJ. 2001; 322(7295): 1154-1158. DOI: https://doi.org/10.1136/bmj.322.7295.1154

Allan L, Richarz U, Simpson K, et al..: Transdermal fentanyl versus sustained release oral morphine in strong-opioid naïve patients with chronic low back pain. Spine (Phila Pa 1976). 2005; 30(22): 2484-2490. DOI: https://doi.org/10.1097/01.brs.0000186860.23078.a8

Caldwell JR, Rapoport RJ, Davis JC, et al..: Efficacy and safety of a once-daily morphine formulation in chronic, moderate-tosevere osteoarthritis pain: Results from a randomized, placebocontrolled, double-blind trial and an open-label extension trial. J Pain Symptom Manage. 2002; 23(4): 278-291. DOI: https://doi.org/10.1016/S0885-3924(02)00383-4

Hale M, Tudor IC, Khanna S, et al..: Efficacy and tolerability of once-daily OROS hydromorphone and twice-daily extendedrelease oxycodone in patients with chronic, moderate to severe osteoarthritis pain: Results of a 6-week, randomized, openlabel, noninferiority analysis. Clin Ther. 2007; 29(5): 874-888. DOI: https://doi.org/10.1016/j.clinthera.2007.05.016

Hale ME, Dvergsten C, Gimbel J: Efficacy and safety of oxymorphone extended release in chronic low back pain: Results of a randomized, double-blind, placebo- and active-controlled phase III study. J Pain. 2005; 6(1): 21-28. DOI: https://doi.org/10.1016/j.jpain.2004.09.005

Katz N, Sun S, Johnson F, et al..: ALO-01 (morphine sulfate and naltrexone hydrochloride) extended-release capsules in the treatment of chronic pain of osteoarthritis of the hip or knee: Pharmacokinetics, efficacy, and safety. J Pain. 2010; 11(4): 303-311. DOI: https://doi.org/10.1016/j.jpain.2009.07.017

Nicholson B, Ross E, Sasaki J, et al..: Randomized trial comparing polymer-coated extended-release morphine sulfate to controlled-release oxycodone HCl in moderate to severe nonmalignant pain. Curr Med Res Opin. 2006; 22(8): 1503-1514. DOI: https://doi.org/10.1185/030079906X115603

Matsumoto AK, Babul N, Ahdieh H: Oxymorphone extended-release tablets relieve moderate to severe pain and improve physical function in osteoarthritis: Results of a randomized, double-blind, placebo- and active-controlled phase III trial. Pain Med. 2005; 6(5): 357-366. DOI: https://doi.org/10.1111/j.1526-4637.2005.00057.x

Niemann T, Madsen LG, Larsen S, et al..: Opioid treatment of painful chronic pancreatitis. Int J Pancreatol. 2000; 27(3): 235- 240. DOI: https://doi.org/10.1385/IJGC:27:3:235

Rauck RL, Bookbinder SA, Bunker TR, et al..: The ACTION study: A randomized, open-label, multicenter trial comparing once-a-day extended-release morphine sulfate capsules (AVINZA) to twice-a-day controlled-release oxycodone hydrochloride tablets (OxyContin) for the treatment of chronic, moderate to severe low back pain. J Opioid Manag. 2006; 2(3): 155-166. DOI: https://doi.org/10.5055/jom.2006.0025

Sarton E, Olofsen E, Romberg R, et al..: Sex differences in morphine analgesia: An experimental study in healthy volunteers. Anesthesiology. 2000; 93(5): 1245-1254. DOI: https://doi.org/10.1097/00000542-200011000-00018

Niesters M, Dahan A, Kest B, et al..: Do sex differences exist in opioid analgesia? A systematic review and meta-analysis of human experimental and clinical studies. Pain. 2010; 151(1): 61-68. DOI: https://doi.org/10.1016/j.pain.2010.06.012

Webster LR: Pharmacogenetics of pain: The future of personalized medicine. In Moore RJ (ed.): Handbook of Pain and Palliative Care: Biobehavioral Approaches for the Life Course. New York, NY: Springer Science+Business Media, LLC, 2012: 431-438. DOI: https://doi.org/10.1007/978-1-4419-1651-8_26

Smith HS: Opioid metabolism. Mayo Clin Proc. 2009; 84(7): 613-624. DOI: https://doi.org/10.4065/84.7.613

Madadi P, Hildebrandt D, Gong IY, et al..: Fatal hydrocodone overdose in a child: Pharmacogenetics and drug interactions. Pediatrics. 2010; 126(4): e986-e989. DOI: https://doi.org/10.1542/peds.2009-1907

Chou WY, Wang CH, Liu PH, et al..: Human opioid receptor A118G polymorphism affects intravenous patient-controlled analgesia morphine consumption after total abdominal hysterectomy. Anesthesiology. 2006; 105(2): 334-337. DOI: https://doi.org/10.1097/00000542-200608000-00016

Zhang W, Chang YZ, Kan QC, et al..: Association of human mu-opioid receptor gene polymorphism A118G with fentanyl analgesia consumption in Chinese gynaecological patients. Anaesthesia. 2010; 65(2): 130-135. DOI: https://doi.org/10.1111/j.1365-2044.2009.06193.x

Pan L, Xu J, Yu R, et al..: Identification and characterization of six new alternatively spliced variants of the human mu opioid receptor gene, Oprm. Neuroscience. 2005; 133(1): 209-220. DOI: https://doi.org/10.1016/j.neuroscience.2004.12.033

Webster LR, Fine PG: Review and critique of opioid rotation practices and associated risks of toxicity. Pain Med. 2012; 13(4): 562-570. DOI: https://doi.org/10.1111/j.1526-4637.2012.01357.x

US Department of Health and Human Services, US Food and Drug Administration: Information for healthcare professionals: methadone hydrochloride, text version. 2010. Available at http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm142841.htm. Accessed May 9, 2014.

Hale M, Khan A, Kutch M, et al..: Once-daily OROS hydromorphone ER compared with placebo in opioid-tolerant patients with chronic low back pain. Curr Med Res Opin. 2010; 26(6): 1505-1518. DOI: https://doi.org/10.1185/03007995.2010.484723

Wallace M, Rauck RL, Moulin D, et al..: Once-daily OROS hydromorphone for the management of chronic nonmalignant pain: A dose-conversion and titration study. Int J Clin Pract. 2007; 61(10): 1671-1676. DOI: https://doi.org/10.1111/j.1742-1241.2007.01500.x

Wallace M, Rauck RL, Moulin D, et al..: Conversion from standard opioid therapy to once-daily oral extended-release hydromorphone in patients with chronic cancer pain. J Int Med Res. 2008; 36(2): 343-352. DOI: https://doi.org/10.1177/147323000803600218

Shaheen PE, Walsh D, Lasheen W, et al..: Opioid equianalgesic tables: Are they all equally dangerous? J Pain Symptom Manage. 2009; 38(3): 409-417. DOI: https://doi.org/10.1016/j.jpainsymman.2009.06.004

Fine PG, Portenoy RK: Establishing “best practices” for opioid rotation: Conclusions of an expert panel. J Pain Symptom Manage. 2009; 38(3): 418-425. DOI: https://doi.org/10.1016/j.jpainsymman.2009.06.002

Webster LR, Fine PG: Overdose deaths demand a new paradigm for opioid rotation. Pain Med. 2012; 13(4): 571-574. DOI: https://doi.org/10.1111/j.1526-4637.2012.01356.x

Webster LR, Cochella S, Dasgupta N, et al..: An analysis of the root causes for opioid-related overdose deaths in the United States. Pain Med. 2011; 12(Suppl 2): S26-S35. DOI: https://doi.org/10.1111/j.1526-4637.2011.01134.x

US Department of Health and Human Services, Centers for Disease Control and Prevention, National Center for Injury Prevention and Control: Prescription painkiller overdoses in the US. November 2011. Available at http://www.cdc.gov/VitalSigns/pdf/2011-11-vitalsigns.pdf. Accessed May 9, 2014.

Cai R, Crane E, Poneleit K, et al..: Emergency department visits involving nonmedical use of selected prescription drugs—United States, 2004-2008. MMWR Morb Mortal Wkly Rep. 2010; 59(23): 705-709. DOI: https://doi.org/10.3109/15360288.2010.503730

Butler SF, Fernandez KC, Chang A, et al..: Measuring attractiveness for abuse of prescription opioids. Pain Med. 2010; 11(1): 67-80. DOI: https://doi.org/10.1111/j.1526-4637.2009.00736.x

Webster LR, Bath B, Medve RA: Opioid formulations in development designed to curtail abuse: Who is the target? Expert Opin Investig Drugs. 2009; 18(3): 255-263. DOI: https://doi.org/10.1517/13543780902751622

Cicero TJ, Ellis MS, Paradis A, et al..: Determinants of fentanyl and other potent micro opioid agonist misuse in opioiddependent individuals. Pharmacoepidemiol Drug Saf. 2010; 19(10): 1057-1063. DOI: https://doi.org/10.1002/pds.1989

Maxwell JC, for JBS International, Inc: Diversion and Abuse of Buprenorphine: A Brief Assessment of Emerging Indicators. Rockville, MD: Substance Abuse and Mental Health Services Administration Center for Substance Abuse Treatment, Division of Pharmacologic Therapies, November 2006.

Cicero TJ, Ellis MS, Surratt HL: Effect of abuse-deterrent formulation of OxyContin. N Engl J Med. 2012; 367(2): 187-189. DOI: https://doi.org/10.1056/NEJMc1204141

Dart R: RADARS® System Sixth Annual Meeting. April 24, 2012. Available at http://www.radars.org/Portals/1/Newsletters/2012Q2-Q3-RADARS-System-Newsletter.pdf. Accessed May 9, 2014.

Schug SA, Gandham N: Opioids: Clinical use. In McMahon S, Koltzenburg M (eds.): Wall and Melzack's Textbook of Pain. London, United Kingdom: Churchill Livingstone, 2005: 443-458. DOI: https://doi.org/10.1016/B0-443-07287-6/50033-3

Donner B, Zenz M, Tryba M, et al..: Direct conversion from oral morphine to transdermal fentanyl: A multicenter study in patients with cancer pain. Pain. 1996; 64(3): 527-534. DOI: https://doi.org/10.1016/0304-3959(95)00180-8

Zacny JP, Lichtor SA: Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers. Psychopharmacology (Berl). 2008; 196(1): 105-116. DOI: https://doi.org/10.1007/s00213-007-0937-2

Walsh SL, Nuzzo PA, Lofwall MR, et al..: The relative abuse liability of oral oxycodone, hydrocodone and hydromorphone assessed in prescription opioid abusers. Drug Alcohol Depend. 2008; 98(3): 191-202. DOI: https://doi.org/10.1016/j.drugalcdep.2008.05.007

Schoedel KA, McMorn S, Chakraborty B, et al..: Positive and negative subjective effects of extended-release oxymorphone versus controlled-release oxycodone in recreational opioid users. J Opioid Manag. 2011; 7(3): 179-192. DOI: https://doi.org/10.5055/jom.2011.0061

Stoops WW, Hatton KW, Lofwall MR, et al..: Intravenous oxycodone, hydrocodone, and morphine in recreational opioid users: Abuse potential and relative potencies. Psychopharmacology (Berl). 2010; 212(2): 193-203. DOI: https://doi.org/10.1007/s00213-010-1942-4

Comer SD, Sullivan MA, Whittington RA, et al..: Abuse liability of prescription opioids compared to heroin in morphinemaintained heroin abusers. Neuropsychopharmacology. 2008; 33(5): 1179-1191. DOI: https://doi.org/10.1038/sj.npp.1301479

Nakamura A, Hasegawa M, Ito H, et al..: Distinct relations among plasma concentrations required for different pharmacological effects in oxycodone, morphine, and fentanyl. J Pain Palliat Care Pharmacother. 2011; 25(4): 318-334. DOI: https://doi.org/10.3109/15360288.2011.620689

Paulozzi LJ, Mack KA, Jones CM: Vital signs: Risk for overdose from methadone used for pain relief—United States, 1999-2010. MMWR Morb Mortal Wkly Rep. 2012; 61(26): 493-497.

Jones JD, Mogali S, Comer SD: Polydrug abuse: A review of opioid and benzodiazepine combination use. Drug Alcohol Depend. 2012; 125(1-2): 8-18. DOI: https://doi.org/10.1016/j.drugalcdep.2012.07.004

Severtson SG, Bucher-Bartelson B, Davis J, et al..: Fatalities and Polysubstance Use Among Prescription Opioid Abuse Cases in the RADARS System Poison Center Program. April 2012. RADARS System Technical Report 2012Q2-1. Available at http://www.radars.org/Portals/1/TechReports/2012Q1-RADARSSystem-Technical-Report.pdf. Accessed March 27, 2014.

Faroqui MH, Cole M, Curran J: Buprenorphine, benzodiazepines and respiratory depression. Anaesthesia. 1983; 38(10): 1002-1003. DOI: https://doi.org/10.1111/j.1365-2044.1983.tb12045.x

Paulozzi LJ, Ryan GW: Opioid analgesics and rates of fatal drug poisoning in the United States. Am J Prev Med. 2006; 31(6): 506-511. DOI: https://doi.org/10.1016/j.amepre.2006.08.017

Published

07/01/2014

How to Cite

Passik, PhD, S. D., and L. Webster, MD. “Review Article. Opioid Analgesics: Does Potency Matter?”. Journal of Opioid Management, vol. 10, no. 4, July 2014, pp. 263-75, doi:10.5055/jom.2014.0214.