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Opioid Reduction Strategies
Sarah Ashley Low, MD
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KEY FACTS

  • Clinical Implications

    • Opioid Sparing

      TERMINOLOGY

      • Definitions

        • Opiates: Naturally occurring; harvested from poppy plant
        • Opioids: Synthetic or partially synthetic drugs
        • Narcotics: Umbrella term that includes both opiates and opioids
        • Tolerance: Higher dose of drug is needed for same physiologic effect
        • Dependence: Physical reliance on drug, as exhibited by tolerance to drug or withdrawal symptoms when substance is discontinued
        • Addiction: Behavioral changes outside of individuals normal habits that is preoccupied by obtaining drug
        • Opioid-induced hyperalgesia: Nociceptive sensitization after exposure to opioids
        • Adjuvant analgesics: Nonopioid analgesics used in conjunction with opioid regimen to reduce amount of narcotics required for analgesic effect
        • Therapeutic index: Ratio that compares toxic dose of drug to therapeutic dose needed to elicit response in 50% of treated individuals

      CLINICAL IMPLICATIONS

      • Background

        • Opioid Receptors and Pain Circuitry

          • Off-Target Effects of Opioids

            • Splice Variants

              OPIOID SPARING

                Selected References

                1. Hermanns H et al: Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review. Br J Anaesth. 123(3):335-49, 2019
                2. Wang D et al: Functional divergence of delta and mu opioid receptor organization in CNS pain circuits. Neuron. 98(1):90-108.e5, 2018
                3. Corder G et al: Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia. Nat Med. 23(2):164-73, 2017
                4. Kumar K et al: A review of opioid-sparing modalities in perioperative pain management: methods to decrease opioid use postoperatively. Anesth Analg. 125(5):1749-60, 2017
                5. Xu J et al: Stabilization of morphine tolerance with long-term dosing: association with selective upregulation of mu-opioid receptor splice variant mRNAs. Proc Natl Acad Sci U S A. 112(1):279-84, 2015
                6. Bardoni R et al: Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn. Neuron. 81(6):1443, 2014
                7. Pasternak GW et al: Mu opioids and their receptors: evolution of a concept. Pharmacol Rev. 65(4):1257-317, 2013
                8. Majumdar S et al: Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects. Proc Natl Acad Sci U S A. 108(49):19778-83, 2011
                9. Porreca F et al: Nausea and vomiting side effects with opioid analgesics during treatment of chronic pain: mechanisms, implications, and management options. Pain Med. 10(4):654-62, 2009
                10. Mantyh PW: Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci. 7(10):797-809, 2006
                11. Weaver LC et al: Autonomic dysreflexia after spinal cord injury: central mechanisms and strategies for prevention. Prog Brain Res. 152:245-63, 2006
                12. Bailey CP et al: Opioids: cellular mechanisms of tolerance and physical dependence. Curr Opin Pharmacol. 5(1):60-8, 2005
                13. Wadenberg ML: A review of the properties of spiradoline: a potent and selective kappa-opioid receptor agonist. CNS Drug Rev. 9(2):187-98, 2003
                14. Walsh SL et al: Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans. Psychopharmacology (Berl). 157(2):151-62, 2001
                15. Cashman JN: The mechanisms of action of NSAIDs in analgesia. Drugs. 52 Suppl 5:13-23, 1996
                16. Trujillo KA et al: Inhibition of opiate tolerance by non-competitive N-methyl-D-aspartate receptor antagonists. Brain Res. 633(1-2):178-88, 1994
                17. Hayes RL et al: Differential effects of spinal cord lesions on narcotic and non-narcotic suppression of nociceptive reflexes: further evidence for the physiologic multiplicity of pain modulation. Brain Res. 155(1):91-101, 1978
                18. Basbaum AI et al: Reversal of morphine and stimulus-produced analgesia by subtotal spinal cord lesions. Pain. 3(1):43-56, 1977
                Related Anatomy
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                References
                Tables

                Tables

                KEY FACTS

                • Clinical Implications

                  • Opioid Sparing

                    TERMINOLOGY

                    • Definitions

                      • Opiates: Naturally occurring; harvested from poppy plant
                      • Opioids: Synthetic or partially synthetic drugs
                      • Narcotics: Umbrella term that includes both opiates and opioids
                      • Tolerance: Higher dose of drug is needed for same physiologic effect
                      • Dependence: Physical reliance on drug, as exhibited by tolerance to drug or withdrawal symptoms when substance is discontinued
                      • Addiction: Behavioral changes outside of individuals normal habits that is preoccupied by obtaining drug
                      • Opioid-induced hyperalgesia: Nociceptive sensitization after exposure to opioids
                      • Adjuvant analgesics: Nonopioid analgesics used in conjunction with opioid regimen to reduce amount of narcotics required for analgesic effect
                      • Therapeutic index: Ratio that compares toxic dose of drug to therapeutic dose needed to elicit response in 50% of treated individuals

                    CLINICAL IMPLICATIONS

                    • Background

                      • Opioid Receptors and Pain Circuitry

                        • Off-Target Effects of Opioids

                          • Splice Variants

                            OPIOID SPARING

                              Selected References

                              1. Hermanns H et al: Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review. Br J Anaesth. 123(3):335-49, 2019
                              2. Wang D et al: Functional divergence of delta and mu opioid receptor organization in CNS pain circuits. Neuron. 98(1):90-108.e5, 2018
                              3. Corder G et al: Loss of μ opioid receptor signaling in nociceptors, but not microglia, abrogates morphine tolerance without disrupting analgesia. Nat Med. 23(2):164-73, 2017
                              4. Kumar K et al: A review of opioid-sparing modalities in perioperative pain management: methods to decrease opioid use postoperatively. Anesth Analg. 125(5):1749-60, 2017
                              5. Xu J et al: Stabilization of morphine tolerance with long-term dosing: association with selective upregulation of mu-opioid receptor splice variant mRNAs. Proc Natl Acad Sci U S A. 112(1):279-84, 2015
                              6. Bardoni R et al: Delta opioid receptors presynaptically regulate cutaneous mechanosensory neuron input to the spinal cord dorsal horn. Neuron. 81(6):1443, 2014
                              7. Pasternak GW et al: Mu opioids and their receptors: evolution of a concept. Pharmacol Rev. 65(4):1257-317, 2013
                              8. Majumdar S et al: Truncated G protein-coupled mu opioid receptor MOR-1 splice variants are targets for highly potent opioid analgesics lacking side effects. Proc Natl Acad Sci U S A. 108(49):19778-83, 2011
                              9. Porreca F et al: Nausea and vomiting side effects with opioid analgesics during treatment of chronic pain: mechanisms, implications, and management options. Pain Med. 10(4):654-62, 2009
                              10. Mantyh PW: Cancer pain and its impact on diagnosis, survival and quality of life. Nat Rev Neurosci. 7(10):797-809, 2006
                              11. Weaver LC et al: Autonomic dysreflexia after spinal cord injury: central mechanisms and strategies for prevention. Prog Brain Res. 152:245-63, 2006
                              12. Bailey CP et al: Opioids: cellular mechanisms of tolerance and physical dependence. Curr Opin Pharmacol. 5(1):60-8, 2005
                              13. Wadenberg ML: A review of the properties of spiradoline: a potent and selective kappa-opioid receptor agonist. CNS Drug Rev. 9(2):187-98, 2003
                              14. Walsh SL et al: Enadoline, a selective kappa opioid agonist: comparison with butorphanol and hydromorphone in humans. Psychopharmacology (Berl). 157(2):151-62, 2001
                              15. Cashman JN: The mechanisms of action of NSAIDs in analgesia. Drugs. 52 Suppl 5:13-23, 1996
                              16. Trujillo KA et al: Inhibition of opiate tolerance by non-competitive N-methyl-D-aspartate receptor antagonists. Brain Res. 633(1-2):178-88, 1994
                              17. Hayes RL et al: Differential effects of spinal cord lesions on narcotic and non-narcotic suppression of nociceptive reflexes: further evidence for the physiologic multiplicity of pain modulation. Brain Res. 155(1):91-101, 1978
                              18. Basbaum AI et al: Reversal of morphine and stimulus-produced analgesia by subtotal spinal cord lesions. Pain. 3(1):43-56, 1977