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opioid receptor agonist (narcotic)

Any morphine-like compound, natural or synthetic, that stimulates opioid receptors producing bodily effects including pain relief, sedation, constipation, & respiratory depression. Indications: - treatment of moderate-severe acute pain or chronic pain - maximum dose for chronic pain = 90 mg morphine QD [26] - cough Contraindications: - avoid morphine in patients with renal failure - hydromorphone is an effective alternative if renal failure [8] - reduce dose with liver failure [8] - methadone 1/2life averages 25 hours - transdermal fentanyl safest opiate in renal failure & liver failure [8] - use only in opioid-tolerant patients [8] - meperidine is not recommended due to increased risk for seizures [8] - tramadol has drug interactions with other serotoninergic agent [8] - methadone 1/2life averages 25 hours [8] Dosage: - rescue dose for breakthrough pain should be 10% of daily dose [5] - when switching opioids, lower the dose of the new opioid by at least 25-50% of the calculated equianalgesic dose to account for inter-patient variability in response to opioids [30] - opioids do not have ceiling of analgesic efficacy [8] Relative opioid receptor potency: (mg for equipotent effects) (also see reference [5]) drug route dose (mg) morphine IM, SC 10 morphine PO 30 hydromorphone (Dilaudid) IM, SC 1.5 hydromorphone (Dilaudid) PO 7.5 oxymorphone (Numorphan) IM, SC 1 oxymorphone (Numorphan) PR 5 oxymorphone (Numorphan) PO 10 levorphanol (Levo-Dromoran) IM, SC 2 levorphanol (Levo-Dromoran) PO 4 methadone (Dolophine) IM 5 methadone (Dolophine) PO 10 meperidine IM, SC 75 meperidine PO 300 fentanyl* (Sublimaze) IM 0.1 hydrocodone (Hycodan) PO 30 oxycodone (OxyContin) PO 20 propoxyphene PO 65 pentazocine (Talwin) IM, SC 60 pentazocine (Talwin) PO 180 nalbuphine (Nubain) IM 10 butorphanol (Stadol) IM 10 Antitussive/antidiarrheal doses: diphenoxlate PO 5 loperamide PO 2 codeine IM 60 codeine PO 180 * see fentanyl for patch equivalent to oral morphine Combination drugs containing opiate Percodan, Percocet, Endocet: see oxycodone Darvon, Darvocet: see propoxyphene * coprescribing naloxone with opioids for chronic pain may diminish opioid-related emergency department visits [22] Pharmacokinetics: 1) metabolized by cyt P450 - glucuronide metablites excreted in urine 2) duration of action: a) generally 4-6 hours b) exceptions: 1] meperidine 3-5 hours 2] fentanyl 1-2 hours 3) 1/2 lives more variable than duration of action 4) accumulation of glucuronide metablites with renal failure or in elderly patients taking high doses of morphine for prolonged periods 5) hydromorphone, fentanyl, methadone, buprenorphine, hydrocodone show minimal pharmacokinetic changes in patients with renal failure [35] Adverse effects: 1) sedation a) level of arousal dose-dependent b) tolerance develops within a few days 2) supression of the hypothalamic-pituitary axis - decreased secretion of gonadotropins (LH, FSH) - hypogonadism (both genders), erectile dysfunction [12] - central origin; down regulation of GnRH [8] - decreased secretion of ACTH [31] - suboptimal morning cortisol in as many as 10% 3) nausea/vomiting (tolerance develops within a few days) 4) constipation - prevention & treatment of constipation (all patients - stimulant laxative (senna, bisacodyl) with or without docusate [8] - stool softener (dosusate) may not add benefit to senna [24] - osmotic agent (polyethylene glycol, sorbitol, lactulose) - naldemedine, naloxegol, or naltrexone - methylnaltrexone may help relieve constipation in palliative care patients without negating analagesic effect of opioid [8] - tolerance does NOT develop to constipating effects [13] 5) distal esophageal spasm resulting in esophagogastric outflow obstruction [38] 6) urinary retention [13] 7) respiratory depression (tolerance develops) 8) higher risk for invasive pneumococcal infection [29] 9) hypotension 10) hypothermia 11) hyporeflexia 12) pruritus, hives, flushing due to release of histamine from mast cells [6] 13) miosis (usually) 14) true allergy uncommon, generally adverse effect [6] 15) opioid-induced hyperalgesia - worsening pain (hyperalgesia) despite increase in opioid dosage - cognitive slowing, hyperreflexia, myoclonus [8] 16) long-acting opioids prescribed for non-cancer pain associated with increased risk for all-cause mortality (RR=1.72) & cardiovascular mortality (RR=1.65) [21] 17) increased risk of major depression & anxiety & stress-related disorders [34] 18) sleep disordered breathing: central sleep apnea - 70% of patient on chronic opioid therapy [37] also see opioid overdose also see abuse-deterrent opioid * Boxed warnings: - risks for abuse, addiction, and misuse [19] - immediate-release opioids q4-6 hours only for severe pain not relieved by alternative treatments - treatment should not be stopped suddenly in patients who are physically dependent on the drugs - pregnant women who chronically use opioids put their newborns at risk for neonatal opioid withdrawal syndrome * evaluate for opiate abuse if indicated [8,15] * concurrent opioid prescriptions from multiple providers increases risk for opioid-related hospitalization [17] Drug interactions: - avoid coadministation of CNS depressants [30] - benzodiazepines should not be used in combination Laboratory: - see ARUP consult [14] Complications: - children of parents who use prescription opioids are more likely to attempt suicide (0.37% vs 0.14%) [32] - also see opioid overdose Management: - CDC's 2022 guidelines cover acute, subacute, & chronic pain [36] - at hospital discharge, inquire about existing opioids at home [30] Notes: - FDA advisory panel endorses mandatory training for clinicians who prescribe opiates [20] - DEA to reduce opioid manfacturing by 25% in 2017 [25] - higher opioid prescribing at the county level associated with - higher proportion of non-Hispanic whites - more uninsured & Medicaid patients - lower education levels - higher unemployment - greater density of primary care physicians - higher incidence of diabetes, arthritis, & disability

Interactions

drug interactions drug adverse effects (more general classes)

Related

long-term opiate therapy opioid maintenance therapy Opioid Overdose opioid prescribing practices opioid receptor antagonist or narcotic antagonist

Specific

6-monoacetylmorphine abuse-deterrent opioid alfentanil (Alfenta, ALF) butorphanol (Stadol, Stadol NS) carfentanil codeine diacetylmorphine (diamorphine, heroin) difelikefalin (Korsuva) difenoxin dihydrocodeine fentanyl (Sublimaze, Subsys, Fentanyl Oralet, Actiq, Fentora, Onsolis, Abstral, Lazanda) hydromorphone; dihydromorphinone (Dilaudid, Palladone) levorphanol (Levo-Dromoran) meperidine (Demerol, Isonipecaine, Chlorbycyclen, Centralgin) methadone (Dolophine, Methadose, Physeptone, Algolysin) metonitazene Mitragyna speciosa; kratom mixed opioid agonist-antagonist (analgesic narcotic partial-mixed agonist) morphine (morphine sulfate [MS], MS Contin, Roxanol, Oramorph SR, Kadian, Avinza, DepoDur, Duromorph) narcotic combination normeperidine (Norpethidine) normorphine; desmethylmorphine; demethylmorphine oliceridine (Olinvyk) opioid partial agonist oxycodone (Roxicodone, OxyContin, OxyIR, OxyFast, Oxecta, Xtampza ER) oxymorphone (Numorphan, Opana, Opana ER) propoxyphene (Darvon, Dolene, Proxagesic, Novopropoxyn) sufentanil (Sufenta,Dsuvia) tapentadol (Nucynta) thiafentanil oxalate (Thianil) tianeptine tramadol (Ultram)

General

analgesic (antalgic) receptor agonist sedative/hypnotic (tranquilizer)

Properties

References

  1. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  2. The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996 pg 535
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 682-683
  4. VA Greater Los Angeles Healthcare System
  5. Prescriber's Letter 21(4): 2014 Equianalgesic Dosing of Opioids for Pain Management Detail-Document#: 300405 (subscription needed) http://www.prescribersletter.com
  6. Prescriber's Letter 13(2): 2006 Opioid Intolerance Decision Algorithm Detail-Document#: 220201 (subscription needed) http://www.prescribersletter.com
  7. Prescriber's Letter 15(3): 2008 Detail-Document#: 240312 Dosing frequency of long-acting opioids (subscription needed) http://www.prescribersletter.com
  8. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17, 18. American College of Physicians, Philadelphia 2009, 2012, 2015, 2018. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  9. Prescriber's Letter 17(7): 2010 Equianalgesic Dosing of Opioids for Pain Management Detail-Document#: 260701 (subscription needed) http://www.prescribersletter.com - Prescriber's Letter 17(12): 2010 CHART: Equianalgesic Dosing of Opioids for Pain Management Detail-Document#: 261201 (subscription needed) http://www.prescribersletter.com
  10. Bohnert ASB et al. Association between opioid prescribing patterns and opioid overdose-related deaths. JAMA 2011 Apr 6; 305:1315. PMID: 21467284
  11. Prescriber's Letter 18(6): 2011 COMMENTARY: REMS for Long-Acting and Extended-Release Opioids CHART: Prescription Drug Monitoring Programs Detail-Document#: 270611 (subscription needed) http://www.prescribersletter.com
  12. Prescriber's Letter 19(2): 2012 Hormonal Effects of Opioids Detail-Document#: 280205 (subscription needed) http://www.prescribersletter.com
  13. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
  14. ARUP Consult: Opioids The Physician's Guide to Laboratory Test Selection & Interpretation https://www.arupconsult.com/browse-all-topics
  15. Dunn KM, Saunders KW, Rutter CM et al Opioid prescriptions for chronic pain and overdose: a cohort study. Ann Intern Med. 2010 Jan 19;152(2):85-92 PMID: 20083827
  16. FDA News Release: Sept. 10, 2013 FDA announces safety labeling changes and postmarket study requirements for extended-release and long-acting opioid analgesics. New boxed warning to include neonatal opioid withdrawal syndrome. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm367726.htm - New Safety Measures Announced for Extended-release and Long-acting Opioids. http://www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/ucm363722.htm
  17. Jena AB, Goldman D, Weaver L, Karaca-Mandic P et al Opioid prescribing by multiple providers in Medicare: retrospective observational study of insurance claims. BMJ 2014;348:g1393 PMID: 24553363 http://www.bmj.com/content/348/bmj.g1393
  18. Centers for Disease Control and Prevention (CDC) Proposed 2016 Guideline for Prescribing Opioids for Chronic Pain. Federal Register. Dec 14, 2015 https://www.federalregister.gov/articles/2015/12/14/2015-31375/proposed-2016-guideline-for-prescribing-opioids-for-chronic-pain - Draft CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016 http://www.regulations.gov/#!documentDetail;D=CDC-2015-0112-0002
  19. FDA Safety Alert. March 23, 2016 Opioid Pain Medicines: Drug Safety Communication - New Safety Warnings Added to Prescription Opioid Medications. http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm491715.htm
  20. Herman AO, Sofair A, Chavey WE FDA Advisers: Opioid Prescribing Training Should Be Mandatory. Physician's First Watch, May 6, 2016 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
  21. Ray WA et al Prescription of Long-Acting Opioids and Mortality in Patients With Chronic Noncancer Pain. JAMA. 2016;315(22):2415-2423 PMID: 27299617 http://jama.jamanetwork.com/article.aspx?articleid=2528212
  22. Coffin PO, Behar E, Rowe C et al Nonrandomized Intervention Study of Naloxone Coprescription for Primary Care Patients Receiving Long-Term Opioid Therapy for Pain. Ann Intern Med. Published online 28 June 2016 PMID: 27366987 http://annals.org/article.aspx?articleid=2531366 - Walley AY, Green TC Mainstreaming Naloxone Through Coprescription to Patients Receiving Long-Term Opioid Therapy for Chronic Pain. Ann Intern Med. Published online 28 June 2016 PMID: 27367047 http://annals.org/article.aspx?articleid=2531367
  23. Huang AR, Mallet L. Prescribing opioids in older people. Maturitas. 2013 Feb;74(2):123-9. Review. PMID: 23201325
  24. Tarumi Y, Wilson MP, Szafran O, Spooner GR. Randomized, double-blind, placebo-controlled trial of oral docusate in the management of constipation in hospice patients. J Pain Symptom Manage. 2013 Jan;45(1):2-13. PMID: 22889861
  25. DEA Public Affairs. Oct 4, 2016 DEA Reduces Amount of Opioid Controlled Substances to be Manufactured in 2017. https://www.dea.gov/divisions/hq/2016/hq100416.shtml
  26. Anello J, Feinberg B, Heinegg J et al New Guidelines and Recommendations Guideline on opioid administration by Veterans Affaris and U.S. Department of Defense http://reference.medscape.com/features/slideshow/guidelines/2017/april
  27. Guy GP Jr., Zhang K, Bohm MK, et al. Vital Signs: Changes in Opioid Prescribing in the United States, 2006-2015. MMWR Morb Mortal Wkly Rep 2017;66:697-704 https://www.cdc.gov/mmwr/volumes/66/wr/mm6626a4.htm
  28. Centers for Disease Control & Prevention (CDC) CDC Guideline for Prescribing Opioids for Chronic Pain - United States, 2016. https://www.cdc.gov/mmwr/volumes/65/rr/rr6501e1.htm
  29. Wiese AD, Griffin MR, Schaffner W et al Opioid Analgesic Use and Risk for Invasive Pneumococcal Diseases: A Nested Case - Control Study. Ann Intern Med. 2018. Feb 13 PMID: 29435555 http://annals.org/aim/article-abstract/2672601/opioid-analgesic-use-risk-invasive-pneumococcal-diseases-nested-case-control - Dublin S, Von Korff M. Prescription Opioids and Infection Risk: Research and Caution Needed. Ann Intern Med. 2018. Feb 13 PMID: 29435579 http://annals.org/aim/article-abstract/2672606/prescription-opioids-infection-risk-research-caution-needed
  30. Herzig SJ, Mosher HJ, Calcaterra SL et al Improving the Safety of Opioid Use for Acute Noncancer Pain in Hospitalized Adults: A Consensus Statement From the Society of Hospital Medicine. J. Hosp. Med. 2018 April;13(4):263-271 PMID: 29624189 https://www.journalofhospitalmedicine.com/jhospmed/article/161927/hospital-medicine/improving-safety-opioid-use-acute-noncancer-pain - Herzig SJ, Calcaterra SL, Mosher HJ Safe Opioid Prescribing for Acute Noncancer Pain in Hospitalized Adults: A Systematic Review of Existing Guidelines. J Hosp Med. 2018 Apr;13(4):256-262. PMID: 29624188
  31. NEJM Knowledge+ Internal Medicine Board Review https://myknowledgeplus.nejm.org/flow/flowjs.html
  32. Brent DA, Hur K, Gibbons RD Association Between Parental Medical Claims for Opioid Prescriptions and Risk of Suicide Attempt by Their Children. JAMA Psychiatry. Published online May 22, 2019. PMID: 31116357 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2733148
  33. Centers for Disease Control & Prevention (CDC) Guideline for Prescribing Opioids for Chronic Pain https://www.cdc.gov/drugoverdose/pdf/Guidelines_Factsheet-a.pdf - Interactive Training Webinar for providers who prescribe opioids https://www.cdc.gov/drugoverdose/prescribing/guideline.html
  34. Brooks M New Risks of Prescription Opioids Discovered. Medscape - Nov 17, 2020. https://www.medscape.com/viewarticle/941170 - Rosoff DB, Smith GD, Lohoff FW Prescription Opioid Use and Risk for Major Depressive Disorder and Anxiety and Stress-Related Disorders, A Multivariable Mendelian Randomization Analysis. JAMA Psychiatry. Published online November 11, 2020 PMID: 33175090 PMCID: PMC7658804 Free PMC article https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2772881
  35. Davison NS Clinical pharmacology considerations in pain management in patients with advanced kidney failure. Clin J Am Soc Nephrol 2019 14(6):917-931 PMID: 30833302 PMCID: PMC6556722 Free PMC article
  36. George J CDC Just Changed Its Opioid Prescribing Guidelines. Here's What to Know. Guidance covers acute, subacute, and chronic pain and replaces 2016 guidelines. MedPage Today November 3, 2022 https://www.medpagetoday.com/neurology/opioids/101559 - Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. CDC Clinical Practice Guideline for Prescribing Opioids for Pain - United States, 2022. MMWR Recomm Rep 2022;71(No. RR-3):1-95 PMID: 36327391 PMCID: PMC9639433 Free PMC article https://www.cdc.gov/mmwr/volumes/71/rr/rr7103a1.htm - Dowell D, Ragan KR, Jones CM, Baldwin GT, Chou R. Prescribing opioids for pain - The new CDC clinical practice guideline. N Engl J Med 2022 Nov 3; [e-pub] PMID: 36326116 https://www.nejm.org/doi/10.1056/NEJMp2211040
  37. NEJM Knowledge+ Pain Management and Opioids: Recharge - Van Ryswyk E, Antic NA. Opioids and Sleep-Disordered Breathing. Chest. 2016 Oct;150(4):934-944. PMID: 27262224 Review.
  38. Niu C, Zhang J, Bapaye J et al. Systematic review with meta-analysis: Chronic opioid use is associated with esophageal dysmotility in symptomatic patients. Am J Gastroenterol 2023 Dec; 118:2123 PMID: 37463432 https://journals.lww.com/ajg/abstract/2023/12000/systematic_review_with_meta_analysis__chronic.13.aspx
  39. Gallagher R. Opioid-induced neurotoxicity. Can Fam Physician. 2007 Mar;53(3):426-7. PMID: 17872676 PMCID: PMC1949075 Free PMC article.

Component-of

narcotic combination