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Opioids: Follow the evidence

By: Kim Kuebler, DNP, APRN, ANP-BC, FAAN

Be prepared to participate in safe use.


  • Nurses are responsible for understanding safe opioid practices.
  • Differentiating types of pain can aid appropriate clinical management.
  • Understanding how to access and implement the 2022 CDC Clinical Practice Guideline for Prescribing Opioids for Pain can help guide nursing practice.

To ensure safety and effective care, nurses must maintain their knowledge and understanding of opioid pharmacologic properties and best practices when caring for patients with acute and chronic non-cancer pain. Powerful, pain-reducing prescription opioid analgesics offer benefits but also present serious risks. When equipped with an understanding of the physiologic effects of opioids, you’re better prepared to participate in their safe use.

Opioid crisis overview

Many Americans are affected by the significant adverse consequences associated with opioid analgesics. Despite multiple state and federal efforts, the scope of the opioid crisis continues to grow. The Centers for Disease Control and Prevention (CDC) estimate that 108,000 people died from opioid medication overdoses from January to December 2021 (an increase of 28.5% from 78,056 deaths in 2020), the highest recorded in U.S. history.

Many federal agencies, including the U.S. Department of Health and Human Services, CDC, Food and Drug Administration (FDA), and Agency for Healthcare Research and Quality, continue to implement initiatives to address opioid misuse and abuse. To help reduce the opioid crisis, the FDA maintains a chronological timeline of significant opioid-related events.

The CDC Clinical Practice Guideline for Prescribing Opioids – United States, 2022 offers over 200 pages of evidence-based recommendations to ensure safe opioid use for outpatient adults age 18 years and older. The guideline includes the effective management of acute pain (duration ≤1 month), subacute pain (duration of 1 to 3 months), or chronic pain (duration ≥3 months).

Physiologic mechanisms of action

Opioids, natural and synthetic opium-like compounds, bind to one or more of the three opioid receptor sites (mu, kappa, and delta) that mediate analgesia in the central and peripheral nervous system. The binding of an opioid at a specific receptor site determines its pharmacologic action. Opioids act at these receptor sites as agonists (binding to a receptor site), antagonists (blocking opioids at the receptor site), or partial agonists (binding to a receptor but providing only partial efficacy). Additional classifications include mode of synthesis into alkaloids, semi-synthetic, and synthetic preparations. (See Mu receptor and opioid action.)

Equianalgesic dosing compares one opioid medication to another with the same effectiveness, using morphine as the gold standard against which to measure all other opioids. The amount of opioid that binds or has affinity to one or more of the opioid receptor sites determines the specific strength or bioavailability of that medication. Nurses must understand the differences in dosing among different opioids and how the administration route (oral, parenteral, transdermal, rectal) determines the dose. For example, Bhatnagar and Pruskowski recommend short-acting opioids for acute pain and when initiating opioid analgesia. (See Equianalgesic dosing.)

Drug–drug interactions

Several opioid agents (including tramadol, oxycodone, fentanyl, methadone, codeine, dextromethorphan, and buprenorphine) affect serotonin kinetics when combined with selective serotonin reuptake inhibitors (SSRIs). Because these opioids can precipitate serotonin syndrome, providers should use them cautiously in patients taking SSRIs for depression. In 2016, the FDA issued a Black Box Warning for the combination of opioids with benzodiazepines or anti-anxiety medications and other central nervous system depressants, including alcohol.

The risk for respiratory depression and death increases when opioids are combined with muscle relaxants, sleep medications, antipsychotics, opioid cough medications, and anticholinergic medications. Several studies that prompted an FDA Black Box Warning found a 10-times greater risk for overdose death when combining a benzodiazepine with an opioid vs. patients prescribed opioids alone. Patients diagnosed with certain conditions, including heart failure, diabetes, kidney failure, and chronic obstructive pulmonary disease, face a severe risk for respiratory depression when receiving opioid analgesia.

Stay informed

To ensure safe administration and appropriate patient and family education, take the time to fully understand the specific class of prescribed medication and its associated risk factors. The CDC 2022 guidelines provide the standard of care for effectively managing non-cancer acute and chronic pain. In addition, downloading the free Epocrates application on a smartphone provides a quick and easy resource for accessing basic information for all medications and offers a drug–drug interaction tool to recognize important risk factors associated with multiple co-medications. (See CDC 2022 guideline highlights.)

Kim Kuebler is founder and director of Multiple Chronic Conditions Resource Center in Pleasant Lake, Michigan.

Key Words: opioids, safe prescribing, pain management, non-cancer pain

American Nurse Journal. 2023; 18(2). Doi: 10.51256/ANJ022317;


Agency for Healthcare Research and Quality. Opioid treatments for chronic pain. May 17, 2022. effectivehealthcare.ahrq.gov/products/opioids-chronic-pain/research

Bhatnagar M, Pruskowski J. Opioid equivalency. StatPearls. September 12, 2022. ncbi.nlm.nih.gov/books/NBK535402

Centers for Disease Control and Prevention. Drug overdose deaths in the U.S. top 100,000 annually. November 17, 2021. cdc.gov/nchs/pressroom/nchs_press_releases/2021/20211117.htm

Centers for Disease Control and Prevention. Opioids: Healthcare professionals. August 6, 2021. cdc.gov/opioids/providers/prescribing/guideline.html

Centers for Disease Control and Prevention. Summary of the 2022 clinical practice guideline for prescribing opioids for pain. November 3, 2022. cdc.gov/opioids/patients/guideline.html

Centers for Disease Control and Prevention. U.S. overdose deaths in 2021 increased half as much as in 2020 – But are still up 15%. May 11, 2022. cdc.gov/nchs/pressroom/nchs_press_releases/2022/202205.htm

ClinCalc.com. Equivalent opioid calculator. clincalc.com/Opioids

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Food and Drug Administration. FDA drug safety communication: FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiaze­pines; requires its strongest warning. September 20, 2017. fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-warns-about-serious-risks-and-death-when-combining-opioid-pain-or

Kishner S. Opioid equivalents and conversions. December 2022. emedicine.medscape.com/article/2138678-overview

Tick H, Nielsen A, Gardiner PM, Simmons S, Hansen KA, Dusek JA. Comment from the Academic Consortium for Integrative Medicine & Health on the CDC clinical practice guideline for prescribing opioids – United States, 2022. Global Adv in Health and Med. 2022;11: 2164957X221104093. doi:10.1177/2164957X221104093

U.S. Food & Drug Administration. Timeline of selected FDA activities and significant events addressing opioid misuse and abuse. October 4, 2022. fda.gov/drugs/information-drug-class/timeline-selected-fda-activities-and-significant-events-addressing-opioid-misuse-and-abuse

U.S. Department of Health and Human Services. Pain management best practices inter-agency task force report. December 16, 2022. hhs.gov/opioids/prevention/pain-management-options/index.html

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