Last updated: August 11, 2023

Summarytoggle arrow icon

Opioids, in the broad sense used throughout this article, are a class of natural (endogenous and exogenous), synthetic, and semisynthetic substances that act on μ-, κ-, and δ-opioid receptors, i.e., antagonists as well as agonists. In the more narrow sense, opioids are distinguished from opiates, with the former including only synthetic, semisynthetic, or endogenous substances with opium-like pharmacological effects and the latter strictly referring to exogenous alkaloids derived from opium, the dried latex of the opium poppy (Papavum somniferum). Morphine, the original opiate, was first extracted from opium in 1804 and revolutionized medicine as the first drug to provide effective analgesia. Today, opioids are still most commonly used to treat severe acute or chronic pain. In addition to their analgesic effects, opioids induce sedation, constipation, and respiratory depression, which represent potentially life-threatening adverse effects but also have clinical uses (e.g., as anesthetic, antidiarrheal, or antitussive drugs). Opioid-receptor agonists induce a strong sense of euphoria and their recreational use, both in the form of illicit drugs (e.g., heroin) and prescription drugs (e.g., oxycodone, hydrocodone), is widespread, with severe effects on public health and other aspects of society. Continued use of opioids can lead to physical dependence (the physical adaptation to the substance associated with symptoms of tolerance and withdrawal) and psychological dependence (substance-seeking behavior in response to biochemical changes in the brain from continued exposure to the substance; often referred to as “addiction”). Acute opioid intoxication is a life-threatening condition typically characterized by altered mental status, severe respiratory depression, and miosis. Treatment of acute opioid intoxication requires emergency measures and administration of a fast-acting opioid receptor antagonist (e.g., naloxone) to counter the symptoms of acute intoxication. Since the duration of action of naloxone is shorter than that of many opioid receptor agonists, a long-acting opioid receptor antagonist (e.g., naltrexone) should be administered subsequently to detoxification to prevent opioid dependence relapse.

Pharmacology of opioidstoggle arrow icon


  • Opioids
    • Classically used to describe only synthetic and semisynthetic substances with opium-like pharmacological properties (e.g., heroin)
    • Today used in the broader sense to describe any (i.e., natural, synthetic, or semisynthetic) substance that binds to opioid receptors (agonists as well as antagonists).
  • Opiates: alkaloids derived from the opium poppy (e.g., morphine)


According to effect on opioid receptors

According to origin

Endogenous opioids [1][2]

Exogenous opioids

Opioid receptors [1][2][3]

μ (mu), δ (delta), κ (kappa)


  • Effects of opioids depend on relative binding affinity of different opioid receptors.
  • Mainly used as analgesics, but also used as sedatives, antidiarrheals, and antitussives [4]
  • Pain relief primarily via the two following mechanisms:
    • Raising the pain threshold
    • Change in pain perception
Overview of opioid effects [5][6]
Site of action Clinical uses Adverse effects of opioids
μ-opioid receptor
  • Strong analgesia
  • Slowed gastrointestinal transit
δ-opioid receptor
κ-opioid receptor
  • Analgesia
  • Sedation
  • Slowed gastrointestinal transit
Nonspecific/other sites of action
  • None

At correct dosage, clinically relevant respiratory depression is unlikely in the treatment of chronic pain.

While the sedative, orthostatic, and emetic effects of opioids go down with tolerance, miosis and constipation remain unaffected.

Receptor affinity, intrinsic activity, and ceiling effect [3][7]

Receptor affinity

Receptor affinity describes the extent to which a ligand binds to a target receptor.

Opioids of different potency should not be combined!

Intrinsic activity (efficacy) [8]

Intrinsic activity is defined as the extent to which a drug activates a receptor after binding to it.

Ceiling effect

The ceiling effect describes the pharmacological phenomenon that once the therapeutic limit is reached, an increase in dose will no longer increase the functional response, but only the side effects.

Relative analgesic potency [9]

Indicationstoggle arrow icon

Pain management

Acute pain management [10]

Chronic pain management

See “Chronic noncancer pain management.”

Opioids for pain management

Overview of opioids used for pain management [12][13][14][15]
Route of administration and corresponding analgesic potency Duration of analgesic action Receptor interaction Indications Side effects and other features
  • Oral: 1
  • Parenteral: 3
  • 3–6 hours
  • 3–6 hours
  • Morphine is the standard to which other opioids are compared to in terms of potency
  • Parenteral: 10
  • 3–5 hours
  • Not metabolized via CYP450 enzymes [16]


  • Parenteral: 5
  • 3–4 hours
  • ↓ Risk of respiratory depression compared to full agonists
  • Co-administration with full agonist may induce withdrawal
  • Effects are difficult to reverse with naloxone
  • Oral: 1.5–2
  • 3–6 hours
  • Oral: 0.15
  • Parenteral: 0.08–0.1
  • 4–6 hours
  • Mild to moderate pain
  • Oral: 0.25
  • 4–6 hours
  • Drug of choice for treatment of moderate chronic pain [18]


  • Oral: 0.1
  • Parenteral: 0.13
  • 2–4 hours
  • Parenteral: 0.2–0.33
  • 3–4 hours
  • Moderate to severe pain
  • Oral: 7.75
  • 4–8 hours
Buprenorphine [20]
  • Parenteral: 33
  • Sublingual: 40
  • Topical (transdermal): 100–115
  • 4–8 hours
  • Parenteral: 85
  • 1–1.5 hours
  • Strong lipophilia
    • Rapid onset and CNS penetration
    • Continuous administration leads to significant accumulation


  • Parenteral (intramuscular): 0.7–0.8 [21]
  • 3–6 hours
  • Moderate to severe pain

Antagonization of buprenorphine requires high doses of naloxone or naltrexone due to its very high receptor affinity.

Cough management

Diarrhea management

Treatment of opioid use disorder

Opioid receptor antagoniststoggle arrow icon

Opioid receptor antagonists bind to opioid receptors without activating them. Antagonists with high affinity to the opioid receptors can be used as antidotes in acute opioid intoxication due to their ability to displace opioids from the receptors.

Centrally acting opioid-receptor antagonists

Overview of centrally acting opioid-receptor antagonists
Naloxone Naltrexone
Routes of administration
  • PO, IM, IV, SC, IO
  • Intranasally (in form of a spray)
  • PO, IM
  • Rapid action
  • Short half-life (60 minutes on average; ranges from 30 to 90 minutes) [23]
  • Long half-life (4–10 hours) [24]
  • Long, dose-dependent duration of action: 24–72 hours

“Use nalTRACKsone to get back on TRACK:” Naltrexone is used to prevent opioid relapse.

Peripherally acting μ-opioid receptor antagonists

Contraindicationstoggle arrow icon

Absolute contraindications [25]

Relative contraindications [25]

Risk factors for opioid-related harm [10]

There is an increased risk of adverse effects with opioid use in patients with any of the following; consider alternative analgesia and/or additional monitoring:

We list the most important contraindications. The selection is not exhaustive.

Referencestoggle arrow icon

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  2. Hall M. Is morphine indicated in acute pulmonary oedema. Emergency Medicine Journal. 2005; 22 (5): p.391-391.doi: 10.1136/emj.2003.011460 . | Open in Read by QxMD
  3. $Equianalgesic Dosing of Opioids for Pain Management .
  4. Smith H, Passik S. Pain and Chemical Dependency. Oxford University Press ; 2008: p. 195
  5. Mahler DL, Forrest WH. Relative Analgesic Potencies of Morphine and Hydromorphone in Postoperative Pain. Anesthesiology. 1975; 42 (5): p.602-607.doi: 10.1097/00000542-197505000-00021 . | Open in Read by QxMD
  6. Lasheen W, Walsh D, Mahmoud F, et al. The intravenous to oral relative milligram potency ratio of morphine during chronic dosing in cancer pain. Palliat Med. 2009; 24 (1): p.9-16.doi: 10.1177/0269216309346595 . | Open in Read by QxMD
  7. Gregory TB. Hydromorphone: Evolving to Meet the Challenges of Today’s Health Care Environment. Clin Ther. 2013; 35 (12): p.2007-2027.doi: 10.1016/j.clinthera.2013.09.027 . | Open in Read by QxMD
  8. Brennan MJ. The Effect of Opioid Therapy on Endocrine Function. Am J Med. 2013; 126 (3): p.S12-S18.doi: 10.1016/j.amjmed.2012.12.001 . | Open in Read by QxMD
  9. Besic N, Smrekar J, Strazisar B. Acute pain and side effects after tramadol in breast cancer patients: results of a prospective double-blind randomized study. Scientific Reports. 2020; 10 (1).doi: 10.1038/s41598-020-75961-2 . | Open in Read by QxMD
  10. Bricker L, Lavender T. Parenteral opioids for labor pain relief: A systematic review. Am J Obstet Gynecol. 2002; 186 (5): p.S94-S109.
  11. Cote J, Montgomery L. Sublingual Buprenorphine as an Analgesic in Chronic Pain: A Systematic Review. Pain Medicine. 2014; 15 (7): p.1171-1178.doi: 10.1111/pme.12386 . | Open in Read by QxMD
  12. Beaver WT, Feise GA. A comparison of the analgesic effect of intramuscular nalbuphine and morphine in patients with postoperative pain.. J Pharmacol Exp Ther. 1978; 204 (2): p.487-96.
  13. Zheng Zeng, Jianhua Lu, Chang Shu, Yuanli Chen, Tong Guo, Qing-ping Wu, Shang-long Yao, Ping Yin. A Comparision of Nalbuphine with Morphine for Analgesic Effects and Safety : Meta-Analysis of Randomized Controlled Trials. Scientific Reports. 2015; 5 (1).doi: 10.1038/srep10927 . | Open in Read by QxMD
  14. Dowell D, Haegerich TM, Chou R. CDC Guideline for Prescribing Opioids for Chronic Pain—United States, 2016. JAMA. 2016; 315 (15): p.1624.doi: 10.1001/jama.2016.1464 . | Open in Read by QxMD
  15. Ghelardini C, Di cesare mannelli L, Bianchi E. The pharmacological basis of opioids. Clin Cases Miner Bone Metab. 2015; 12 (3): p.219-221.doi: 10.11138/ccmbm/2015.12.3.219 . | Open in Read by QxMD
  16. Pathan H, Williams J. Basic opioid pharmacology: an update. Br J Pain. 2012; 6 (1): p.11-16.doi: 10.1177/2049463712438493 . | Open in Read by QxMD
  17. Katzung B,Trevor A. Basic and Clinical Pharmacology. McGraw-Hill Education ; 2014
  18. Bolser DC, Davenport PW. Codeine and cough: an ineffective gold standard. Curr Opin Allergy Clin Immunol. 2007; 7 (1): p.32-36.doi: 10.1097/aci.0b013e3280115145 . | Open in Read by QxMD
  19. Edwards RT, McCormick-Deaton C, Hosanagar A. Acute urinary retention secondary to buprenorphine administration. Am J Emerg Med. 2013; 32 (1): p.109.e1-109.e2.doi: 10.1016/j.ajem.2013.08.022 . | Open in Read by QxMD
  20. Fountas A, Chai ST, Kourkouti C, Karavitaki N. MECHANISMS OF ENDOCRINOLOGY: Endocrinology of opioids. European Journal of Endocrinology. 2018; 179 (4): p.R183-R196.doi: 10.1530/eje-18-0270 . | Open in Read by QxMD
  21. Kelly E. Efficacy and ligand bias at the μ-opioid receptor. Br J Pharmacol. 2013; 169 (7): p.1430-1446.doi: 10.1111/bph.12222 . | Open in Read by QxMD
  22. Salahudeen MS, Nishtala PS. An overview of pharmacodynamic modelling, ligand-binding approach and its application in clinical practice. Saudi Pharmaceutical Journal. 2016; 25 (2): p.165-175.doi: 10.1016/j.jsps.2016.07.002 . | Open in Read by QxMD
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  24. Rzasa Lynn R, Galinkin J. Naloxone dosage for opioid reversal: current evidence and clinical implications. Therapeutic Advances in Drug Safety. 2017; 9 (1): p.63-88.doi: 10.1177/2042098617744161 . | Open in Read by QxMD
  25. Crabtree BL. Review of naltrexone, a long-acting opiate antagonist.. Clin Pharm. 1984; 3 (3): p.273-80.

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