How Do Opioid Analgesics Work?

Reviewed on 9/22/2021

How do opioid analgesics work?

Opioid analgesics are medications prescribed for the management of acute and chronic pain in many conditions. Opioid analgesics are also used to treat opioid use disorder. Opioid medications have a high risk for addiction and must be used with great caution.

All opioid analgesics bind to opioid receptors but work in different ways. Opioid receptors are protein molecules on nerve cell (neuron) membranes in the central and peripheral nervous systems. Opioid receptors mediate the body’s response to most hormones and some of their functions include modulating pain, stress response, respiration, digestion, mood, and emotion.

The five different opioid receptors discovered in the human body are:

  • Mu receptor (MOR)
  • Kappa receptor (KOR)
  • Delta receptor (DOR)
  • Nociceptin receptor (NOR)
  • Zeta receptor (ZOR)

Opioid analgesics work by binding to one or more of the opioid receptors. Opioid analgesics are primarily of three types:

  • Opioid agonists: Full opioid agonists relieve pain by stimulating opioid receptors on neurons, which inhibit the release of chemicals (neurotransmitters) that transmit pain signals.
  • Partial opioid agonists: Partial opioid agonists elicit a partial functional response because they work as agonists in some receptors and antagonists in others, and consequently, produce fewer adverse effects than full agonists while being effective for pain relief (analgesia).
  • Opioid antagonists: Opioid antagonists bind to opioid receptors but do not produce any functional response. Opioid antagonists prevent agonists from binding to the particular opioid receptor and are useful in treating opioid dependence.

How are opioid analgesics used?

Opioid analgesics come in many formulations and strengths. Opioid analgesics are administered through several routes such as:

  • Oral: Tablets, capsules, syrups, solutions, lozenges
  • Rectal: Suppositories
  • Ureteral: Suppositories
  • Transmucosal:
    • Buccal film: Applied inside the cheek (buccal tissue) and left to dissolve and be absorbed
    • Sublingual film or tablet: Placed under the tongue
  • Nasal: Sprayed into the nostril
  • Injections
    • Subcutaneous: Injected into the tissue under the skin
    • Long-acting subcutaneous injection: Monthly injection into the tissue under the skin
    • Intramuscular: Injected into the muscle
    • Intravenous: Injected into the vein
    • Epidural: Injected into the space outside the uppermost layer (dura) of the spinal canal 
    • Intrathecal: Injected into the cerebrospinal fluid in the spinal canal
  • Subdermal: Implant placed under the skin on the inner side of the upper arm, for slow release of medication that lasts up to six months
  • Transdermal: Applied as a skin patch that slowly releases medication over 7 days, and is absorbed through the skin

Opioid analgesics are used to manage severe pain when alternative treatments are inadequate, and to treat opioid use disorder. Some opioid analgesics are used to treat diarrhea because they inhibit stomach acid secretion and gastrointestinal propulsion and motility. Opioid analgesics should be used with caution in patients with kidney or liver impairment.

Opioid overdose can have severe consequences, and naloxone, an opioid antagonist, is administered to reverse opioid effects in case of opioid overdose. Opioid analgesics are typically never abruptly discontinued, but tapered with an opioid agonist/antagonist combination before weaning off.

Opioid analgesics may be used in conditions that include:

  • Severe acute pain
  • Moderate to severe pain
  • Severe chronic pain
  • Breakthrough pain in conditions such as cancer, sickle-cell disease
  • Diabetic peripheral neuropathy
  • HIV-associated neuropathy
  • Postherpetic neuralgia
  • Labor pain
  • Preoperative and preanesthesia
  • Balanced anesthesia
  • General and local anesthesia
  • Adjunct anesthesia
  • Conscious analgesia
  • Continuous sedation and analgesia
  • Post-operative analgesia
  • Cyanotic Tetralogy of Fallot (congenital heart defects that lead to low oxygen and bluish skin color in premature newborns)
  • Weaning off from full opioid agonists
  • Opioid addiction and dependence (opioid use disorder)
  • Diarrhea
  • Chronic low back pain
  • Opioid-induced pruritus (itching), off-label
  • Cough (off-label)

What are side effects of opioid analgesics?

Side effects of opioid analgesics may include the following:

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

What are names of some opioid analgesic drugs?

Generic and brand names of some opioid analgesic drugs include:


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