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[Pharmacology](https://durgical.com/en/pharmacology/) · Class

# Opioids and antagonists

Drugs acting on opioid receptors: agonists relieve severe pain, and antagonists such as naloxone reverse an overdose.

Updated 2026-11-01

## What they are

Opioid agonists (morphine, fentanyl and others) are the strongest analgesics for severe acute pain, cancer pain and anesthesia. Antagonists (naloxone) occupy the same receptor without activating it and displace the agonist.

## Mechanism of action

The μ, κ and δ opioid receptors are Gi/o-coupled receptors. An agonist inhibits adenylyl cyclase, opens potassium channels (hyperpolarizing the neuron) and closes presynaptic calcium channels, so less glutamate and substance P are released in the pain pathway. An antagonist competes for the same site and does not activate the G protein.

Target: μ-opioid receptor (and κ and δ receptors)

## Key points

- Overdose shows as the triad of coma, respiratory depression and pinpoint pupils.
- Tolerance develops to analgesia, sedation and respiratory depression, but hardly at all to miosis or constipation.
- Naloxone is shorter-acting than many opioids: the patient can drift off and stop breathing again after waking.
- Codeine and tramadol need CYP2D6 for activation; ultrarapid metabolizers risk toxicity, especially children.
- Opioids plus benzodiazepines or alcohol add up respiratory depression and are a common cause of overdose deaths.

## Drugs in this class

- [**Morphine** The reference opioid for severe pain and cancer pain. It activates the μ receptor; it can depress breathing and causes… μ-opioid receptor](https://durgical.com/en/pharmacology/morphine/)
- [**Fentanyl** A very potent, fast synthetic opioid, key in anesthesia and cancer pain. Illegally made fentanyl drives a severe… μ-opioid receptor](https://durgical.com/en/pharmacology/fentanyl/)
- [**Naloxone** An opioid antagonist: it pushes opioids off their receptor and reverses an overdose within minutes. It does almost… μ-opioid receptor](https://durgical.com/en/pharmacology/naloxone/)
- [**Codeine** A weak opioid for mild to moderate pain and cough. It is a prodrug: CYP2D6 turns it into morphine, which makes it… μ-opioid receptor (through the morphine it forms)](https://durgical.com/en/pharmacology/codeine/)
- [**Tramadol** A dual-action analgesic: a weak opioid and a serotonin and noradrenaline reuptake inhibitor. It can cause seizures and… μ-opioid receptor (mainly through the metabolite M1) and the serotonin and noradrenaline transporters](https://durgical.com/en/pharmacology/tramadol/)
- [**Hydromorphone** A μ-opioid agonist several times more potent than morphine, for severe pain. Mix-ups between its strengths, or with… μ-opioid receptor](https://durgical.com/en/pharmacology/hydromorphone/)
- [**Methadone** A long-acting opioid for opioid use disorder and chronic pain. It accumulates, prolongs the QT interval and its… μ-opioid receptor](https://durgical.com/en/pharmacology/methadone/)
- [**Buprenorphine** A high-affinity partial μ agonist with a ceiling on respiratory depression. It treats opioid use disorder and pain; it… μ-opioid receptor (partial agonist; also acts at κ, δ and nociceptin receptors)](https://durgical.com/en/pharmacology/buprenorphine/)
- [**Naltrexone** A long-acting oral opioid antagonist that helps prevent relapse in alcohol and opioid dependence. It precipitates… μ-opioid receptor (antagonist)](https://durgical.com/en/pharmacology/naltrexone/)
- [**Oxycodone** A semi-synthetic oral μ agonist for severe pain, alone or combined with paracetamol. Its CYP3A4 metabolism exposes it… μ-opioid receptor](https://durgical.com/en/pharmacology/oxycodone/)
- [**Hydrocodone** A semi-synthetic μ agonist for severe pain and, in some countries, cough; often combined with paracetamol. Part of it… μ-opioid receptor](https://durgical.com/en/pharmacology/hydrocodone/)
- [**Pethidine** A short-acting synthetic opioid. Its metabolite norpethidine builds up and causes tremor and seizures; with MAOIs it… μ-opioid receptor](https://durgical.com/en/pharmacology/pethidine/)
- [**Butorphanol** An opioid agonist-antagonist: a partial μ agonist and a full κ agonist. It has a respiratory ceiling but can cause… κ (agonist) and μ (partial agonist) opioid receptors](https://durgical.com/en/pharmacology/butorphanol/)
- [**Nalbuphine** An injectable κ-agonist, μ-antagonist opioid. It has a respiratory ceiling and can partly reverse μ-agonist… κ (agonist) and μ (antagonist) opioid receptors](https://durgical.com/en/pharmacology/nalbuphine/)
- [**Pentazocine** A partial μ and κ-agonist opioid. By mouth it is combined with naloxone to prevent injection misuse; at high doses it… κ (agonist) and μ (partial agonist) opioid receptors](https://durgical.com/en/pharmacology/pentazocine/)
- [**Remifentanil** An ultra-short μ opioid for anaesthesia, broken down by blood esterases. Its effect is gone minutes after stopping… μ-opioid receptor](https://durgical.com/en/pharmacology/remifentanil/)
- [**Sufentanil** A μ opioid of the fentanyl family and one of the most potent in clinical use. It is used in general anaesthesia and… μ-opioid receptor](https://durgical.com/en/pharmacology/sufentanil/)

## Others in the class

- codeine
- tramadol
- hydromorphone
- oxycodone
- methadone
- buprenorphine
- remifentanil
- naltrexone

## Test yourself

Think of the answer, then tap the question to see it.

## To which opioid effects does tolerance hardly develop?

Miosis and constipation. That is why constipation persists in chronic use and pinpoint pupils remain a clue in overdose.

## How does a μ agonist reduce pain transmission in the spinal cord?

It closes calcium channels in the presynaptic terminal (less glutamate and substance P) and opens potassium channels in the postsynaptic neuron, which hyperpolarizes.

## Why should a patient who woke up with naloxone stay under observation?

Because naloxone wears off sooner than many opioids; when it does, respiratory depression can return.

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Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given.

Sources: [Opioid overdose](https://www.who.int/news-room/fact-sheets/detail/opioid-overdose) (World Health Organization, 2025); [Morphine: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a682133.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Pain Relievers | Analgesics | Painkillers | MedlinePlus](https://medlineplus.gov/painrelievers.html) (MedlinePlus (U.S. National Library of Medicine), 2025).

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/classes/opioids-and-antagonists/