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# Non-opioid analgesic antipyretics

Medicines that ease pain and bring down fever with little or no anti-inflammatory effect, such as paracetamol and metamizole.

Updated 2026-11-01

## What they are

A group of non-opioid analgesics and antipyretics kept apart from the NSAIDs because, at usual doses, they barely reduce inflammation or harm the stomach lining. Its two members are paracetamol (acetaminophen), the most widely used antipyretic in the world, and metamizole (dipyrone), which is not approved in the United States because of its adverse reactions but is still used in many other countries.

## Mechanism of action

Their mechanism is not fully settled. Paracetamol weakly inhibits the cyclooxygenases, above all in the central nervous system, where the peroxide tone is low; in inflamed tissue, rich in peroxides, it loses that effect, which is why it hardly reduces inflammation or affects platelets. Metamizole is a prodrug: its active metabolites reduce prostaglandin-driven hyperalgesia and also relax smooth muscle.

## Key points

- Paracetamol is the antipyretic of choice when NSAIDs are contraindicated, for example until dengue has been ruled out (bleeding risk).
- Paracetamol overdose causes centrilobular liver necrosis through build-up of the metabolite NAPQI; the antidote is N-acetylcysteine, which works best the earlier it is given.
- Many combination products contain paracetamol: taking several at once is a common cause of accidental overdose.
- The typical serious risk of metamizole is agranulocytosis, which does not depend on the dose and can appear at any time during treatment or shortly after stopping it.
- Neither inhibits platelet function to a relevant degree at usual doses, unlike acetylsalicylic acid.

## Drugs in this class

- [**Paracetamol** The most widely used painkiller and fever reducer. Safe at correct doses, but overdose destroys the liver; its… Cyclooxygenases, mainly in the central nervous system (mechanism not fully established)](https://durgical.com/en/pharmacology/paracetamol/)
- [**Metamizole** A strong analgesic and antipyretic that also relaxes smooth muscle. Its serious risk is agranulocytosis, unrelated to… Active metabolites that reduce prostaglandin-driven hyperalgesia (mechanism not fully established)](https://durgical.com/en/pharmacology/metamizole/)

## Others in the class

- propyphenazone

## Test yourself

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

## Why does paracetamol lower fever but hardly reduce inflammation?

It inhibits the cyclooxygenases only where the peroxide tone is low, as in the central nervous system; in inflamed, peroxide-rich tissue it loses that effect.

## Which antipyretic is preferred for a patient with fever in an area where dengue circulates, and why?

Paracetamol, because NSAIDs such as ibuprofen or acetylsalicylic acid increase the risk of bleeding if the illness is dengue.

## Which symptoms suggest agranulocytosis in a patient receiving metamizole?

Fever, chills, sore throat and painful sores on the mucous membranes (mouth, nose, throat, genital or anal area). The drug is stopped and a full blood count with differential is done at once.

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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: [Acetaminophen: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a681004.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [ACETAMINOPHEN injection, solution](https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=8481d9f3-d2a5-457f-b92c-99445d063c8f) (DailyMed (U.S. National Library of Medicine), 2026); [Metamizole-containing medicinal products - referral](https://www.ema.europa.eu/en/medicines/human/referrals/metamizole-containing-medicinal-products-0) (European Medicines Agency, 2024); [Metamizole](https://pubchem.ncbi.nlm.nih.gov/compound/3111#section=Pharmacology) (PubChem (NCBI), 2026).

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