Pharmacology · Non-opioid analgesic antipyretics
Paracetamol !
The most widely used painkiller and fever reducer. Safe at correct doses, but overdose destroys the liver; its antidote is N-acetylcysteine.
Updated 2026-11-01
Also called: acetaminophen
Mechanism of action
The exact mechanism of paracetamol is not established. It is thought to act mainly in the central nervous system: it weakly and reversibly inhibits the cyclooxygenases, lowering the prostaglandins that raise the hypothalamic set point and amplify pain. In inflamed, peroxide-rich tissue the effect is lost, so it barely reduces inflammation, does not harm the stomach lining and does not alter platelet function.
- Weakly inhibits the cyclooxygenases in the central nervous system
- Fewer prostaglandins raise the hypothalamic set point
- Vasodilation and sweating: the body loses heat and the fever falls
- Less pain, with little anti-inflammatory and no platelet effect
Pharmacokinetics
- Absorption
- Well absorbed by mouth; also given intravenously.
- Distribution
- Spreads to almost every tissue except fat; low binding to plasma proteins.
- Metabolism
- Liver: mainly glucuronidation and sulfation. A small fraction is oxidised by CYP2E1 to NAPQI, a toxic metabolite neutralised by glutathione.
- Elimination
- Kidney, almost all as conjugated metabolites.
- Half-life
- About 2 to 3 hours in adults.
Indications
- Fever and pain in dengue, where NSAIDs are avoided because of bleeding risk Dengue →
- Fever and joint pain in chikungunya Chikungunya →
- Mild to moderate pain and fever in general, children included
Adverse effects
Common
- Nausea and vomiting
- Headache
- Insomnia
- In children, constipation and itching with the intravenous route
Contraindications
- Hypersensitivity to paracetamol
- Severe hepatic impairment or severe active liver disease
Key interactions
- Alcohol and drugs that induce CYP2E1
- May increase NAPQI formation and the risk of liver injury; chronic alcohol use is a classic risk factor.
- Warfarin
- Regular, prolonged paracetamol use can raise the INR.
- Other paracetamol-containing products
- Adding up combination products (cold remedies, opioid combinations) is the most common cause of accidental overdose.
What is monitored
- Total daily paracetamol from all sources
- Liver function tests in long-term use, liver disease or after an overdose
- Suspected overdose: serum paracetamol level (not earlier than 4 hours after ingestion) and serial liver enzymes
Administration and safety
- Intravenously, confusing milligrams with millilitres is a serious medication error: the dose is double-checked and the infusion pump programmed with care.
- In low-weight patients the dose is weight-based; calculation errors have caused fatal overdoses.
- Before giving it, check whether the patient already receives paracetamol in another product (oral, intravenous or combination).
Nursing care
- Ask about every over-the-counter medicine: many cold remedies and painkillers contain paracetamol.
- Identify risk factors for liver injury: alcohol use, malnutrition, fasting, liver disease and hypovolaemia.
- Poisoning can go unnoticed at first: nausea, vomiting, sweating and malaise; the liver injury becomes evident over the following days.
- With a possible overdose, report it at once: N-acetylcysteine protects more the earlier it starts.
- Teach the patient to stop the medicine and seek care if a skin rash appears.
Pregnancy and breastfeeding
Epidemiological studies have not shown a clear link with birth defects or miscarriage. In animal studies, high doses showed fetal toxicity.
Test yourself
Think of the answer, then tap the question to see it.
Why does a paracetamol overdose damage the liver?
Glucuronidation and sulfation saturate, more drug is oxidised by CYP2E1 to NAPQI, liver glutathione runs out and free NAPQI binds hepatocyte proteins, causing centrilobular necrosis.
How does N-acetylcysteine work in paracetamol poisoning, and why does timing matter?
It replenishes glutathione (and may conjugate NAPQI directly). It protects most the earlier it starts, before liver necrosis is established.
Why can a patient with a paracetamol overdose look almost well on the first day?
The first symptoms are mild (nausea, vomiting, sweating, malaise), and clinical and laboratory evidence of liver injury can take days to appear.
When is the serum paracetamol level measured after an acute ingestion, and why?
Not earlier than 4 hours after ingestion; the value is plotted on the Rumack-Matthew nomogram against the time since ingestion to decide on N-acetylcysteine.
Which intravenous paracetamol administration errors does the label warn about?
Confusing milligrams with millilitres, not weight-basing the dose in small patients or programming the pump wrongly, and adding paracetamol from other sources: all can cause overdose.
Related drugs
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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 (MedlinePlus (U.S. National Library of Medicine), 2026); ACETAMINOPHEN injection, solution (DailyMed (U.S. National Library of Medicine), 2026); Acetaminophen (PubChem (NCBI), 2026); Dengue (World Health Organization, 2025).
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