Paracetamol (Acetaminophen)

What is Paracetamol?

Paracetamol, also known as acetaminophen, is a centrally acting analgesic (pain-relieving) and antipyretic (fever-reducing) medication widely used across all age groups.

Unlike traditional non-steroidal anti-inflammatory drugs (NSAIDs), paracetamol produces minimal gastric irritation, does not significantly affect platelet function, and is considered safe for short-term use when taken at recommended doses.

Chemical Structure & Medicinal Chemistry

Paracetamol is a para-aminophenol derivative whose therapeutic behavior is closely tied to its functional groups. The phenolic hydroxyl group contributes to analgesic activity, while the acetamide portion improves tolerability compared to older aniline-derived compounds.

• IUPAC: N-(4-hydroxyphenyl)acetamide
• Molecular Formula: C₈H₉NO₂
• Key Functional Groups: Phenol, Amide

This balance between efficacy and safety is a classic example of how small chemical modifications can significantly influence pharmacological behavior.

Mechanism of Action

Paracetamol primarily inhibits prostaglandin synthesis within the central nervous system by modulating cyclooxygenase (COX) activity in the brain. Reduced prostaglandin levels elevate the pain threshold and help regulate the hypothalamic heat-control center, thereby lowering fever.

Because its action is largely central rather than peripheral, paracetamol demonstrates minimal anti-inflammatory activity compared to NSAIDs.

Clinical Uses

• Mild to moderate pain (headache, muscle pain, dental pain)
• Fever management in adults and children
• Post-vaccination fever
• Cold and influenza symptom relief
• Preferred analgesic when NSAIDs are contraindicated

Pharmacokinetics

• Rapid gastrointestinal absorption
• Peak plasma concentration within 30–60 minutes
• Extensive hepatic metabolism
• Primarily eliminated via renal excretion

Safety and Recommended Use

Paracetamol is considered safe when used within therapeutic limits. However, exceeding recommended doses can overwhelm metabolic pathways, leading to accumulation of toxic intermediates.

Overdose & Liver Toxicity

In overdose situations, normal conjugation pathways become saturated, causing more drug to be converted into N-acetyl-p-benzoquinone imine (NAPQI), a highly reactive metabolite.

When hepatic glutathione stores are depleted, NAPQI binds to liver proteins and can trigger acute liver failure.

Antidote: N-acetylcysteine (NAC) restores glutathione levels and is most effective when administered early.

Who Should Use Caution?

• Individuals with severe liver disease
• Chronic alcohol users
• Patients taking enzyme-inducing medications
• Those with known hypersensitivity

Drug Interactions

• Alcohol — increases hepatotoxic risk
• Warfarin — prolonged use may enhance anticoagulant effect
• Enzyme inducers — may accelerate toxic metabolite formation

References

• World Health Organization (WHO)
• U.S. Food and Drug Administration (FDA)
• PubChem Drug Database
• National Center for Biotechnology Information (NCBI)