Pharmacology of Paracetamol/Acetaminophen


Paracetamol, commonly known as acetaminophen in some regions, stands as a cornerstone in the realm of over-the-counter medications. Renowned for its analgesic (pain-relieving) and antipyretic (fever-reducing) properties, it’s often the first line of defense against mild to moderate pain and fever, primarily due to its commendable safety profile when adhering to recommended dosages.

Mechanism of Action:

While the precise mechanism remains a topic of research, it’s widely accepted that paracetamol operates by curbing the production of prostaglandins within the brain. These chemicals, prostaglandins, are responsible for promoting inflammation, pain, and fever. Notably, paracetamol differentiates itself from other NSAIDs by not exerting anti-inflammatory effects and by not influencing the cardiovascular or coagulation systems.

Paracetamol is a weak inhibitor of COX-3. COX-3 is a splice variant of COX-1, and it is thought to be involved in inflammation. Paracetamol has been shown to inhibit COX-3 with an IC50 value of 64 μM, whereas IC50 values for COX-1 and COX-2 were 2.1 μM and 92.4 μM, respectively. This means that paracetamol is more likely to inhibit COX-3 than COX-1 or COX-2.

However, it is important to note that the clinical relevance of COX-3 inhibition by paracetamol is still unclear. Some studies have shown that paracetamol can relieve pain and inflammation in rodents, but other studies have not found the same results. More research is needed to determine the exact role of COX-3 in pain and inflammation and to see if paracetamol can be used to target this enzyme without causing the same side effects as other NSAIDs.


Explanation of the Detailed Diagram:

  1. Paracetamol: The drug that is metabolized in the liver and inhibits COX-3 enzymes.
  2. COX-3: A variant of the Cyclooxygenase enzyme that is inhibited by Paracetamol.
  3. Prostaglandins: Molecules that are produced by COX-3 and act on the central nervous system.
  4. Central Nervous System (CNS): The site where prostaglandins act to reduce pain and fever.
  5. Pain: A sensation reduced by the action of Paracetamol on the CNS.
  6. Fever: Elevated body temperature reduced by the action of Paracetamol on the CNS.


  1. Absorption: Once ingested, paracetamol is swiftly absorbed from the gastrointestinal tract, reaching peak plasma concentrations within 30 to 60 minutes.
  2. Distribution: It doesn’t play favorites, distributing uniformly across most body tissues.
  3. Metabolism: The liver takes charge here, metabolizing paracetamol primarily through three pathways: conjugation with glucuronide, conjugation with sulfate, and oxidation via the cytochrome P450 enzyme system.
  4. Excretion: The kidneys step in for the final act, excreting the metabolites within 24 hours.

Pharmacological Actions:

  • Central Nervous System: Beyond its pain-relieving prowess, paracetamol ensures patients remain alert, causing no sedation.
  • Musculoskeletal System: It’s worth noting that paracetamol doesn’t exert anti-inflammatory effects, meaning signs of inflammation remain unchanged post-administration.

Therapeutic Uses and Doses:

  • Pain Relief: For mild to moderate pain, the standard adult dose is 500 mg to 1000 mg every 4 to 6 hours, not exceeding 4000 mg in a 24-hour period.
  • Fever Reduction: To combat elevated body temperatures, the recommended adult dose mirrors that of pain relief: 500 mg to 1000 mg every 4 to 6 hours, ensuring not to surpass 4000 mg within a day.

Side Effects:

  • Common: Side effects are a rarity when sticking to recommended doses. However, straying into overdose territory can usher in severe complications.
  • Liver: The most significant risk lies in liver damage, which, in extreme cases, can be fatal. This risk amplifies with doses exceeding 4000 mg daily.

Paracetamol Poisoning:

Overdosing paracetamol can severely compromise liver health. This risk intensifies in individuals with pre-existing liver conditions or those who consume alcohol regularly. Early symptoms (within 24 hours of overdose) include pallor, nausea, vomiting, loss of appetite, and abdominal discomfort.


Treatment of Paracetamol Poisoning:

Time is of the essence in such cases. Within the first hour post-ingestion, gastric lavage or induced vomiting can be beneficial. Administering activated charcoal can further prevent absorption. N-acetylcysteine (NAC) serves as the antidote, with its efficacy peaking when given within 8 hours of overdose.


Explanation of the Complete Diagram:

  1. Paracetamol: The drug that is metabolized in the liver.
  2. Liver (5% Overdose Pathway, 95% Normal Pathway): The primary site of Paracetamol metabolism, with percentages indicating the likelihood of each pathway.
  3. Non-toxic Metabolites: Produced through the normal metabolic pathway.
  4. NAPQI (Toxic): Produced in the case of overdose, a toxic metabolite.
  5. Glutathione: A molecule that neutralizes NAPQI.
  6. Detoxified NAPQI (N-acetyl-p-benzoquinone imine): The non-toxic form of NAPQI after being neutralized by Glutathione.
  7. Poisoning: Occurs when NAPQI accumulates due to glutathione depletion.
  8. Treatment: Medical intervention for Paracetamol poisoning.
  9. N-Acetylcysteine (NAC): Administered to replenish glutathione levels.


  • Liver Impairments: Those with liver ailments or chronic alcohol consumption habits should steer clear of paracetamol.
  • Hypersensitivity: Any known allergy to paracetamol or its ingredients warrants avoidance.

Drug Interactions:

  • Alcohol: Concurrent consumption can escalate the risk of liver damage.
  • Warfarin: Regular paracetamol use can amplify the anticoagulant effects of warfarin.
  • Other Hepatotoxic Drugs: Combining paracetamol with other liver-affecting drugs can compound the risk of liver damage.

This detailed guide offers a panoramic view of paracetamol’s pharmacological landscape. Specialized pharmacology resources or primary research articles are invaluable for those seeking a deeper dive.

Disclaimer: This article is for informational purposes only and should not be taken as medical advice. Always consult with a healthcare professional before making any decisions related to medication or treatment.

Disclaimer: This article is for informational purposes only and does not constitute medical advice. Always seek the advice of a healthcare provider with any questions regarding a medical condition.

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