Wednesday 1 June 2011

Paracetamol is a widely used over-the-counter analgesic (pain reliever) and antipyretic (fever reducer).


Paracetamol is commonly used for the
1.Relief of headaches,
2.Other minor aches and pains. (analgesic) 
3. Fever Reducer (antipyretic)
4.In combination with opioid analgesics, paracetamol can also be used in the management of more severe pain such as post surgical pain and providing palliative care in advanced cancer patients.
5. Common colds & flu

Dosage & onset of action:
Paracetamol BP 500mg + caffeine 65mg/tablet
The onset of analgesia is approximately 11 minutes after oral administration of paracetamol, and its half-life is 1–4 hours.
Generally safe for use at recommended doses (1,000 mg per single dose and up to 4,000 mg per day for adults, up to 2,000 mg per day if drinking alcohol).
Side-effect  :
Daily use increases the risk of upper gastrointestinal complications such as stomach bleeding, and may cause kidney or liver damage.Until 2010 paracetamol was believed to be safe in pregnancy.
Over dosage:
overdose can lead to liver failure and death within days.

Mechanisms of Action of Paracetamol:
Over 100 years after it was first discovered, we are now learning what the mechanism of action is that makes paracetamol such an effective and useful medicine. It now appears paracetamol has a highly targeted action in the brain, blocking an enzyme involved in the transmission of pain.

As with many medicines, the effectiveness of paracetamol was discovered without knowing how it works. Its mode of action was known to be different to other pain relievers, but although it produces pain relief throughout the body the exact mechanism was not clear.


The production of prostaglandins is part of the body's inflammatory response to injury, and inhibition of prostaglandin production around the body by blocking the cyclooxygenase enzymes known as COX-1 and COX-2 has long been known to be the mechanism of action of aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen. However, their action in blocking COX-1 is known to be responsible for also causing the unwanted gastrointestinal side effects associated with these drugs.
Paracetamol has no significant action on COX-1 and COX-2, which left its mode of action a mystery but did explain its lack of anti-inflammatory action and also, more importantly, its freedom from gastrointestinal side effects typical of NSAIDs.

Early work (1) had suggested that the fever reducing action of paracetamol was due to activity in the brain while its lack of any clinically useful anti-inflammatory action was consistent with a lack of prostaglandin inhibition peripherally in the body.

Now, recent research (2) has shown the presence of a new, previously unknown cyclooxygenase enzyme COX-3, found in the brain and spinal cord, which is selectively inhibited by paracetamol, and is distinct from the two already known cyclooxygenase enzymes COX-1 and COX-2. It is now believed that this selective inhibition of the enzyme COX-3 in the brain and spinal cord explains the effectiveness of paracetamol in relieving pain and reducing fever without having unwanted gastrointestinal side effects.