Sunday, May 9, 2010


Paracetamol (INN) (pronounced /ˌpærəˈsiːtəmɒl, ˌpærəˈsɛtəmɒl/) or acetaminophen (/əˌsiːtəˈmɪnɵfɨn/ ( listen)) (USAN) is a widely used over-the-counter analgesic (pain reliever) and antipyretic (fever reducer).
It is commonly used for the relief of headaches, and other minor aches and pains, and is a major ingredient in numerous cold and flu remedies. In combination with opioid analgesics, paracetamol could be used also in the management of more severe pain (such as in advanced cancer).
While 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), acute overdoses of paracetamol can cause potentially fatal liver damage and, in rare individuals, a normal dose can do the same; the risk is heightened by alcohol consumption. Paracetamol toxicity is the foremost cause of acute liver failure in the Western world, and accounts for most drug overdoses in the United States, the United Kingdom, Australia and New Zealand.
Paracetamol is part of the class of drugs known as "aniline analgesics"; it is the only such drug still in use today. It is the active metabolite of phenacetin, once popular as an analgesic and antipyretic in its own right, but unlike phenacetin and its combinations, paracetamol is not considered to be carcinogenic at therapeutic doses. The words acetaminophen (used in the United States, Canada, Hong Kong, Iran, Colombia and other Latin American countries) and paracetamol (used elsewhere) both come from chemical names for the compound: para-acetylaminophenol and para-acetylaminophenol. In some contexts, it is simply abbreviated as APAP, for N-acetyl-para-aminophenol.
There is confusion in terminology of paracetamol. It could be considered a nonsteroidal antiinflammatory drug (NSAID), but paracetamol has very little anti-inflammatory effect in many tissues. However, aspirin, paracetamol and other NSAIDs all act by the same mechanism (inhibition of prostaglandin (PG) synthesis) and all show varying levels of analgesic, anti-inflammatory, antipyretic and antiplatelet actions.

The World Health Organization (WHO) recommends that paracetamol be given to children with fever higher than 38.5 °C (101.3 °F).
Paracetamol is much more effective than aspirin, especially in patients where excessive gastric acid secretion or prolongation of bleeding time may be a concern. While paracetamol has analgesic and antipyretic properties comparable to those of aspirin, its anti-inflammatory effects are weak. Because paracetamol is well tolerated, available without a prescription, and lacks the gastric side effects of aspirin, it has in recent years increasingly become a common household drug.
Acetaminophen is used for the relief of fevers, aches and pains associated with many parts of the body. Acetaminophen relieves pain in mild arthritis but has no effect on the underlying inflammation, redness, and swelling of the joint. If the pain is not due to inflammation, acetaminophen is as effective as aspirin. It is as effective as the non-steroidal antiinflammatory drug ibuprofen (Motrin) in relieving the pain of osteoarthritis of the knee. Unless directed by physician, acetaminophen should not be used for longer than 10 days.

Efficacy and side effects
Paracetamol, unlike other common analgesics such as aspirin and ibuprofen, has relatively little anti-inflammatory activity, so it is not considered to be a non-steroidal anti-inflammatory drug (NSAID).

Regarding comparative efficacy, studies show conflicting results when compared to NSAIDs. A randomized controlled trial of chronic pain from osteoarthritis in adults found similar benefit from paracetamol and ibuprofen.
A randomized controlled trial of acute musculoskeletal pain in children found that the standard OTC dose of ibuprofen gives greater relief of pain than the standard dose of paracetamol. Another study has questioned the benefits of this drug as an antipyretic in children

Adverse effects
In recommended doses, paracetamol does not irritate the lining of the stomach, affect blood coagulation as much as NSAIDs, or affect function of the kidneys. However, some studies have shown that high dose-usage (greater than 2,000 mg per day) does increase the risk of upper gastrointestinal complications such as stomach bleeding. The researchers found that heavy use of aspirin or paracetamol - defined as 300 grams a year (1 g per day on average) - was linked to a condition known as small, indented and calcified kidneys (SICK). Paracetamol is safe in pregnancy, and does not affect the closure of the fetal ductus arteriosus as NSAIDs can. Unlike aspirin, it is safe in children, as paracetamol is not associated with a risk of Reye's syndrome in children with viral illnesses.
Like NSAIDs and unlike opioid analgesics, paracetamol has not been found to cause euphoria or alter mood in any way. In 2008, the largest study to date on the long term side effects of paracetamol in children was published in The Lancet. Conducted on over 200,000 children in 31 countries, the study found that the use of paracetamol for fever in the first year of life was associated with an increase in the incidence of asthmatic symptoms at 6–7 years, and that paracetamol use, both in the first year of life and in children aged 6–7 years, was associated with an increased incidence of rhinoconjunctivitis and eczema. The authors acknowledged that their "findings might have been due to confounding by indication", i.e. that the association may not be causal but rather due to the disease being treated with paracetamol, and emphasized that further research was needed. Furthermore a number of editorials, comments, correspondence and their replies have been published in The Lancet concerning the methodology and conclusions of this study. The UK regulatory body the Medicines and Healthcare products Regulatory Agency, also reviewed this research and published a number of concerns over data interpretation, and offer the following advice for healthcare professionals, parents, and carers: "The results of this new study do not necessitate any change to the current guidance for use in children. Paracetamol remains a safe and appropriate choice of analgesic in children. There is insufficient evidence from this research to change guidance regarding the use of antipyretics in children."
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