The World Health Organization (WHO) recommends that paracetamol be given to children with fever higher than 38.5 °C (101.3 °F).[46]
Paracetamol/acetaminophen is used for the relief of fevers, aches and pains associated with many parts of the body. It has analgesic and antipyretic properties comparable to those of aspirin, while its anti-inflammatory effects are weaker. It is better tolerated than aspirin in patients where excessive gastric acid secretion or prolongation of bleeding time may be a concern. Available without a prescription, it has in recent years increasingly become a common household drug.[47]
Acetaminophen can relieve pain in mild arthritis but has no effect on the underlying inflammation, redness, and swelling of the joint. It is as effective as the nonsteroidal anti-inflammatory drug ibuprofen (Motrin, Advil) in relieving the pain of osteoarthritis of the knee. Unless directed by physician, acetaminophen should not be used for longer than 10 days.
[edit] Efficacy and side effects
วันเสาร์ที่ 24 กรกฎาคม พ.ศ. 2553
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).
[edit] Efficacy
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.[48][unreliable source?][49]
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.[50][unreliable source?] Another study has questioned the benefits of this drug as an antipyretic in children.[51]
[edit] 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.[citation needed] 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.[52] 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.[53] Paracetamol is safe in pregnancy, and does not affect the closure of the fetal ductus arteriosus as other NSAIDs can.[54] Unlike aspirin, it is safe in children, as paracetamol is not associated with a risk of Reye's syndrome in children with viral illnesses.[55]
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.[56] 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.[57][58][59][60][61][62][63] 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."[64]
[edit] Efficacy
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.[48][unreliable source?][49]
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.[50][unreliable source?] Another study has questioned the benefits of this drug as an antipyretic in children.[51]
[edit] 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.[citation needed] 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.[52] 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.[53] Paracetamol is safe in pregnancy, and does not affect the closure of the fetal ductus arteriosus as other NSAIDs can.[54] Unlike aspirin, it is safe in children, as paracetamol is not associated with a risk of Reye's syndrome in children with viral illnesses.[55]
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.[56] 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.[57][58][59][60][61][62][63] 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."[64]
Toxicity
Main articles: Paracetamol toxicity and Analgesic nephropathy
Paracetamol hepatotoxicity is, by far, the most common cause of acute liver failure in both the United States and the United Kingdom.[6][65] Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance.[66] Signs and symptoms of paracetamol toxicity may initially be absent or vague. Untreated, overdose can lead to liver failure and death within days. Treatment is aimed at removing the paracetamol from the body and replacing glutathione. Activated charcoal can be used to decrease absorption of paracetamol if the patient presents for treatment soon after the overdose. While the antidote, acetylcysteine, (also called N-acetylcysteine or NAC) acts as a precursor for glutathione, helping the body regenerate enough to prevent damage to the liver, a liver transplant is often required if damage to the liver becomes severe.[3]
There are tablets available (brandname in the UK Paradote) which combine paracetamol with an antidote (methionine), to protect the liver in case of an overdose.
In June 2009, an FDA advisory committee recommended that new restrictions should be placed on paracetamol usage in the United States to help protect people from the potential toxic effects. The maximum dosage to be consumed at any given time would be decreased from 1000 mg to 650 mg, while combinations of paracetamol and narcotic analgesics would be prohibited. Committee members were particularly concerned by the fact that the present maximum dosages of paracetamol had been shown to produce alterations in hepatic function.[67] The FDA has not implemented their recommendations as of March 2010.[68]
Paracetamol hepatotoxicity is, by far, the most common cause of acute liver failure in both the United States and the United Kingdom.[6][65] Paracetamol overdose results in more calls to poison control centers in the US than overdose of any other pharmacological substance.[66] Signs and symptoms of paracetamol toxicity may initially be absent or vague. Untreated, overdose can lead to liver failure and death within days. Treatment is aimed at removing the paracetamol from the body and replacing glutathione. Activated charcoal can be used to decrease absorption of paracetamol if the patient presents for treatment soon after the overdose. While the antidote, acetylcysteine, (also called N-acetylcysteine or NAC) acts as a precursor for glutathione, helping the body regenerate enough to prevent damage to the liver, a liver transplant is often required if damage to the liver becomes severe.[3]
There are tablets available (brandname in the UK Paradote) which combine paracetamol with an antidote (methionine), to protect the liver in case of an overdose.
In June 2009, an FDA advisory committee recommended that new restrictions should be placed on paracetamol usage in the United States to help protect people from the potential toxic effects. The maximum dosage to be consumed at any given time would be decreased from 1000 mg to 650 mg, while combinations of paracetamol and narcotic analgesics would be prohibited. Committee members were particularly concerned by the fact that the present maximum dosages of paracetamol had been shown to produce alterations in hepatic function.[67] The FDA has not implemented their recommendations as of March 2010.[68]
Effects on animals
Paracetamol is extremely toxic to cats. Cats lack the necessary glucuronyl transferase enzymes to safely break paracetamol down, and minute portions of a tablet may prove fatal. Initial symptoms include vomiting, salivation and discolouration of the tongue and gums. Unlike an overdose in humans, liver damage is rarely the cause of death; instead, methaemoglobin formation and the production of Heinz bodies in red blood cells inhibit oxygen transport by the blood, causing asphyxiation (methemoglobemia and hemolytic anemia).[69] Treatment with N-acetylcysteine, methylene blue or both is sometimes effective after the ingestion of small doses of paracetamol. According to one paper female cats may have a better survival rate although sample size was small.[70]
Although paracetamol is believed to have no significant anti-inflammatory activity, it has been reported to be as effective as aspirin in the treatment of musculoskeletal pain in dogs.[71] A paracetamol-codeine product (trade name Pardale-V)[72] licensed for use in dogs is available on veterinary prescription in the UK.[73] It should be administered to dogs only on veterinary advice. The main effects of toxicity in dogs is liver damage.[74] N-acetylcysteine treatment is efficacious in dogs when administered within a few hours of paracetamol ingestion.[71]
Paracetamol is also lethal to snakes, and has been suggested as chemical control program for the brown tree snake (Boiga irregularis) in Guam.[75]
Although paracetamol is believed to have no significant anti-inflammatory activity, it has been reported to be as effective as aspirin in the treatment of musculoskeletal pain in dogs.[71] A paracetamol-codeine product (trade name Pardale-V)[72] licensed for use in dogs is available on veterinary prescription in the UK.[73] It should be administered to dogs only on veterinary advice. The main effects of toxicity in dogs is liver damage.[74] N-acetylcysteine treatment is efficacious in dogs when administered within a few hours of paracetamol ingestion.[71]
Paracetamol is also lethal to snakes, and has been suggested as chemical control program for the brown tree snake (Boiga irregularis) in Guam.[75]
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2.^ Acetaminophen
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