Chemical structure of paracetamol500 mg Panadol suppositoriesTablets are the most common form of paracetamol.
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Acetaminophen

Paracetamol (INN) (IPA: ) or acetaminophen (USAN) is a common analgesic and antipyretic drug that is used for the relief of fever, headaches, and other minor aches and pains. It is a major ingredient in numerous cold and flu medications and many prescription analgesics. It is remarkably safe in standard doses, but, because of its wide availability, deliberate or accidental overdoses are fairly common. more...

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Paracetamol, unlike other common analgesics such as aspirin and ibuprofen, has no anti-inflammatory properties, and so it is not a member of the class of drugs known as non-steroidal anti-inflammatory drugs or NSAIDs. In normal doses, paracetamol does not irritate the lining of the stomach or affect blood coagulation, the kidneys, or the fetal ductus arteriosus (as NSAIDs can).

Like NSAIDs and unlike opioid analgesics, paracetamol has not been found to cause euphoria or alter mood in any way. Paracetamol and NSAIDs have the benefit of bearing no risk of addiction, dependence, tolerance and withdrawal.

The words acetaminophen and paracetamol both come from the chemical names for the compound: N-acetyl-para-aminophenol and para-acetyl-amino-phenol.

History

In ancient and medieval times, the only antipyretic agents known were compounds contained in willow bark (a family of chemicals known as salicins, which led to the development of aspirin), and compounds contained in cinchona bark. Cinchona bark was also used to create the anti-malaria drug quinine. Quinine itself also has antipyretic effects. Efforts to refine and isolate salicin and salicylic acid took place throughout the middle- and late-19th century.

When the cinchona tree became scarce in the 1880s, people began to look for alternatives. Two alternative antipyretic agents were developed in the 1880s: Acetanilide in 1886 and Phenacetin in 1887. By this time, paracetamol had already been synthesized by Harmon Northrop Morse via the reduction of p-nitrophenol with tin in glacial acetic acid. While this was first performed in 1873, paracetamol was not used medically for another two decades. In 1893, paracetamol was discovered in the urine of individuals who had taken phenacetin, and was concentrated into a white, crystalline compound with a bitter taste. In 1899, paracetamol was found to be a metabolite of acetanilide. This discovery was largely ignored at the time.

In 1946, the Institute for the Study of Analgesic and Sedative Drugs awarded a grant to the New York City Department of Health to study the problems associated with analgesic agents. Bernard Brodie and Julius Axelrod were assigned to investigate why non-aspirin agents were associated with the development of methemoglobinemia, a non-lethal blood condition. In 1948, Brodie and Axelrod linked the use of acetanilide with methemoglobinemia and determined that the analgesic effect of acetanilide was due to its active metabolite paracetamol. They advocated the use of paracetamol (acetaminophen), since it did not have the toxic effects of acetanilide. (Brodie and Axelrod, 1948)

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Acetaminophen
From Gale Encyclopedia of Medicine, 4/6/01 by Nancy Ross-Flanigan

Definition

Acetaminophen is a medicine used to relieve pain and reduce fever.

Purpose

Acetaminophen is used to relieve many kinds of minor aches and pains -- headaches, muscle aches, backaches, toothaches, menstrual cramps, arthritis, and the aches and pains that often accompany colds.

Description

This drug is available without a prescription. Acetaminophen --or APAP -- is sold under various brand names, including Tylenol, Panadol, Aspirin Free Anacin, and Bayer Select Maximum Strength Headache Pain Relief Formula. Many multi-symptom cold, flu, and sinus medicines also contain acetaminophen. Check the ingredients listed on the container to see if acetaminophen is included in the product.

Studies have shown that acetaminophen relieves pain and reduces fever about as well as aspirin. But differences between these two common drugs exist. Acetaminophen is less likely than aspirin to irritate the stomach. However, unlike aspirin, acetaminophen does not reduce the redness, stiffness, or swelling that accompany arthritis.

Recommended dosage

The usual dosage for adults and children age 12 and over is 325-650 mg every 4- 6 hours as needed. No more than 4 grams (4000 mg) should be taken in 24 hours. Because the drug can potentially harm the liver, people who drink alcohol in large quantities should take considerably less acetaminophen and possibly should avoid the drug completely.

For children ages 6-11 years, the usual dose is 150-300 mg, three to four times a day. Check with a physician for dosages for children under age 6 years.

Precautions

Never take more than the recommended dosage of acetaminophen unless told to do so by a physician or dentist.

Patients should not use acetaminophen for more than 10 days to relieve pain (5 days for children) or for more than 3 days to reduce fever, unless directed to do so by a physician. If symptoms do not go away -- or if they get worse -- contact a physician. Anyone who drinks 3 or more alcoholic beverages a day should check with a physician before using this drug and should never take more than the recommended dosage. A risk of liver damage exists from combining large amounts of alcohol and acetaminophen. People who already have kidney or liver disease or liver infections should also consult with a physician before using the drug. So should women who are pregnant or breastfeeding.

Smoking cigarettes may interfere with the effectiveness of acetaminophen. Smokers may need to take higher doses of the medicine, but should not take more than the recommended daily dosage unless told by a physician to do so.

Many drugs can interact with one another. Consult a physician or pharmacist before combining acetaminophen with any other medicine. Do not use two different acetaminophen-containing products at the same time.

Acetaminophen interferes with the results of some medical tests. Before having medical tests done, check to see whether taking acetaminophen will affect the results. Avoiding the drug for a few days before the tests may be necessary.

Side effects

Acetaminophen causes few side effects. The most common one is lightheadedness. Some people may experience trembling and pain in the side or the lower back. Allergic reactions do occur in some people, but they are rare. Anyone who develops symptoms such as a rash, swelling, or difficulty breathing after taking acetaminophen should stop taking the drug and get immediate medical attention. Other rare side effects include yellow skin or eyes, unusual bleeding or bruising, weakness, fatigue, bloody or black stools, bloody or cloudy urine, and a sudden decrease in the amount of urine.

Overdoses of acetaminophen may cause nausea, vomiting, sweating, and exhaustion. Very large overdoses can cause liver damage. In case of an overdose, get immediate medical attention.

Interactions

Acetaminophen may interact with a variety of other medicines. When this happens, the effects of one or both of the drugs may change or the risk of side effects may be greater. Among the drugs that may interact with acetaminophen are alcohol, nonsteroidal anti-inflammatory drugs (NSAIDs) such as Motrin, oral contraceptives, the antiseizure drug phenytoin (Dilantin), the blood-thinning drug warfarin (Coumadin), the cholesterol-lowering drug cholestyramine (Questran), the antibiotic Isoniazid, and zidovudine (Retrovir, AZT). Check with a physician or pharmacist before combining acetaminophen with any other prescription or nonprescription (over-the-counter) medicine.

Key Terms

Arthritis
Inflammation of the joints. The condition causes pain and swelling.
Fatigue
Physical or mental weariness.
Inflammation
A response to irritation, infection, or injury, resulting in pain, redness, and swelling.

Further Reading

Gale Encyclopedia of Medicine. Gale Research, 1999.

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