Acetaminophen

(CC) Image: David E. Volk
Acetaminophen (paracetamol)

Acetaminophen, also widely called acetaminofen, paracetamol or paracetanol, is an analgesic and antipyretic drug widely used for the treatment of headaches, fever and other minor aches and pains. Many cold and flu medications and some prescription analgesics contain acetaminophen. It has no mood altering effects and is not addictive although it can be combined with narcotic analgesics which have these effects such as oxycodone or hydrocodone with the brand names of Percocet and Vicodin respectively. Acetaminophen inhibits cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) indirectly through a hypothesized yet unknown enzyme called COX-3, in the central nervous system and endothelial cells and thus suppresses the synthesis of prostaglandin and heightens the pain threshold. However, it does not inhibit COX enzymes in the peripheral tissues, and thus has no peripheral anti-inflammatory effects. Although it is sold under hundreds of names, it is popularly known as Tylenol®.

While it is generally safe and effective, the margin between a safe and toxic dosage is narrower than once believed. In particular, overdoses are dangerous to the liver, once to be the case only in patients with alcohol-induced hepatic damage. While not yet a firm recommendation, there is increasing sentiment that patients taking it should not drink any alcohol while being treated.

Another hazard being addressed by safety and regulatory groups is that acetaminophen is extensively used as a combination, with other drugs, in single-dose forms. When the other drugs contain opioids, the primary purpose is to keep the oral dose from being diverted to recreational injection. The combination also has some therapeutic sense, because acetaminophen and opioids affect different mechanisms of pain. Unfortunately, there have been cases where raising the combined-tablet dose, usually to provide more opioid and often under medical orders, inadvertently produced acetaminophen toxicity.

Effectiveness

Analgesia

Acetaminophen one gram orally four times a day had similar efficacy to ibuprofen in reducing pain in randomized controlled trial of patients with mild to moderate osteoarthritis or the hip or knee.

For lumbalgia, acetaminophen one gram orally four times a day combined with diclofenac, a non-steroidal anti-inflammatory agent, was not better than acetaminophen alone in a randomized controlled trial.

Intravenous acetaminophen one gram was as effective as morphine 0.1 mg/kg for renal colic.

Fever

For reducing fever, acetaminophen combined with ibuprofen may be better than either drug alone according to a randomized controlled trial.

Toxicity and drug interactions

It may cause liver, blood cell, and kidney damage in a limited number of people. Alcolol intake increases its liver toxicity. The toxic effects of acetaminophen are due to a minor metabolite N-acetyl-p-benzo-quinone imine, which reacts with sulfhydryl groups. At usual doses, it is detoxified by combining with glutathione to produce a non-toxic conjugate that gets excreted by the kidneys.

The anticoagulation effects of acenocoumarol, anisindione, dicumarol and warfarin are increased when taken with acetaminophen. Increased liver toxicity occurs when used in combination with imatinib, isoniazid or alcohol.

One third of patients taking a full doxe (1 gram four times a day) may have their liver function tests rise to three times the upper limit of normal.

Dosage

The Food and Drug Administration may reduce the recommended dose to 650 milligrams per dose and no more than 4250 milligrams per day.

External links

• The most up-to-date information about Acetaminophen and other drugs can be found at the following sites.
• Acetaminophen - FDA approved drug information (drug label) from DailyMed (U.S. National Library of Medicine).
• Acetaminophen - Drug information for consumers from MedlinePlus (U.S. National Library of Medicine).
• Acetaminophen - Detailed information from DrugBank.