Acetaminophen
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. Although it is sold under hundreds of names, it is popularly known as Tylenol®.
It has no mood altering effects and is not addictive although it can be combined with opioid analgesics which have these effects such as oxycodone or hydrocodone with the brand names of Percocet and Vicodin respectively.
A hazard is that acetaminophen is combined with other drugs, into single pills. When the other drugs contain opioid analgesics, 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.
Pharmacology
Mechanism of action
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.
Metabolism
Glucuronosyltransferase is part of the phase II drug metabolism of acetaminophen.[1]
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.[2]
Intravenous acetaminophen one gram was as effective as morphine 0.1 mg/kg for renal colic.[3]
Combination therapy
According to a systematic review sponsored by industry, combining acetaminophen with Non-steroidal anti-inflammatory agents may help treatment of posteroperative pain.[4]
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.[5]
Fever
For reducing fever, acetaminophen combined with ibuprofen may be better than either drug alone according to a randomized controlled trial.[6]
Toxicity and drug interactions
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.
It may cause liver, blood cell, and kidney damage in a limited number of people. Alcohol 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.[7]
Dosage
The Food and Drug Administration may reduce the recommended dose to 650 milligrams per dose and no more than 4250 milligrams per day.[8]
References
- ↑ de Wildt SN, Kearns GL, Leeder JS, van den Anker JN (1999). "Glucuronidation in humans. Pharmacogenetic and developmental aspects.". Clin Pharmacokinet 36 (6): 439-52. PMID 10427468.
- ↑ Bradley JD, Brandt KD, Katz BP, Kalasinski LA, Ryan SI (1991). "Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee". N. Engl. J. Med. 325 (2): 87–91. PMID 2052056. [e]
- ↑ Bektas F, Eken C, Karadeniz O, Goksu E, Cubuk M, Cete Y (2009). "Intravenous paracetamol or morphine for the treatment of renal colic: a randomized, placebo-controlled trial.". Ann Emerg Med 54 (4): 568-74. DOI:10.1016/j.annemergmed.2009.06.501. PMID 19647342. Research Blogging.
- ↑ Ong CK, Seymour RA, Lirk P, Merry AF (2010). "Combining paracetamol (acetaminophen) with nonsteroidal antiinflammatory drugs: a qualitative systematic review of analgesic efficacy for acute postoperative pain.". Anesth Analg 110 (4): 1170-9. DOI:10.1213/ANE.0b013e3181cf9281. PMID 20142348. Research Blogging.
- ↑ Hancock MJ, Maher CG, Latimer J, et al (2007). "Assessment of diclofenac or spinal manipulative therapy, or both, in addition to recommended first-line treatment for acute low back pain: a randomised controlled trial". Lancet 370 (9599): 1638–43. DOI:10.1016/S0140-6736(07)61686-9. PMID 17993364. Research Blogging.
- ↑ Hay AD, Costelloe C, Redmond NM, et al (2008). "Paracetamol plus ibuprofen for the treatment of fever in children (PITCH): randomised controlled trial". BMJ 337: a1302. PMID 18765450. PMC 2528896. [e]
- ↑ Watkins PB, Kaplowitz N, Slattery JT, et al (2006). "Aminotransferase elevations in healthy adults receiving 4 grams of acetaminophen daily: a randomized controlled trial". JAMA 296 (1): 87–93. DOI:10.1001/jama.296.1.87. PMID 16820551. Research Blogging.
- ↑ The Associated Press: FDA group recommends acetaminophen liver warnings. Retrieved on 2009-05-29.
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.