Paracetamol

Paracetamol (or acetaminophen) is a common analgesic, a drug that is used to relieve pain. It can also be used to reduce fever, and some kinds of headache. This makes it an antipyretic, something that reduces fevers. It is used in many drugs that treat the flu and colds.

Paracetamol

Clinical data
Pronunciation	Paracetamol: /ˌpærəˈsiːtəmɒl/ Acetaminophen: /əˌsiːtəˈmɪnəfɪn/ (listen)
Trade names	Tylenol, Panadol, others[1]
Synonyms	N-acetyl-para-aminophenol (APAP), acetaminophen (USAN US)
AHFS/Drugs.com	Monograph
MedlinePlus	a681004
License data	US DailyMed: Acetaminophen US FDA: Acetaminophen
Pregnancy category	AU: A[2]
Routes of administration	By mouth, rectal, intravenous (IV)
Drug class	Analgesics and antipyretics
ATC code	N02BE01 (WHO) N02BE51 (WHO) N02BE71 (WHO)
Legal status
Legal status	AU: S4 (Rx), OTC, and unscheduled UK: General sales list (GSL, OTC) US: OTC / Rx-only
Pharmacokinetic data
Bioavailability	63–89%[3]: 73
Protein binding	negligible to 10–25% in overdose[4]
Metabolism	Predominantly in the liver[5]
Metabolites	APAP gluc, APAP sulfate, APAP GSH, APAP cys, AM404, NAPQI[6]
Onset of action	Pain relief onset by route: By mouth – 37 minutes[7] Intravenous – 8 minutes[7]
Elimination half-life	1.9–2.5 hours[4]
Excretion	Urine[4]
Identifiers
IUPAC name N-(4-hydroxyphenyl)acetamide
CAS Number	103-90-2 Y
PubChem CID	1983
PubChem SID	46506142
IUPHAR/BPS	5239
DrugBank	DB00316 Y
ChemSpider	1906 Y
UNII	362O9ITL9D
KEGG	D00217 Y C06804
ChEBI	CHEBI:46195 Y
ChEMBL	ChEMBL112 Y
PDB ligand	TYL (PDBe, RCSB PDB)
ECHA InfoCard	100.002.870
Chemical and physical data
Formula	C8H9NO2
Molar mass	151.17 g·mol−1
3D model (JSmol)	Interactive image
Density	1.263 g/cm3
Melting point	169 °C (336 °F) [8][9]
Solubility in water	7.21 g/kg (0 °C)[10] 8.21 g/kg (5 °C)[10] 9.44 g/kg (10 °C)[10] 10.97 g/kg (15 °C)[10] 12.78 g/kg (20 °C)[10] ~14 mg/ml (20 °C)
SMILES CC(=O)Nc1ccc(O)cc1
InChI InChI=1S/C8H9NO2/c1-6(10)9-7-2-4-8(11)5-3-7/h2-5,11H,1H3,(H,9,10) Y Key:RZVAJINKPMORJF-UHFFFAOYSA-N Y
(verify)

The words acetaminophen and paracetamol both come from the names of the chemicals used in the compound: N-acetyl-para-aminophenol and para-acetyl-amino-phenol. Sometimes, it is shortened to APAP, for N-acetyl-para-aminophenol.

Harmon Northrop Morse was the first to make Paracetamol, in the year 1878. Drugs made with Paracetamol became common in the 1950s. Today, these drugs are some of the most used, together with those containing salicylic acid, Ibuprofen or Diclofenac. Unlike these, Paracetamol has no anti-inflammatory properties. In the year 1977, Paracetamol was added to the List of Essential Medicines of the WHO.

Safety and dosage

Paracetamol is considered safe for use. The drug is easily available without a prescription. People often take too much Paracetamol. Sometimes this is because people do not know how much they should take. The recommended dose may not work for some people. Other times it is because they are trying to commit suicide. Very often, a person's liver can be hurt when they take too much Paracetamol.^[11] A dose of 150 milligrams for every kilogram of the person's weight (about 10 grams for most adults) will lead to permanent liver damage, and may cause the liver to fail. For people whose livers have already been damaged, such as alcoholics, and for those with a limited secretion of Paracetamol, this amount can be much smaller.^[12][13][14] In England and Wales, about 30.000 people per year go to the hospital after taking too much paracetamol (called paracetamol poisoning), and about 150 die of the poisoning. Since a law was passed saying that Paracetamol packets cannot be too large, fewer people have been committing suicide with Paracetamol.^[15] In Great Britain^[16] and the United States Paracetamol is the main reason for acute liver failure. About half of the cases are because of an 'unintentional overdose'.^[11]

In 1982, there was a case of sabotage:^[17][18] Packets of paracetamol had been tampered with: Seven peoppel died, because they had taken poisoned samples. As a result, the FDA made stricter regulations. Also, Paracetamol-products worth 100 million US dollars were called back.

References

1. International Drug Names
2. "Acetaminophen Use During Pregnancy". Drugs.com. 14 June 2019. Archived from the original on 9 March 2020. Retrieved 25 February 2020.
3. Working Group of the Australian and New Zealand College of Anaesthetists and Faculty of Pain Medicine (2015). Schug SA, Palmer GM, Scott DA, Halliwell R, Trinca J (eds.). Acute Pain Management: Scientific Evidence (4th ed.). Melbourne: Australian and New Zealand College of Anaesthetists (ANZCA), Faculty of Pain Medicine (FPM). ISBN 978-0-9873236-7-5. Archived from the original (PDF) on 31 July 2019. Retrieved 28 October 2019.
4. Forrest JA, Clements JA, Prescott LF (1982). "Clinical pharmacokinetics of paracetamol". Clin Pharmacokinet. 7 (2): 93–107. doi:10.2165/00003088-198207020-00001. PMID 7039926. S2CID 20946160.
5. "Codapane Forte Paracetamol and codeine phosphate product information" (PDF). TGA eBusiness Services. Alphapharm Pty Limited. 29 April 2013. Archived from the original on 6 February 2016. Retrieved 10 May 2014.
6. "Acetaminophen Pathway (therapeutic doses), Pharmacokinetics". Archived from the original on 4 March 2016. Retrieved 13 January 2016.
7. Pickering G, Macian N, Libert F, Cardot JM, Coissard S, Perovitch P, Maury M, Dubray C (September 2014). "Buccal acetaminophen provides fast analgesia: two randomized clinical trials in healthy volunteers". Drug Design, Development and Therapy. 8: 1621–1627. doi:10.2147/DDDT.S63476. PMC 4189711. PMID 25302017. In postoperative conditions for acute pain of mild to moderate intensity, the quickest reported time to onset of analgesia with APAP is 8 minutes9 for the iv route and 37 minutes6 for the oral route.
8. Karthikeyan M, Glen RC, Bender A (2005). "General Melting Point Prediction Based on a Diverse Compound Data Set and Artificial Neural Networks". Journal of Chemical Information and Modeling. 45 (3): 581–590. doi:10.1021/ci0500132. PMID 15921448.
9. "melting point data for paracetamol". Lxsrv7.oru.edu. Archived from the original on 30 June 2012. Retrieved 19 March 2011.
10. Granberg RA, Rasmuson AC (1999). "Solubility of paracetamol in pure solvents". Journal of Chemical & Engineering Data. 44 (6): 1391–95. doi:10.1021/je990124v.
11. Larson A. M.; et al. (2005). "Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study". Hepatology. 42 (6): 1364–1372. doi:10.1002/hep.20948. PMID 16317692. S2CID 24758491.
12. Roberts, L. Jackson; Morrow, Jason D. (2001). "Analgesic-antipyretic and antiinflammatory agents and drugs employed in the treatment of gout". In Gilman, Alfred; Goodman, Louis Sanford; Hardman, Joel G.; Limbird, Lee E. (ed.). Goodman & Gilman's the pharmacological basis of therapeutics. New York: McGraw-Hill. pp. 687–732. ISBN 0-07-112432-2.{{cite book}}: CS1 maint: multiple names: authors list (link)
13. Williams, Roger Lawrence; Jean-Pierre Benhamou; Lee, William Thomas (1997). Acute liver failure. Cambridge, UK: Cambridge University Press. ISBN 0-521-55381-4.{{cite book}}: CS1 maint: multiple names: authors list (link)
14. "8 Paracetamol Guidelines for Patients". PR Fire. Archived from the original on 2021-01-24. Retrieved 2021-02-12.
15. Morgan OW, Griffiths C, Majeed A (April 2007). "Interrupted time-series analysis of regulations to reduce paracetamol (acetaminophen) poisoning". PLOS Med. 4 (4): e105. doi:10.1371/journal.pmed.0040105. PMC 1845154. PMID 17407385.{{cite journal}}: CS1 maint: multiple names: authors list (link)
16. Chun, L. J.; et al. (2009). "Acetaminophen hepatotoxicity and acute liver failure". J Clin Gastroenterol. 43 (4): 342–349. doi:10.1097/MCG.0b013e31818a3854. PMID 19169150.
17. G. Dunea: Death over the counter. In: Br Med J. 1983, 286, pp. 211–212. PMID 6401533; PMC 1546319.
18. K. A. Wolnik, F. L. Fricke, E. Bonnin, C. M. Gaston, R. D. Satzger: The Tylenol tampering incident – tracing the source. In: Anal. Chem. 56, 1984, pp. 466A–470A, 474A. PMID 6711821.