Acetaminophen

Acetaminophen, also called paracetamol and most commonly known as tylenol, is one of the most common household painkillers.1 It is a small chemical, with the formula C8H9NO2 and its IUPAC name is N-(4-hydroxyphenyl)acetamide.1 The main use of acetaminophen is the treatment of pain that is mild or moderate and the reduction of fever.1 The exact mechanism of action by which acetaminophen works has not been established, despite this it is such a widely distributed and used drug.1 The most prominent theory seems to be that it increases the pain threshold.1 Simplifying how they think this is done, is that it indirectly inhibits two enzymes (COX-1 and COX-2) which help to make the molecules prostaglandins, these are lipids which are responsible for pain sensations.1, 3 Acetaminophen is moderately lipid- and water-soluble,4 therefore it is absorbed into the body well.5 This is due to our cell membranes being composed of a lipid bilayer that allows free transport of molecules that are lipid-soluble.5 This property is what allows acetaminophen to cross the blood-brain barrier and be absorbed in the body via the intestines.1 The LD50 of acetaminophen is 1944mg/kg.1 If a human does ingest too much acetaminophen there can be; renal tubular necrosis, hypoglycemic coma, and thrombocytopenia, liver necrosis, and liver failure.1 The toxic effects that can occur from an overdose of acetaminophen are due to a by-product of its metabolism, called NAPQI.1,6 The most available alternative to taking acetaminophen is ibuprofen (advil), which is an anti-inflammatory, analgesic, and antipyretic.7 Multiple mechanisms of action for ibuprofen are known to cause the various effects, including its ability to inhibit COX-1 and COX-2.7 The LD50 of ibuprofen is of 636 mg/kg in rat,8 this is lower than acetaminophen suggesting that more acetaminophen is needed for an overdose. References 1Acetaminophen. DrugBank. (2005, June). https://go.drugbank.com/drugs/DB00316. (accessed Mar. 4, 2021) 2Merriam-Webster. Medical Terms and Abbreviations: Merriam-Webster Medical Dictionary. Merriam-Webster. https://www.merriam-webster.com/medical. 3Graham, G., Scott, K. Mechanism of action of paracetamol. American journal of therapeutics. [Online] 2005 Jan-Feb; 12(1), 46-55. doi: 10.1097/00045391-200501000-00008 (accessed Mar. 4, 2021) 4Prescott, L. F. Kinetics and metabolism of paracetamol and phenacetin. BPS Publications. Br. J. clin. Pharmac. 1980, 10, 291-298. https://bpspubs.onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2125.1980.tb01812.x. (accessed Mar. 4, 2021) 5Honek, J., Dieckmann, T., Chan, A., & Palmer, M. Biochemical Pharmacology, 1st edition, pg.47. 6Hazai, E., Vereczkey, L., & Monostory, K. Reduction of Toxic Metabolite Formation of Acetaminophen. Biochemical and Biophysical Research Communications. [Online] 2002, 291(4), 1089-1094. https://doi.org/10.1006/bbrc.2002.6541 (accessed Mar. 4, 2021) 7PubChem Compound Summary for CID 3672, Ibuprofen. [Online] National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/Ibuprofen. (accessed Mar. 4, 2021) 8Ibuprofen. [Online] DrugBank. (June 2005) https://go.drugbank.com/drugs/DB01050 (accessed Mar. 4, 2021)