Phenacetin

Overview

Phenacetin (/fɪˈnæsɪtɪn/; acetophenetidin, N-(4-ethoxyphenyl)acetamide) is a pain-relieving and fever-reducing drug, which was widely used following its introduction in 1887. It was withdrawn from medicinal use as dangerous from the 1970s (e.g., withdrawn in Canada in 1973, and by the U.S. Food and Drug Administration in 1983).[1][2][3] WP

Uses, dosage and effects

Medical

Phenacetin was widely used until the third quarter of the twentieth century, often in the form of an A.P.C., or "aspirin-phenacetin-caffeine" compound analgesic, as a remedy for fever and pain. An early formulation (1919) was Vincent's APC in Australia. WP

In the United States, the Food and Drug Administration ordered the withdrawal of drugs containing phenacetin in November 1983, due to its carcinogenic and kidney-damaging properties. It was also banned in India. As a result, some branded, and previously phenacetin-based, preparations continued to be sold, but with the phenacetin replaced by safer alternatives. A popular brand of phenacetin was Roche's Saridon, which was reformulated in 1983 to contain propyphenazone, paracetamol and caffeine. Coricidin was also reformulated without phenacetin. Paracetamol is a metabolite of phenacetin with similar analgesic and antipyretic effects, but the new formulation has not been found to have phenacetin's carcinogenicity.[4][5] WP

Other

Phenacetin has been used as a cutting agent to adulterate cocaine in the UK and Canada, due to the similar physical properties. There, it has been given the nickname "magic".[6] WP

Due to its low cost, phenacetin is used for research into the physical and refractive properties of crystals. It is an ideal compound for this type of research.[1][7] WP

In Canada, phenacetin is used as a laboratory reagent, and in a few hair dye preparations (as a stabilizer for hydrogen peroxide). While it is considered a prescription drug, no marketed drugs contain phenacetin.[8] WP

Risks and side effects

Safety

Phenacetin, and products containing phenacetin, have been shown in an animal model to have the side effect and after-effect of carcinogenesis. In humans, many case reports have implicated products containing phenacetin in urothelial neoplasms, especially urothelial carcinoma of the renal pelvis. Phenacetin is classified by the International Agency for Research on Cancer (IARC) as carcinogenic to humans. In one prospective series, phenacetin was associated with an increased risk of death due to urologic or renal diseases, death due to cancers, and death due to cardiovascular diseases. In addition, people with glucose-6-phosphate dehydrogenase deficiency may experience acute hemolysis, or dissolution of blood cells, while taking this drug. Acute hemolysis is possible in the case of patients who develop an IgM response to phenacetin leading to immune complexes that bind to erythrocytes in blood. The erythrocytes are then lysed when the complexes activate the complement system.[1][9] WP

Chronic use of phenacetin is known to lead to analgesic nephropathy characterized by renal papillary necrosis. This is a condition which results in destruction of some or all of the renal papillae in the kidneys. It is believed that the metabolite p-phenetidine is at least partly responsible for these effects.[10–13] WP

One notable death that can possibly be attributed to the use of this drug was that of the aviation pioneer Howard Hughes. He had been using phenacetin extensively for the treatment of chronic pain; it was stated during his autopsy that phenacetin use may have been the cause of his kidney failure.[14] WP

Askit Powders, a once-popular headache cure on the UK market, have been associated with kidney failure in chronic users due to containing phenacetin until 1966, when they were reformulated to remove it.[15] WP

History

History

Phenacetin was introduced in 1887 in Elberfeld, Germany, by German company Bayer, and was used principally as an analgesic; it was one of the first synthetic fever reducers to go on the market. It is also known historically to be one of the first non-opioid analgesics without anti-inflammatory properties. Although paracetamol (acetaminophen) was produced earlier, a historical accident saw it ignored after Joseph von Mering's 1893 assessment.[16] WP

Prior to World War One, Britain imported phenacetin from Germany. During the war, a team including Jocelyn Field Thorpe and Martha Annie Whiteley developed a synthesis in Britain.[17] WP

In popular culture

A 1974 episode of the Yorkshire Television series Justice, "Duty of Care", features a court case that resulted from a woman dying of phenacetin poisoning, as a result of taking A.P.C. for five years. This explained that phenacetin caused renal papillary necrosis.[18] WP

In the book Zen and the Art of Motorcycle Maintenance chapter 4, "APCs for headaches" is included in a list of valuable things to take on motorcycle trips.[19] WP

Chemistry

Formula

C10H13NO2 PC

Molar mass (g/mol)

179.22 PC

IUPAC name (computed by PubChem)

N-(4-ethoxyphenyl)acetamide PC

SMILES

CCOC1=CC=C(C=C1)NC(=O)C PC

InChIKey

CPJSUEIXXCENMM-UHFFFAOYSA-N PC

PubChem CID

4754

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Gralak B, Enoch S, Tayeb G. Anomalous refractive properties of photonic crystals. Journal of the Optical Society of America A. June 2000. doi:10.1364/JOSAA.17.001012 · PMID 10850471
2. Harm reduction site Phenacetin
3. Journal / agency Drugs withdrawn from the market containing phenacetin. 5 October 1983
4. Other Federal Register of October 5, 1983 (48 FR 45466)
5. Other Drugs banned in India
6. Other Cancer chemical in street cocaine. 23 November 2006
7. Journal / agency Studenikin PA, Zagumennyi AI, Zavartsev YD, Popov PA, Shcherbakov IA. GdVO4as a new medium for solid-state lasers: Some optical and thermal properties of crystals doped with Cd3+, Tm3+, and Er3+ions. Quantum Electronics. 1995. doi:10.1070/QE1995v025n12ABEH000556
8. Other Health - Product safety - Chemical substances - Phenacetin information sheet. 18 April 2017
9. Journal / agency Dubach UC, Rosner B, Stürmer T. An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987). The New England Journal of Medicine. January 1991. doi:10.1056/NEJM199101173240304 · PMID 1984193
10. Journal / agency Cochran AJ, Lawson DH, Linton AL. Renal papillary necrosis following phenacetin excess. Scottish Medical Journal. July 1967. doi:10.1177/003693306701200702 · PMID 6036245
11. Journal / agency Tan GH, Rabbino MD, Hopper J. Is Phenacetin a Nephrotoxin?: A Report on Twenty-three Users of the Drug. California Medicine. August 1964. PMID 14180501 · PMC1515485
12. Journal / agency Brix AE. Renal papillary necrosis. Toxicologic Pathology. 2002. doi:10.1080/01926230290166760 · PMID 12512867
13. Journal / agency Kankuri E, Solatunturi E, Vapaatalo H. Effects of phenacetin and its metabolite p-phenetidine on COX-1 and COX-2 activities and expression in vitro. Thrombosis Research. June 2003. doi:10.1016/S0049-3848(03)00416-X · PMID 14592552
14. Journal / agency Tennant F. Howard Hughes & Pseudoaddiction. Practical Pain Management. July–August 2007
15. Other Taggart star's Askit questions over mother's death. January 9, 2018
16. Other Sneader W. Drug Discovery: A History. 2005
17. Journal / agency Creese MR. Martha Annie Whiteley (1866-1956): Chemist and Editor. Bulletin for the History of Chemistry. 1997. doi:10.70359/bhc1997n20p042
18. Other Duty of Care. 31 May 1974
19. Other Pirsig, Robert M. Zen and the Art of Motorcycle Maintenance. 1985

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.