Phenacetin

Phenacetin
Systematic (IUPAC) name
N-(4-ethoxyphenyl)ethanamide
Identifiers
CAS number	62-44-2
ATC code	N02BE03
PubChem	4754
DrugBank	EXPT03306
Chemical data
Formula	C10H13NO2
Mol. mass	179.216 g/mol
Physical data
Melt. point	134-136 °C (-79 °F) (decomposes)
Pharmacokinetic data
Bioavailability	?
Metabolism	?
Half life	?
Excretion	?
Therapeutic considerations
Pregnancy cat.	?
Legal status
Routes	?

WikiDoc Resources for Phenacetin
Articles
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Evidence Based Medicine
Cochrane Collaboration on Phenacetin Bandolier on Phenacetin TRIP on Phenacetin
Clinical Trials
Ongoing Trials on Phenacetin at Clinical Trials.gov Trial results on Phenacetin Clinical Trials on Phenacetin at Google
Guidelines / Policies / Govt
US National Guidelines Clearinghouse on Phenacetin NICE Guidance on Phenacetin NHS PRODIGY Guidance FDA on Phenacetin CDC on Phenacetin
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Phenacetin in the news Be alerted to news on Phenacetin News trends on Phenacetin
Commentary
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Definitions
Definitions of Phenacetin
Patient Resources / Community
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Healthcare Provider Resources
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Continuing Medical Education (CME)
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International
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Experimental / Informatics
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Overview

Phenacetin, introduced in 1887, was used principally as an analgesic, and was the first NSAID and fever reducer to go on the market. Typical doses of 300mg to 500mg a day result in an analgesic effect. Its analgesic effects are due to its actions on the sensory tracts of the spinal cord. In addition, phenacetin has a depressant action of the heart, where it acts as a negative inotrope. It is an antipyretic, acting on the brain to decrease the temperature set point. It is also used to treat rheumatoid arthritis (subacute type), intercostal neuralgia, and some forms of ataxia.

Phenacetin, and products containing phenacetin have been shown in an animal model to be carcinogenic. In humans, many case reports have implicated products containing phenacetin in urothelial neoplasms, especially transitional cell carcinoma of the renal pelvis. 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 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 cascade.

Synthesis (Northern Kentucky University)

ETHER SYNTHESIS: CONVERSION OF ACETAMINOPHEN INTO PHENACETIN Required Pre-lab readings: Ege, 5th Ed., sect 13.4, pp 498-501; Morhig, Chapter 19. Techniques you must be prepared to use: reflux; extraction; rotary evaporation; recrystallization. In the reaction today you will be converting 4-acetamidophenol (Acetaminophen) into ethyl 4- acetamidophenyl ether (Phenacetin). Both compounds are ingredients in many over-the-counter analgesics. This reaction is an example of the Williamson ether synthesis. For most ether syntheses strong bases such as amide ion are necessary to generate the nucleophile.

In a 50 mL round-bottomed flask place 12 mmol of liquid ethyl iodide, 15 mL of methyl ethyl ketone (2-butanone; MEK) as solvent, Acetaminophen (1.5 g; ?? mmol.), and powered anhydrous K2CO3 (2.5 g; ?? mmol). Mechanically stir this mixture and reflux for 1 hour. After the reflux is complete cool the flask in an ice/water bath and gravity filter the contents into a separatory funnel. Use small amounts of ether to insure that you have quantitatively transferred all the organic material from the flask to the funnel. Wash the organic phase with 5% aq. NaOH (what is the purpose of this step?), then dry it (Na2SO4) and decant into a flask and remove the solvents by rotary evaporation. The product is purified by recrystallization from water. Allow the purified product to air dry.

Phenacetin was widely used until the third quarter of the twentieth century, but was then largely replaced by non-carcinogenic drugs. Some branded 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. 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.

Connection between chronic phenacetin use and renal papillary necrosis

Chronic use of phenacetin is known to lead to renal papillary necrosis. This is a condition which results in destruction of some or all of the renal papillae in the kidneys.

Use as a filler for illegal cocaine

Phenacetin is now being widely used as a cutting agent to adulterate illegally supplied cocaine due to the similar physical features of the two drugs.

Notes and references

• Carcinogen report from the NIH
• Safety (MSDS) data for phenacetin

Cost Effectiveness of Phenacetin

| group5 = Clinical Trials Involving Phenacetin | list5 = Ongoing Trials on Phenacetin at Clinical Trials.gov • Trial results on Phenacetin • Clinical Trials on Phenacetin at Google

| group6 = Guidelines / Policies / Government Resources (FDA/CDC) Regarding Phenacetin | list6 = US National Guidelines Clearinghouse on Phenacetin • NICE Guidance on Phenacetin • NHS PRODIGY Guidance • FDA on Phenacetin • CDC on Phenacetin

| group7 = Textbook Information on Phenacetin | list7 = Books and Textbook Information on Phenacetin

| group8 = Pharmacology Resources on Phenacetin | list8 = AND (Dose)}} Dosing of Phenacetin • AND (drug interactions)}} Drug interactions with Phenacetin • AND (side effects)}} Side effects of Phenacetin • AND (Allergy)}} Allergic reactions to Phenacetin • AND (overdose)}} Overdose information on Phenacetin • AND (carcinogenicity)}} Carcinogenicity information on Phenacetin • AND (pregnancy)}} Phenacetin in pregnancy • AND (pharmacokinetics)}} Pharmacokinetics of Phenacetin •

| group9 = Genetics, Pharmacogenomics, and Proteinomics of Phenacetin | list9 = AND (pharmacogenomics)}} Genetics of Phenacetin • AND (pharmacogenomics)}} Pharmacogenomics of Phenacetin • AND (proteomics)}} Proteomics of Phenacetin

| group10 = Newstories on Phenacetin | list10 = Phenacetin in the news • Be alerted to news on Phenacetin • News trends on Phenacetin</small>

| group11 = Commentary on Phenacetin | list11 = Blogs on Phenacetin

| group12 = Patient Resources on Phenacetin | list12 = Patient resources on Phenacetin • Discussion groups on Phenacetin • Patient Handouts on Phenacetin • Directions to Hospitals Treating Phenacetin • Risk calculators and risk factors for Phenacetin

| group13 = Healthcare Provider Resources on Phenacetin | list13 = Symptoms of Phenacetin • Causes & Risk Factors for Phenacetin • Diagnostic studies for Phenacetin • Treatment of Phenacetin

| group14 = Continuing Medical Education (CME) Programs on Phenacetin | list14 = CME Programs on Phenacetin

| group15 = International Resources on Phenacetin | list15 = Phenacetin en Espanol • Phenacetin en Francais

| group16 = Business Resources on Phenacetin | list16 = Phenacetin in the Marketplace • Patents on Phenacetin

| group17 = Informatics Resources on Phenacetin | list17 = List of terms related to Phenacetin

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