Phenacetin
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Phenacetin
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| Systematic (IUPAC) name | |
| N-(4-Ethoxyphenyl)acetamide | |
| Identifiers | |
| CAS number | |
| ATC code | N02 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C10H13NO2 |
| Mol. mass | 179.216 g/mol |
| Physical data | |
| Density | 1.24 g/cm³ |
| Melt. point | 134-136 °C (-79 °F) (decomposes) |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
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| Legal status | |
| Routes | ? |
Phenacetin, introduced in 1887, was used principally as an analgesic, and was one of the first synthetic fever reducers to go on the market. It is also known historically to be the first analgesic without anti-inflammatory properties. Typical doses of 300mg to 500mg a day result in an analgesic effect. Recently, its use as an analgesic has declined due to its association with several adverse side effects, some of which are described below. 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.
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[edit] Preparation
The first synthesis was reported in 1878 by Harmon Northrop Morse.[1]
Phenacetin may be synthesized as an example of the Williamson ether synthesis: ethyl iodide, Paracetamol, and anhydrous potassium carbonate are refluxed in butanone to give the crude product, which is recrystallized from water.[citation needed]
[edit] Uses
Phenacetin was widely used until the third quarter of the twentieth century, often in the form of an "APC" (aspirin, phenacetin, caffeine) tablet, 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. 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.
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. [2]
[edit] Safety
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.[3] 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.
Chronic use of phenacetin is known to lead to renal papillary necrosis.[4][5][6] This is a condition which results in destruction of some or all of the renal papillae in the kidneys.
[edit] Notes and references
- ^ H. N. Morse (1878). "Ueber eine neue Darstellungsmethode der Acetylamidophenole". Berichte der deutschen chemischen Gesellschaft 11 (1): 232-233. doi:.
- ^ "Cancer chemical in street cocaine", BBC News, 23 November 2006.
- ^ Dubach U, Rosner B, Stürmer T (1991). "An epidemiologic study of abuse of analgesic drugs. Effects of phenacetin and salicylate on mortality and cardiovascular morbidity (1968 to 1987)". N Engl J Med 324 (3): 155-60. PMID 1984193.
- ^ Cochran A, Lawson D, Linton A (1967). "Renal papillary necrosis following phenacetin excess.". Scott Med J 12 (7): 246-50. PMID 6036245.
- ^ Tan G, Rabbino M, Hopper J (1964). "Is Phenacetin a Nephrotoxin? A Report on Twenty-three Users of the Drug.". Calif Med 101: 73-7. PMID 14180501.
- ^ Brix A. "Renal papillary necrosis.". Toxicol Pathol 30 (6): 672-4. PMID 12512867.
