The Malignant Couple

8/14/2019 The Malignant Couple

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THE MALIGNANT COUPLE:THE MALIGNANT COUPLE:

PHENACETINPHENACETIN

NEPHROPATHY-NEPHROPATHY-

UROTHELIAL TUMORSUROTHELIAL TUMORS

Scientific coordinatorsScientific coordinators::

MITITIUC IRINA,PhDMITITIUC IRINA,PhDHOGAS SIMONA,MDHOGAS SIMONA,MD

AuthorAuthor: Pricop Mariana: Pricop Mariana

CoauthorsCoauthors: Pricop Daniela: Pricop Daniela

Biru DianaBiru Diana

-Madalina-Madalina


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Phenacetin, introduced in1887, was used principallyas an analgesic, and was

one of the first syntheticfever reducers to go on themarket.

It is also knownhistorically to be the firstanalgesic without anti-inflammatory properties.


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PHENACETINPHENACETIN Phenacetin was widely used until the third quarter of

the twentieth century, but was then largely replacedby non-carcinogenic drugs.

Some branded phenacetin-based preparationscontinued to be sold, but with the phenacetinreplaced by safer alternatives.

A popular brand of phenacetin was Roche's Saridon,

which was reformulated in 1983 to containpropyphenazone, paracetamol and caffeine.

Paracetamol is a metabolite of phenacetin withsimilar analgesic and antipyretic effects, but the new

formulation has not been found to have phenacetin'scarcino enicit .


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UROTHELIAL TUMORSUROTHELIAL TUMORS Analgesic nephropathy occurs in about 4 out of

100,000 people, mostly women over 30. The rate hasdecreased significantly since phenacetin is no longerwidely available in OTC preparations.

Risk factors include:* Use of OTC analgesics containing more than one

active ingredient

* Chronic headache

* Chronic backache or musculoskeletal pain* Emotional or behavioral changes

* History of dependent behaviors including smoking,alcoholism, and excessive use of tranquilizers

* Pain with menstrual periods


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The cardinal features of the AnalgesicSyndrome:





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PHENACETIN NEPHROPATHY-PHENACETIN NEPHROPATHY-


In general, phenacetin is metabolized by

acetaminophen after dehydration in the liver andthereafter it undergoes either sulfate acid orglutamic conjugation in the kidneys;

The remaining free phenacetin is then excreted into

the urine. Excessive acetaminophen results in thedepletion of glutathione and the accumulation ofacetaminophen oxides and an activated reactionmay thus occur.


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The reflux of acetaminophen into the kidneys and itsconcentration in the renal medulla contribute to theinhibition of prostaglandin synthesis, thus leading torenal medullary ischemia and renal papillarynecrosis.

The resulting tubular obstruction promotes anenlargement of the renal cortex and the formation of

a histological background of interstitinal nephritis.




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Regarding the development of urotherial tumorassociated with phenacetin abuse, N-hydroxylationproducts, the intermediate metabolite of phenacetinsuch as N-hydroxy-p-phenetidine and 2-hydroxyphetidine, seemed to be potentialcarcinogens.

The process of carcinogenesis in urotherium byexposure of the potential carcinogens in phenacetinmetabolic products are considered to take at least10 years under excessive .

Therefore, almost all reported cases of urotherial

tumor associated with phenacetin abuse had ahistory of excessive phenacetin use for more than 10




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PHENACETIN ABUSEPHENACETIN ABUSE

Double target onDouble target on

reno-urinary systemreno-urinary system


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Specific kidney injuriesSpecific kidney injuries renal papillary necrosisrenal papillary necrosis

-- chronic interstitial nephritischronic interstitial nephritis (the neprhopathy is a result from decreased blood flow to

the kidneyrapid consumption of antioxidants subsequent oxidative

damage )

This damage may lead to progressive chronic renalThis damage may lead to progressive chronic renalfailure, abnormal urinalysisfailure, abnormal urinalysisresults high blood pressure and anemia. Aresults high blood pressure and anemia. A

proportion of individuals with phenacetinproportion of individuals with phenacetinnephropathy may develop end-stage kidney disease.nephropathy may develop end-stage kidney disease.

Also the phenacetin abuse is directly related to theAlso the phenacetin abuse is directly related to theurothelial tumors.urothelial tumors.

Phenacetin abuse-daily consume for at least 5ears minimum total dose=2-7k




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Drug-induced acute interstitialnephritis


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Papillary necrosis


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B.I.,male,65years old,PascaniB.I.,male,65years old,Pascani

1978-amputation left leg1978-amputation left leg

Pain in the amputated leg -> chronical abuse ofPain in the amputated leg -> chronical abuse ofphenacetinphenacetin --3-603-60 tablets/daytablets/day forfor 19 years19 years ((3030 kgkg))

MicroscopicMicroscopic hematury-high suspicion of vesicalhematury-high suspicion of vesicaltumorstumors

1997-phenacetin nephropathy1997-phenacetin nephropathy

--




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S.F.,female,75years old,IasiS.F.,female,75years old,Iasi

Abuse of phenacetin-headaches->Abuse of phenacetin-headaches->3-6 tablets/day for3-6 tablets/day for

2020 years(4-8kg)years(4-8kg)

2000-CRF stage 5,peritoneal dialysis2000-CRF stage 5,peritoneal dialysis

2001-after 5 episode of peritonitis->hemodialysis2001-after 5 episode of peritonitis->hemodialysis

2007-2007-multiplemultiple vesical tumorsvesical tumors ->endoscopic resection->endoscopic resection

2009-fever with unknown etiology-suspicion of2009-fever with unknown etiology-suspicion ofmetastasismetastasis




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Conclusionsin memoriam phenacetinnephropathy

The asociation between phenacetin and urothelialtumors is a reality .

Every patient with phenacetin nephropathy needs

to be closely observed for urothelial tumors

The cases of phenacetin nephropathy are amongthe last ones because products containingphenacetin the drug was withdrawn from the market

in Western countries in the 1980s and also in Japanin 2001.

The evolution is slowly progression to chronic renalfailure

Stoping the phenacetin ingestion can stabilize the


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Stop to the consumption of over thecounter pain medications!

It could affect permanently andirreversible your reno-urinary system!


21/21THANK YOU!THANK YOU!

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The Malignant Couple