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Results for “Phenacetin”

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At least 19 recordsLinked to original sources
PubMed1986

The 3-methylcholanthrene-mimetic effect of 4,4'-dichlorobiphenyl-treatment on phenacetin-induced hepatic glutathione depletion and liver microsomal phenacetin O-deethylation in rats.

Both 4,4'-dichlorobiphenyl (4,4'-DCB) and 3-methylcholanthrene (3-MC) caused a substantial increase of phenacetin-induced hepatic glutathione (GSH) depletion, whereas phenobarbital (PB) had no effect, suggesting that 4,4'-DCB possesses cytochrome P-448 inducing activity. The O-deethylation of phenacetin by liver microsomes from control and PB- and 4,4'-DCB-treated rats showed biphasic Michaelis-Menten kinetics, in contrast to the monophasic course after pretreatment with 3-MC. Hepatic phenacetin levels indicated that in vivo interaction with only a high affinity site is involved in the O-deethylation of phenacetin. 4,4'-DCB and 3-MC caused marked increases in intrinsic clearance and extraction ratio of phenacetin, whereas control values were obtained after PB-treatment. Because of an absence of a spectral change at low phenacetin concentrations, it could not be demonstrated whether the observed differences in metabolism should be ascribed to a change in binding of phenacetin to cytochrome P-450. The results of this study indicate that after pretreatment with various enzyme inducers the phenacetin-induced hepatic GSH depletion strongly correlates with microsomal phenacetin O-deethylation. Further, these findings suggest a discrepancy between 4,4'-DCB and PB in cytochrome P-450 inducing activity, as 4,4'-DCB mimics 3-MC in the induction of phenacetin O-deethylase. The difference between 4,4'-DCB and PB is discussed in relation to the multiplicity and induction of cytochrome P-450 isoenzymes.

Acetaminophen↗
PubMed1976

Phenacetin and the liver. The influence of phenacetin in acute and chronic doses on membrane-bound mitochondrial enzymes in the rat.

Following the administration of phenacetin in single and in multiple high doses, enzymes bound to the inner mitochondrial membrane of the liver were determined. Acute doses of phenacetin (75% of oral LD50) failed to produce any effect. The chronic administration of phenacetin provoked a small but statistically significant decrease in the TD-trnashydrogenase activity. This observation indicates that liver damage may occur in patients with phenacetin abuse.

Animals↗
PubMed1985

Suppression of phenacetin-induced methemoglobinemia by diethyldithiocarbamate and carbon disulfide and its relation to phenacetin metabolism in mice.

Oral pretreatment with diethyldithiocarbamate (DTC) and carbon disulfide (CS2) prevented mice from methemoglobinemia induced by phenacetin. This treatment resulted in marked elevation of plasma p-phenetidine concentrations, prolongation of phenacetin levels, and lowering of N-acetyl-p-aminophenol and p-aminophenol levels. Both DTC and CS2 also suppressed p-phenetidine-induced methemoglobinemia with a delay in plasma p-phenetidine disappearance. In vitro, methemoglobin formation by p-phenetidine was decreased in liver microsomes isolated from DTC- or CS2-treated mice. The liver microsomal phenacetin and p-phenetidine O-deethylation activities and p-phenetidine N-hydroxylation activity decreased 1 h after administration of DTC or CS2, whereas deacetylation of phenacetin and N-acetyl-p-aminophenol by microsomes and acetylation of p-phenetidine by a soluble fraction from a liver homogenate were scarcely affected. The suppression of methemoglobinemia by DTC and CS2 may result from an inhibition of metabolic conversion of p-phenetidine to methemoglobin-forming substances such as N-hydroxy-p-phenetidine which is of most importance, p-aminophenol and 2-hydroxy-p-phenetidine by the microsomal cytochrome P-450-containing monooxygenase system in the liver.

Animals↗
PubMed1982

[Phenacetin abuse V: number of phenacetin abusers in Basel autopsy material 1978-1980. Results of a prospective study].

Between 1978-1890 the incidence of analgesic (phenacetin) abuse in autopsies of adult inhabitants of Basle was 3.87%. Only 2.3% of these were known abusers. The incidence of abuse varied considerably in different age groups, with a maximum of 16% in women in the age group 50-59 years. The sex distribution was male/female 1:1.93. It can therefore be assumed that 1500-3000 inhabitants of Basle actively abuse or abused phenacetin containing analgesics. Extension of the prescription requirement to all salicylate and paracetamol containing analgesics is accordingly recommended.

Adult↗
PubMed1986

Detection of N-acetyl-p-benzoquinone imine produced during the hydrolysis of the model phenacetin metabolite N-(pivaloyloxy)phenacetin.

N-Acetyl-p-benzoquinone imine (4) can be detected by UV spectrophotometry and HPLC during the hydrolysis of N-(pivaloyloxy)phenacetin (3c). This material serves as a model for the sulfate and glucuronide conjugates (3a and 3b) of N-hydroxyphenacetin (2). Direct detection of 4 during the hydrolysis of 3a and 3b is precluded by the extreme instability of 3a and the very slow hydrolysis of 3b. Our data show that greater than 90% of the hydrolysis of 3c proceeds through the intermediate 4 at all pH values in the range 1.0-8.0. All our results indicate that 4 is produced through a nitrenium ion mechanism. Many of the differences in the hydrolysis reactions of 3b and 3c can be explained in terms of a mechanism involving tight and solvent-separated nitrenium ion pairs. Other differences may be due to a homolysis pathway, which is more important for the material with the poorer leaving group (3b).

Benzoquinones↗
PubMed1981

Analgesic nephropathy and phenacetin-induced transitional cell carcinoma - analysis of 300 patients with long-term consumption of phenacetin-containing drugs.

In 300 urological patients with long-term intake of phenacetin-containing compounds, renal (papillary necrosis, chronic interstitial nephritis) and extrarenal manifestations appeared after an average latency period of 20 years. Course and prognosis primarily depend on the successful cessation of analgesics and the elimination of the accompanying infection. In the last decade, an increase of transitional cell carcinoma induced by analgesics has been observed. 31 of our patients presented a tumor of the urothelium (i.e. 10.3%) 26 patients presented isolated carcinoma of the bladder, 2 persons were diagnosed as having cancer of the bladder and the renal pelvis, and 1 patient had cancer of the bladder and the ureter. Only 2 persons suffered from isolated carcinoma of the renal pelvis. A further increase of these specific cases if expected.

Albuminuria↗
PubMed1980

[Phenacetin abuse IV. Are cytological urine studies successful and usable in the prevention of tumors in phenacetin abusers?].

971 samples of urine and washes of the urinary bladder in 643 patients were investigated cytologically. Urothelial carcinoma was present in 27 patients. In 11 cases the carcinoma was diagnosed by urinary cytology; 7 of the carcinomas were localized in the urinary bladder, 3 in the renal pelvis and 1 in the ureter. By contrast, all 19 tumors diagnosed in washes were localized in the urinary bladder. Diagnostic sensitivity was 100% in urine and about 75% in bladder washes. In 5 other patients cytologic diagnosis of carcinoma could not be confirmed by histology. In 4 of these, urothelial papillomas were present and in 1 patient a carcinoma of the bladder had been resected previously. Thus, the diagnostic accuracy of urinary cytology is good if essential methodological prerequisites are fulfilled. Therefore, urinary cytology appears to be an appropriate method for screening programmes in high risk patients such as phenacetin abusers. The estimated costs of a screening programme in Basel are 50 000-150 000 Swiss francs. However, a preliminary study to verify the value of such a screening programme is suggested.

Humans↗