Phenacetin Research Paper

After taken orally, paracetamol is well absorbed from the stomach and small intestine. It reaches a peak plasma concentration in one hour but this may be 30 minutes if taken in liquid or rapidly absorbed form. It is mainly inactivated by the liver by conjugation leading to two metabolites; glucuronide or sulfate. It is then renally excreted through urine. When taken in overdose the liver conjugation becomes inundated, causing paracetamol to be metabolised by an alternative pathway. This results in a toxic metabolite, N-acetyl-p-benzoquinone imine (NAPQI), which is itself inactivated by glutathione, rapidly preventing any harm. When glutathione stores are depleted to less than approximately 30%, NAPQI reacts with nucleophilic aspects of the …show more content…
Phenacetin can be metabolized to reactive metabolites by a variety of mechanisms. First Phenacetin can be N-hydroxylated, and the resulting N-hydroxyphenacetin can be sulfated or glucuronidated. Whereas phenacetin N-O sulfate immediately rearranges to form a reactive metabolite which may covalently bind to protein, phenacetin N-O glucuronide slowly rearranges to form reactive metabolites. Incubation of the purified phenacetin N-O glucuronide under a variety of conditions suggests that N-acetyl-p-benzoquinone imine is a reactive metabolite. This metabolite covalently binds to protein, reacts with glutathione to form an acetaminophen-glutathione conjugate, is reduced by ascorbate to acetaminophen or is partially hydrolyzed to acetamide. Second Phenacetin can be O-deethylated to acetaminophen, and acetaminophen can be converted directly to a reactive metabolite which may be also N-acetyl-p-benzoquinone imine. Third Phenacetin can be sequentially N-hydroxylated and O-deethylated to N-hydroxyacetaminophen which spontaneously dehydrates to N-acetyl-p-benzoquinone imine. Fourth Phenacetin can be 3, 4-epoxidated to form an alkylating and an arylating

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