Question

In: Biology

describe the metabolic process that results in the beneficial effects of small doses of Acetaminophen (eg....

describe the metabolic process that results in the beneficial effects of small doses of Acetaminophen (eg. curing your headache), AND the result in the hepatoxic effects of very large doses of Acetamenophen.

Solutions

Expert Solution

  • Paracetamol (acetaminophen) is the demethylated active metabolite of phenacetin.
  • It shows central analgesic action but has weak peripheral anti-inflammatory action.
  • It is well absorbed orally, only 1/4th part bound to plasma proteins and is uniformly distributed in the body.
  • Metabolism occurs mainly by conjugation with glucuronic acid and sulfate, conjugates are rapidly excreted in urine.
  • Plasma half life is 2 - 3 hrs. and effect after an oral dose last for 3 - 5 hrs.
  • N-acetyl-p-benzoquinoneimine (NAPQI) is a highly reactive arylating minor metabolite of paracetamol which is detoxified by conjugation with glutathione.
  • When a very large dose of paracetamol is taken, glucuronidation capacity is saturated which results in more formation of minor metabolites, resulting in hepatic glutathione depletion and the metabolite bind covalently with proteins in liver cells (and renal tubules) causing necrosis.
  • Thus it's toxicity shows a threshold effect, appearing only when glutathione is depleted to a critical point.
  • In chronic alcoholics even 5 - 6 g taken in one day can result in hepatotoxicity as alcoholism induces CYP2E1 that metabolizes paracetamol to NAPQI.

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