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Acetaminophen toxicity: A leading cause for liver transplantation in the US and a cause for almost 1/2 cases of acute liver failure.
ncbi.nlm.nih.gov/pmc/articles/P…
Acetaminophen toxicity: A leading cause for liver transplantation in the US and a cause for almost 1/2 cases of acute liver failure.
ncbi.nlm.nih.gov/pmc/articles/P…
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Although toxic dose are usually>150 mg/kg, this could happen in pts taking safe doses- possibly due to aberrancies at the cellular levels.
The FDA recomdtn- reduce max daily dose to 3250 mg, encourage manufacturers to reduce the amount to 325 mg/dose
archivesofpathology.org/doi/pdf/10.585…
Although toxic dose are usually>150 mg/kg, this could happen in pts taking safe doses- possibly due to aberrancies at the cellular levels.
The FDA recomdtn- reduce max daily dose to 3250 mg, encourage manufacturers to reduce the amount to 325 mg/dose
archivesofpathology.org/doi/pdf/10.585…
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90% acetaminophen is conjugated by UDP-glucuronosyl transferases and sulfotransferase, with conversion to glucouronidated and sulfated metabolites that are eliminated in the urine.
Small, measurable amount excreted in urine without any metabolism.
ncbi.nlm.nih.gov/pmc/articles/P…
90% acetaminophen is conjugated by UDP-glucuronosyl transferases and sulfotransferase, with conversion to glucouronidated and sulfated metabolites that are eliminated in the urine.
Small, measurable amount excreted in urine without any metabolism.
ncbi.nlm.nih.gov/pmc/articles/P…
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10% metabolized by hepatic cytochrome CYP 2E1(lesser extent with(CYP 1A2 and 3A4)to phase I oxidation, resulting in highly toxic metabolite, N-acetyl-para-benzo-quinone imine(NAPQI) resulting in glutathione depletion, oxidative stress and mitochondrial dysfunction& reduced ATP
10% metabolized by hepatic cytochrome CYP 2E1(lesser extent with(CYP 1A2 and 3A4)to phase I oxidation, resulting in highly toxic metabolite, N-acetyl-para-benzo-quinone imine(NAPQI) resulting in glutathione depletion, oxidative stress and mitochondrial dysfunction& reduced ATP
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Determinants of hepatotoxicity is the
1) Drug’s ingested dose,
2) Length of time from acetaminophen ingestion to N-acetylcysteine (NAC) therapy (“time to NAC”)
Determinants of hepatotoxicity is the
1) Drug’s ingested dose,
2) Length of time from acetaminophen ingestion to N-acetylcysteine (NAC) therapy (“time to NAC”)
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Guess what? Acute ethanol ingestion may be protective against acetaminophen hepatotoxicity,mechanism being ethanol’s competitive utilization of the CYP 2E1 substrate, which diminishes the toxic NAPQI byproduct.
The same is not true for chronic ethanol ingestion- detrimental
Guess what? Acute ethanol ingestion may be protective against acetaminophen hepatotoxicity,mechanism being ethanol’s competitive utilization of the CYP 2E1 substrate, which diminishes the toxic NAPQI byproduct.
The same is not true for chronic ethanol ingestion- detrimental
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Use of the Rumack-Matthew nomogram in management of Acetaminophen overdose is acceptable when the acuity of ingestion is known to be within 24 hours. Probable toxicity line is the drug concentration of 200 µg/mL at 4 hours and 25 µg/mL at 16 hours after acute ingestion
Use of the Rumack-Matthew nomogram in management of Acetaminophen overdose is acceptable when the acuity of ingestion is known to be within 24 hours. Probable toxicity line is the drug concentration of 200 µg/mL at 4 hours and 25 µg/mL at 16 hours after acute ingestion
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However for cases with unintentional repeated overdose over days, Rumack-Matthew nomogram is not applicable and tx with NAC is appropriate if acetaminophen concentration is >20 µg/mL
However for cases with unintentional repeated overdose over days, Rumack-Matthew nomogram is not applicable and tx with NAC is appropriate if acetaminophen concentration is >20 µg/mL
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N-acetyl cysteine (NAC) is an antidote, replenishing the hepatic glutathione stores by providing cysteine, the substrate which detoxifies reactive metabolites of acetaminophen.
Liver transplantation can be a lifesaving procedure when there is irreversible liver injury.
N-acetyl cysteine (NAC) is an antidote, replenishing the hepatic glutathione stores by providing cysteine, the substrate which detoxifies reactive metabolites of acetaminophen.
Liver transplantation can be a lifesaving procedure when there is irreversible liver injury.
