Acute hepatic and renal toxicity from low doses of acetaminophen in the absence of alcohol abuse or malnutrition: Evidence for increased susceptibility to drug toxicity due to cardiopulmonary and renal insufficiency
✍ Scribed by Herbert L. Bonkovsky; Robert E. Kane; Dean P. Jones; Raymond E. Galinsky; Barbara Banner
- Publisher
- John Wiley and Sons
- Year
- 1994
- Tongue
- English
- Weight
- 984 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
A 67-yr-old man with chronic cardiopulmonary disease exhibited severe hepatic and moderately severe renal injury after short-term ingestion of therapeutic doses of acetaminophen (1 to 3 @day for 3 days). Drug metabolism and other studies, performed 5 mo after recovery from the acute insult, indicated that the patient had decreased rates of hepatic metabolism of acetaminophen to its primary, nontoxic metabolites and decreased kidney function that was compromised further by acetaminophen ingestion. He also had abnormally low concentrations of hepatic and plasma reduced glutathione. Alcohol abuse and malnutrition could not be implicated in the pathogenesis of injury; rather it appeared that advancing age with chronic renal, cardiac and pulmonary insufficiency contributed to acetaminophen toxicity in this patient. (HEPATOLOGY 1994; 19: 1141-1148.) Acetaminophen is one of the most widely available and used antipyretic/analgesic drugs in the world because of its efficacy and relative safety. However, a large overdose of acetaminophen, often taken with suicidal intent (11, can lead to acute fulminant liver failure and death (2,3). Acetaminophen is eliminated by way of four main pathways. The two major pathways are capacity-limited processes for the formation of acetaminophen sulfate and acetaminophen glucuronide. The two minor pathways are apparent first-order processes. These include the formation of a cytochrome P-450-mediated reactive metabolite and renal excretion of unchanged