Topic
Acetaminophen
About: Acetaminophen is a research topic. Over the lifetime, 4360 publications have been published within this topic receiving 151150 citations.
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TL;DR: In conclusion, acetaminophen hepatotoxicity far exceeds other causes of acute liver failure in the United States, and education of patients, physicians, and pharmacies to limit high‐risk use settings is recommended.
1,705 citations
Journal Article•
TL;DR: A fundamental role of glutathione in the body may be to protect tissues against electrophilic attack by drug metabolites and other alkylating agents.
Abstract: The possibility that glutathione may protect against acetaminophen-induced hepatic necrosis was examined. Pretreatment of mice with diethyl maleate, which depletes hepatic glutathione, potentiated acetaminophen-induced hepatic necrosis, whereas pretreatment with cysteine, a glutathione precursor, prevented hepatic damage. Administration of acetaminophen caused a dose-dependent depletion of hepatic glutathione. Glutathione depletion by acetaminophen was enhanced by treatments that potentiate the hepatic necrosis and covalent binding produced by the toxic metabolite of acetaminophen. Conversely, glutathione depletion was inhibited by treatments that protect against these toxic effects. Moreover, covalent binding of this metabolite to hepatic macromolecules did not occur until the availability of glutathione was exhausted through conjugation with the metabolite. Similarly, alteration of glutathione availability by pretreatment with diethyl maleate or cysteine, respectively, increased or decreased covalent binding of the toxic metabolite. We propose that. a fundamental role of glutathione in the body may be to protect tissues against electrophilic attack by drug metabolites and other alkylating agents.
1,666 citations
Journal Article•
TL;DR: It is proposed thatacetaminophen-induced hepatic necrosis is mediated by a toxic metabolite of acetaminophen, which inhibits synthesis of cytochrome P-450 and thereby prevented the hepatic damage.
Abstract: A number of recent reports indicate that massive overdoses of acetaminophen can produce a fulminant hepatic necrosis in man. Acetaminophen-induced hepatic necrosis thereforne was examised in experimental animals. Centrilobular hepatic necrosis similar to that seen in man was shown to be dose dependent in mice and rats. To determine whether acetaminophen-induced hepatotoxicity was mediated throug an active metabolite, acetaminophen concentrations in rat and mouse tissues were compared with the severity of liver damage after alteration of the rate of metabolism of acetaminophen. Phenobarbital pretreatment stimulated the disappearance of acetaminophen from tissues but markedly potentiated the hepatic necrosis. In contrast, piperonyl butoxide pretreatment inhibited the metabolism and disappearance of acetaminophen from tissues yet dramatically protected against hepatic necrosis. Additional studies demonstrated that pretreatment with 3-methylcholanthrene also potentiated acetaminophen-induced hepatic necrosis whereas cobaltous chloride, which inhibits synthesis of cytochrome P-450, prevented the hepatic damage. We propose that acetaminophen-induced hepatic necrosis is mediated by a toxic metabolite of acetaminophen.
1,431 citations
TL;DR: The relationship between the metabolic disposition of acetaminophen and the susceptibility of hamsters, mice and rats toacetaminophen-induced liver necrosis has been examined.
Abstract: The relationship between the metabolic disposition of acetaminophen and the susceptibility of hamsters, mice and rats to acetaminophen-induced liver necrosis has been examined. The fraction of low dos
1,383 citations
TL;DR: The concomitant administration of ibuprofen but not rofecoxib, acetaminophen, or diclofenac antagonizes the irreversible platelet inhibition induced by aspirin, which may limit the cardioprotective effects of aspirin.
Abstract: Background Patients with arthritis and vascular disease may receive both low-dose aspirin and other nonsteroidal antiinflammatory drugs. We therefore investigated potential interactions between aspirin and commonly prescribed arthritis therapies. Methods We administered the following combinations of drugs for six days: aspirin (81 mg every morning) two hours before ibuprofen (400 mg every morning) and the same medications in the reverse order; aspirin two hours before acetaminophen (1000 mg every morning) and the same medications in the reverse order; aspirin two hours before the cyclooxygenase-2 inhibitor rofecoxib (25 mg every morning) and the same medications in the reverse order; enteric-coated aspirin two hours before ibuprofen (400 mg three times a day); and enteric-coated aspirin two hours before delayed-release diclofenac (75 mg twice daily). Results Serum thromboxane B2 levels (an index of cyclooxygenase-1 activity in platelets) and platelet aggregation were maximally inhibited 24 hours after the...
1,281 citations