Acetaminophen causing

Acetaminophen causes few adverse reactions when used as directed on the label or recommended by the primary health care provider. Adverse reactions associated with the use of acetaminophen usually occur with chronic use or when the recommended dosage is exceeded. Adverse reactions to acetaminophen include skin eruptions, urticaria (hives), hemolytic anemia, pancytopenia (a reduction in all cellular components of the blood), hypoglycemia, jaundice (yellow discoloration of the skin), hepatotoxicily (damage to the liver), and hepatic failure (seen in chronic alcoholics taking the drug). 

The regional expression of xenobiotic metabolizing enzymes determines the zone-specific localization of toxicant damage. Many hepatotoxicants elicit perivenous damage because CYPs are preferentially localized in centrilobular hepatocytes. For example, acetaminophen causes hepatotoxicity because the reactive... 

Acetaminophen reduces pain and fever, but it is not anti-inflammatory, so it is ineffective in treating conditions like arthritis, which have a significant inflammatory component. In large doses, acetaminophen causes liver damage, so dosage recommendations must be carefully followed. 

Acetaminophen causes cytotoxicity in several cell types however, the most widely studied cytotoxicity of acetaminophen is in primary hepatocytes or hepatocyte cell lines. 

According to the Handbook of Poisoning and Toxicology published by the American Pharmaceutical Association, the dose of acetaminophen causing hepatotoxicity is 150 mg/kg. In an adult weighing 70 kg, this would represent the ingestion of about 10.5 g or 21 acetaminophen caplets, each containing 500 mg. 

Dart RC, Bailey E (2007) Does therapeutic use of acetaminophen cause acute liver failure Pharmacotherapy 27 1219-1230... 

McLean and coworkers have reported that inhibitors of MPT (cyclosporine A and trifluoperazine) inhibited acetaminophen toxicity in rat liver slices and in vivo when administered as a cocktail with fructose (Beales and McLean 1996 Nieminen et al. 1997). Also, Dimova et al. (1995) reported that the MPT inhibitor trifluoperazine decreased acetaminophen-induced hepatotoxicity in the mouse. Masubuchi et al. (2005) reported that Cyclosporine A decreased acetaminophen toxicity in mice. Since hepatic glutathione depletion was the same in acetaminophen-treated and acetaminophen plus cyclosporine A-treated mice, it was concluded that the decrease in toxicity was not mediated by inhibition of NAPQI formation. Moreover, they observed that acetaminophen caused a swelling of liver mitochondria and a decrease in mitochondrial membrane potential, both of which were elinrinated by cotreatment with Cyclosporine A. Collectively, the data indicate that MPT is an important mechanism leading to acetaminophen toxicity. 

It is well known that large overdoses of acetaminophen cause fatal hepatic necrosis not only in man (10) but also in several laboratory animal species such as rats (11 12) mice ( ) and hamsters ( >1 ) There is a marked species difference in the sensitivity of the various species to the drug (Table 2). In hamsters, necrosis occurs in most of the animals even at doses as low as 150 mg/kg, whereas in some strains of rats necrosis occurs in less than 10% of the animals even at doses as high as 1.5 g/kg (12). 

Acetaminophen may alter blood glucose test results, causing falsely lower blood glucose values. Use with the barbiturates, hydantoins, isoniazid, and rifampin may increase the toxic effects and possibly decrease the therapeutic effects of acetaminophen. The effects of the loop diuretics may be decreased when administered with acetaminophen. Hepatotoxicity has occurred in chronic alcoholics who are taking moderate doses of acetaminophen. 

Unconjugated hyperbilirubinemia can result from toxin-induced liver dysfunction such as that caused by chloroform, arsphenamines, carbon tetrachloride, acetaminophen, hepatitis virus, cirrhosis, and Amanita... 

Nelson, S.D. (1990). Molecular mechanisms of the hepatotox-icity caused by acetaminophen. Semin. Liver Dis. 10, 267-278. 

Although generally well tolerated, CSFs may cause bone pain in around 25% of patients. This may be managed with acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs), although attention to the platelet count is warranted with the use of NSAIDs. Sargramostim in particular may result... 

In addition to their beneficial effects, some medications may actually cause cellular injury and disease. An example of this phenomenon involves nonsteroidal anti-inflammatory drugs (NSAIDS). These drugs include aspirin (a derivative of salicylic acid), ibuprofen (arylpropionic acid, Advil ), and acetaminophen (para-aminophenol derivative, Tylenol ). Because of their beneficial pharmacological effects, consumption of these agents has increased significantly in recent years. NSAIDS have the ability to treat fever, pain, acute inflammation, and chronic inflammatory diseases such as arthritis. They are also used prophylactically to prevent heart disease, stroke, and colon cancer. 

The answer is c. (Hardman, pp 632-633.) Nausea, vomiting, abdominal pain, and diarrhea are early signs of the severe liver toxicity caused by high levels of acetaminophen other symptoms of acetaminophen toxicity include dizziness, excitement, and disorientation. N-acetyl-L-cysteine is the appropriate treatment for acetaminophen overdose. 

Use in moderate pain Weak analgesic most effective when used with NSAIDs, aspirin, or acetaminophen This drug is not recommended in the elderly Will cause carbamazepine levels to increase 100 mg of napsylate salt = 65 mg of HCI salt Third-line agent for moderate-to-severe pain... 

Drugs Acetaminophen. Drug Classes = antipyretic (reduces fever by acting directly on the hypothalamic heat-regulation center to cause vasodilation and sweating, which helps dissipates heat), and analgesic-non-narcotic (site and mechanism of action unclear). 

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