Aspirin hepatotoxicity

Although aspirin hepatotoxicity has usually been reported in patients with connective tissue diseases, it has occurred in a yoimg adult with nothing more than tension headaches and a cold, though the patient... 

In addition to the common side effects listed above, aspirin s main adverse effects at antithrombotic doses are gastric upset (intolerance) and gastric and duodenal ulcers. Hepatotoxicity, asthma, rashes, gastrointestinal bleeding, and renal toxicity rarely if ever occur at antithrombotic doses. 

Aspirin, 325-650 mg every 4-6 hours Bayer Aspirin, Ecotrin, Bufferin, various generic children who cannot chew or swallow tablets. Do not exceed a total daily acetaminophen dose of 4 g (2 g/d in regular alcohol users). Aspirin should be used cautiously in certain individuals (see text). Use of OTC products containing aspirin, other salicylates, acetaminophen, ibuprofen, or naproxen may increase the risk of hepatotoxicity and gastrointestinal hemorrhage in individuals who consume 3 or more alcoholic drinks daily. Long-term continuous use of NSAIDs may increase the risk of heart attack or stroke. 

Valproate Care must be exercised when administering valproate with aspirin, warfarin, or other hepatotoxic drugs. 

Nearly all NSAIDs have the potential to induce hepatic injury, although this effect has not been documented in the horse. In other species, hepatic injury associated with most NSAIDs is an idiosyncratic reaction with a low incidence of occurrence. The hepatotoxicity of carprofen in dogs, for example, was not observed until the NSAID was in widespread use in the USA (MacPhail et al 1998). The heptatoxicity of a few compounds, such as aspirin and acetaminophen (paracetamol), however, is a dose-dependent side-effect that is well described (Fry Seeff 1995). 

Hushing and pruritus (use aspirin [ASAJ), rashes, hyperuricemia, hyperglycemia, hepatotoxic- ty, GI ulcer exacerbation. 

C. Toxicity Cutaneous flushing is a common adverse effect. Pretreatment with aspirin or other NSAIDs reduces the intensity of this flushing, suggesting that it is mediated by prostaglandin release. Tolerance to the flushing reaction usually develops within a few days. Dose-dependent nausea and abdominal discomfort often occur. Pruritus and other skin conditions are reported. Moderate elevations of liver enzymes and even severe hepatotoxicity may occur. Hyperuricemia occurs in about 20% of patients, and carbohydrate tolerance may be moderately impaired. 

A 63-year-old woman who had been taking Iovastatin 80 mg, nicotinic acid 3 g daily, timolol and aspirin for almost 10 years without problems, developed weakness and tenderness in her arms, back and legs within 2 weeks of starting to take itraconazole 100 mg twice daily. A few days later her urine became brown, and positive for haem. She was diagnosed as having acute rhabdomyolysis and hepatotoxicity. The Iovastatin, nicotinic acid and itraconazole were stopped, and she was treated with ubide-carenone. Over the next 18 days her elevated serum enzymes returned to normal, although her plasma cholesterol levels almost doubled. She was restarted on nicotinic acid 11 weeks later without problems. ... 

We have found reports on eight patients whith systemic lupus erythematosus who developed adverse reactions to ibuprofen (Mandell et al. 1976 Szczeklik et al. 1977 a Sonnenblick and Abraham 1978). These reactions were characterized by sudden appearance of high fever, abdominal pain, and rash. Serum transaminases were rased in some patients. Raised concentrations of serum transaminases also seem to be common in patients with active systemic lupus erythematosus, who are receiving aspirin (Seaman et al. 1974). The hepatotoxic effect of aspirin in these patients may be due, not to allergic reaction but to a disturbance in aspirin transformation, resulting in the formation of a toxic metabolite (Anonymous 1974). 

Nurofen Plus contains 12.8 mg of codeine and 200 mg of ibuprofen per tablet, and is prescribed as 1 -2 tablets every 4-6 h as required. When prescribing codeine compounds, caregivers should calculate total daily exposure to acetaminophen, aspirin and ibuprofen to reduce risks of hepatotoxicity and gastrointestinal bleeding Parenteral the recommended starting dose of codeine is 60 mg every 2 h given as intramuscular or subcutaneous injection. 

Compounds containing acetaminophen or aspirin are associated with respective increases in risk of hepatotoxicity or gastrointestinal bleeding. 

Over the last few years there have been numerous further reports of hepatotoxicity following the therapeutic use of aspirin. In almost all cases the patients were receiving the dmg for arthritis and connective tissue diseases, and hepatotoxicity has been restricted largely to children and young adults. Females are affected more often than males. Most reported cases have been in patients with juvenile rheumatoid arthritis. Hepatitis usually resolves when aspirin is discontinued and has recurred on subsequent challenge with aspirin (125 —131 ). 

Severe hepatotoxicity with encephalopathy resembling Reye s syndrome has been reported with therapeutic doses of aspirin (19, 125 ). 

Hepatotoxicity related to the use of aspirin does not seem to have been reported in older patients with rheumatoid arthritis. However, elevation of hepatic alkaline phosphatase has been observed (134 ), and the question has been raised as to whether the abnormal liver function tests found in polymyalgia rheumatica could be caused by the aspirin given to treat this condition (135). 

The main interactions of aspirin and the salicylates were reviewed in SED VIII (p. 174). New papers have appeared on interactions with various anti-flammatory drugs, though data on indomethacin in this connection are contradictory (168 -172 ). There may be species differences in these interactions (172 ). Plasma concentrations of salicylate are markedly reduced (30—70%) by antacids as a result of increased urine pH and enhanced renal clearance of salicylate (173 ). In guinea pigs aspirin enhances the metabolism of paracetamol to the hepatotoxic metabolite which is excreted in the urine as paracetamol mercaptu-ric acid (174). This interaction may potentiate the toxicity of phenacetin and paracetamol. 

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