Nimesulide-Induced Hepatotoxicity in a Previously Healthy Woman

Gallelli, Luca; Ferraro, Maria; Mauro, G.F.; Fazio, Salvatore De; Sarro, Giovambattista De

doi:10.2165/00044011-200525060-00008

Cited by 11 publications

(11 citation statements)

References 24 publications

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“…age (adults are generally more susceptible to hepatotoxicity than are children), sex (women are more commonly affected than men), nutritional factors (obesity and malnutrition are susceptibility factors). Moreover, nonsteroidal anti-inflammatory drugs, could be able to induce an idiosyncratic reactions with hepatocellular or cholestatic patterns [17,18]. In our patient, clinical history and physical evaluation, excluded the presence of risk factors for liver diseases.…”

Section: Discussionmentioning

confidence: 77%

Hepatotoxicity Induced by Methimazole in a Previously Health Patient

Gallelli¹,

Staltari²,

Palleria³

et al. 2009

CDS

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We report a case of hepatotoxicity induced by methimazole treatment in a patient affected by hyperthyroidism. A 54-year-old man, presented to our observation for palpitations, excessive sweating, weakness, heat intolerance and weight loss. On physical examination, his blood pressure was 140/90 mmHg and heart beat was 100/min regular. He had mild tremors and left exophthalmos. Laboratory test revealed a significant increase in serum thyroid hormone levels with a decrease in thyroid stimulating hormone levels. A diagnosis of hyperthyroidism was made and he began treatment with methimazole (30 mg/day). Fourteen days later, he returned for the development of scleral icterus, followed by dark urine, and abdominal pain in the right upper quadrant. Laboratory examinations and liver biopsy performed a diagnosis of cholestatic hepatitis, secondary to methimazole usage. Methimazole was promptly withdrawn and cholestyramine, ursodeoxycholic acid, and chlorpheniramine were given. After five days, abdominal pain resolved and laboratory parameters returned to normal. Naranjo probability scale indicated a probable relationship between hepatotoxicity and methimazole therapy. In conclusion physicians should be aware the risk of hepatotoxicity related with methimazole.

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Section: Discussionmentioning

confidence: 77%

Hepatotoxicity Induced by Methimazole in a Previously Health Patient

Gallelli¹,

Staltari²,

Palleria³

et al. 2009

CDS

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“…It has been associated, similar to other NSAIDs, with rare but serious liver injury in susceptible patients [64][65][66][67][68][69][70][71][72][73][74]. The incidence is very low and the type of toxic response clearly idiosyncratic [73,75].…”

Section: Nimesulidementioning

confidence: 99%

Bioactivation and Hepatotoxicity of Nitroaromatic Drugs

Boelsterli¹,

Ho²,

Zhou³

et al. 2006

CDM

164

116

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Certain drugs containing a nitroaromatic moiety (e.g., tolcapone, nimesulide, nilutamide, flutamide, nitrofurantoin) have been associated with organ-selective toxicity including rare cases of idiosyncratic liver injury. What they have in common is the potential for multistep nitroreductive bioactivation (6-electron transfer) that produces the potentially hazardous nitroanion radical, nitroso intermediate, and N-hydroxy derivative. These intermediates have been associated with increased oxidant stress and targeting of nucleophilic residues on proteins and nucleic acids. However, other mechanisms including the formation of oxidative metabolites and mitochondrial liability, as well as inherent toxicokinetic properties, also determine the drugs' overall potency. Therefore, structural modification not only of the nitro moiety but also of ring substituents can greatly reduce toxicity. Novel concepts have revealed that, besides the classical microsomal nitroreductases, cytosolic and mitochondrial enzymes including nitric oxide synthase can also bioactivate certain nitroarenes (nilutamide). Furthermore, animal models of silent mitochondrial dysfunction have demonstrated that a mitochondrial oxidant stress posed by certain nitroaromatic drugs (nimesulide) can produce significant mitochondrial injury if superimposed on a genetic mitochondrial abnormality. Finally, there may be mechanisms for all nitroaromatic drugs that do not involve bioactivation of the nitro group, e.g., AHR interactions with flutamide. Taken together, the focus of research on the hepatic toxicity of nitroarene-containing drugs has shifted over the past years from the identification of the reactive intermediates generated during the bioreductive pathway to the underlying biomechanisms of liver injury. Most likely one of the next paradigm shifts will include the identification of determinants of susceptibility to nitroaromatic drug-induced hepatotoxicity.

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“…Previously, we recorded that NSAIDs treatment is able to induced the development of side effects such as skin reactions and gastrointestinal toxicity 48‐50…”

Section: Discussionmentioning

confidence: 99%

“…Previously, we recorded that NSAIDs treatment is able to induced the development of side effects such as skin reactions and gastrointestinal toxicity. [48][49][50] In this paper, we did not record any ADR during the acetaminophen treatment -as well as in ibuprofen-group -in association with magnesium probably because of the high safety of both drugs or perhaps related to the short period of treatment and absence of polytherapy.…”

Section: Discussionmentioning

confidence: 99%