COX-2 inhibitor (nimesulide) induced acute liver failure

Stadlmann, Sylvia; Zoller, Heinz; Vogel, Wolfgang; Offner, Felix

doi:10.1007/s00428-002-0612-2

Cited by 19 publications

(18 citation statements)

References 10 publications

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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

165

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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Section: Nimesulidementioning

confidence: 99%

Bioactivation and Hepatotoxicity of Nitroaromatic Drugs

Boelsterli¹,

Ho²,

Zhou³

et al. 2006

CDM

165

116

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“…Несколько НПВП, а именно бромфенак, ибуфенак и беноксапрофен, были изъяты с рынка из-за гепатотоксичности; другие, такие как нимесулид, никогда не продавались в одних странах и перестали использоваться в других. Поступающие сообщения подтвердили возможность развития тяжелых форм повреждения печени, в результате чего национальные органы здравоохранения ряда стран изъяли нимесулид с рынка [18][19][20][21][22][23][24][25][26][27][28][29]. Несмотря на это, использование нимесулида все еще поддерживается в некоторых европейских странах, хотя в отчетах EMEA его рекомендуется использовать только во второй линии терапии, а продолжительность ограничить 15 днями с максимальной дозой 100 мг/сут [30].…”

Section: Conflict Of Interestunclassified

Safe use of meloxicam in clinical practice

Сас

Гриневич

2019

Med. sov.

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Non-steroidal anti-inflammatory drugs (NSAIDs) – means of treatment of acute and chronic pain associated primarily with inflammatory changes, so this group of drugs is widely used in neurology, rheumatology, traumatology, etc. The mechanism of action of the drugs is associated with the effect on cyclooxygenase-2 (COG-2) and blockade of proinflammatory prostaglandins (PG) synthesis, as well as the effect on COG-1 and suppression of cytoprotective PG synthesis, which determines the possibility of side effects from the gastrointestinal tract (GIT). Now application of NPVP is focused not so much on increase of efficiency, as on their big safety. Creation of COG-2-selective inhibitors (meloxicam) and COG-2-high selective inhibitors (coxybes) allowed to reduce significantly the risk of complications from gastrointestinal tract while maintaining high efficiency. Thus, the safety profile of meloxicam, mainly inhibiting COG-2, is estimated in a whole series of studies. In particular, two large prospective controlled trials - MELISSA and SELECT - proved that meloxicam is less toxic to gastrointestinal tract than traditional NSAIDs. Thus, a reasonable conclusion can be made about the high efficacy of meloxicam, which is not inferior to that of non-selective NSAIDs, with good tolerability and safety of the drug against gastrointestinal tract.

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“…In models of cognitive dysfunction in mice, employing scopolamine or lipopolysaccharide treatments or aged animals, nimesulide, rofecoxib and naproxen given repeatedly each day for 7 days significantly reversed the cognitive retention deficits [219]. In conditioned place preference tests in rats, nimesulide at the low doses of 0.1 to 1.0 mg/kg induced place preference [220] inferring that some influence on reward or other behavioural influences may be affected by the drug.…”

Section: Alzheimer's Disease and Neurodegenerative Disordersmentioning

confidence: 99%

“…As evaluated by molecular modelling (docking) [217] the sulphonanilide group of nimesulide (and celecoxib) is a prerequisite for the inhibition of COX-2 but also for the inhibition of metalloproteinase [218]. Furthermore, a sulphonanilide moiety is also important for the inhibition of Tumour necrosis factor Alpha Converting Enzyme (TACE) [219,220]. Further studies are necessary to evaluate if the intracellular accumulation of nimesulide into neutrophils is due to selective uptake by lysosomes or also involve other organelles including the phagosome, whose inside is also acidic.…”

Section: Phagosome and Lysosome Accumulation And Protease Inhibitionmentioning

confidence: 99%

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Nimesulide — Actions and Uses

Rainsford¹

2005

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COX-2 inhibitor (nimesulide) induced acute liver failure

Cited by 19 publications

References 10 publications

Bioactivation and Hepatotoxicity of Nitroaromatic Drugs

Bioactivation and Hepatotoxicity of Nitroaromatic Drugs

Safe use of meloxicam in clinical practice

Nimesulide — Actions and Uses

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