<scp>GM</scp>‐<scp>CSF</scp> as successful salvage therapy of metamizole (dipyrone)‐induced agranulocytosis with Fournier's gangrene and severe septic shock in an adolescent

Winkler, Annegret; Kietz, Silke; Bahlmann, Hagen; Jafarzade, Gunel; Lode, Holger N.; Heckmann, Matthias

doi:10.1002/ccr3.616

Cited by 4 publications

(2 citation statements)

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“…However, upon activation in case of inflammation, macrophages and lymphocytes can metabolically switch to glycolysis in order to adapt to hypoxia [ 40 ]. Indeed, lymphopenia can be observed in patients with metamizole-induced neutropenia [ 21 , 43 , 44 ], supporting the notion that MAA/hemin is more toxic for cells generating ATP by glycolysis than by oxidative phosphorylation.…”

Section: Discussionmentioning

confidence: 90%

Reactive Metamizole Metabolites Enhance the Toxicity of Hemin on the ATP Pool in HL60 Cells by Inhibition of Glycolysis

et al. 2020

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Metamizole is an analgesic, whose pharmacological and toxicological properties are attributed to N-methyl-aminoantipyrine (MAA), its major metabolite. In the presence of heme iron, MAA forms reactive metabolites, which are toxic for granulocyte precursors. Since decreased cellular ATP is characteristic for MAA-associated toxicity, we studied the effect of MAA with and without hemin on energy metabolism of HL60 cells, a granulocyte precursor cell line. The combination MAA/hemin depleted the cellular ATP stronger than hemin alone, whereas MAA alone was not toxic. This decrease in cellular ATP was observed before plasma membrane integrity impairment. MAA/hemin and hemin did not affect the proton leak but increased the maximal oxygen consumption by HL60 cells. This effect was reversed by addition of the radical scavenger N-acetylcysteine. The mitochondrial copy number was not affected by MAA/hemin or hemin. Hemin increased mitochondrial superoxide generation, which was not accentuated by MAA. MAA decreased cellular ROS accumulation in the presence of hemin. In cells cultured in galactose (favoring mitochondrial ATP generation), MAA/hemin had less effect on the cellular ATP and plasma membrane integrity than in glucose. MAA/hemin impaired glycolysis more than hemin or MAA alone, and N-acetylcysteine blunted this effect of MAA/hemin. MAA/hemin decreased protein expression of pyruvate kinase more than hemin or MAA alone. In conclusion, cellular ATP depletion appears to be an important mechanism of MAA/hemin toxicity on HL60 cells. MAA itself is not toxic on HL60 cells up to 100 µM but boosts the inhibitory effect of hemin on glycolysis through the formation of reactive metabolites.

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Section: Discussionmentioning

confidence: 90%

Reactive Metamizole Metabolites Enhance the Toxicity of Hemin on the ATP Pool in HL60 Cells by Inhibition of Glycolysis

et al. 2020

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“…Podávanie metamizolu je u pacientov so zhoršenou funkciou kostnej drene kontraindikované. V dôsledku agra nulocytózy hrozí pacientom zvýšené riziko infek cií a krvácavých stavov (10). Podanie metamizolu môže viesť aj k anafylaktickým reakciám, reakciám na koži, bronchospazmom a vo veľmi zriedkavých prípadoch sa môže vyskytnúť akútne zhoršenie obličkovej funkcie (11).…”

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Metamizole‑affected onset of action of filgrastim

Oleárová¹,

Jurečková²

2019

Klin Farmakol Farm

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Ústav farmakológie a klinickej farmakológie, Lekárska fakulta, Slovenská zdravotnícka univerzita v Bratislave Metamizol je jedno z najpoužívanejších analgetík, ktoré sa vyznačuje aj antipyretickými a spazmolytickými účinkami. Vo viacerých krajinách sa metamizol nepoužíva pre riziko vzniku agranulocytózy. V článku opisujeme kazuistiku 72-ročnej pacientky hospitalizovanej so závažnou pancytopéniou. Zaznamenali sme u nej oneskorený nástup účinku filgrastímu v dôsledku súčasne podávaného metamizolu. Na základe revízie farmakoterapie bol z liečby rizikový metamizol vysadený. Po úprave farmakoterapie a podaní ďalších dvoch dávok filgrastímu počty leukocytov a neutrofilov uspokojivo stúpli. Po podaní podpornej liečby krvnými derivátmi sa stav pacientky postupne zlepšil a v stabilizovanom stave bola z nemocnice prepustená.

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