Characterization of oxalic acid derivatives as new metabolites of metamizol (dipyrone) in incubated hen's egg and human

Johannes), Wessel J. (Wessel; Matyja, Magdalena; Neugebauer, Michael; Kiefer, H; Daldrup, Thomas; Tarbah, Fuad; Weber, Horst

doi:10.1016/j.ejps.2005.11.010

Cited by 28 publications

(25 citation statements)

References 16 publications

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“…Another factor to consider that may contribute to the low sensitivity of diagnostic tests is the incomplete characterization of the chemical structures of metamizole and its metabolites [30]. Four major metamizole metabolites have been described in the literature [31]; however, we recently demonstrated the presence of arachidonoyl metabolites in patients receiving metamizole [32], and additional metabolites, such as oxalic acid derivatives, have been reported elsewhere [33]. It cannot be ruled out that in some patients metamizole metabolites may contribute to hypersensitivity reactions.…”

Section: Discussionmentioning

confidence: 99%

Allergic Reactions to Metamizole: Immediate and Delayed Responses

Blanca‐López

Pérez‐Sánchez²,

Agúndez³

et al. 2016

Int Arch Allergy Immunol

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Background: Pyrazolones are the most common causes of selective nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity. We studied a large group of patients with immediate and delayed selective responses to metamizole. Methods: Patients with suspicion of hypersensitivity to metamizole were evaluated. We verified acetylsalicylic acid tolerance and classified patients as immediate or delayed responders if they showed symptoms less or more than 24 h after metamizole administration. Skin tests were performed and if negative, a basophil activation test (BAT) was performed on immediate responders. If it was negative, we performed a drug provocation test (DPT) with metamizole. Results: A total of 137 patients were included: 132 reacted within 24 h (single NSAID-induced urticaria/angioedema/anaphylaxis; SNIUAA) and 5 after 24 h (single NSAID-induced delayed hypersensitivity reaction; SNIDHR). Most SNIUAA patients developed anaphylaxis (60.60%); for SNIDHR, maculopapular exanthema was the most frequent entity (60%). Skin testing was positive in 62.04% of all cases and BAT in 28% of the SNIUAA patients with negative skin tests. In 5.1% of the cases, DPT with metamizole was needed to establish the diagnosis. In 22.62% of the cases, diagnosis was established by consistent and unequivocal history of repeated allergic episodes in spite of a negative skin test and BAT. Conclusions: SNIUAA to metamizole is the most frequent type of selective NSAID hypersensitivity, with anaphylaxis being the most common clinical entity. It may occur within 1 h after drug intake. SNIDHR occurs in a very low percentage of cases. The low sensitivity of diagnostic tests may be due to incomplete characterization of the chemical structures of metamizole and its metabolites.

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Section: Discussionmentioning

confidence: 99%

Allergic Reactions to Metamizole: Immediate and Delayed Responses

Blanca‐López

Pérez‐Sánchez²,

Agúndez³

et al. 2016

Int Arch Allergy Immunol

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“…From the work done by Gómez et al (2008) on the photodegradation of 4-Methylaminoantipyrine, another metabolite of dipyrone, an additional degradation product was identified: P3 can lose the methyl group attached to the carbonyl and lead to 1-acetyl-1-methyl-2-phenylhydrazide (P8). Wessel et al (2006) have previously reported the latter compound, which was also detected in groundwater samples by Reddersen et al (2002). According to Gómez et al (2008), P5 can lead to the formation of N-phenylacetamide (P7) by cleavage of the NAN bond of the hydrazine.…”

Section: Identification Of Ozone Degradation Productsmentioning

confidence: 95%

High-resolution MS and MSn investigation of ozone oxidation products from phenazone-type pharmaceuticals and metabolites

et al. 2015

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“…There is some evidence suggesting that after prolonged administration metamizole might cause some damage to the blood system, being responsible for leukopenia, agranulocytosis and even aplastic anemia (Hedenmalm and Spigset 2002, García-Martínez et al 2003, Basak et al 2010. This is the reason why the drug has been withdrawn from the market in several countries (Wessel et al 2006, Schug and Manopas 2007, Baumgartner et al 2009, Basak et al 2010. Reports by Hedenmalm and Spigset (2002) suggested that the risk of developing metamizole-induced agranulocytosis is substantial.…”

Section: Side Effectsmentioning

confidence: 99%

“…Sweden, the USA, Japan, the UK, Australia and Iran), but in many more countries (some European states, Asia, South America) it is still broadly used, both in human medicine (as an OTC drug) and in veterinary practice (Edwards et al 2001, Wessel et al 2006, Baumgartner et al 2009, Imagawa et al 2011. In Canada, metamizole is registered for use only on small animals and horses, whereas in the USA it has been prohibited from use on food producing animals (Fajt 2001, Smith et al 2008).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological characteristics of metamizole

Jasiecka¹,

Maślanka²,

Jaroszewski³

2014

Polish Journal of Veterinary Sciences

126

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Metamizole (dipyrone) is a popular analgetic, non-opioid drug, commonly used in human and veterinary medicine. In some cases, this agent is still incorrectly classified as a non-steroidal anti-inflammatory drug (NSAID). Metamizole is a pro-drug, which spontaneously breaks down after oral administration to structurally related pyrazolone compounds. Apart from its analgesic effect, the medication is an antipyretic and spasmolytic agent. The mechanism responsible for the analgesic effect is a complex one, and most probably rests on the inhibition of a central cyclooxygenase-3 and activation of the opioidergic system and cannabinoid system. Metamizole can block both PG-dependent and PG-independent pathways of fever induced by LPS, which suggests that this drug has a profile of antipyretic action distinctly different from that of NSAIDs. The mechanism responsible for the spasmolytic effect of metamizole is associated with the inhibited release of intracellular Ca 2+ as a result of the reduced synthesis of inositol phosphate. Metamizole is predominantly applied in the therapy of pain of different etiology, of spastic conditions, especially affecting the digestive tract, and of fever refractory to other treatments. Co-administration of morphine and metamizole produces superadditive, antinociceptive effects. Metamizole is a relatively safe pharmaceutical preparation although it is not completely free from undesirable effects. Among these side-effects, the most serious one that raises most controversy is the myelotoxic effect. It seems that in the past the risk of metamizole-induced agranulocytosis was exaggerated. Despite the evidence showing no risk of teratogenic and embryotoxic effects, the drug must not be administered to pregnant women, although it is allowed to be given to pregnant and lactating animals. This paper seeks to describe the characteristics of metamizole in the light of current knowledge.

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Characterization of oxalic acid derivatives as new metabolites of metamizol (dipyrone) in incubated hen's egg and human

Cited by 28 publications

References 16 publications

Allergic Reactions to Metamizole: Immediate and Delayed Responses

Allergic Reactions to Metamizole: Immediate and Delayed Responses

High-resolution MS and MSn investigation of ozone oxidation products from phenazone-type pharmaceuticals and metabolites

Pharmacological characteristics of metamizole

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