Inflammation and neurological adverse drugs reactions: a case of long lasting impaired consciousness after oxatomide administration in a patient with gastroenteritis

Antoniazzi, Stefania; Cattaneo, Dario; Perrone, Valentina; Carnovale, Carla; Cherubini, Simonetta; Mugolino, Maria Carmela; Clementi, Francesco; Zuccotti, Gian Vincenzo; Clementi, Emilio; Radice, Sonia

doi:10.1186/1824-7288-38-11

Cited by 7 publications

(3 citation statements)

References 9 publications

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“…A study on the effect of persistent inflammation in patients with renal failure and who were undergoing hemodialysis on the pharmacokinetics of alprazolam, a CYP3A4 substrate, revealed that after a single dose of alprazolam, there was a significant correlation between CYP3A4 activity and CRP level, which suggested that inflammation may clinically down-regulate CYP3A4 activity (Molanaei et al, 2012). Studies in human liver microsomes have shown that oxatomide, an H1-antihistamine, is mainly metabolized by CYP3A4 and CYP2D6, and there has been a report of severe long-lasting impaired consciousness induced by therapeutic doses of oxatomide in a child affected by acute gastroenteritis (Antoniazzi et al, 2012). Other causes of impaired consciousness were excluded and this child was receiving no other medication.…”

Section: Evidence For Potential Phenoconversion Of Dmes In Other Inflmentioning

confidence: 99%

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Shah¹,

2014

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Phenoconversion transiently converts genotypic extensive metabolizers (EMs) into phenotypic poor metabolizers (PMs) of drugs, potentially with corresponding changes in clinical response. This phenomenon, typically resulting from coadministration of medications that inhibit certain drug metabolizing enzymes (DMEs), is especially well documented for enzymes of the cytochrome P450 family. Nonclinical evidence gathered over the last two decades also strongly implicates elevated levels of some proinflammatory cytokines, released during inflammation, in down-regulation of drug metabolism, especially by certain DMEs of the P450 family, thereby potentially causing transient phenoconversion. Clinically, phenoconversion of NAT2, CYP2C19, and CYP2D6 has been documented in inflammatory conditions associated with elevated cytokines, such as human immunodeficiency virus infection, cancer, and liver disease. The potential of other inflammatory conditions to cause phenoconversion has not been studied but experimental and anecdotal clinical evidence supports infectioninduced down-regulation of CYP1A2, CYP3A4, and CYP2C9 as well. Collectively, the evidence supports a hypothesis that certain inflammatory conditions associated with elevated proinflammatory cytokines may cause phenoconversion of certain DMEs. Since inflammatory conditions associated with elevated levels of proinflammatory cytokines are highly prevalent, phenoconversion of genotypic EM patients into transient phenotypic PMs may be more frequent than appreciated. Since drug pharmacokinetics, and therefore the clinical response, is influenced by DME phenotype rather than genotype per se, phenoconversion (whatever its cause) can have a significant impact on the analysis and interpretation of genotype-focused clinical outcome association studies. There is a risk that focusing on genotype alone may miss important associations between clinical outcomes and DME phenotypes, thus compromising future prospects of personalized medicine.

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Section: Evidence For Potential Phenoconversion Of Dmes In Other Inflmentioning

confidence: 99%

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Shah¹,

2014

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“…In children, the same conclusions can be drawn as oxotamide toxicity was observed in 3-year-old children who were not carriers of CYP2D6 or CYP3A4 main allelic variants at the time of the study, meaning that the reduced clearance is not caused by the manifestation of CYP2D6*3, *4, *5, and *6 or CYP3A*1B [47]. It is therefore conceivable that the release of pro-inflammatory molecules such as CRP decreased CYP2D6 and/or CYP3A activities, eventually leading to an increase in the oxatomide plasmatic concentration [47].…”

Section: Cyp Genotypementioning

confidence: 58%

Impact of Inflammation on Cytochromes P450 Activity in Pediatrics: A Systematic Review

et al. 2021

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Background and Objective Cytochromes P450 (CYP) are the major enzymes involved in hepatic metabolism of drugs. Personalization of treatment in pediatrics is a major challenge, as it must not only take into account genetic, environmental, and physiological factors but also ontogeny. Published data in adults show that inflammation had an isoform-specific impact on CYP activities and we aimed to evaluate this impact in the pediatric population. Methods Articles listed in PubMed through 7 January, 2021 that studied the impact of inflammation on CYP activities in pediatrics were included in this systematic review. Sources of inflammation, victim drugs (CYP involved), effect of drugdisease interactions, number and age of subjects, and study design were extracted. Results Twenty-seven studies and case reports were included. The impact of inflammation on CYP activities appeared to be age dependent and isoform-specific, with some drug-disease interactions having significant pharmacokinetic and clinical impact. For example, midazolam clearance decreases by 70%, while immunosuppressant and theophylline concentrations increase three-fold and two-fold with intensive care unit admission and infection. Cytochrome P450 activity appears to return to baseline level when the disease is resolved. Conclusions Studies that have assessed the impact of inflammation on CYP activity are lacking in pediatrics, yet it is a major factor to consider to improve drug efficacy or safety. The scarce current data show that the impact of inflammation is isoform and age dependent. An effort must be made to improve the understanding of the impact of inflammation on CYP activities in children to better individualize treatment.

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“…Although it can improve the clinical symptoms of patients to a certain extent, the long-term use of the efficacy is poor, and it is easy to bring more adverse reactions. Antoniazzi reported a case of persistent impairment of consciousness after administration of oxamide in a patient with gastroenteritis (21). Sulkers et al described the side effects of acute urinary retention following the use of antiemetics in patients with AGE (22).…”

Section: Value Of Roc Curve Analysis Of Serum Crp and Pct Levels To A...mentioning

confidence: 99%

Effects of Gegen Qinlian Decoction combined with Chinese herbal hot package on the expression of PCT, CRP and IL-6 in patients with acute gastroenteritis

Zhang¹,

Yang²,

Rietz³

et al. 2022

Cell Mol Biol (Noisy-le-grand)

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This study was carried out to investigate the clinical efficacy of Gegen Qinlian Decoction combined with a Chinese herbal hot package in the treatment of acute gastroenteritis (AGE), and to analyze the effects on serum PCT, CRP and IL-6 levels. For this purpose, 100 patients with AGE admitted to the hospital from January 2019 to January 2022 were selected for the study and randomly divided into observation and control groups, with 50 cases in each group. Patients in the control group were given conventional Western medical treatment, while patients in the observation group were treated with Gegen Qinlian Decoction combined with a Chinese herbal hot package on this basis. The clinical efficacy, symptom relief time, main symptom scores and serum PCT, CRP and IL-6 levels before and after treatment were compared between the two groups. Results showed that the total effective rate of patients in the observation group was significantly higher than that in the control group (P<0.05). After treatment, the disappearance time of diarrhea, abdominal pain, fever and vomiting was significantly shorter in the observation group than in the control group (P<0.05). After treatment, the stool properties, number of stools and abdominal pain symptom scores of patients in both groups were lower than those before treatment, and the symptom scores of patients in the observation group were lower than those in the control group (P<0.05). The PCT, CRP and IL-6 levels of patients in both groups were significantly lower after treatment than before treatment, and the PCT, CRP and IL-6 levels of patients in the observation group were significantly lower than those in the control group (P<0.05). It was concluded that the clinical efficacy of Gegen Qinlian Decoction combined with Chinese herbal hot package in the treatment of AGE is remarkable, which can effectively improve the clinical symptoms and reduce the inflammatory reaction of patients and is worthy of clinical promotion.

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Inflammation and neurological adverse drugs reactions: a case of long lasting impaired consciousness after oxatomide administration in a patient with gastroenteritis

Cited by 7 publications

References 9 publications

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Inflammation-Induced Phenoconversion of Polymorphic Drug Metabolizing Enzymes: Hypothesis with Implications for Personalized Medicine

Impact of Inflammation on Cytochromes P450 Activity in Pediatrics: A Systematic Review

Effects of Gegen Qinlian Decoction combined with Chinese herbal hot package on the expression of PCT, CRP and IL-6 in patients with acute gastroenteritis

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