Acute Cholestatic Hepatitis Probably Associated with Risperidone

Tello, Francisca Llinares; Prats, Carmen Hernández; Ros, N. Bosacoma; Martínez, Eduardo; Grana, Eduardo Climent; Polo, J.N. Navarro; Baines, Juan Pablo Ordovás

doi:10.2190/5xrb-d2xx-x8ah-32kb

Cited by 16 publications

(5 citation statements)

References 17 publications

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“…Therefore, many incidents of hepatotoxicity of various drugs have been reported (Biour et al 1998;Fontana and Quallich 2001;Ayonrinde et al 2005;Llinares Tello et al 2005). Attrition rates in the development of new drug candidates are still high due to adverse effects (Caldwell et al 2001;Cuatrecasas 2006;Smith and Schmid 2006).…”

Section: Introductionmentioning

confidence: 99%

Metabolomics and biomarker discovery: NMR spectral data of urine and hepatotoxicity by carbon tetrachloride, acetaminophen, and d-galactosamine in rats

Kim

Chung

et al. 2008

Metabolomics

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The primary objective of this study was to discover biomarkers which are correlated with hepatotoxicity induced by chemicals using 1 H NMR spectral data of urine. A procedure of nuclear magnetic resonance (NMR) urinalysis using pattern recognition was proposed for early screening of the hepatotoxicity of CCl 4 , acetaminophen (AAP), and D-galactosamine (GalN) in rats. The hepatotoxic compounds were expected to induce necrosis in hepatocytes. This was confirmed through blood biochemistry and histopathology. CCl 4 (1 ml/kg, po) or GalN (0.8 g/kg, ip) was single administered to Sprague-Dawley (S-D) rats and urine was collected every 24 h. Animals were sacrificed 24 h or 48 h post-dosing. AAP (2 g/kg, po) was administered for 2 days and then the animals were sacrificed 24 h after the last treatment. NMR spectroscopy revealed evidently different clustering between control groups and hepatotoxicant treatment groups in global metabolic profilings as indicated by partial least square (PLS)-discrimination analysis (DA). In targeted profilings, endogenous metabolites of allantoin, citrate, taurine, 2-oxoglutarate, acetate, lactate, phenylacetyl glycine, succinate, phenylacetate, 1-methylnicotinamide, hippurate, and benzoate were selected as putative biomarkers for hepatoxicity by CCl 4 , AAP, and GalN. Comparison of our rat 1 H NMR PLS-DA data with histopathological changes suggests that 1 H NMR urinalysis can be used to predict hepatotoxicity induced by CCl 4 , AAP, and GalN.

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Section: Introductionmentioning

confidence: 99%

Metabolomics and biomarker discovery: NMR spectral data of urine and hepatotoxicity by carbon tetrachloride, acetaminophen, and d-galactosamine in rats

Kim

Chung

et al. 2008

Metabolomics

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“…It has been mentioned that more than thousand drugs are responsible for hepatic side effects; 16% of these agents were neuropsychiatric drugs [27], one of which being risperidone. Until today, neuropsychiatric drugs have been studied using clinical [28], experimental [6], post-mortem [29], molecular [30] and toxicopathological methods and focusing on a lot of organs or systems such as the liver [31], cardiac [32], extrapyramidal [33] and the endocrine system [34]. In these studies, it was claimed that risperidone, which has a different pharmacokinetic profile, when metabolized by cytochrome P450 2D6 phenotypes induced hepatotoxicity [10].…”

Section: Discussionmentioning

confidence: 99%

Chronically Administered Risperidone Did Not Change the Number of Hepatocytes in Rats: A Stereological and Histopathological Study

Halıcı¹,

Keleş²,

Ünal³

et al. 2008

Basic Clin Pharma Tox

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Risperidone, an antipsychotic agent, has been used in the therapy of patients with acute and chronic schizophrenia. The strategy in the choice of antipsychotic agent should take into account the hepatic tolerance. The aim of the present study was to analyse whether or not the chronic administration of risperidone has a toxic effect on rat livers. Rats were divided into three groups. Low dose (n = 5) and high dose (n = 5) groups that were given 0.5 and 1 mg/kg intraperitoneal doses of risperidone daily for 6 weeks, respectively. The control group received distilled water as a vehicle. At the end of the experiment, the rats were killed, and livers were dissected out immediately and transferred into the fixation solution. Both conventional light and transmission electron microscopic tissue preparation procedures were applied to liver tissues and they were evaluated using stereological and histopathological methods; in this respect, this is the first study using stereological methods for searching the effects of risperidone on liver. There were no significant differences about the total hepatocyte number and their numerical density of rat liver between groups (P > 0.05). Stereological results were also confirmed by the histopathological findings that come from both structural and ultrastructural levels examination. The results of the current study indicate that neither low nor high doses of risperidone resulted in damage to the rat livers at cellular level. In conclusion, we did not find any evidence for hepatotoxicity of risperidone rats. Larger-scale, prospective studies are needed in order to confirm these findings.Antipsychotic agents are divided by two main categories: typical or conventional and atypical. Risperidone is a potent antipsychotic agent that was introduced into clinical practice in 1993 and is commonly used in the management of both positive and negative symptoms of schizophrenia by reducing the extrapyramidal symptoms [1]. Due to the lower incidence and severity of adverse effects in comparison to phenothiazines, risperidone has been widely used in recent years [2]. Classed among the atypical antipsychotic drugs, major targets for risperidone action are dopaminergic D 2 receptors and serotonergic 5-HT 2 receptors [3]. Risperidone has shown a higher affinity for 5-HT 2 (five times) and α 1 (two times) receptors than D 2 receptors. Thus, risperidone has shown a broad spectrum of brain neurotransmitter receptors as previously reported [3,4]. Although antipsychotics are commonly used as a drugs in schizophrenia treatment, they are admittedly known to induce side effects such as impairment of fat cell lipolysis by altering the lipid metabolism [5], changing of whole-body insulin sensitivity in a dose-dependent [6], alterations in the striatal protein profile that may be involved in antipsychotic drug-induced extrapyramidal symptoms include metabolic dysfunction and oxidative stress [7]. Well-known adverse reactions to risperidone mainly involve the central nervous system and gastrointestinal ...

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“…Results from controlled clinical trials, reports of spontaneous adverse events, and published studies/case reports suggest that severe hepatotoxicity may be rare in the pediatric population (Szigethy et al 1999;Zuddas et al 2000;Malone et al 2002;Turgay et al 2002;Masi et al 2003). However, several cases of hepatotoxicity with long-term use of risperidone and other antipsychotic agents have been reported recently in adults and in the pediatric population (Kumra et al 1997;Krebs et al 2001;Mouradian-Stamatiadis et al 2002;Llinares et al 2005). Furthermore, weight gain during risperidone therapy has already been documented along with fatty infiltration of the liver, which has been reported to occur in obese children and adolescents (Moran et al 1983;Ratzoni et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Six Months of Treatment with Risperidone May Be Associated with Nonsignificant Abnormalities of Liver Function Tests in Children and Adolescents: A Longitudinal, Observational Study from Turkey

Erdoğan

Karaman²,

Özdemir³

et al. 2010

Journal of Child and Adolescent Psychopharmacology

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These findings suggest that risperidone treatment in the long term commonly leads to liver function changes, although at therapeutic doses in children and adolescents it may rarely induce a serious hepatic toxicity. Concomitant use of antidepressants and methylphenidate and variations in age and pubertal status are limitations of present study. Further studies are needed to assess the importance and role of other variables over LFT abnormalities in youth population.

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Acute Cholestatic Hepatitis Probably Associated with Risperidone

Abstract: We recommend obtaining baseline liver function tests before starting risperidone and regular monitoring to screen patients for liver damage during therapy whenever a patient is also receiving fluoxetine.

Cited by 16 publications

References 17 publications

Metabolomics and biomarker discovery: NMR spectral data of urine and hepatotoxicity by carbon tetrachloride, acetaminophen, and d-galactosamine in rats

Metabolomics and biomarker discovery: NMR spectral data of urine and hepatotoxicity by carbon tetrachloride, acetaminophen, and d-galactosamine in rats

Chronically Administered Risperidone Did Not Change the Number of Hepatocytes in Rats: A Stereological and Histopathological Study

Six Months of Treatment with Risperidone May Be Associated with Nonsignificant Abnormalities of Liver Function Tests in Children and Adolescents: A Longitudinal, Observational Study from Turkey

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