RESUMO
BACKGROUND: Drug-induced liver enzyme abnormalities may indicate hepatic injury. Antipsychotic drugs also may cause increase in the liver enzymes and serum bilirubin levels. The present report evaluates the case of a patient with risperidone-associated hepatocellular damage. CASE SUMMARY: A 19-year-old Caucasian man was admitted to the Department of Psychiatry with paranoid schizophrenia and risperidone was administered in a gradually increasing dose up to 8 mg/day. After 3 weeks of treatment, he experienced asthenia and weight loss. The level of aspartate aminotransferase was 283 IU/L (normal: <30 IU/L), and the alanine aminotransferase level was 778 IU/L (normal: <36 IU/L). Treatment with risperidone was immediately discontinued. Six days after drug withdrawal, the alanine aminotransferase level fell more than 50%, and a complete return to normalcy was seen within 2 months. RESULTS: In the present case, a possible causal association between risperidone and hepatocellular damage has been observed due to the temporal relationship between the administration of the drug and the onset of hepatic abnormalities, and a following rapid recovery after stopping the drug. As the hepatic damage could be related to the plasma concentration of risperidone which is highly influenced by the hepatic enzyme CYP2D6, the patient was genotyped for CYP2D6. He was classified as homozygous wild type for CYP2D6. CONCLUSIONS: The risk for developing hepatotoxicity during risperidone therapy cannot be supported by the patient CYP2D6 genotype. In clinical practice, it may be recommended to obtain baseline liver function tests before starting risperidone and regular screening for liver enzyme changes during therapy.
Assuntos
Antipsicóticos/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/enzimologia , Citocromo P-450 CYP2D6/genética , Risperidona/efeitos adversos , Adulto , Antipsicóticos/administração & dosagem , Antipsicóticos/farmacocinética , Antipsicóticos/uso terapêutico , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Homozigoto , Humanos , Testes de Função Hepática , Masculino , Risperidona/administração & dosagem , Risperidona/farmacocinética , Risperidona/uso terapêutico , Adulto JovemAssuntos
Antipsicóticos/toxicidade , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/genética , Piperazinas/toxicidade , Polimorfismo Genético/genética , Transtornos Psicóticos/tratamento farmacológico , Transtornos Psicóticos/genética , Quinolonas/toxicidade , Receptor 5-HT2A de Serotonina/genética , Receptores de Dopamina D2/genética , Adolescente , Alelos , Antipsicóticos/uso terapêutico , Aripiprazol , Relação Dose-Resposta a Droga , Esquema de Medicação , Humanos , Masculino , Piperazinas/uso terapêutico , Quinolonas/uso terapêutico , Fatores de RiscoRESUMO
Disulfiram and calcium carbimide are two alcohol deterrants widely used in alcoholism treatment, however, there exist great concerns over their safety. Reports on hepatotoxicity, mainly related to disulfiram therapy, have been published. The hepatotoxic potential of calcium carbimide is less well characterized. Here, we describe four cases of liver damage related to this therapeutic group that were submitted to a Registry of hepatotoxicity and point out the limitations that we face when prescribing these compounds. A reassessment of the role of these compounds in the management of alcohol dependence is clearly needed.
Assuntos
Dissuasores de Álcool/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas , Cianamida/efeitos adversos , Dissulfiram/efeitos adversos , Fígado/efeitos dos fármacos , Adulto , Interações Medicamentosas , Feminino , Humanos , Fígado/patologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To explore the effect of intravenous N-acetylcysteine (NAC) on the prothrombin time (PT) in patients with paracetamol overdose and persistent normal liver profile. MATERIALS AND METHODS: This retrospective case series study examined all admissions with a diagnosis of paracetamol poisoning in a tertiary hospital between 1989 and 2002. Patients were included if they had ever received NAC infusion, had no biochemical evidence of liver damage, and had more than two measurements of PT. Patients who had also ingested other drugs were excluded. RESULTS: Of 65 admissions wtih paracetamol poisoning, 18 patients (10 men) met the inclusion criteria. The median age was 29 years, and the median quantity of paracetamol ingested was 186 mg/kg. The mean number of PT measurements per patient was 4.8. The baseline PT (as a percentage) 8.6 h after paracetamol ingestion was 89.6%. During NAC infusion the PT fell in all patients (range, 4.8-53.4% relative to baseline; P < 0.0001) at 14 h. The PT was less than 60% in 28% of the patients. Eight hours after the initiation of NAC there was a 16% fall in PT (range, 4.3-34%; P < 0.0001). At the end of NAC infusion all PTs returned to values close to baseline. Nine patients were hospitalized. CONCLUSIONS: In patients with paracetamol overdose without evidence of liver damage a marked decrease in PT often occurs, which seems to be due to the overload of NAC infused at the beginning of treatment. This particular feature should be noted in clinical practice guidelines as a potentially misleading indicator of the development of severe liver dysfunction.