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ABSTRACT Delirium is a common disorder in intensive care units, being associated with greater morbidity and mortality. However, in neonatal intensive care units, delirium is rarely diagnosed, due to the low familiarity of the neonatologist with the subject and the difficulties in the applicability of diagnostic questionnaires. This case report aimed to assess the presence of this disorder in this group of patients and identify the difficulties encountered in the diagnosis and treatment. We report the case of a premature newborn with necrotizing enterocolitis during hospitalization and underwent three surgical approaches. The newborn exhibited intense irritability, having received high doses of fentanyl, dexmedetomidine, clonidine, ketamine, phenytoin, and methadone, without the control of the symptoms. A diagnosis of delirium was then made and treatment with quetiapine was started, with a complete reversal of the symptoms. This is the first case reported in Brazil and the first describing the withdrawal of the quetiapine.
RESUMO Delirium é uma síndrome comum em unidades de terapia intensiva, associando-se a maiores morbidade e mortalidade. No entanto, nas unidades de terapia intensiva neonatal, ele raramente é diagnosticado em razão da baixa familiaridade do neonatologista com a suspeita diagnóstica e das dificuldades na aplicabilidade dos questionários diagnósticos. Este relato de caso tem como objetivos mostrar que delirium está presente nesse grupo de pacientes e apontar as dificuldades encontradas no seu diagnóstico e tratamento. Relatamos o caso de um recém-nascido prematuro com enterocolite necrosante, submetido a três abordagens cirúrgicas. O recém-nascido apresentou intensa irritabilidade, tendo recebido altas doses de fentanil, dexmedetomidina, clonidina, cetamina, fenitoína e metadona, sem controle dos sintomas. Em seguida, foi feita a hipótese diagnóstica de delirium e iniciado tratamento com quetiapina, com reversão completa dos sintomas. Este é o primeiro caso notificado no Brasil e o primeiro que descreve a suspensão da quetiapina.
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Humans , Infant, Newborn , InfantABSTRACT
Objective:To investigate the efficacy of quetiapine fumarate combined with lithium carbonate in the treatment of bipolar disorder and its effect on cognitive function.Methods:Sixty patients with bipolar disorder, who received treatment in Zhuji Fifth People's Hospital from January 2017 to December 2019, were included in this study. They were randomly assigned to receive either lithium carbonate (control group, n = 30) or quetiapine fumarate combined with lithium carbonate treatment (combined treatment group, n = 30). All patients received 4 weeks of treatment. Manic and depressive symptoms pre- and post-treatment, clinical efficacy, cognitive function, and adverse reactions were compared between the two groups. Fasting venous blood was taken before and 4 weeks after treatment to measure superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), and glutathione peroxidase (GSH-Px) levels. Results:The scores of the Bech-Rafaelsdn Mania Rating Scale (BRMS) and the Hamilton Rating Scale for Depression (HAMD) in each group were significantly decreased after treatment compared with before treatment ( t = 10.39, 12.47, both P < 0.001). The score of the Mini-Mental State Examination in each group significantly increased after treatment compared with before treatment ( t = 8.36, 14.52, both P < 0.001). The scores of BRMS and HAMD post-treatment were significantly lower in the combined treatment group than in the control group ( t = 5.86, 5.54, both P < 0.001). The score of MMSE post-treatment was significantly higher in the combined treatment group than in the control group ( t = 2.40, P = 0.020). The response rate was significantly higher in the combined treatment group than in the control group ( Z = 2.16, P = 0.030). After treatment, serum MDA level significantly decreased in each group compared with before treatment ( t = 8.72, 15.47, both P < 0.001). After treatment, SOD, CAT and GSH-Px levels were significantly increased in each group compared with before treatment (SOD: tcontrol group = 2.84, P = 0.006, tcombined treatment group = 4.05, P < 0.001; CAT: tcontrol group = 5.20, P < 0.001, tcombined treatment group = 9.86, P < 0.001; GSH-Px: tcontrol group = 2.67, P = 0.010, tcombined treatment group = 3.71, P = 0.001). Serum MDA level post-treatment was significantly lower in the combined treatment group than in the control group ( t = 12.38, P < 0.001). Serum SOD and CAT levels post-treatment were significantly higher in the combined treatment group than in the control group ( tSOD = 2.24, P = 0.029; tCAT = 2.72, P = 0.009). There was no significant difference in the incidence of adverse reactions between the combined treatment and control groups [20.00% (6/30) vs. 16.67% (5/30), χ2 = 1.02, P = 0.907). Conclusion:Quetiapine fumarate combined with lithium carbonate can greatly improve clinical symptoms and cognitive function and reduce the over-activation of oxidative stress in patients with bipolar disorder. The combined therapy is of certain clinical application value.
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Autoimmune hemolytic anemia is a disease characterized with destruction of erythrocytes as a result of antibody produce against patient's own erythrocytes and anemia. Autoimmune hemolytic anemia can be roughly stratified into two groups according to serological features and secondary causes including drugs induced hemolytic anemia. Drugs induced autoimmune hemolytic anemia is very rare in pediatric patients. Even though hematological side effects such as leucopenia, agranulocytosis, eosinophilia, thrombocytopenic purpura and aplastic anemia might occur due to psychotropic drug use; to the best of our knowledge there is no autoimmune hemolytic anemia case due to quetiapine, an atypical antipsychotics, in literature. We hereby describe the first child case of autoimmune hemolytic anemia during quetiapine treatment.We also are pointing out that one should keep in mind serious hematological side effects with atypical antipsychotic drug use with this case report.
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Child , Humans , Agranulocytosis , Anemia , Anemia, Aplastic , Anemia, Hemolytic , Anemia, Hemolytic, Autoimmune , Antipsychotic Agents , Eosinophilia , Erythrocytes , Purpura, Thrombocytopenic , Quetiapine FumarateABSTRACT
Objective To establish a LC-MS analytical method for determination of N,N-dimethylaniline which is genotoxic impurity in quetiapine fumarate.Methods The method was achieved by an Waters ACQUITY UPLC CSHTM PhenylHexyl(2.1 mm× 100 mm,1.7 μm) utilizing a mobile phase of buffer-methanol(900∶ 100) (A)-acetonitrile(B) with gradient elution at the flow rate of 0.4 mL·min-1.The temperature of column was set at 50 ℃;The DIONEX Ultimate 3000 HPLC-AB Science 4000 QTrap Tripling Four bar LC-MS to detect N,N-Dimethylaniline (ESI source,in MRM positive mode).Results Standard curve was linear in the range of 0.4-8.0 ng(r =0.999 3);The limit of detection was 0.2 ng;The limit of quantification of N,N-dimethylaniline was 0.4 ng,respectively.The average recovery of N,N-dimethylaniline was 103.3 ％;RSD was 4.3％ (n =9),respectively.Conclusion The method is convenient and sensitive for the determination of N,N-dimethylaniline in quetiapine fumarate.
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BACKGROUND/AIMS: Cancer-induced bone pain (CIBP) is one of the most common pains in patients with advanced neoplasms. Because of treatment-associated side effects, more than half of cancer patients are reported to have inadequate and undermanaged pain control. New mechanism-based therapies must be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug. We report a study of the potential analgesic effects of quetiapine in a mouse model of CIBP and examine the mechanism of bone pain by analyzing the expression of various nociceptors. METHODS: Fifteen male C3H/HeN mice were arbitrarily divided into five groups: control and, CIBP with no treatment, quetiapine treatment, opioid treatment, and melatonin treatment. The mice were tested for mechanical hyperalgesia by determining the nociceptive hind paw withdrawal pressure threshold. Tissues from tibia were removed and subjected to quantitative and qualitative evaluations of transient receptor potential vanilloid 1 (TRPV1), TRPV4, acid-sensing ion channel 1 (ASIC1), ASIC2, and ASIC3 expression. RESULTS: Paw withdrawal pressure threshold was improved in the quetiapine treatment group compared with the CIBP group. Expression of TRPV1, TRPV4, ASIC1, ASIC2, and ASIC3 in the CIBP with quetiapine treatment group was significantly lower than that in the CIBP group. CONCLUSIONS: Our results suggest an analgesic effect of quetiapine in the CIBP animal model and implicate TRPV and ASICs as potential targets for cancer pain management.
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Animals , Humans , Male , Mice , Evaluation Studies as Topic , Hyperalgesia , Ion Channels , Melatonin , Models, Animal , Nociceptors , Pain Management , Quetiapine Fumarate , TibiaABSTRACT
Objective To establish a method for the determination of quetiapine fumarate in human serum by RP‐HPLC and apply it into clinical .Methods Extracting with ethyl ether after serum‐drug was alkalized ,and then determined by RP‐HPLC .The determination was performed on Zorbax Eclipse XDB‐C18 column with mobile phase consisted of methanol‐water (70∶30 ,containing 0 .5% triethylamine and 0 .4% glacial acetic acid) at the flow rate of 0 .6 ml/min .The detection wave‐length was set at 254 nm ,and the column temperature was 35 ℃ .The method would be applied into analysis of clinical medica‐tion .Results Quetiapine fumarate and the impurities could be completely separated ,and the linear range of quetiapine fumar‐ate were 50‐1 000 ng/ml(r=0 .999 5) .The recovery of the method was 98 .2%‐100 .1% and the recovery of extracting was 75 .2%‐84 .6% .RSD of intra‐day was within 0 .8%‐3 .7% and RSD of inter‐day was within 1 .4%‐5 .1% .The limit of quantita‐tion for quetiapine fumarate was 2 .1 ng/ml .This method had been applied into clinical pharmacy and achieved a good effects . Conclusions The method is simple ,accurate ,reproducible ,and sensitive for determination of quetiapine fumarate in human se‐rum .It has important significance on instructing the rational use of clinical medicine and discovering the unreasonable drug combination .
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OBJECTIVE:To prepare and evaluate the quality of Quetiapine fumarate solid lipid nanoparticles(QF-SLN)in situ nasal gel. METHODS:With the oil phase of dissoned glycerin monostearate,emulsifier of sorbitan oleate,and co-emulsifier of n-butyl alcohol,the proportion of emulsifier and co-emulsifier (Km) was screened by ternary phase diagrams. QF-SLN was pre-pared through the micro-emulsion technology,the gelling temperature was set as index,the mass fraction of poloxamerln 407 (P407)and P188 of in situ gel formulation was optimized by the central composite design-response surface methodology. in situ for-mation of QF-SLN was examined by transmission electron microscope,the particle size and potential distribution were determined by Malvern laser granularity equipment,and the encapsulation efficiency and stability were determined by the ultrafiltration centri-fuge tube and HPLC. RESULTS:The formulation of solid lipid nanoparticlesl was biggest at Km=1∶9. The optimized formulation was with 21% P407,5.6% P188 and 73.4% water. The prepared QF-SLN in situ nasal gel was uniform sphere,with an average particle size of (136.3 ± 6.4) nm and encapsulation efficiency of (97.60 ± 0.48)%. There were no obvious changes in the particle size and entrapment efficiency at 4℃within one month. CONCLUSIONS:The QF-SLN in situ nasal gel is successfully prepared.
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The aim of present study was to develop and evaluate buccoadhesive Quetiapine Fumarate (QF) tablets, which is extensively metabolised by liver. Buccoadhesive tablets of QF were prepared using HPMC K4M, HPMC K15M and combination of carbopol and HPC as mucoadhesive polymers by direct compression method. Sodium deoxycholate was added to formulation to improve the permeation of drug. The formulations were tested for bioadhesion strength, ex vivo residence time, swelling time and in vitro dissolution studies and ex vivo permeation studies. Optimized formulation (F3) showed 92% in vitro release in 8 h and 67% permeation of drug through porcine buccal mucosa and followed fickian release mechanism with zero order kinetics. FTIR studies of optimized formulation showed no evidence of interaction between the drug and polymers. In vivo mucoadhesive behaviour of optimized formulation was performed and subjective parameters were evaluated.
O objetivo do presente estudo foi desenvolver e avaliar os comprimidos bucoadesivos de fumarato de quetiapina (FQ), que é extensivamente metabolizada no fígado. Os comprimidos bucoadesivos de FQ foram preparados utilizando-se HPMC K4M, HPMC K15M e a combinação de carbopol e HPC como polímeros mucoadesivos pelo método de compressão direta. O desoxicolato de sódio foi adicionado à formulação para melhorar a permeação do fármaco. As formulações foram testadas quanto à força de bioadesão, tempo de residência ex vivo, tempo de inchamento, dissolução in vitro e permeação ex vivo. A formulação otimizada (F3) mostrou 92% de liberação in vivo em 8 h e 67% de permeação do fármaco através da mucosa bucal de porco e seguiu o mecanismo fickiano de liberação com cinética de ordem zero. Os estudos de FTIR da formulação otimizada não mostraram evidência da interação entre o fármaco e os polímeros. O comportamento mucoadesivo in vivo da formulação otimizada foi efetuado e avaliaram-se os parâmetros subjetivos.
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Animals , Tablets/classification , Chemistry, Pharmaceutical/instrumentation , /classification , Quetiapine Fumarate/analysis , Mouth MucosaABSTRACT
<b>Objective</b>: Novel antipsychotic agents less frequently cause extrapyramidal side effects compared to conventional antipsychotic agents, contributing to improvement in the QOL. Recently, these agents have also been increasingly prescribed to females who may become pregnant. In Japan, no epidemiological survey regarding the application of novel antipsychotic agents in pregnant women has been published. In this study, we investigated the influence on fetuses in pregnant women receiving novel antipsychotic agents.<br><b>Methods</b>: In pregnant women on novel antipsychotic agents who consulted the Pregnancy and Drug Consultation Outpatient Clinic of Toranomon Hospital, the outcome of pregnancy was confirmed.<br><b>Results</b>: Twenty-nine pregnant women took novel antipsychotic agents in the organogenesis phase, in which the risk of teratogenicity is the highest. The agents consisted of olanzapine in 8 patients, risperidone in 11, quetiapine fumarate in 7, and perospirone hydrochloride hydrate in 4. The outcomes of pregnancy were full-term delivery in 24 patients, premature delivery in 1, spontaneous abortion in 2, and artificial abortion in 2. Of the 29 patients, 15 (60%) had continuously taken these agents until delivery. All 25 neonates were healthy without malformation.<br><b>Conclusion</b>: This report describes the first prospective survey in Japan regarding infants delivered by pregnant women receiving novel antipsychotic agents. All patients delivered healthy neonates; the incidence of congenital anomalies did not exceed that in the general population. This survey included a small number of patients; cohort studies should be conducted to evaluate the safety in fetuses.
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Objective To investigate the influence of quetiapine fumarate on the liver function of patients with schizophrenia.Method Liver function change of 63 patients with schizophrenia were compared before treat- ment and at the end of six weeks after treatment with the method of self comparison.Results Patients'ALT in- creased evidently after treatment,A/G decreased(P0.05).Conclusions Quetiapine fumarate induces symptomless abnormal ALT and AST.But it has a great effect of estimation.