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Emergency department management of acute agitation in the reproductive age female and pregnancy

World Journal of Emergency Medicine 2024年第2期15卷 83-90页

作者： Ariella Gartenberg Kayla Levine Alexander Petrie Department of Emergency Medicine Jacobi Medical Center and Montefiore Medical CenterNY 10461USA Department of Psychiatry and Behavioral Sciences Albert Einstein College of Medicine and Montefiore Medical CenterNY 10461USA Department of Emergency Medicine Jacobi Medical Center and North Central Bronx HospitalNY 10461USA

BACKGROUND:Agitation is a common presentation within emergent departments(EDs).Agitation during pregnancy should be treated as an obstetric emergency,as the distress may jeopardize both the patient and fetus.The safety of psychotropic medications in the reproductive age female has not been well established.This review aimed to explore a summary of general agitation recommendations with an emphasis on ED management of agitation during pregnancy.METHODS:A literature review was conducted to explore the pathophysiology of acute agitation and devise a preferred treatment plan for ED management of acute agitation in the reproductive age or pregnant female.RESULTS:While nonpharmacological management is preferred,ED visits for agitation often require medical management.Medication should be selected based on the etiology of agitation and the clinical setting to avoid major adverse effects.Adverse effects are common in pregnant females.For mild to moderate agitation in pregnancy,diphenhydramine is an effective sedating agent with minimal adverse effects.In moderate to severe agitation,high-potency typical psychotropics are preferred due to their neutral effects on hemodynamics.haloperidol has become the most frequently utilized psychotropic for agitation during pregnancy.Second generation psychotropics are often utilized as second-line therapy,including risperidone.Benzodiazepines and ketamine have demonstrated adverse fetal outcomes.CONCLUSION:While randomized control studies cannot be ethically conducted on pregnant patients requiring sedation,animal models and epidemiologic studies have demonstrated the effects of psychotropic medication exposure in utero.As the fetal risk associated with multiple doses of psychotropic medications remains unknown,weighing the risks and benefits of each agent,while utilizing the lowest effective dose remains critical in the treatment of acute agitation within the EDs.

关键词： Agitation Pregnancy haloperidol Ketamine Benzodiazepines

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STON2风险变异通过影响Syt1转运和突触功能导致精神分裂症样行为

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Science Bulletin 2024年第10期69卷 1458-1471页

作者：马远林高凯孙晓璇王金鑫杨扬武建荧柴安平姚立刘楠郁昊苏怡卢天兰王力芳岳伟华章晓辉徐林张岱李俊 Peking University Sixth Hospital Peking University Institute of Mental HealthNHC Key Laboratory of Mental Health(Peking University)National Clinical Research Center for Mental Disorders(Peking University Sixth Hospital)Key Laboratory of Mental HealthChinese Academy of Medical SciencesBeijing 100191China The First Affiliated Hospital Chongqing Medical UniversityChongqing Key Laboratory of NeurologyChongqing 400016China Changping Laboratory Beijing 102206China d Chinese Institute for Brain Research Beijing 102206China Laboratory of Learning and Memory Kunming Institute of ZoologyChinese Academy of SciencesKunming 650201China Shenzhen Key Laboratory of Translational Research for Brain Diseases The Brain Cognition and Brain Disease InstituteShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research InstitutionsShenzhen 518055China State Key Laboratory of Cognitive Neuroscience and Learning IDG/McGovern Institute for Brain ResearchBeijing Normal UniversityBeijing 100875China PKU-IDG/McGovern Institute for Brain Research Peking UniversityBeijing 100871China

Synaptic dysfunction is a core component of the pathophysiology of schizophrenia.However,the genetic risk factors and molecular mechanisms related to synaptic dysfunction are still not fully understood.The Stonin 2(STON2)gene encodes a major adaptor for clathrin-mediated endocytosis(CME)of synaptic vesicles.In this study,we showed that the C-C(307Pro-851Ala)haplotype of STON2 increases the susceptibility to schizophrenia and examined whether STON2 variations cause schizophrenia-like behaviors through the regulation of CME.We found that schizophrenia-related STON2 variations led to protein dephosphorylation,which affected its interaction with synaptotagmin 1(Syt1),a calcium sensor protein located in the presynaptic membrane that is critical for CME.STON2307Pro851Ala knockin mice exhibited deficits in synaptic transmission,short-term plasticity,and schizophrenia-like behaviors.Moreover,among seven antipsychotic drugs,patients with the C-C(307Pro-851Ala)haplotype responded better to haloperidol than did the T-A(307Ser-851Ser)carriers.The recovery of deficits in Syt1 sorting and synaptic transmission by acute administration of haloperidol effectively improved schizophrenia-like behaviors in STON2307Pro851Ala knockin mice.Our findings demonstrated the effect of schizophreniarelated STON2 variations on synaptic dysfunction through the regulation of CME,which might be attractive therapeutic targets for treating schizophrenia-like phenotypes.

关键词： STON2 variations Schizophrenia Synaptic dysfunction Syt1 haloperidol

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Successful management of delirium with dexmedetomidine in a patient with haloperidol-induced neuroleptic malignant syndrome:A case report

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World Journal of Clinical Cases 2022年第2期10卷 625-630页

作者： Chi-Ju Yang Ching-Tang Chiu Yu-Chang Yeh Anne Chao Department of Pharmacy National Taiwan University HospitalTaipei 100220Taiwan Department of Anesthesiology National Taiwan University HospitalTaipei 100220Taiwan

BACKGROUND We report a case of lorazepam-induced agitated delirium treated with haloperidol,which in turn triggered the onset of neuroleptic malignant syndrome(NMS).The latter condition,a medical emergency,was effectively treated with medical treatment and dexmedetomidine,a versatile and highly selective shortacting alpha-2 adrenergic agonist with sedative-hypnotic and anxiolytic effects.CASE SUMMARY A 65-year-old man with a history of bipolar disorder presented to the emergency department with severe abdominal discomfort after binge eating.During his hospital stay,he received intravenous lorazepam for insomnia.On the next day,he became delirious and was thus treated with seven doses(5 mg each)of haloperidol over a 48 h period.Signs of NMS(hyperthermia,rigidity,myoclonus of upper limbs,impaired consciousness,tachypnea,and dark urine)became apparent and haloperidol was immediately suspended and brisk diuresis was initiated.On intensive care unit admission,he was confused,disoriented,and markedly agitated.Dexmedetomidine infusion was started with the goal of achieving a Richmond Agitation-Sedation Scale score of-1 or 0.NMS was resolved gradually and the patient stabilized,permitting discontinuation of dexmedetomidine after 3 d.CONCLUSION Dexmedetomidine may be clinically helpful for the management of NMS,most likely because of its sympatholytic activity.

关键词： haloperidol Dexmedetomidine Delirium Neuroleptic malignant syndrome Alpha-2 adrenergic agonists Case report

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Biphasic effects of haloperidol on sodium currents in guinea pig ventricular myocytes

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Acta Pharmacologica Sinica 2007年第6期28卷 783-788页

作者： Subat TURDI Parhat KERRAM Department of Pharmacology School of PharmacyXinjiang Medical UniversityUrumqi 830054China

Aim:To study the effects of haloperidol on sodium currents (INa) in guinea pigventricular myocytes.Method:Whole-cell patch clamp technique was employedto evaluate the effects of haloperidol on INain individual ventricular myocytes.Results:haloperidol (0.1-3 μmol/L) inhibited INain a concentration-dependentmanner with an IC50of 0.253±0.015 μmol/L.The inhibition rate of haloperidol (0.3μmol/L) on INawas 22.14%±0.02%,and the maximum conductance was reduced.haloperidol significantly reduced the midpoints for the activation and inactiva-tion of INaby 2.09 and 4.09 mV,respectively.The time constant of recovery wasincreased.The increase in time intervals could only recover by 90.14%±1.4%(n=6);however,haloperidol at 0.03 μmol/L enhanced INaconductance.The mid-points for the activation and inactivation of INawere shifted by 1.38 and 5.69 mV,respectively,at this concentration of haloperidol.Conclusion:haloperidol dis-played a biphasic effect on INain guinea pig cardiac myocytes.High concentra-tions of haloperidol inhibited INa,while lower concentrations of haloperidol shiftedthe activation and inactivation curve to the left.Full recovery of recovery curvewas not achieved after 0.3 μmol/L haloperidol administration,indicating that thedrug affects the inactivated state of sodium channels.

关键词： haloperidol sodium current ventricular myocytes

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Effects of (-)-stepholidine on NMDA receptors:comparison with haloperidol and clozapine

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Acta Pharmacologica Sinica 2007年第7期28卷 953-958页

作者： Wei-hua GU~2,Shen YANG~2,Wei-xing SHI~3,Xue-chu ZHEN~2,Guo-zhang JIN~(2,4)~2 Department of Pharmacology,State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Shanghai Institutes ofBiological Sciences,Graduate School of the Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai 201203,China ~3 Neuropsychopharmacological Research Unit,Department of Psychiatry,Yale University School of Medicine,New Haven,Connecticut06511,USA Department of Pharmacology State Key Laboratory of Drug Research Shanghai Institute of Materia Medica Shanghai Institutes of Biological Sciences Graduate School of the Chinese Academy of Sciences Chinese Academy of Sciences Shanghai China Department of Psychiatry Neuropsychopharmacological Research Unit Yale University School of Medicine New Haven USA

Aim:To examine whether （-）-stepholidine （SPD） has a direct effect on the N-methyl-D-aspartic acid receptors （NMDAR） containing the NMDA receptor sub-units NR2A or NR2B and to compare its effect with those of haloperidol （Hal） andclozapine （Cloz）.Methods:NMDAR was transiently expressed in human embry-onic kidney 293 （HEK293） cells.Changes in intracellular calcium concentration([Ca2+]i) induced by NMDAR activation were monitored with Fura-2 ratio imagingtechniques.Results:SPD had no significant effects on either subunit of NMDARat a concentration of less than 100 μmol/L.Hal selectively inhibited NMDARcontaining the NR2B subunit,whereas Cloz inhibited both subunits of NMDAR.Although both Hal and Cloz inhibited NR1a/NR2B receptor-mediated Ca2+influx,their effects were different.Hal was more potent and had a faster peak effect thanCloz.Conclusion:Both Hal and Cloz inhibit NMDAR-mediated function,whereasSPD produced only a little inhibition at a high concentration.Based on our otherstudies,the modulation of SPD on NMDAR function may be via D1receptoraction underlying an indirect mechanism.

关键词： (-)-stepholidine haloperidol clozapine NMDA receptor calcium imaging neuroleptics

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Electrophysiological effects of haloperidol on isolated rabbit Purkinje fibers and guinea pigs papillary muscles under normal and simulated ischemia

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Acta Pharmacologica Sinica 2007年第8期28卷 1155-1160页

作者： Subat TURDI Parhat KERRAM Department of Pharmacology Xinjiang Medical University Urumqi 830054China

Aim:Overdoses of haloperidol are associated with major ventricular arrhythmias,cardiac conduction block,and sudden death.The aim of this experiment was tostudy the effect of haloperidol on the action potentials in cardiac Purkinje fibersand papillary muscles under normal and simulated ischemia conditions in rabbitsand guinea pigs.Methods:Using the standard intracellular microelectrodetechnique,we examined the effects of haloperidol on the action potential param-eters[action potential amplitude（APA）,phase 0 maximum upstroke velocity(Vmax),action potential amplitude at 90% of repolarization(APD90),and effective refrac-tory period（ERP）]in rabbit cardiac Purkinje fibers and guinea pig cardiac papillarycells,in which both tissues were under simulated ischemic conditions.Results:Under ischemic conditions,different concentrations of haloperidol depressed APAand prolonged APD90in a concentration-dependent manner in rabbit Purkinjefibers.haloperidol（3μmol/L）significantly depressed APA and prolonged APD90,and from 1μmol/L,haloperidol showed significant depression on Vmax;ERP wasnot significantly affected.In guinea pig cardiac papillary muscles,the thresholdsof significant reduction in APA,Vmax,EPR,and APD90were 10,0.3,1,and1μmol/L,respectively,for haloperidol.Conclusion:Compared with cardiac con-ductive tissues,papillary muscles were more sensitive to ischemic conditions.Under ischemia,haloperidol prolonged ERP and APD90in a concentration-depen-dent manner and precipitated the decrease in Vmaxinduced by ischemia.Theshortening of ERP and APD90in papillary muscle action potentials may be inhibi-ted by haloperidol.

关键词： haloperidol Purkinje fibers ischemic action potential arrhythmia

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Solid lipid nanoparticles for nose to brain delivery of haloperidol:in vitro drug release and pharmacokinetics evaluation

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Acta Pharmaceutica Sinica B 2014年第6期4卷 454-463页

作者： Mohd Yasir Udai Vir Singh Sara Department of Pharmacy Uttarakhand Technical UniversityDehradun 248007UttarakhandIndia Department of Pharmaceutics ITS Pharmacy CollegeMuradnagarGhaziabad 201206Uttar PradeshIndia College of Pharmaceutical Sciences Raj Kumar Goel Institute of TechnologyGhaziabad 201201Uttar PradeshIndia

In the present study,haloperidol(HP)-loaded solid lipid nanoparticles(SLNs)were prepared to enhance the uptake of HP to brain via intranasal(i.n.)delivery.SLNs were prepared by a modified emulsification-diffusion technique and evaluated for particle size,zeta potential,drug entrapment efficiency,in vitro drug release,and stability.All parameters were found to be in an acceptable range.In vitro drug release was found to be 94.1674.78%after 24 h and was fitted to the Higuchi model with a very high correlation coefficient(R2¼0.9941).Pharmacokinetics studies were performed on albino Wistar rats and the concentration of HP in brain and blood was measured by high performance liquid chromatography.The brain/blood ratio at 0.5 h for HP-SLNs i.n.,HP sol.***.n.and HP sol.***.v.was 1.61,0.17 and 0.031,respectively,indicating direct nose-to-brain transport,bypassing the blood-brain barrier.The maximum concentration(Cmax)in brain achieved from i.***.administration of HP-SLNs(329.17720.89 ng/mL,Tmax 2 h)was significantly higher than that achieved after i.v.(76.9577.62 ng/mL,Tmax 1 h),and i.n.(90.1376.28 ng/mL,Tmax 2 h)administration of HP sol.The highest drug-targeting efficiency(2362.43%)and direct transport percentage(95.77%)was found with HP-SLNs as compared to the other formulations.Higher DTE(%)and DTP(%)suggest that HP-SLNs have better brain targeting efficiency as compared to other formulations.

关键词： Brain targeting haloperidol Intranasal route Pharmacokinetics Solid lipid nanoparticles

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Antipsychotics preserve telomere length in peripheral blood mononuclear cells after acute oxidative stress injury

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Neural Regeneration Research 2022年第5期17卷 1156-1160页

作者： Gabriel B.Polho Giancarlo M.Cardillo Daniel S.Kerr Thais Chile Wagner F.Gattaz Orestes V.Forlenza Helena P.Brentani Vanessa J.De-Paula Laboratório de Neurociências(LIM-27) Departamento e Instituto de PsiquiatriaHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de São PauloSPBrasil Laboratório de Psicobiologia(LIM-23) Departamento e Instituto de PsiquiatriaHospital das Clinicas HCFMUSPFaculdade de MedicinaUniversidade de São PauloSPBrasil

Antipsychotics may prolong or retain telomere length,affect mitochondrial function,and then affect the metabolism of nerve cells.To validate the hypothesis that antipsychotics can prolong telomere length after oxidative stress injury,leukocytes from healthy volunteers were extracted using Ficoll-Histopaque density gradient.The mononuclear cells layer was resuspended in cell culture medium.Oxidative stress was induced with hydrogen peroxide in cultured leukocytes.Four days later,leukocytes were treated with aripiprazole,haloperidol or clozapine for 7 days.Real-time PCR revealed that treatments with aripiprazole and haloperidol increased the telomere length by 23%and 20%in peripheral blood mononuclear cells after acute oxidative stress injury.These results suggest that haloperidol and aripiprazole can reduce the damage to telomeres induced by oxidative stress.The experiment procedure was approved by the Ethics Committee of Faculty of Medicine of the University of Sao Paulo(FMUSP/CAAE approval No.52622616.8.0000.0065).

关键词： antipsychotic aripiprazole cell culture clozapine haloperidol oxidative stress peripheral blood mononuclear cell telomere length

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A Comparison Study of the Efficacy of Rapid Titration Quetiapine and haloperidol in Agitated Adults in an Emergency Setting

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Open Journal of Psychiatry 2014年第3期4卷 189-194页

作者： Akikur Mohammad Eugene Laska Marius Campaneau Fauzia Syed Rebecca Ninah Joseph Wanderling George Simpson Department of Psychiatry LAC-USC Los Angeles CA USA Nathan Kline Institute New York NY USA

Objective: Intramuscular (IM) Benzodiazepines and/or haloperidol alone or with benzodiazepines are frequently used to treat agitation. Based on emerging literature regarding Quetiapine used for the control of anxiety we examined Quetiapine as a possible alternative in selected cases. Methods: This study was a single-blind randomized study comparing Quetiapine PO (300 mg) with a combination of haloperidol (5 mg), Benztropine mesylate (2 mg) and lorazepam (2 mg) administered IM to treat agitated patients seeking care in a busy psychiatric emergency setting. Male or female patients (18 - 60), deemed by the attending (admitting) psychiatrist to be indicative of agitated and/or aggressive behavior and had a Positive and Negative Syndrome Score-Excited Component (PANSS-EC), as evaluated by the Research Psychiatrist, and total score equal to or greater than 15. Patients deemed competent were randomized into one of the following treatment groups: Quetiapine 300 or haloperidol 5 mg, benztropine mesylate, or lorazepam given by the IM route. Two scales, PANSS-EC and CGI-C were used to assess patients in the trial. The primary outcome measure PANSS-EC at 2 hours after administration of the medication. Results: Sixty-eight patients were included in the study. There were no significant treatment group differences in baseline condition. There was no significant difference between the two conditions. There was, however, a significant within-group decrease from baseline condition. Conclusion: Finding no significant differences suggests that in general the two treatments were equivalent. To sum up, Quetiapine 300 mg as a single dose appeared safe and effective in agitated patients treated in an ER. The results were similar to a comparison group receiving an intra-muscular combination of haloperidol, Lorazepam and Benztropine. This study has significant limitations. The study was single blind and the use of a placebo would have strengthened the design but would be considered unethical. The sample size was relatively small and the g

关键词： Quetiapine (Oral) haloperidol (Parenteral) Agitation Excitement Psychoses

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Establishment and Effects of Ginger and Kikyoto of a haloperidol-Induced Dysphagia Model in Guinea Pigs

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Pharmacology & Pharmacy 2016年第2期7卷 97-105页

作者： Takahiro Mizoguchi Mitsue Ishisaka Yui Kobatake Hiroaki Kamishina Yasuhiko Nishioka Tsukasa Kirimoto Masamitsu Shimazawa Hideaki Hara Molecular Pharmacology Department of Biofunctional Evaluation Gifu Pharmaceutical University Gifu Japan Department of Veterinary Medicine Faculty of Applied Biological Sciences Gifu University Gifu Japan Taiho Pharmaceutical Co. Ltd. Tokushima Japan

Dysphagia induces aspiration and causes aspiration pneumonia. There is no treatment for dysphagia fundamentally. haloperidol reportedly induces dysphagia. In the present study, we established a haloperidol-induced dysphagia model in guinea pigs, and evaluated the effects of ginger, kikyoto, and a mixture of ginger and kikyoto on swallowing. Swallowing ability was evaluated using behavioral tests, computed tomography (CT), and videofluoroscopic examination of swallowing. To investigate the effect of ginger and kikyoto on swallowing, ginger, kikyoto, or a mixture of ginger and kikyoto was administered orally to guinea pigs with haloperidol-induced dysphagia. Effects of these compounds were evaluated with behavioral tests. Chronic administration of haloperidol reduced the number of swallows, as evaluated by the behavioral test and videofluoroscopic examination of swallowing. In our model, these compounds improved swallowing dysfunction. Our results suggest that this model might be useful in revealing the pathogenesis of dysphagia and evaluating compounds that might improve swallowing.

关键词： Dysphagia Guinea Pig Videofluoroscopic Examination of Swallowing haloperidol Ginger

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