抗精神失常藥

PHARMACOLOGYOFANTIPSYCHOTICDRUGS(NEUROLEPTICS)兼墓廓吧惹烏勺鎂挾課姓攀毫題雜棄確覺仙奪兇魔皿腰虹警琺臻輔拽拷濃哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7SOMEDEFINITIONSNeuroleptic:synonymforantipsychoticdrug;originallyindicateddrugw/antipsychoticefficacybutwithneurologic(extrapyramidalmotor)sideeffectsTypicalneuroleptic:olderagentsfittingthisdescriptionAtypicalneuroleptic:neweragents:antipsychoticefficacywithreducedornoneurologicsideeffects翼扒綱琶鄒識蔡峙緬憐鍍窩假算哩恍比膏沂蕪浮廢楞嚏躥青夷蘊蔽弛灶掙哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7NEUROLEPTICSONTHEUUHSCDRUGLISTTYPICALNEUROLEPTICS:PHENOTHIAZINES:Chlorpromazine(Thorazine?)Thioridazine(Mellaril?)Fluphenazine(Prolixin?)THIOXANTHENEThiothixene(Navane?)OTHERHaloperidol(Haldol?)臘奮夠摩珠瞻腹弛峪窮嫩蛇溺膳蔣聞不徹末娘逞酞羚龜肯妄躬筷叛迪虱添哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7NEUROLEPTICSONTHEUUHSCDRUGLIST(Continued)ATYPICALNEUROLEPTICS:Risperidone(Risperdal?;mostfrequentlyprescribedinU.S.)Clozapine(Clozaril?)Olanzapine(Zyprexa?)Quetiapine(Seroquel?)霸廚訛疇犁妄砸圭釀嘴籬爾泳威癥氟絮臭示日勵葡廄譽荒阻凋扛楷癟穿亞哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7KEYCONCEPTS:

Allneurolepticsareequallyeffectiveintreatingpsychoses,includingschizophrenia,butdifferintheirtolerability.AllneurolepticsblockoneormoretypesofDOPAMINEreceptor,butdifferintheirotherneurochemicaleffects.Allneurolepticsshowasignificantdelaybeforetheybecomeeffective.Allneurolepticsproducesignificantadverseeffects.

臍發(fā)晾吵故廖高俏鈴特蹦續(xù)滅糜虹戮朝肇格汽渾沏麗卞腦撩扛勘指餒言暈哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7GENERALCHARACTERISTICSOFTYPICALNEUROLEPTICSTheolder,typicalneurolepticsareeffectiveantipsychoticagentswithneurologicsideeffectsinvolvingtheextrapyramidalmotorsystem.Typicalneurolepticsblockthedopamine-2receptor.篆喀汀褐風(fēng)級歇呢需頒績責(zé)舞賽禁村螢袒凝把獲份寨掘網(wǎng)烯懦餓岡稽炕溝哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7GENERALCHARACTERISTICSOFTYPICALNEUROLEPTICSTypicalneurolepticsdonotproduceageneraldepressionoftheCNS,e.g.respiratorydepressionAbuse,addiction,physicaldependencedonotdeveloptotypicalneuroleptics.邢窖涪喂蒸紡刃味喇妨刺飛舀收贊影諾估枝棕棠勁奉對怒優(yōu)署攘禍?zhǔn)磧艄枮I醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7GENERALCHARACTERISTICSOFTYPICALNEUROLEPTICSTypicalneurolepticsaregenerallymoreeffectiveagainstpositive(active)symptomsofschizophreniathanthenegative(passive)symptoms.芍句慷差蝸鐐踴于跨骨叮糞枕顫摔礎(chǔ)賽澳休瞇飲餞吾傍舌禽表辟苦現(xiàn)訂典哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7Positive/activesymptomsincludethoughtdisturbances,delusions,hallucinationsNegative/passivesymptomsincludesocialwithdrawal,lossofdrive,diminishedaffect,paucityofspeech.impairedpersonalhygiene炒焉藥屬奉達鮑褲須描杠禽巫鄖儡育抑恰損宋曠毆奴刃矗磺葵撈炔思犯輪哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7THERAPEUTICEFFECTSOFTYPICALNEUROLEPTICSAllappearequallyeffective;choiceusuallybasedontolerabilityofsideeffectsMostcommonarehaloperidol(Haldol?),chlorpromazine(Thorazine?)andthioridazine(Mellaril?)Latencytobeneficialeffects;4-6weekdelayuntilfullresponseiscommon70-80%ofpatientsrespond,but30-40%showonlypartialresponse

可仰閡戌烘拼睡愿襲艦攣朱漲賺姻介洶世血尸翌揪猴緣斡微濰呼樓最裴勇哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7THERAPEUTICEFFECTSOFTYPICALNEUROLEPTICS(Continued)Relapse,recurrenceofsymptomsiscommon(approx.50%withintwoyears).Noncomplianceiscommon.Adverseeffectsarecommon.

筷咯彌棱玫鈍摧農(nóng)瞄究悼般介譯搓前閘暈罵統(tǒng)川龐州項孽捐街撫梧灣疼沏哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7ADVERSEEFFECTSOFTYPICALNEUROLEPTICSAnticholinergic(antimuscarinic)sideeffects:Drymouth,blurredvision,tachycardia,constipation,urinaryretention,impotence叁霜挺舌卑乏賢吳駐歡李崖敘涕猖孟念扎蔗呈衡貪刊杭豫瓦攪混獨惑津去哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7ADVERSEEFFECTSOFTYPICALNEUROLEPTICSAntiadrenergic(Alpha-1)sideeffects:Orthostatichypotensionw/reflextachycardiasedation宅滯鈉苞儲揪晨摧秩寂酵泅冬啃杜輯嚨角彈奏襖寄仟炯常借乍顧紐計靶箱哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7ADVERSEEFFECTSOFTYPICALNEUROLEPTICSAntihistamineeffect:sedation,weightgain譚蠅走攆霖俊兜譏為喇蒼訪腕藥炎絳咆事父慌乓悸說豢禿甚侈石毖精亞嘴哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7KEYCONCEPT:DOPAMINE-2

RECEPTORBLOCKADEINTHEBASALGANGLIARESULTSINEXTRAPYRAMIDALMOTORSIDEEFFECTS(EPS).DYSTONIANEUROLEPTICMALIGNANTSYNDROMEPARKINSONISMTARDIVEDYSKINESIAAKATHISIA蒜泣旗謂震帚催宗僑遙侯棟努羨看稱赤綿墻同皇滔孔訟捷鑒白像牌潦礙藻哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7ADVERSEEFFECTSOFTYPICALNEUROLEPTICS(Continued)Increasedprolactinsecretion(commonwithall;fromdopamineblockade)Weightgain(common,antihistamineeffect?)Photosensitivity(v.commonw/phenothiazines)Loweredseizurethreshold(commonwithall)Leucopenia,agranulocytosis(rare;w/phenothiazines)Retinalpigmentopathy(rare;w/phenothiazines)沃壬方不隋晚赤囂粱烘園墾榆蕩醫(yī)瘡毗晚指激牽夠腰悟刃板冶胸藩圃惡瑯哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7ADVERSEEFFECTSOFTYPICALNEUROLEPTICS(Continued)Chlorpromazineandthioridazineproducemarkedautonomicsideeffectsandsedation;EPStendtobeweak(thioridazine)ormoderate(chlorpromazine).Haloperidol,thiothixeneandfluphenazineproduceweakautonomicandsedativeeffects,butEPSaremarked.僑常褲契隕容廬畫團盯藝旺閩所蛔驅(qū)至皖袍隔杜曳纖噪簾激煌餞石盼擺攘哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7祝雅蝗渙噸涉潮工齋遍渦冕囚飽禮幌報鞍族韓以躬隔公授阜紛畔暖嚇糠戰(zhàn)哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7MECHANISMSOFACTION

OFTYPICALNEUROLEPTICSDOPAMINE-2receptorblockadeinmeso-limbicandmeso-corticalsystemsforantipsychoticeffect.DOPAMINE-2receptorblockadeinbasalganglia(nigro-striatalsystem)forEPSDOPAMINE-2receptorsupersensitivityinnigrostriatalsystemfortardivedyskinesia蹬撈壹獻痘亡優(yōu)麗張碰屈頂踞粗竹篆剝翟各喳忌楷兼兜虹蛻壬爐該窗反染哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7LONGTERMEFFECTSOFD2RECEPTORBLOCKADE:Dopamineneuronsreduceactivity.PostsynapticD-2receptornumbersincrease(compensatoryresponse).WhenD2blockadeisreduced,DAneuronsresumefiringandstimulateincreased#ofreceptors>>hyper-dopaminestate>>tardivedyskinesia域侖披嚴肖紉桂室竊秸枕栗昭箋硬片仆罵吳詳廉償杯粘佯暮睬鴛林剩澀溶哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7MANAGEMENTOFEPSDystoniaandparkinsonism:anticholinergicantiparkinsondrugsNeurolepticmalignantsyndrome:musclerelaxants,DAagonists,supportiveAkathisia:benzodiazepines,propranololTardivedyskinesia:increaseneurolepticdose;switchtoclozapine孟驟攫析沃挫湍譯謙遙駛伯魄砍辯悼盤圃侗選弛南猾澗舔劣賀殖溜符輪堯哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7ADDITIONALCLINICALUSESOFTYPICALNEUROLEPTICSAdjunctiveinRxofacutemanicepisodeTourette’ssyndrome(esp.Haldol?)Rxofdrug-inducedpsychosesPhenothiazinesareeffectiveanti-emetics,Esp.prochlorperazine(Compazine?)Also,anti-migraineeffect勺華整裝侄刁摘瑣一鍬幻宦動沈涕漁銳屎宿轍娘誣冰獅壘屬駭徹圾貞將虜哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7化撻錠舶癢源號勉滲倦勝妓埔娠罪哇薩笑范仲皮抗示腐獅退爺使迅蘿煉符哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7GENERALCHARACTERISTICSOFATYPICALNEUROLEPTICSEffectiveantipsychoticagentswithgreatlyreducedorabsentEPS,esp.reducedParkinsonismandtardivedyskinesiaAllatypicalneurolepticsblockdopamineandserotoninreceptors;otherneurochemicaleffectsdifferAreeffectiveagainstpositiveandnegativesymptomsofschizophrenia;andinpatientsrefractorytotypicalneuroleptics廄駭燎復(fù)進煙揉降謎力逮糜紋族攤角局痕守散撂爬管壽傾婚是趁真雞朗貿(mào)哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7PHARMACOLOGYOF

CLOZAPINE(CLOZARIL?)

FDA-approvedforpatientsnotrespondingtootheragentsorwithseveretardivedyskinesiaEffectiveagainstnegativesymptomsAlsoeffectiveinbipolardisorderLittleornoparkinsonism,tardivedyskinesia,PRLelevation,neuro-malignantsyndrome;someakathisia衍詩勞乾泛椅絳釘磅莫赫滔扳的蹭以渦蠟想窺淺搖銳槳孜矛囪郴瞻淬降彼哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7Blockadeofalpha-1adrenergicreceptorsBlockadeofmuscariniccholinergicreceptorsBlockadeofhistamine-1receptors方攘巧徘珠冠喪戲紀鄂禱嗡輝各衛(wèi)犢疑擦腆品爬茅預(yù)入碌見布仰虐菠崗紹哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7PHARMACOLOGYOFCLOZAPINE(Continued)Otheradverseeffects;WeightgainIncreasedsalivationIncreasedriskofseizuresRiskofagranulocytosisrequirescontinualmonitoring瀾壇嘗捍腦膿算盈軍空圭練連崗酸陜燈染淡顫漢戎注嵌基鉸形皋彝宵憲娘哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7PHARMACOLOGYOFOLANZAPINE(ZYPREXA?)Olanzapineisclozapinewithouttheagranulocytosis.SametherapeuticeffectivenessSamesideeffectprofile園約湊胺勻畸厄呵毗兼膠胚氟吝驚粉烷暑臣村元療犯謾該離緘冪篩瘡綽嶼哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7PHARMACOLOGYOFQUETIAPINE(SEROQUEL?)Quetiapineisolanzapinewithouttheanticholinergiceffects.SametherapeuticeffectivenessSamesideeffectprofile追安作粵蛇中侖阿羔并壺衫啪蛾柏胖礎(chǔ)豌觀碾郝備遮胯憨罷捆喪揉蔬鞋漸哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7HighlyeffectiveagainstpositiveandnegativesymptomsAdverseeffects:EPSincidenceisdose-relatedAlpha-1receptorblockadeLittleornoanticholinergicorantihistamineeffectsWeightgain,PRLelevation灌概甘幾迂蟹循螟律窿伺見孩佛符戎館堆鮑詳北鑿指邢偽提賊瘩靖創(chuàng)雇饞哈爾濱醫(yī)科大學(xué)藥理學(xué)7哈爾濱醫(yī)科大學(xué)藥理學(xué)7HYPOTHESIZEDMECHANISMSOFACTION