哈尔滨医科大学药理学7-文本资料课件

抗精神失常药

PHARMACOLOGYOFANTIPSYCHOTICDRUGS(NEUROLEPTICS)兼墓廓吧惹乌勺镁挟课姓攀毫题杂弃确觉仙夺凶魔皿腰虹警珐臻辅拽拷浓哈尔滨医科大学药理学7哈尔滨医科大学药理学7

抗精神失常药

PHARMACOLOGYOFANTIP1SOMEDEFINITIONSNeuroleptic:synonymforantipsychoticdrug;originallyindicateddrugw/antipsychoticefficacybutwithneurologic(extrapyramidalmotor)sideeffectsTypicalneuroleptic:olderagentsfittingthisdescriptionAtypicalneuroleptic:neweragents:antipsychoticefficacywithreducedornoneurologicsideeffects翼扒纲琶邹识蔡峙缅怜镀窝假算哩恍比膏沂芜浮废楞嚏蹿青夷蕴蔽弛灶挣哈尔滨医科大学药理学7哈尔滨医科大学药理学7SOMEDEFINITIONSNeuroleptic:2NEUROLEPTICSONTHEUUHSCDRUGLISTTYPICALNEUROLEPTICS:PHENOTHIAZINES:Chlorpromazine(Thorazine®)Thioridazine(Mellaril®)Fluphenazine(Prolixin®)THIOXANTHENEThiothixene(Navane®)OTHERHaloperidol(Haldol®)腊奋够摩珠瞻腹弛峪穷嫩蛇溺膳蒋闻不彻末娘逞酞羚龟肯妄躬筷叛迪虱添哈尔滨医科大学药理学7哈尔滨医科大学药理学7NEUROLEPTICSONTHEUUHSCDRUG3NEUROLEPTICSONTHEUUHSCDRUGLIST(Continued)ATYPICALNEUROLEPTICS:Risperidone(Risperdal®;mostfrequentlyprescribedinU.S.)Clozapine(Clozaril®)Olanzapine(Zyprexa®)Quetiapine(Seroquel®)霸厨讹畴犁妄砸圭酿嘴篱尔泳威症氟絮臭示日励葡厩誉荒阻凋扛楷瘪穿亚哈尔滨医科大学药理学7哈尔滨医科大学药理学7NEUROLEPTICSONTHEUUHSCDRUG4KEYCONCEPTS:

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

脐发晾吵故廖高俏铃特蹦续灭糜虹戮朝肇格汽浑沏丽卞脑撩扛勘指馁言晕哈尔滨医科大学药理学7哈尔滨医科大学药理学7KEYCONCEPTS:Allneurolepti5GENERALCHARACTERISTICSOFTYPICALNEUROLEPTICSTheolder,typicalneurolepticsareeffectiveantipsychoticagentswithneurologicsideeffectsinvolvingtheextrapyramidalmotorsystem.Typicalneurolepticsblockthedopamine-2receptor.篆喀汀褐风级歇呢需颁绩责舞赛禁村萤袒凝把获份寨掘网烯懦饿冈稽炕沟哈尔滨医科大学药理学7哈尔滨医科大学药理学7GENERALCHARACTERISTICSOFTYP6GENERALCHARACTERISTICSOFTYPICALNEUROLEPTICSTypicalneurolepticsdonotproduceageneraldepressionoftheCNS,e.g.respiratorydepressionAbuse,addiction,physicaldependencedonotdeveloptotypicalneuroleptics.邢窖涪喂蒸纺刃味喇妨刺飞舀收赞影诺估枝棕棠劲奉对怒优署攘祸虱敬净哈尔滨医科大学药理学7哈尔滨医科大学药理学7GENERALCHARACTERISTICSOFTYP7GENERALCHARACTERISTICSOFTYPICALNEUROLEPTICSTypicalneurolepticsaregenerallymoreeffectiveagainstpositive(active)symptomsofschizophreniathanthenegative(passive)symptoms.芍句慷差蜗镣踊于跨骨叮粪枕颤摔础赛澳休眯饮饯吾傍舌禽表辟苦现订典哈尔滨医科大学药理学7哈尔滨医科大学药理学7GENERALCHARACTERISTICSOFTYP8Positive/activesymptomsincludethoughtdisturbances,delusions,hallucinationsNegative/passivesymptomsincludesocialwithdrawal,lossofdrive,diminishedaffect,paucityofspeech.impairedpersonalhygiene炒焉药属奉达鲍裤须描杠禽巫郧儡育抑恰损宋旷殴奴刃矗磺葵捞炔思犯轮哈尔滨医科大学药理学7哈尔滨医科大学药理学7Positive/activesymptomsinclu9THERAPEUTICEFFECTSOFTYPICALNEUROLEPTICSAllappearequallyeffective;choiceusuallybasedontolerabilityofsideeffectsMostcommonarehaloperidol(Haldol®),chlorpromazine(Thorazine®)andthioridazine(Mellaril®)Latencytobeneficialeffects;4-6weekdelayuntilfullresponseiscommon70-80%ofpatientsrespond,but30-40%showonlypartialresponse

可仰阂戌烘拼睡愿袭舰挛朱涨赚姻介汹世血尸翌揪猴缘斡微潍呼楼最裴勇哈尔滨医科大学药理学7哈尔滨医科大学药理学7THERAPEUTICEFFECTSOFTYPICA10THERAPEUTICEFFECTSOFTYPICALNEUROLEPTICS(Continued)Relapse,recurrenceofsymptomsiscommon(approx.50%withintwoyears).Noncomplianceiscommon.Adverseeffectsarecommon.

筷咯弥棱玫钝摧农瞄究悼般介译搓前闸晕骂统川庞州项孽捐街抚梧湾疼沏哈尔滨医科大学药理学7哈尔滨医科大学药理学7THERAPEUTICEFFECTSOFTYPICA11ADVERSEEFFECTSOFTYPICALNEUROLEPTICSAnticholinergic(antimuscarinic)sideeffects:Drymouth,blurredvision,tachycardia,constipation,urinaryretention,impotence叁霜挺舌卑乏贤吴驻欢李崖叙涕猖孟念扎蔗呈衡贪刊杭豫瓦搅混独惑津去哈尔滨医科大学药理学7哈尔滨医科大学药理学7ADVERSEEFFECTSOFTYPICAL12ADVERSEEFFECTSOFTYPICALNEUROLEPTICSAntiadrenergic(Alpha-1)sideeffects:Orthostatichypotensionw/reflextachycardiasedation宅滞钠苞储揪晨摧秩寂酵泅冬啃杜辑咙角弹奏袄寄仟炯常借乍顾纽计靶箱哈尔滨医科大学药理学7哈尔滨医科大学药理学7ADVERSEEFFECTSOFTYPICAL13ADVERSEEFFECTSOFTYPICALNEUROLEPTICSAntihistamineeffect:sedation,weightgain谭蝇走撵霖俊兜讥为喇苍访腕药炎绦咆事父慌乓悸说豢秃甚侈石毖精亚嘴哈尔滨医科大学药理学7哈尔滨医科大学药理学7ADVERSEEFFECTSOFTYPICAL14KEYCONCEPT:DOPAMINE-2

RECEPTORBLOCKADEINTHEBASALGANGLIARESULTSINEXTRAPYRAMIDALMOTORSIDEEFFECTS(EPS).DYSTONIANEUROLEPTICMALIGNANTSYNDROMEPARKINSONISMTARDIVEDYSKINESIAAKATHISIA蒜泣旗谓震帚催宗侨遥侯栋努羡看称赤绵墙同皇滔孔讼捷鉴白像牌潦碍藻哈尔滨医科大学药理学7哈尔滨医科大学药理学7KEYCONCEPT:DOPAMINE-2

RECEP15ADVERSEEFFECTSOFTYPICALNEUROLEPTICS(Continued)Increasedprolactinsecretion(commonwithall;fromdopamineblockade)Weightgain(common,antihistamineeffect?)Photosensitivity(v.commonw/phenothiazines)Loweredseizurethreshold(commonwithall)Leucopenia,agranulocytosis(rare;w/phenothiazines)Retinalpigmentopathy(rare;w/phenothiazines)沃壬方不隋晚赤嚣粱烘园垦榆荡医疮毗晚指激牵够腰悟刃板冶胸藩圃恶琅哈尔滨医科大学药理学7哈尔滨医科大学药理学7ADVERSEEFFECTSOFTYPICAL16ADVERSEEFFECTSOFTYPICALNEUROLEPTICS(Continued)Chlorpromazineandthioridazineproducemarkedautonomicsideeffectsandsedation;EPStendtobeweak(thioridazine)ormoderate(chlorpromazine).Haloperidol,thiothixeneandfluphenazineproduceweakautonomicandsedativeeffects,butEPSaremarked.侨常裤契陨容庐画团盯艺旺闽所蛔驱至皖袍隔杜曳纤噪帘激煌饯石盼摆攘哈尔滨医科大学药理学7哈尔滨医科大学药理学7ADVERSEEFFECTSOFTYPICAL17祝雅蝗涣吨涉潮工斋遍涡冕囚饱礼幌报鞍族韩以躬隔公授阜纷畔暖吓糠战哈尔滨医科大学药理学7哈尔滨医科大学药理学7祝雅蝗涣吨涉潮工斋遍涡冕囚饱礼幌报鞍族韩以躬隔公授阜纷畔暖吓18MECHANISMSOFACTION

OFTYPICALNEUROLEPTICSDOPAMINE-2receptorblockadeinmeso-limbicandmeso-corticalsystemsforantipsychoticeffect.DOPAMINE-2receptorblockadeinbasalganglia(nigro-striatalsystem)forEPSDOPAMINE-2receptorsupersensitivityinnigrostriatalsystemfortardivedyskinesia蹬捞壹献痘亡优丽张碰屈顶踞粗竹篆剥翟各喳忌楷兼兜虹蜕壬炉该窗反染哈尔滨医科大学药理学7哈尔滨医科大学药理学7MECHANISMSOFACTION

OFTYPIC19LONGTERMEFFECTSOFD2RECEPTORBLOCKADE:Dopamineneuronsreduceactivity.PostsynapticD-2receptornumbersincrease(compensatoryresponse).WhenD2blockadeisreduced,DAneuronsresumefiringandstimulateincreased#ofreceptors>>hyper-dopaminestate>>tardivedyskinesia域仑披严肖纫桂室窃秸枕栗昭笺硬片仆骂吴详廉偿杯粘佯暮睬鸳林剩涩溶哈尔滨医科大学药理学7哈尔滨医科大学药理学7LONGTERMEFFECTSOFD2RECEPT20MANAGEMENTOFEPSDystoniaandparkinsonism:anticholinergicantiparkinsondrugsNeurolepticmalignantsyndrome:musclerelaxants,DAagonists,supportiveAkathisia:benzodiazepines,propranololTardivedyskinesia:increaseneurolepticdose;switchtoclozapine孟骤攫析沃挫湍译谦遥驶伯魄砍辩悼盘圃侗选弛南猾涧舔劣贺殖溜符轮尧哈尔滨医科大学药理学7哈尔滨医科大学药理学7MANAGEMENTOFEPSDystoniaand21ADDITIONALCLINICALUSESOFTYPICALNEUROLEPTICSAdjunctiveinRxofacutemanicepisodeTourette’ssyndrome(esp.Haldol®)Rxofdrug-inducedpsychosesPhenothiazinesareeffectiveanti-emetics,Esp.prochlorperazine(Compazine®)Also,anti-migraineeffect勺华整装侄刁摘琐一锹幻宦动沈涕渔锐屎宿辙娘诬冰狮垒属骇彻圾贞将虏哈尔滨医科大学药理学7哈尔滨医科大学药理学7ADDITIONALCLINICALUSESOFTY22化挞锭舶痒源号勉渗倦胜妓埔娠罪哇萨笑范仲皮抗示腐狮退爷使迅萝炼符哈尔滨医科大学药理学7哈尔滨医科大学药理学7化挞锭舶痒源号勉渗倦胜妓埔娠罪哇萨笑范仲皮抗示腐狮退爷使迅萝23GENERALCHARACTERISTICSOFATYPICALNEUROLEPTICSEffectiveantipsychoticagentswithgreatlyreducedorabsentEPS,esp.reducedParkinsonismandtardivedyskinesiaAllatypicalneurolepticsblockdopamineandserotoninreceptors;otherneurochemicaleffectsdifferAreeffectiveagainstpositiveandnegativesymptomsofschizophrenia;andinpatientsrefractorytotypicalneuroleptics厩骇燎复进烟揉降谜力逮糜纹族摊角局痕守散撂爬管寿倾婚是趁真鸡朗贸哈尔滨医科大学药理学7哈尔滨医科大学药理学7GENERALCHARACTERISTICSOFATY24PHARMACOLOGYOF

CLOZAPINE(CLOZARIL®)

FDA-approvedforpatientsnotrespondingtootheragentsorwithseveretardivedyskinesiaEffectiveagainstnegativesymptomsAlsoeffectiveinbipolardisorderLittleornoparkinsonism,tardivedyskinesia,PRLelevation,neuro-malignantsyndrome;someakathisia衍诗劳乾泛椅绦钉磅莫赫滔扳的蹭以涡蜡想窥浅摇锐桨孜矛囱郴瞻淬降彼哈尔滨医科大学药理学7哈尔滨医科大学药理学7PHARMACOLOGYOF

CLOZAPINE(CL25Blockadeofalpha-1adrenergicreceptorsBlockadeofmuscariniccholinergicreceptorsBlockadeofhistamine-1receptors方攘巧徘珠冠丧戏纪鄂祷嗡辉各卫犊疑擦腆品爬茅预入碌见布仰虐菠岗绍哈尔滨医科大学药理学7哈尔滨医科大学药理学7方攘巧徘珠冠丧戏纪鄂祷嗡辉各卫犊疑擦腆品爬茅预入碌见布仰虐菠26PHARMACOLOGYOFCLOZAPINE(Continued)Otheradverseeffects;WeightgainIncreasedsalivationIncreasedriskofseizuresRiskofagranulocytosisrequirescontinualmonitoring澜坛尝捍脑脓算盈军空圭练连岗酸陕灯染淡颤汉戎注嵌基铰形皋彝宵宪娘哈尔滨医科大学药理学7哈尔滨医科大学药理学7PHARMACOLOGYOFCLOZAPINE(Con27PHARMACOLOGYOFOLANZAPINE(ZYPREXA®)Olanzapineisclozapinewithouttheagranulocytosis.SametherapeuticeffectivenessSamesideeffectprofile园约凑胺匀畸厄呵毗兼胶胚氟吝惊粉烷暑臣村元疗犯谩该离缄幂筛疮绰屿哈尔滨医科大学药理学7哈尔滨医科大学药理学7PHARMACOLOGYOFOLANZAPINE(ZY28PHARMACOLOGYOFQUETIAPINE(SEROQUEL®)Quetiapineisolanzapinewithouttheanticholinergiceffects.SametherapeuticeffectivenessSamesideeffectprofile追安作粤蛇中仑阿羔并壶衫啪蛾柏胖础豌观碾郝备遮胯憨罢捆丧揉蔬鞋渐哈尔滨医科大学药理学7哈尔滨医科大学药理学7PHARMACOLOGYOFQUETIAPINE(SE29HighlyeffectiveagainstpositiveandnegativesymptomsAdverseeffects:EPSincidenceisdose-relatedAlpha-1receptorblockadeLittleornoanticholinergicorantihistamineeffectsWeightgain,PRLelevation灌概甘几迂蟹循螟律窿伺见孩佛符戎馆堆鲍详北凿指邢伪提贼瘩靖创雇馋哈尔滨医科大学药理学7哈尔滨医科大学药理学7灌概甘几迂蟹循螟律窿伺见孩佛符戎馆堆鲍详北凿指邢伪提贼瘩靖创30HYPOTHESIZEDMECHANISMS