神經(jīng)系統(tǒng)藥理-魏爾清抗精神失常課件

Part11

DrugsusedintheTreatmentofPsychologicalDisordersAntipsychoticdrugsAntidepressantandantimanicdrugsAnxiolyticsBox1

精神分裂癥(schizophrenia)表現(xiàn)表現(xiàn)為基本個(gè)性改變，思維、情感、行為的分裂，精神活動(dòng)與社會(huì)環(huán)境不協(xié)調(diào)。起病緩慢，發(fā)病年齡多在16～40歲之間，20～30歲更為多見(jiàn)?！龌緜€(gè)性改變與人的關(guān)系方面，病人逐漸變得少言寡語(yǔ)，不愿與人交往；在工作與學(xué)習(xí)方面，他們懶于勞動(dòng)，工作、學(xué)習(xí)，不守紀(jì)律，工作或?qū)W習(xí)質(zhì)量逐漸下降；在個(gè)人生活方面，病人懶于料理個(gè)人生活，有的常年不理發(fā)、不更衣、不洗澡、不打掃房間衛(wèi)生等，自己不干也不允許別人幫助。A.Antipsychoticdrugs■感知覺(jué)改變突出的表現(xiàn)是產(chǎn)生幻覺(jué)：①幻聽(tīng)，病人可聽(tīng)到別人聽(tīng)不到的聲音，往往長(zhǎng)時(shí)間存在，可以是談話聲、叫喊聲、咒罵聲等，而且內(nèi)容與他有關(guān)。②幻視，可在意識(shí)清醒的情況下看到奇怪的景象，內(nèi)容可以是模糊的形象，也可能是清晰的人、動(dòng)物、怪物或整套景象，甚至還能看到腦內(nèi)、體內(nèi)的東西。③幻嗅，可嗅到常人嗅不到的怪味，往往是令人厭惡的氣味，如糞便、農(nóng)藥、血腥味等。④幻觸，可感覺(jué)到皮膚上有電刺、蟲(chóng)爬感覺(jué)。⑤本體幻覺(jué)，感到自己的內(nèi)臟被扭轉(zhuǎn)、斷裂、穿孔、游走或晃動(dòng)（內(nèi)臟幻覺(jué)）；感到運(yùn)動(dòng)的物體處于靜止，靜止的物體在運(yùn)動(dòng)（運(yùn)動(dòng)幻覺(jué)）；感到自己的身體在傾斜，不能保持平衡（前庭幻覺(jué)）?！鐾?/p>

①被害妄想，整天疑神疑鬼，擔(dān)心別人會(huì)傷害、殺害他，給他吃的東西懷疑是下了毒的，看到別人手里的東西懷疑是殺他的刀子。②關(guān)系妄想，懷疑別人背后議論他、說(shuō)他的壞話、或跟蹤、監(jiān)視他。③夸大妄想，可自稱(chēng)是某一偉人的后代，或自己就是一個(gè)地位很高的人物，甚至認(rèn)為自己是“地球球長(zhǎng)”、“宇宙長(zhǎng)”。④妒嫉妄想，可長(zhǎng)期無(wú)端地懷疑自己的妻子或丈夫有外遇，進(jìn)行跟蹤、盤(pán)問(wèn)、糾纏。⑤鐘情妄想，還有部分病人感到某一異性對(duì)自己有好感，想與自己交友，對(duì)方回避他，也認(rèn)為是怕難為情。⑥被洞悉妄想，覺(jué)得自己的一舉一動(dòng)都在別人監(jiān)視之下，內(nèi)心的想法都被別人知道。⑦特殊意義妄想，感到電影、電視里或周?chē)说囊慌e一動(dòng)，都有某種特殊的意義，均與自己有關(guān)。■情感改變病人面無(wú)表情，缺乏常人的喜怒哀樂(lè)及內(nèi)心體驗(yàn)，對(duì)朋友疏遠(yuǎn)，對(duì)親人缺乏關(guān)心和體貼?？梢杂孟矏偟恼Z(yǔ)氣描述悲慘的事情。部分病人木無(wú)表情，如同一尊塑像?！鲂袨楦淖儾∪丝梢栽诨糜X(jué)或妄想的支配下采取異常的行動(dòng)，例如在被害妄想支配下可以采取傷人或自傷的行動(dòng)。平時(shí)的行為混亂，亂寫(xiě)亂畫(huà)、擠眉弄眼、胡亂打扮、傷人損物、大喊大叫、做事不分場(chǎng)合、不知羞恥，如當(dāng)眾赤身裸體、隨地大小便。有的病人哭笑無(wú)常、經(jīng)常無(wú)故暴怒、不知不覺(jué)中卻又平靜如初。精神分裂癥－正常的軀體，異常的思維■陽(yáng)性和陰性癥狀

陽(yáng)性癥狀指典型的幻覺(jué)、荒謬偏執(zhí)的妄想、不合情理的恐懼等；陰性癥狀則指情感淡漠、情緒退縮、言語(yǔ)內(nèi)容貧乏以及快感體驗(yàn)喪失；認(rèn)知障礙包括記憶缺陷和智能低下，病人的社會(huì)功能受損。Brainregionsrelatedtoauditory-verbalhallucinations聽(tīng)覺(jué)-語(yǔ)言幻覺(jué)生產(chǎn)相關(guān)的腦區(qū)Box2

精神分裂癥治療■藥物治療可分成：以氯丙嗪、泰爾登為代表的低效價(jià)藥物，鎮(zhèn)靜作用強(qiáng)，對(duì)心、肝等臟器的毒性大，錐體外系反應(yīng)相對(duì)較輕，需要?jiǎng)┝看?；以?shī)^乃靜、氟哌啶醇等為代表的高效價(jià)藥物，鎮(zhèn)靜作用小，錐體外系反應(yīng)大，心、肝等的毒副反應(yīng)相對(duì)較輕。還可分為：典型的抗精神分裂癥藥，對(duì)陽(yáng)性癥狀非常有效，主要通過(guò)阻斷多巴胺D2受體起作用，如氯丙嗪、氟哌啶醇等，這些藥物都引起錐體外系反應(yīng)。非典型的抗精神分裂癥藥，對(duì)陰性癥狀往往有效，如氯氮平、舒必利、甲硫達(dá)嗪和美呱隆等，錐體外系反應(yīng)低?！銎渌委煼椒ㄟ€有音樂(lè)療法、工作娛樂(lè)治療、中醫(yī)辯證施治、針灸療法、大腦局限性損傷（精神外科治療）、胰島素休克（現(xiàn)已少用）等等，可以根據(jù)病人特點(diǎn)和具體條件采用。■社會(huì)的關(guān)注精神分裂癥病人給家庭和社會(huì)帶來(lái)沉重負(fù)擔(dān)。由于是慢性病，病人不可能常年住在醫(yī)院，又不能讓病人流落街頭、傷人和自傷，因此，需要全社會(huì)共同關(guān)愛(ài)這些病人。條件成熟的地方，可以建立社區(qū)的精神康復(fù)組織，讓病人在有組織的環(huán)境中，進(jìn)行治療和回歸社會(huì)的訓(xùn)練。每個(gè)正常的人都不應(yīng)鄙視這些病人，應(yīng)當(dāng)關(guān)心和愛(ài)護(hù)他們。Phenothiazines（吩噻嗪類(lèi)）Chlorpromazine氯丙嗪A.Antipsychoticdrugs1.Pharmacologicaleffects(1)CentraleffectsBlockingcentralD2dopaminereceptorsA.AntipsychoticdrugsDopaminergicpathwaysintheCNSA.mesolimbicandmesocorticalpathwaysrelatedtopsychologicalactivitiesandthetherapeuticeffectsofdrugsB.nigrostriatalpathwayrelatedtoextrapyramidalfunctionandtheadverseeffectsofdrugsC.tuberoinfundibularpathwayrelatedtohypothalamusendocrineeffectsofthedrugsA.Antipsychoticdrugs精神分裂癥假說(shuō)：多巴胺D2受體功能亢進(jìn)D1受體功能低下ps.D4receptorover-expressiona)Antipsychoticeffects(neurolepticeffects)

fortreatmentofschizophreniacontrollingexcitationandthenhallucinations(weekstomonths)b)Antiemeticeffects

inhibitingchemoreceptortriggerzone(CTZ)dopaminergicfunctionA.Antipsychoticdrugs(2)Autonomicnervoussystemeffectsa)Hypotensiveeffectsreceptorblockade,posturalhypotensionb)Anticholinergiceffectsdrymouth,constipation,blurredvision,urinaryretention,ect.A.Antipsychoticdrugs2.Clinicaluses(1)Treatmentofschizophrenia(2)Treatmentsofemesisandhiccoughusedforemesisandhiccough（呃逆）

butineffectiveonmotionsickness(3)Hypothermicanesthesiaandartificialhibernation

combinedwithloweringroomtemperatureA.Antipsychoticdrugs3.Adverseeffects(1)Sideeffects

centraldepression

peripheraleffects:

posturalhypotension,drymouth,andothereffectsresultingfrommuscarinicandreceptorblockadeA.Antipsychoticdrugs(2)ExtrapyramidaleffectsDuotoDAreceptorblock:a)Parkinsonismb)Akathisiac)Acutedystonia

attenuatedbycentralmuscarinicantagonistsDuotosupersensitivetoDA:

Tardivedyskinesia

(遲發(fā)性運(yùn)動(dòng)障礙)A.Antipsychoticdrugs黑質(zhì)-紋狀體通路中腦-皮層通路結(jié)節(jié)-漏斗通路Substantianigro-striatumdopaminergicpathway

isinvolvedinPDpathogenesis(5)CVSreactions

arrhythmiahypotension:treatedby

receptoragonistssuddendeath(elderlywithCVSdiseases)(6)Endocrinereactionshyperplasiaofmammaryglands(乳腺增生),galactorrhea(溢乳),amenorrhea(閉經(jīng)),childgrowthretardA.Antipsychoticdrugs(6)Acuteintoxication

severeCNSdepression,coma,severehypotension(7)ContraindicationsepilepsycomaelderlywithCVSdisordersseverehepaticandrenaldysfunctionA.AntipsychoticdrugsOtherphenothiazinesperphenazine奮乃靜fluphenazine氟奮乃靜trifluoperazine三氟拉嗪thioridazine硫利達(dá)嗪morepotenttherapeuticeffectsandextrapyramidaleffectsA.AntipsychoticdrugsThioxanthenes(硫雜蒽類(lèi))Chlorprothixene

氯普噻噸（泰爾登）UsedforthepatientswithsymptomsofdepressionandanxietyA.AntipsychoticdrugsButyrophenones（丁酰苯類(lèi)）Haloperidol氟哌啶醇Droperidol氟哌利多（氟哌啶）Combinedwithfentanyl:neuroleptanalgesia（神經(jīng)安定[鎮(zhèn)痛]麻醉術(shù)）A.AntipsychoticdrugsOthersPenfluridol五氟利多Longerdurationofaction,takingonceweeklySulpride舒必利selectivelyactsonmesolimbicD2receptorsfewextrapyramidalreactionsClozapine氯氮平BlockingD4and5-HTreceptorsPhenothiazines

利培酮BlockingD2

and5-HT2receptorsA.AntipsychoticdrugsDisordersofMoodDisordersofmood(affectivedisorders

情感障礙)areextremelycommoninmedicalpractice.Theseverityoftheseconditionscoversanextraordinarilybroadrange,fromnormalgriefreactionsanddysthymiatosevere,incapacitatingillnessthatmayresultindeath.Emotion（情緒）referstotransientresponsestoenvironmental,internal,andcognitivestimuli,whilemood

（心境）referstothepredominantemotionalstateovertime.Thesymptomsofdepressionareintensefeelingsofsadness,hopelessness,despair,andinabilitytoexperiencepleasureinusualactivity.Maniaischaracterizedbytheoppositebehavior,thatis,enthusiasm,rapidthoughtandspeechpatterns,andextremeself-confidenceandimpairedjudgment.Anxiety,astatecharacterizedbyarousal,vigilance,physiologicpreparedness,andnegativesubjectivestates,maysharecertaincriticalcircuitswithfear.DisordersofMoodLimbiclobe–RegionformodulatingemotionB.AntimanicDrugsLithiumcarbonateCarbamazepineChlorpromazineOtherrelatedantiepilepticandantipsychoticdrugsB.AntimanicDrugs1.PharmacologicaleffectsandclinicalusesMood-stabilizingagent(1)InhibitingNEandDArelease(2)Interferingphosphatidylinositol(PI)metabolismLithiumcarbonate碳酸鋰2.AdverseeffectsRelatedtotheserumconcentrationofLi+

0.8–1.5mmol/L:

therapeuticlevel

1.6–2.0mmol/L:

GIreactions

>2.0mmol/L:

CNStoxicityMonitoringserumconcentrationofLi+ifpossibleB.AntimanicDrugs(1)SideeffectsNausea,vomiting,abdominalpain,diarrhea,sedation,fingertremor,polyuria,etc.(2)AcuteintoxicationMentalconfusion,coma,hyperreflexia,grosstremor,dysarthria,seizures,etc.(3)OthersBenignthyroidenlargement,renaldamageB.AntimanicDrugsC.AntidepressantDrugsEnhancementofmonoamine(5-HT,NE)transmitterfunctionInhibitionofmonoaminereuptakeInhibitionofmonoaminedegradationMonoaminehypothesis（單胺假說(shuō)）

5-HT—geneticbasisofdepression&maniaNE—depressionNE—maniaModulationofmonoaminesinthesynapticspaceand/ortherelatedpost-synapticreceptorsisoftherapeuticimportanceSerotonin(5-HT)systemrelatedtodepressionNorepinephrinesystemrelatedtodepressionImipramine丙咪嗪（米帕明）TricyclicstructureC.AntidepressantDrugs1.Pharmacologicaleffects(1)CentraleffectsInhibitingreuptakeofmonoaminetransmittersImprovingpatient’smoodafter2weeksSedativeeffectsinnormalsubjects(2)AutonomiceffectsMuscarinicblockingeffects(3)CardiovasculareffectsHypotension,tachycardia,arrhythmiaC.AntidepressantDrugs2.Clinicaluses(1)DepressionEndogenous,melancholic,etc.(2)Enuresis(遺尿)(3)AnxietyandpanicdisorderC.AntidepressantDrugs3.Adverseeffects(1)Antimuscariniceffectsdrymouth,constipation,intraocularpressureincrease,blurredvision,urinaryretention,ect.Contraindicatedinprostatauxeandglaucoma(2)CNSreactionsConfusionordelirium,depression-mania(bipolarpatients)(3)CVSreactionsPosturalhypotension,sinustachycardia,potentialofarrhythmiaC.AntidepressantDrugs4.Druginteractions(1)Plasmaproteinbindingdisplacementbyphenytoin,aspirin,scopolamine,phenothiazines,ect.(2)MAOinhibitorspotentiatingtheeffectsofTCA,

contraindicatedforcombinationwithMAOIs(3)PotentiatingtheeffectsofCNSdepressantdrugsC.AntidepressantDrugsC.AntidepressantDrugsInteractionofTCAwithothertypesofdrugsC.AntidepressantDrugsOthertricyclicantidepressants

amitriptyline

(阿米替林)

clomipramine

(氯米帕明、氯丙咪嗪)

doxepin

(多塞平)C.AntidepressantDrugsNEreuptakeinhibitors(NRIs)Selectivenorepinephrinereuptakeinhibitsrapidactionsweakersedative,anticholinergicandhypotensiveeffectsdesipramine(地昔帕明)maprotiline(馬普替林)nortriptyline(去甲替林)

protriptylin(普羅替林)amoxapine(阿莫沙平)Sitesofantidepressantdrugsthatactingonnorepinephrinesystem

C.AntidepressantDrugsSelective5-HTreuptakeinhibitors

Selectiveserotoninreuptakeinhibits(SSRIs)weakersedativeeffectswithanti-anxietyeffectsfluoxetine(氟西汀，百憂解)paroxetine(帕羅西汀)sertraline(舍曲林)Sitesofantidepressantdrugsthatactingonserotoninsystem

C.AntidepressantDrugs5-HT/NEreuptakeinhibitors

Mixedserotonin/norepinephrinereuptakeinhibits(SNRIs)rapidactionlessaffinitywithreceptorshighersafetyvenlafaxine(文拉法幸)milnacipram(米那普侖)

lofepramine(洛夫帕明)C.AntidepressantDrugsNoradrenergicandspecificserotonergicantidepressant

(NaSSA)mirtezapine(米氮平)

blocking

presynaptic(auto-orhetero-)2receptoronbothnorepinephrineandserotonin(5-HT)presynapticaxons

-increasingNEand5-HTrel