藥理學(xué)英文版教學(xué)課件：Chapter 17 Drugs for Psychiatric Disorders

DrugsforPsychiatricDisordersCase122yrsoldmale,laid-offworker3yrsago,sincefailedhisuniversityentranceexam,hebecametaciturnity（沉默）,worriedalldaylongandwasunhappy.Onceworkedinaprivatecompany,butquitsoonbecauseofmaladjustmenttotheworkingenvironment.Hebeganbehavedweird（奇怪的）6monthsago:talktohimself;heardsomeoneunfamiliaraskedhimtodosomething;claimedsmellingdeadpeopleodorathome;believedhimmindwascontrolledbysomeequipment.Diagnosis:schizophrenia(精神分裂癥)Treatment：chlorpromazine300mg，BidMentalIllnessesSchizophrenia（精神分裂癥）breakdownofpersonality;normalconversationimpossiblelossofcontactwithreality;inappropriateandunpredictablebehaviorDelusions(妄想)andhallucinations（幻覺）Depression（抑郁）mooddisturbancesgeneralizedhopelessfeelingsNeuroses（神經(jīng)官能癥）:fearandanxietyManiac（躁狂）Anxiety§1AntipsychoticDrugs(抗精神病藥)AlsocalledAntischizophrenicdrugsMajortranquilizers（強(qiáng)安定藥）Neuroleptics（精神安定劑）精神病=神經(jīng)?。縉OTypeI----PositivesymptomsTypeII----NegativesymptomsHistory1933：Insulinshock（胰島素休克）1937：electricshock（電休克）1943：provethematerialityforschizophrenia1950：findingchlorpromazineFourdopaminepathwaysinthebrain

(2000NobelPrize)D2Substantianigra-striatumpathway調(diào)節(jié)錐體外系運(yùn)動功能Midbrain-limbicsystempathway調(diào)控情緒反應(yīng)Midbrain-cortexpathway調(diào)控認(rèn)知、思想、感覺和推理能力Tubercle-funnelpathway調(diào)控垂體激素的分泌Mechanismsofneuroleptics(精神安定藥)1.BlocktheD2receptorsofmidbrain-limbicsystem&midbrain-cortexsystem2.Blockthe5-HTreceptorsClassificationofneurolepticsAccordingtochemicalstructuresPhenothiazines(吩噻嗪類)Thioxanthenes(硫雜蒽類)Botyrophenones(丁酰苯類)Others:clozapine,risperidoneI.Phenothiazinederivatives(吩噻嗪類)

Chlorpromazine(氯丙嗪)Alsocalled-----Wintermine(冬眠靈)Pharmacologicaleffectsandmechanisms1.onCNS:A.AntischizophreniaeffectBlockdopamineD2receptorsinmidbrain-cortex&midbrain-limbicsystempathwaysB.stopvomitingandhiccup:CTZD2（呃逆）C.inhibitthermotaxis（體溫調(diào)節(jié)）:bothfever&normalbeings2.effectsonautonomoussystemBlockαadrenoceptorBlockMcholinoceptor3.effectsonendocrinesystemInhibitthesecretionofhypothalamus（下丘腦）hormones:prolactinreleasinginhibitor,resultinginhyperprolactinaemia,bigbreast&milksecretionInhibitthesecretionofgrowthhormoneinpituitary（腦垂體），atreatmentforgigantism（巨人癥）.Clinicaluses1.schizophrenia2.vomit&hiccup3.hypothermiaanaesthesia&artificialhibernation（低溫麻醉和人工冬眠）Chlorpromazine+Dolantin+promethazine

（氯丙嗪杜冷丁異丙嗪）Adversereaction1.CNSdepression;α&Mblockeffects;2.extrapyramidalreactions(錐體外系反應(yīng))D2blockadeParkinsonismAkathisia（靜坐不能）Acutedystonia（急性肌張力障礙）D2enhancementTardivedyskinesia（遲發(fā)性運(yùn)動障礙）3.spiritualeffects4.seizure&epilepsy5.allergicreaction6.Cardiovascular&endocrinesystemreactions7.acutetoxication，BP?8.increasedCNSdepressionifcombinedwithotherCNSinhibitorsOtherPhenothiazinesPerphenazine(奮乃靜)Fluphenazine(氟奮乃靜)Trifluperazine(三氟拉嗪)Thioridazine(硫利達(dá)嗪):selectivetomidbrain-limbicD2,lessextrapyramidalreactionII.Thioxanthenes(硫雜蒽類)Chlorprothixene(氯普噻噸,泰爾登tardan)GoodforpatientswithanxietyordepressionFlupenthixol(氟哌噻噸)III.Butyrophenones(丁酰苯類)Haloperidol(氟哌啶醇)：usedinpatientsnoteffectiveforchlorpromazineDroperidol(氟哌利多)Withfentanyl:neuroleptanalgesia(神經(jīng)安定鎮(zhèn)痛術(shù))Pimozide(匹莫齊特)IV.OtherneurolepticsClozapine(氯氮平)SelectiveD4antagonist,weakD2agonistBlockalphaandMreceptorsNoextrapyramidalsymptomSulpiride(舒必利）：D2blockerbutnoextrapyramidalreactionRisperidone(利培酮)Block5-HT2&D2receptorsLightextrapyramidalsymptom§2AntimanicDrugsmanic-depressivepsychosis(躁狂抑郁癥)monophasictype（repeatedmaniaordepression）bipolardisorder（interchangeofmaniaordepression）

Relatedwithimbalanceofbrainmonoaminefunctions:5-HT↓NAincreasedNAdecreasedLithiumcarbonate(碳酸鋰)Firstusedasantimanicat1949Mechanism:InhibitthereleasingofNAfromnerveterminalFaciliatetheuptakeofNAInhibitthesignaltransductionAffectthedistributionofcations(陽離子)Clinicaluses:ManicBipolardisorderAdversereaction:LowTI,effectiveconcentration:0.8~1.5mmol/L,MTC=2mmol/LNaCli.v.dropforoverdosetoxication§3AntidepressivedrugsClassification:Tricycleantidepressants:imipramine丙米嗪NAuptakeinhibitor:desipramine地西帕明5-HTuptakeinhibitors:fluoxetine氟西汀Otherdrugs:venlafaxine文拉法辛TricycleantidepressantsImipramine(米帕明，丙咪嗪)inhibituptakeofNE、5-HTPhysiologicaleffects:1.onCNS:improvedepressionbutnoeffectonnormalperson2.onautonomicsystem:antiMreceptors3.oncardiovascularsystem:Clinicaluses1.depression2.nocturia（夜尿癥）3.anxiety,phobia（恐懼癥）Adversereaction:Mblockage