药理学英文版教学课件：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(精神分裂症)Treatment：chlorpromazine300mg，BidMentalIllnessesSchizophrenia（精神分裂症）breakdownofpersonality;normalconversationimpossiblelossofcontactwithreality;inappropriateandunpredictablebehaviorDelusions(妄想)andhallucinations（幻觉）Depression（抑郁）mooddisturbancesgeneralizedhopelessfeelingsNeuroses（神经官能症）:fearandanxietyManiac（躁狂）Anxiety§1AntipsychoticDrugs(抗精神病药)AlsocalledAntischizophrenicdrugsMajortranquilizers（强安定药）Neuroleptics（精神安定剂）精神病=神经病？NOTypeI----PositivesymptomsTypeII----NegativesymptomsHistory1933：Insulinshock（胰岛素休克）1937：electricshock（电休克）1943：provethematerialityforschizophrenia1950：findingchlorpromazineFourdopaminepathwaysinthebrain

(2000NobelPrize)D2Substantianigra-striatumpathway调节锥体外系运动功能Midbrain-limbicsystempathway调控情绪反应Midbrain-cortexpathway调控认知、思想、感觉和推理能力Tubercle-funnelpathway调控垂体激素的分泌Mechanismsofneuroleptics(精神安定药)1.BlocktheD2receptorsofmidbrain-limbicsystem&midbrain-cortexsystem2.Blockthe5-HTreceptorsClassificationofneurolepticsAccordingtochemicalstructuresPhenothiazines(吩噻嗪类)Thioxanthenes(硫杂蒽类)Botyrophenones(丁酰苯类)Others:clozapine,risperidoneI.Phenothiazinederivatives(吩噻嗪类)

Chlorpromazine(氯丙嗪)Alsocalled-----Wintermine(冬眠灵)Pharmacologicaleffectsandmechanisms1.onCNS:A.AntischizophreniaeffectBlockdopamineD2receptorsinmidbrain-cortex&midbrain-limbicsystempathwaysB.stopvomitingandhiccup:CTZD2（呃逆）C.inhibitthermotaxis（体温调节）:bothfever&normalbeings2.effectsonautonomoussystemBlockαadrenoceptorBlockMcholinoceptor3.effectsonendocrinesystemInhibitthesecretionofhypothalamus（下丘脑）hormones:prolactinreleasinginhibitor,resultinginhyperprolactinaemia,bigbreast&milksecretionInhibitthesecretionofgrowthhormoneinpituitary（脑垂体），atreatmentforgigantism（巨人症）.Clinicaluses1.schizophrenia2.vomit&hiccup3.hypothermiaanaesthesia&artificialhibernation（低温麻醉和人工冬眠）Chlorpromazine+Dolantin+promethazine

（氯丙嗪杜冷丁异丙嗪）Adversereaction1.CNSdepression;α&Mblockeffects;2.extrapyramidalreactions(锥体外系反应)D2blockadeParkinsonismAkathisia（静坐不能）Acutedystonia（急性肌张力障碍）D2enhancementTardivedyskinesia（迟发性运动障碍）3.spiritualeffects4.seizure&epilepsy5.allergicreaction6.Cardiovascular&endocrinesystemreactions7.acutetoxication，BP?8.increasedCNSdepressionifcombinedwithotherCNSinhibitorsOtherPhenothiazinesPerphenazine(奋乃静)Fluphenazine(氟奋乃静)Trifluperazine(三氟拉嗪)Thioridazine(硫利达嗪):selectivetomidbrain-limbicD2,lessextrapyramidalreactionII.Thioxanthenes(硫杂蒽类)Chlorprothixene(氯普噻吨,泰尔登tardan)GoodforpatientswithanxietyordepressionFlupenthixol(氟哌噻吨)III.Butyrophenones(丁酰苯类)Haloperidol(氟哌啶醇)：usedinpatientsnoteffectiveforchlorpromazineDroperidol(氟哌利多)Withfentanyl:neuroleptanalgesia(神经安定镇痛术)Pimozide(匹莫齐特)IV.OtherneurolepticsClozapine(氯氮平)SelectiveD4antagonist,weakD2agonistBlockalphaandMreceptorsNoextrapyramidalsymptomSulpiride(舒必利）：D2blockerbutnoextrapyramidalreactionRisperidone(利培酮)Block5-HT2&D2receptorsLightextrapyramidalsymptom§2AntimanicDrugsmanic-depressivepsychosis(躁狂抑郁症)monophasictype（repeatedmaniaordepression）bipolardisorder（interchangeofmaniaordepression）

Relatedwithimbalanceofbrainmonoaminefunctions:5-HT↓NAincreasedNAdecreasedLithiumcarbonate(碳酸锂)Firstusedasantimanicat1949Mechanism:InhibitthereleasingofNAfromnerveterminalFaciliatetheuptakeofNAInhibitthesignaltransductionAffectthedistributionofcations(阳离子)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（夜尿症）3.anxiety,phobia（恐惧症）Adversereaction:Mblockage