抗精神病药、抗抑郁药和麻醉药

神经系统药理5一、抗精神病药和抗抑郁药二、麻醉药1一、抗精神病药和抗抑郁药Antidepressantandantimanicdrugs

抗抑郁和抗躁狂药Anxiolytics/antianxietics

抗焦虑药Antipsychoticdrugs

抗精神分裂药2Disordersofmood(affectivedisorders

情感障碍)areextremelycommoninmedicalpractice.Theseverityoftheseconditionscoversanextraordinarilybroadrange,fromnormalgrief(悲伤)reactionsanddysthymia(心境恶劣)tosevere,incapacitatingillnessthatmayresultindeath.Emotion（情绪）referstotransientresponsestoenvironmental,internal,andcognitivestimuli,whilemood

（心境）referstothepredominantemotionalstateovertime.DisordersofMood3Thesymptomsofdepressionareintensefeelingsofsadness,hopelessness,despair,andinabilitytoexperiencepleasureinusualactivity.Maniaischaracterizedbytheoppositebehavior,thatis,enthusiasm,rapidthoughtandspeechpatterns,andextremeself-confidenceandimpairedjudgment.Anxiety,astatecharacterizedbyarousal,vigilance,physiologicpreparedness,andnegativesubjectivestates,maysharecertaincriticalcircuitswithfear.DisordersofMood4MonoaminehypothesisofDepression

（单胺假说）

5-HT—geneticbasisofdepression&maniaNE—depressionNE—maniaModulationofmonoaminesinthesynapticspaceand/ortherelatedpost-synapticreceptorsisoftherapeuticimportance5Long-termadaptationstoantidepressanttreatment67ClassesofAntidepressantsTricyclicAntidepressants(TCAs)MonoamineOxidaseInhibitors(MAOIs)NorepinephrineReuptakeInhibitors(NARIs)SelectiveSerotoninReuptakeInhibitors(SSRIs)SerotoninandNorepinephrineReuptakeInhibitors(SNRIs)Noradrenergicandspecificserotonergicantidepressants(NaSSAs)8Modeloftheneurotrophichypothesisofantidepressanttreatmentsandstress-relateddisorders9Imipramine丙米嗪（米帕明）TricyclicstructureA.AntidepressantDrugsTricyclicAntidepressants(TCAs)1011丙咪嗪阿米替林氯丙咪嗪多塞平临床应用副作用121.Pharmacologicaleffects(1)CentraleffectsInhibitingreuptakeofmonoaminetransmittersImprovingpatient’smoodafter2weeksSedativeeffectsinnormalsubjects(anti-histaminergicora-adrenergicblockingproperties)(2)AutonomiceffectsMuscarinicblockingeffects(3)CardiovasculareffectsHypotension,tachycardia,arrhythmiaImipramine丙米嗪（米帕明）132.Clinicaluses(1)DepressionEndogenous,melancholic,etc.(2)Enuresis

(遗尿)(3)Anxiety(焦虑)andpanicdisorder(惊恐症)Imipramine丙米嗪（米帕明）143.Adverseeffects(1)Antimuscariniceffectsdrymouth,constipation(便秘),intraocularpressureincrease,blurredvision,urinaryretention,etc.Contraindicatedinprostatauxeandglaucoma(2)CNSreactionsConfusionordelirium(谵妄),depression-mania(bipolarpatients)(3)CVSreactionsPosturalhypotension,sinustachycardia,potentialofarrhythmiaImipramine丙米嗪（米帕明）154.Druginteractions(1)Plasmaproteinbindingdisplacementbyphenytoin,aspirin,scopolamine(东莨菪碱),phenothiazines(吩噻嗪类),etc.(2)MAOinhibitorspotentiatingtheeffectsofTCA,

contraindicatedforcombinationwithMAOIs(3)PotentiatingtheeffectsofCNSdepressantdrugsImipramine丙米嗪（米帕明）16InteractionofTCAwithothertypesofdrugs17A.AntidepressantDrugsMonoamineoxidaseinhibitors(MAOIs)SelectiveforcentralMAO-B,lessselectiveforentericMAO-A;Usedintreatmentsofdepression(non-sensitivetoTCAs)andParkinsondisease

phenelzine

(苯乙肼):non-selective

selegiline

(司来吉兰):alsousedinParkinsondisease18MAOIsandDietaryInteractionsTyramine(酪胺)isnormallymetabolizedbyMAOTyramineissympathomimetic(itacutelydisplacesNEfromterminalstoactivatereceptors)IngestingtyramineduringMAOinhibitionresultsinhypertension,headache,palpitations,nausea,vomitingTyramineispresentinanumberoffoodstuffs,suchasagedcheese,redwine,etc.19A.AntidepressantDrugsNEreuptakeinhibitors(NRIs)Selectivenorepinephrinereuptakeinhibitsrapidactionsweakersedative,anticholinergicandhypotensiveeffects

desipramine

(地昔帕明)

maprotiline

(马普替林)

nortriptyline

(去甲替林)

protriptylin

(普罗替林)

amoxapine

(阿莫沙平)20A.AntidepressantDrugsSelective5-HTreuptakeinhibitors

Selectiveserotoninreuptakeinhibits(SSRIs)weakersedativeeffectswithanti-anxietyeffects

fluoxetine

(氟西汀，百忧解)：抑郁症、神经性贪食症

paroxetine

(帕罗西汀)

sertraline

(舍曲林)21A.AntidepressantDrugs5-HT/NEreuptakeinhibitors

Mixedserotonin/norepinephrinereuptakeinhibits(SNRIs)rapidactionlessaffinitywithreceptorshighersafety

venlafaxine

(文拉法辛)

milnacipram

(米那普仑)

lofepramine

(洛夫帕明)22A.AntidepressantDrugsNoradrenergicandspecificserotonergicantidepressant

(NaSSA)mirtezapine

(米氮平)

blocking

presynaptic(auto-orhetero-)2receptoronbothnorepinephrineandserotonin(5-HT)pre-synapticaxons

-increasingNEand5-HTrelease;

stimulatingpostsynaptic1receptorsonserotonergiccellbodies

-increasingthefiringrateofserotonergicneurons

potentlyblockingpostsynaptic5-HT2A,5-HT2Cand5-HT3receptors–attenuating5-HT2C-mediatedanxietyThenetoutcomeoftheseeffectsis：increasednoradrenergicactivityincreasedserotonergicactivity,esp.5-HT1Areceptors23B.

AntimanicDrugsLithiumcarbonateCarbamazepineChlorpromazineOtherrelatedantiepilepticandantipsychoticdrugs24B.AntimanicDrugs1.PharmacologicaleffectsandclinicalusesMood-stabilizingagent(1)InhibitingNEandDArelease(2)Interferingphosphatidylinositol(PI)metabolism(3)SubstituteforsodiumingeneratingactionpotentialsandinNa+-K+exchangeacrossthemembrane.Lithiumcarbonate碳酸锂25262.AdverseeffectsRelatedtotheserumconcentrationofLi+

0.8–1.5mmol/L:

therapeuticlevel

1.6–2.0mmol/L:

GIreactions

>2.0mmol/L:

CNStoxicityMonitoringserumconcentrationofLi+ifpossibleB.AntimanicDrugs27(1)SideeffectsNausea,vomiting,abdominalpain,diarrhea,sedation,fingertremor,polyuria,etc.(2)AcuteintoxicationMentalconfusion,coma,hyperreflexia(反射亢进),grosstremor,dysarthria(构音困难),seizures,etc.(3)OthersBenignthyroidenlargement,renaldamageB.AntimanicDrugs28C.Anxiolyticdrugs1.BenzodiazepinesseedetailsinSedative-HypnoticDrugs2.Buspirone（丁螺环酮）5-HT1Areceptorselectivepartialagonist,lowering5-HTreleaseFewersedative,hypnotic,memory-deficienteffectsNocrosstolerancetobenzodiazepines,andlesspotentialofdependence29Schizophrenia(精神分裂症)

NeurologicalDisorder-impairsabilitytoperceive,understand&interprettheenvironmentImpairedsocialandoccupationalfunctionBehavioralSyndrome–predictableornotEtiologyandbiologyremainunclear-familialtendency,DAandotherneurotransmittersHistory–earlydementia,unremittingbadcourse30Signs&SymptomsPositive

symptomsDelusions(妄想)-fixedfalsebeliefoutsideculturalnorm (bizarrevs.nonbizarre)Hallucinations(幻觉)-perceptual(hearing),havenooutsidesource“Likemyvoice”Notanillusion(amistakenperceptionforwhichthereisanactualexternalstimulus)Disorganization

(思维紊乱)-patternofspeechorbehavior,makingupwordswithoutameaning(neologisms)31Negative

symptomsAffectiveflatteningAvolition/Amotivation(decreasedmotivation)Autistic(孤独)behaviors(socialwithdrawal)Anhedonia(inabilitytoexperiencepleasure)Ambivalence(coexistenceofopposingattitudesorfeelings，矛盾心态)Anosognosia(疾病感缺失)(impairedawarenessofillness)Signs&Symptoms321.Phenothiazines（吩噻嗪类）Chlorpromazine

氯丙嗪perphenazine

奋乃静；

fluphenazine

氟奋乃静trifluoperazine

三氟拉嗪；thioridazine

硫利达嗪2.Thioxanthenes(硫杂蒽类)Chlorprothixene

氯普噻吨（泰尔登）3.Butyrophenones（丁酰苯类）Haloperidol氟哌啶醇Droperidol

氟哌利多（氟哌啶）ClassifiedaccordingtochemicalstructuresD.AntipsychoticdrugsTypicalantipsychoticdrugsaredopamineD2receptorantagonistsTypical33OthersPenfluridol

五氟利多

Longerdurationofaction,takingonceweeklySulpride

舒必利

selectivelyactsonmesolimbicD2receptorsfewextrapyramidalreactionsClozapine

氯氮平

BlockingD4and5-HTreceptorsRisperidone

利培酮

BlockingD2

and5-HT2receptorsActionsofsomesecondarygenerationdrugsAtypical34D.AntipsychoticdrugsHighpotencyLowpotency螺环哌啶酮苯哌利多三氟哌啶醇氟哌利多普马嗪35D.AntipsychoticdrugsThedopaminehypothesisofschizophreniaTheserotoninhypothesisofschizophreniaTheglutamatehypothesisofschizophrenia36Phenothiazines（吩噻嗪类）Chlorpromazine氯丙嗪D.Antipsychoticdrugs371.PharmacologicaleffectsCentraleffects:BlockingcentralD2dopaminereceptorsa)Antipsychoticeffects(neurolepticeffects)fortreatmentofschizophreniacontrollingexcitationandthenhallucinations(weekstomonths)b)Antiemeticeffects(镇吐作用)inhibitingchemoreceptortriggerzone(CTZ)dopaminergicfunctionc)Poikilothermiceffects(体温调节作用)

hypothermicanesthesiaartificialhibernation(人工冬眠)d)Extrapyramidaleffects

primaryadverseeffectse)Potentiatingtheeffectsofcentraldepressantssedative-hypnotics,analgesics,generalanesthetics,ethanolD.Antipsychoticdrugs38(2)Autonomicnervoussystemeffectsa)Hypotensiveeffectsreceptorblockade,posturalhypotensionb)Anticholinergiceffectsdrymouth,constipation,blurredvision,urinaryretention,etc.(3)EndocrineeffectsprolactinACTH,growthhormoneD.Antipsychoticdrugs392.Clinicaluses(1)Treatmentofschizophrenia(2)Treatmentsofemesisandhiccough

usedfor

emesis（止吐）and

hiccough（呃逆）

butineffectiveonmotionsickness(3)Hypothermicanesthesia(combinedwithloweringroomtemperature)andartificialhibernation(combinedwithPethidine

哌替啶andpromethazine异丙嗪)

D.Antipsychoticdrugs403.Adverseeffects(1)Sideeffects

CentraldepressionPeripheraleffects:

posturalhypotension,drymouth,andothereffectsresultingfrommuscarinicandreceptorblockadeD.Antipsychoticdrugs41(2)ExtrapyramidaleffectsDuetoDAreceptorblock:a)Parkinsonismb)Akathisia(静坐不能)c)Acutedystonia(急性肌张力障碍)

attenuatedbycentralmuscarinicantagonistsDuetosupersensitivetoDA:

Tardive

dyskinesia

(迟发性运动障碍)D.Antipsychoticdrugs42(3)Othercentralreactions

neurolepticmaglinantsyndrome(神经阻滞药恶性综合征）

psychoticreactions(药源性精神异常)epilepsyandconvulsion:loweringseizurethreshold(4)Allergicandhemologicalreactions

skinreactions,leukopenia,obstructivejaundice,liverdamageD.Antipsychoticdrugs43(5)CVSreactions

arrhythmiahypotension:treatedby

receptoragonistssuddendeath(elderlywithCVSdiseases)(6)Endocrinereactionshyperplasiaofmammaryglands(乳腺增生),galactorrhea(溢乳),amenorrhea(闭经

),childgrowthretard(生长抑制)D.Antipsychoticdrugs44(6)Acuteintoxication

severeCNSdepression,coma,severehypotension(7)ContraindicationsepilepsycomaelderlywithCVSdisordersseverehepaticandrenaldysfunctionD.Antipsychoticdrugs45Otherphenothiazinesperphenazine奋乃静fluphenazine氟奋乃静trifluoperazine三氟拉嗪thioridazine硫利达嗪morepotenttherapeuticeffectsandextrapyramidaleffectsD.Antipsychoticdrugs46Thioxanthenes(硫杂蒽类)Chlorprothixene

氯普噻吨（泰尔登）UsedforthepatientswithsymptomsofdepressionandanxietyD.Antipsychoticdrugs47Butyrophenones（丁酰苯类）Haloperidol氟哌啶醇Droperidol氟哌利多（氟哌啶）Combinedwithfentanyl:

neuroleptanalgesia（神经安定[镇痛]麻醉术）D.Antipsychoticdrugs48OthersPenfluridol五氟利多Longerdurationofaction,takingonceweeklySulpride舒必利selectivelyactsonmesolimbicD2receptorsfewextrapyramidalreactionsClozapine氯氮平BlockingD4and5-HTreceptorsRisperidone

利培酮BlockingD2

and5-HT2receptorsD.Antipsychoticdrugs49局部麻醉药50LocalAnesthetics(LAs)Definition:drugsthatcauselossofsensationwithoutlossofconsciousnessReversiblyblocknerveconductionActoneverytypeofnervefiberAlsoactoncardiacmuscle,skeletalmuscleandthebrainNostructuraldamagetothenervecell51可卡因普鲁卡因丁卡因苯佐卡因allareweakbasesBH+B+H+StructuralClasses:EstersandAmides52利多卡因甲哌卡因布比卡因布比卡因丙胺卡因5354Use-dependentBlockade55ActionsofLAsIonicgradientandrestingmembranepotentialareunchangedDecreasetheamplitudeoftheactionpotentialSlowtherateofdepolarizationIncreasethefiringthresholdSlowimpulseconductionProlongtherefractoryperiod56CNSToxicityCorrelationbetweenpotencyandseizurethresholdBupivacaine2ug/mlLidocaine10ug/ml57CardiovascularToxicityAttributabletotheirdirecteffectoncardiacmuscleContractilityNegativeinotropiceffectthatisdose-relatedandcorrelateswithpotencyInterferencewithcalciumsignalingmechanismsAutomaticityNegativechronotropiceffectRhythmicityandConductivityVentriculararrhythmias58Absorption

(injectedortopical)-affectedbyvascularity(血供)-presenceofadditionalvasoconstrictor(血管收缩剂)-Durationprolongedbyvasoconstrictor(epinephrine) -localizesagenttositeofaction -contraindicatedinextremities(末梢部位)-SystemicToxicEffects:CNS,cardiovascularPharmacokinetics59Alphaphase(快速吸收相)

–rapidlyredistributedtowell-perfusedtissuesBetaphase(再分布相)–distributiontolessperfusedorslowlyequilibratingtissuesGammaphase(消除相)–clearancerepresentingmetabolismandexcretionDistribution-LAsbindinthebloodtoa1-glycoproteinandalbuminPharmacokinetics6061Usesoflocalanesthesia/ModesofAdministrationTopicallocal(surface)anesthesia(表面麻醉):foreye,ear,nose,andthroatproceduresandforcosmeticsurgeryInfiltrationanesthesia(浸润麻醉):localinjectionaroundtheregiontobeoperated.Conductionanesthesia(传导麻醉):localinjectionaroundtheperipheralnervetrunkEpiduralansthesia(硬膜下麻醉):localinjectionintotheepiduralspaceSubarachnoidanesthesia(蛛网膜下腔麻醉):orSpinalanesthesia(脊髓麻醉，腰麻):localinjectionintothecerebrospinalfluidinsubarachnoidcavity626364AdversereactionsToxicity:CNS,CVSAllergicReactionsMetaboliteof“ester”LAsPara-aminobenzoicacidAllergenAllergyto“amide”LAsisextremelyrare65LidocaineOneofthemostwidelyusedlocalanestheticsRapidonset,mediumdurationAlsoavailableinointment（软膏）,jelly（凝胶）,andaerosol（喷雾剂）Otheruses:anti-arrhythmic66EutecticMixtureofLocalAnesthetic(EMLA)Containslidocaine(2.5%),prilocaine(丙胺卡因

2.5%),emulsifier乳化剂,thickener增稠剂,distilledwater (aeutecticmixturehasameltingpointbelowroomtemperatureandthereforebothlocalanestheticsexistasaliquidoilratherthanascrystals)Mustbeappliedonehourpriortoprocedure67全身性麻醉剂68WHATISGeneralANESTHESIA?Anesthesiaisnecessaryforsomediagnostic,therapeutic,andsurgicalinterventionThephysiologicstateinducedbygeneralanestheticstypicallyincludesanalgesia,amnesia,lossofconsciousness,inhibitionofsensoryandautonomicreflexes,andskeletalmusclerelaxation.TypesofGeneralAnesthesia:

InhaledAnesthetics(gasesor“vapors”)

IntravenousAnesthetics(begivenintravenously).69Inhaledanesthetics

(吸入麻醉药)Manydifferent,apparentlyunrelatedmoleculesproducegeneralanesthesia–inertgases,simpleinorganic&organiccompounds,morecomplexorganiccompoundsCharacteristics–rapidonset,rapidreversibility,relationshipbetweenlipidsolubility&potency70Stagesofanesthesia(ether)StageI:analgesia–sensoryblockinspinalcordStageII:paradoxicalexcitationduetolossofsomeinhibitorytoneanddirectstimulationofexcitatorytransmissionStageIII:surgicalanesthesia–blockoftheascendingreticularactivatingsystemStageIV:failure–cardiovascularandrespiratorycollapseduetoinhibition71SignsforanestheticdepthTachycardiaHypertensionEyelidreflexLacrimationSwallowingLaryngospasmMovementTOOLIGHTTOODEEP

HypotensionOrganfailure72Gasatroomtemperature73DiethylEther(乙醚)VolatileliquidsatroomtemperatureHalothane(氟烷)Isoflurane(异氟醚)Desflurane(地氟醚)74Inhaledanestheticdeliverysystem75Vaporizingtheanestheticliquid76Gasflowmeters77Mask78HigherbloodsolubilityisshownasalargerbloodboxHighersolubilitymeansgasrapidlymovesintoblood,butconcentrationthatreachesbrainincreasesmoreslowlyBlood:gaspartitioncoefficient:anindexforsolubilityBrain:BloodPartitionCoefficient79MAC–minimumalveolaranestheticconcentrationMACistheanestheticconcentrationthatproducesimmobilityin50%ofpatientsexposedtoanoxiousstimulus.AdditionofMAC80FactorsthatalterMACIncreaseMAC–Beingyoung,hyperthermia,chronicETOH,CNSstimulants,hyperthyroidismDecreaseMAC–Oldage,hypothermia,acuteETOH,CNSdepressantdrugsincludingnarcotics&benzodiazepines81GeneralcharacteristicsAnalgesia–weakexceptfornitrousoxidePotency–high,exceptfor