藥理學(xué)教學(xué)課件：Chapter 18 Drugs Used for Treatment of Mental Disorders

“WorldMentalHealthDay”——Oct.10

“19Centuryisthecenturyofinfectiousdiseases，

20Centuryisthecenturyofsomaticdiseases，

21Centurywillbethecenturyofmentaldisease”Thelabornewspaperreport(ReporterLipei,Oct.10,2011)：Thereisatleast1among5personsoncehadmentalandbehaviordisorders.Andthereisatleast1among8personshavingsomementalandbehaviordisorders.Chapter18DrugsUsedforTreatmentofMentalDisorders

Classifications：

AAntipsychoticDrugs

（Neuroleptics）

BAntimanicDrugs

CAntidepressants

DAnxiolytics

Schizophrenia：

Thecommonpsychoticdeseasecharacterizeduncoordinationwiththinking、emotion、behavior.Themainfeaturesarethedisconnectionofmentalactivitiesandreality.

EtiologyofSchizophrenia：

Internalcause

(geneticfactors)Externalcause

(Environmentalandsocialfactorsetc.)HistoryoftheDrugsAnti-mentalDisordersA.1933InsulinShock

(treatingschizophrenia)B.1937ElectricShock

(treatingseveredepression)C.1949CadeReportedLithiumSalts(treatingmania)D.1952ParaireChlorpromazine(treatingschizophrenia)

AntipsychoticDrugsClassificationsofSchizophreniaTypeⅠ：Positivesymptoms（IllusionandDelusion）arethemainexpressions.TypeⅡ：Negativesymptoms（Apathy、Lackofinitiative）arethemainexpressions.CategoriesofDrugsofAnti-SchizophreniaAPhenothiazinesBThioxanthenesCButyrophenonesDOthersIPhenothiazines

Chlorpromazine【PharmacologicalEffectsandMechanism】EffectsonCNSA.AntipsychoticEffects(—)D2-likeRonmidbrainLimbicsystemEmotionStable(—)D2-likeRonmidbraincortexsystemCalmB.Anti-Vomitting(一)D2-likeRonemeticchemicalzoneofmedullaoblongataC.ReducingtheTemperature(一)RegulationcenterofbodytemperatureinhypothalamusCombinedwithphysicalcoolingmethods,inducingthetemperature——downdependentasenvironment

ComparisonofCoolingCharacteristicsbetweenChlorpromazineandAspirin

ChlorpromazineAspirinNormalTemperature－

SetPointMalfunctionDowntoNormalCoolingMannerHeatProduction

DissipateHeat

EffectsonAutonomicNervousSystem(一)αRstronger，B.P.↓(一)MRweaker，Drymouth.Constipation.Etc.

EffectsonEndocrinesystem(一)D2-like

RonTubercle-FunnelPathwayPRLsecretion↑Galactorrhea

Gonadotropichormonesecretion↓delayedovulation

Glucocorticoidssecretion↓Growthhormonesecretion↓【TheInVivoProcess】Absorption:

AbsorbedslowlyandirregularlybyP.O.LargeindividualvariationsinblooddrugconcentrationDistribution:90%combinedwithplasmaproteinThebrainconcentration10times＞

BloodconcentrationElimination:

Metablizedinliverandexcretedbykidney.【ClinicalApplication

】

MentalDiseaseaSchizophreniaBettereffectstotypeⅠ、AcutetypeⅡ、ChronicbMania

VomittingandIntractableHiccup

stopvomitting

HypothermicAnesthesiaandArtificialHibernation

HibernationMixture＋PhysicalCoolingChlorpromazinePethidine

Promethazine【AdverseReaction】CommonAdverseReaction

CNSinhibitorysymptomsSleepinessMRblockingsymptomsDrymouth、Constipationetc.

αRblockingsymptomsOrthostatichypotensionLocalIrritantStrongerExtrapyramidalSystemReaction

(一)D2-likeRinSN-Striatum

Acute：

A.acutedystonia1～5dayTeenagersB.Parkinsonsyndrome5～30daytheelderlyParalysisagitansC.Akathisia5～60dayMiddleageBeontenterhooks

Tardive：

dyskenesiamonths～yearsAdultsStereotypedmovement

MentalInhibitorySymptomsConvulsionsandEpilepsyAllergicreaction：

Rash、Dermatitis，

Lesspatients——Jaundice、Granulocyte↓

CardiovascularandEndocrinesystemreactionAcutePoisoning

Largedosemedication→Lethargy,dropinbloodpressure

NAissuitbleinBoostingBP

CharacteristicComparisonofOtherPhenothiazineDrugDose(mg/d)CalmStopExtrapyramidalReducevomittingreactionsBPChlorpromazine

300~800+++++++++Perphenazine8~32+++++++++Fluphenazine2.5~20++++++++Trifluoperazine6~20++++++++Thioridazine200~300+++++++II

Thioxanthenes

Chlorprothixene（Tardan）AWeakeranti-illusion、delusioneffectthanChlorpromazineBStrongereffectofcalm，someanti-anxietyandanti-depressioneffects.Especiallysuitbletobeusedinschizophreniapatientswithanxietyanddepression,thepatientsofanxiety、compulsivedisorderandclimactericdepressionCWeakerblockingeffectsofα、MR，mildextrapyramidalreaction，sotheadversereactionisless.

Flupenthixol

Usedinthetreatmentofdepressionorthedepressionwithanxiety.HasspecificstimulatingeffectstoCNSandisforbiddentobeusedinmania

III

Butyrophenones

Haloperidol

Hasverystongeffectofanti-psychoticandsevereextrapyramidalreaction.

Application:A.ExcitingandRestlesssymptoms——ofchoiceB.Anti-VomittingandAnti-Hiccup——fine

Others:Droperidol，PimozideIVOtherAntipsychoticDrugs

PenfluridolAntipsychoticdrugwithlastingeffectsbyp.o.andsuitbleforchronicschizophrenia.

SulpirideGoodeffectstoschizophreniaof

tensiontype.Showeffectsquiklyandhasthenameof“DrugElectricShock”.

Clozapine

Showeffectsquicklyandstrongeffectsofantipsychotic.Hasalsoeffectswhichotherdrugsareineffective.SelectivelyblockingD4subtyperecepterandblocking5—HT2Areceptertoo.Hashardlyextrapyramidalreaction.Hasanti-choline、anti-histamineandanti-αadrenergiceffects.

Maycausegranulocyte↓，CountandexaminationofWBCshouldbetakenbeforeandwithinmedication.

Risperidone

Hasblockingeffectsto５－ＨＴRandＤ２subtypeR．

Hasgoodeffectstonotonlypositivebutalsonegativesymptomsofschizophrenia．Suitbletoacutepatientswithfirstattackandchronicpatients.Mildextrapyramidalreaction.AntimanicDrugs

AffectiveMentalDisorder:Akindofmentaldisorderwithemotionactivitiesdisorder.Basicsymptoms:emotionactivitiesrepresentover-upsurgeorover-lowmorbidly.Classifications：Mono-Phase：Oneofmaniaordepressionrepeatedattack.Double-Phase：

Maniaanddepressionalternatelyattack.

LithiumCarbonate

Thedrugstablizingemotion.Hasobviouslyeffectstomania.【TheInVivoProcess】AAbsorbedquicklyandcompletelybyp.o.BExcretedmainlythrouthkidney.Re-absorptioncompetitivelywithNa+:bundantofNa+，excretedmore，

lackofNa+，excretedless……easytobeaccumulated.

【PossibleMechanism】A.InhibitthereleaseofNA、DAfromnerveendingsmediatedbyNa+、Ca2+.B.PromotetheretakeofCAinthesynapticcleftandelimination.C.InhibittheresponsemediatedbyadenylatecyclaseandPhospholipaseC.D.InfluencethedistributionofNa+、Ca2+、Mg2+andglucosematablism.【AdverseReaction】ANausea、Vomitting、DiarrheaandLimbFibrillationetc；BThyroidEnlargement；CPoisoning→MuscularFibrillation、AtaxiaandComaetc.Safetyrange：0.8-1.2mmol/L（TherapeuticConcentration）

>1.5mmol/L（EmergenceofPoisoning）

>2.0mmol/L（SeverePoisoning）AntidepressantDrugsITricyclicAntidepressantDrugs

Imipramine【PharmacologicalEffect】AEffectsonCNSHeartenspirit，

BlocktheretakeofNE、5-HTattheendingofnerve.Antidepressant，Showeffectsslowly.

EffectsonAutonomicNervousSystem

BlockMRobviously.

EffectsonCardiovascularSystem

Induceorthostatichypotension、arrhythmiaetc.【TheInVivoProcess】Absorption:

AbsorbedwellbyP.O.Distribution:

DistributedextensivelyElimination:

MetablizedinliverandExcretedbykidney.

【ClinicalApplication

】ADepressionGoodeffectstoendogenousdepression、

climactericdepression.BEnuresisCAnxietyandPhobia【AdverseReaction】AAnti-cholineSymptomsDrymouth、Constipation、BlurredvisionandPalpitations.BDysorderinliverfunction、OrthostaticHypotension、AgranulocytosisCOthers：Hyperhidrosis、Dizzyness、Insomnia、Ataxiaetc.

Doxepin

Havingstrongeffectsofantianxiety.Especiallysuitbletothetreatmentofdepressionwithanxiety.

Others:Amitriptyline

ClomipramineComparisonofcharacteristicsofcommonlyusedTCAsDrugst1/2(h)InhibitionEffectsonReuptake5-HTNESedationAnticholinergicActionImipramine

9~24++++++++Desipramine

14~760+++++Amitrptyline

17~40++++++++++Doxepin

8~24weakweak++++++Note:TCAs=tricyclicanti-depressantsIIInhibitingDrugsofNEUptake

DesipramineAStronginhibitingdrugsofNAuptake.BlockingH1Rstronglyandblockingα、MRweakly.BQuicklyabsorbedbyP.O.Plasmaproteinbindingrateis90%.

MetablizedinliverandExcretedbykidney.CHavinggoodeffectstomild、moderatedepression.

Maprotiline

InhibitingthereuptakeofNArespectively.Usedintreatingdepression