双精神失常药课件

Chapter18

DrugsforPsychiatricDisordersYuantongTianDepartmentofPharmacologyGannanMedicalUniversity

ContentsClassificationofPsychosisDrugsforSchizophrenia

DrugsforAffectivedisorder

ClassificationofPsychosis

Schizophrenia

(thinkingdisorder)精神分裂症

Affectivedisorder

(mooddisorder)

情感障碍Neurosis&Anxiety

神经衰弱/焦虑症WhatistheBiopsychologyofPsychiatricDisorders?神经衰弱和癔病，焦虑不安。PropertiesofAffectivedisordersBipolardisorder–Alternatingperiodsofmaniaanddepression 1%ofthepopulationafflictedatsomepointintheirlife EquallyfrequentinmenandwomenUnipolardisorder–Depressionwithoutmania 2or3threetimesmorelikelyinwomenthanmen Somecasesofmaniawithoutdepression–butrareDepression–lowenergylevels,anhedonia,lossofappetiteforfoodand 抑郁症sex,sleepingproblems,constipation!

Mania–euphoria,delusional,poorattentionspan,lackofsleep,self躁狂症

importantAffectivedisorderBack情绪高涨、妄想、自大、注意力不集中等。情绪低落，反应迟钝，食欲性、欲降低，悲观厌世，有自杀倾向。HypothesisrelatedtopsychosisDopaminehypothesis——Schizophrenia

FunctionaloveractivityofdopamineinthelimbicsystemorcerebralcortexinschizophreniaormaniaTryptophanhypothesisMonoaminetheory——Affectivedisorder

>Functionalexcessofamineneurotransmittersformania>Functionaldeficitofaminetransmittersfordepression5-HT缺乏NA功能亢进NA功能不足躁狂抑郁Back基底神经节额前皮质中脑边缘通路中脑皮质通路腹侧被盖区黑质参与协调运动功能。与精神活动、思维、情感反应有关。DA-R及其亚型：D1-R：（在外周）致血管扩张，心缩力增强；D2-R：（在中枢）存在于脑内DA能神经通路。已经证实脑内存在5种DA亚型受体：

D1、D2、D3、D4、D5D1样受体：D1和D5亚型受体在药理学特征上符合上述的D1亚型受体，D2样受体：D2、D3、D4受体①黑质—纹状体通路（D1、D2样受体）：是锥体外系运动功能的高级中枢。

DA↓——帕金森病（帕金森综合症）

DA↑——不自主运动（手足徐动症、舞蹈病）②中脑边缘系统通路③中脑皮质通路④结节—漏斗通路（

D2样受体）（D2样受体）与精神活动、思维、情感反应有关。DR↑I型精神分裂多巴胺能神经通路及主要功能调控下丘脑激素分泌调节体温Back§1AntischizophreniadrugsPhenothiazines:Chlorpromazine(氯丙嗪)Perphenazine(奋乃静)Fluphenazine(氟奋乃静)Trifluoperazine(三氟拉嗪)Butyrophenones：Haloperidol(氟哌啶醇)Thioxanthenes：Chlorprothixene(氯普噻吨）Others:Clozapine（氯氮平）吩噻嗪类丁酰苯类噻吨类PHARMACOKINETICS

AbsorptionandDistribution

>absorbedirregularly>bindingtomanytissuesresultsinalargeVd(>7L/kg)>highlylipid-solubleandprotein-bound(92-99%)>longerclinicaldurationofactionMetabolismandExcretion

>beingmetabolizedinliver>Therearemanydrugmetabolites.>excretedinurineIndividualdifference

Back

Chlorpromazine（Wintermine)MechanismofActionMechanismofantipsychosis:

blockadeofthesynapticdopamin(D2)–likereceptorsinthemesolimbicandmesocorticalareasinthebrain,andinactivatingdopaminergicneurotransmission.Mechanismofadverseeffects:

blockadeofthepostsynapticdopamineD2-likereceptorsinthetuberoinfundibularandnigrostriatalareas.氯丙嗪CentralnervoussystemAntipsychoticEffectMECHANISM:blockadeofthepostsynapticD2–likereceptors

inthemesolimbicandmesocorticalpathways.Antiemetic（止吐）EffectLowdoses:blockingD2-likereceptorsintheChemoreceptorTriggerZone(CTZ)ofmedulla（催吐化学感受区）>Highdoses:directlyinhibitionofthevomitingcentre

（呕吐中枢）>Noeffectonvomitingcausedbyvestibular（前庭）stimulation.>InhibittheHiccoughCentreneartheCTZ.（呃逆）PHARMACOLOGICEFFECTS皮层中枢呕吐反射催吐化学感受区autonomicnervesystem

1、cardiovascular(-)-R(-)血管运动中枢dilatethebloodvesseldirectlyBP↓orthostatichypotension

体位性低血压adrenalinereversal肾上腺素cannotuseinthehypertension高血压:tolerance2、(-)M–Rdrymouth,constipation(便秘),blurredvision(视力模糊)…Effectsonendocrinesystem

PHARMACOLOGICEFFECTSTHERAPEUTICUSESTreatmentofschizophreniaEffectiveineliminatingthepositivesymptoms(delusions,hallucinationsandthoughtdisorders),especiallyforacutecases.Lesseffectiveonnegativesymptoms(withdrawal,bluntedemotions）

Antiemeticeffects

Treatmentofemesiscausedbysomedrugs,butnoeffectonemesiscausedbyvestibularstimulation.HibernationtherapyIntractablehiccough（呃逆）Clinicaluses1）hypothermalanesthesia

低温麻醉

2）artificialhibernation

人工冬眠

CPZ+pethidine(哌替啶)

+promethazine(异丙嗪)hibernationmixture配合物理降温使体温降至34℃以下机体进入“冬眠”状态。BMR，对各种病理刺激的反应性，组织对缺氧的耐受力。

mostlyusedfor

严重感染、中毒性休克、高热惊厥、甲状腺危象等辅助治疗。人工冬眠Back氯丙嗪阻断的受体种类DA受体（D2）：抗精神病M-受体：抗胆碱作用（口干、便秘、排尿困难等）-受体：致体位性低血压、镇静H1-受体：镇静5-HT受体：潜在的抗精神病ADVERSEREACTIONS

GeneraladversereactionsCNSinhibitorysymptomsAnticholinergiceffects：Urinaryretention,Drymouth,

抗自主神经效应Constipation,blurredvisionAntiadrenergiceffects：Orthostatichypotension,

抗肾上腺素效应cardiopalmus,nasalobstructionNeuroendocrineeffects：amenorrhea(闭经),

神经内分泌效应galactorrhea

(泌乳)

Antihistaminergiceffects：sedation（antagonismofH1

抗组胺效应receptorinCNS).ADVERSEEFFECTSAntiadrenergic(Alpha-1)sideeffects:Orthostatichypotensionw/reflextachycardiasedationADVERSEEFFECTSAntihistamineeffect:sedation,weightgain

Extrapyramidalreactions

①Parkinson'ssyndrome②

Akathisia

(静坐不能)

③Acutedystonia

(急性肌张力障碍)④Tardive

dyskinesiaAllergicresponse

skinrash,

photosensitivedermatitis（光敏性皮炎）,hepaticinjury,agranulocytosis

(粒细胞缺乏)EmotionaldisturbanceinducedbydrugsConvulsionandepilepsyinducedbydrugsAcutetoxicreaction锥体外系反应机制:

是氯丙嗪阻断黑质一纹状体DA受体,胆碱能神经功能相对占优势所致.可用中枢性抗胆碱药(安坦或东莨菪碱)而不能用左旋多巴治疗.迟发生运动障碍长期用药出现,停药后不消失,抗胆碱药反加重症状,可试用利血平或毒扁豆碱治疗.

机理:DA受体向上调节①黑质—纹状体通路（D1、D2样受体）：是锥体外系运动功能的高级中枢。

DA↓——帕金森病（帕金森综合症）

DA↑——不自主运动（手足徐动症、舞蹈病）②中脑边缘系统通路③中脑皮质通路④结节—漏斗通路（

D2样受体）（D2样受体）与精神活动、思维、情感反应有关。DA↑I型精神分裂多巴胺能神经通路及主要功能调控下丘脑激素分泌调节体温

otherantipsychoticdrugsp.269硫杂蒽类tardan泰尔登

丁酰苯类haloperidol氟哌啶醇

其他口服长效类penfluridol五氟利多

sulpiride舒必利

clozapine氯氮平

risperidone利培酮BriefSummaryCPZ

blocking中脑-皮质通路D2-R中脑-边缘叶通路D2-R抗精神病作用黑质-纹状体通路DA-R锥体外系反应结节-漏斗通路DA-R影响内分泌§2Antimanicdrugslithiumcarbonate

碳酸锂

[characteristics]

1.absorbedwell；widedistribution；2.Na+-Li+compete

Na+enhancetheexcretionofLi+;

incept

Na+renaldischarge

Li+3.onsetofeffectisslow（显效慢）,

individualvariation（个体差异）;4.mechanismiscomplex;p.1595.maniaandthemanicstateofschizophreniaclinicalfirstchoice;6.adversereaction

safemarginisnarrow;commonadversereaction

acutetoxication:CNS(–)coma…,death.

withdrawal,treatment:1.6mM,iv.0.9%NaCl§3AntidepressantdrugsImipramine米帕明（丙咪嗪）［characteristics］

1.po.absorbedwell；widedistribution；

2.Antidepressantselectivity

high;actionslow;