抗胆碱酯酶药和胆碱酯酶复活药优秀课件

Chapter7

cholinesteraseinhibitingdrugs&cholinesterasereactivators

第七章

抗胆碱酯酶药和胆碱酯酶复活药TAISHANmedicaluniversityzhangfengCholinesterase（胆碱酯酶，AChE）acetylcholinesterase（乙酰胆碱酯酶）也称真性胆碱酯酶：主要存在于胆碱能神经末梢突触间隙。Pseudocholinesterase（假性胆碱酯酶）：主要存在于血液及肝脏中。Neostigmine（新斯的明）1.Pharmacologicaleffects

①cholinesteraseinhibitor

②verystrongeffectonskeletalmuscle--directactivatingN2receptors--releaseAChatthemotornerveendings（运动神经）

③strongstimulatingeffectongastrointestinaltract（胃肠道平滑肌）andgallbladdersmoothmuscle（胆囊平滑肌）I.易逆性抗胆碱酯酶药

2.ClinicalUses

①myastheniagravis（重症肌无力）

②Postoperativeileus（术后肠梗阻）andurinaryretention（尿潴留）

③Paroxysmalsupraventriculartachycardia（阵发性室上性心动过速）

④Overdosageofmusclerelaxants

⑤Atropineintoxication3.SideEffectslargedosage----nausea（恶心）,vomiting（呕吐）,abdominalpain（腹痛）,HR,fibrillationofmusclefibers（肌束颤动）,“cholinergiccrisis”（胆碱能危机）4.Contraindications

①Mechanicalintestinalobstruction(ileus)（机械性肠梗阻）②urinaryobstruction（尿路阻塞）③bronchialasthma（支气管哮喘）Physostigmine(毒扁豆碱，又称Eserine）ClinicalUses

①glaucoma（青光眼）

②awakeningoftraditionalChineseherbanesthesia（中药麻醉的催醒）

③atropineintoxication病例讨论Ⅱ.难逆性抗胆碱酯酶药

Organophosphates(有机磷酸酯类，OPs）1.Classification①Organophosphorus--dipterex（敌百虫）,rogor（乐果）,DDVP,Parathion（对硫磷）,Malathion（马拉硫磷）--usedasaninsecticide.--rapidlyabsorbed–skin,respiratory,GIetc.②Nervegases--tabun（塔崩）,sarin（沙林）,soman（梭曼）有机磷酸酯类抑制胆碱酯酶过程示意图2.Mechanismof

OrganophosphateIntoxication

①WithexposuretoOpsanticholinesteraseagents,theenzyme(AChE)isphosphorylated（使磷酸化）andbecomesunabletofunction.②Acetylcholinebuild-up,whichcausesinterfer-encewithnerveimpulsetransmissionatnerveendings.4.ChronicIntoxication

ReductionofAChE,headache,dizziness,fatigue（疲劳）,sometimesmusclefasciculation,miosis（瞳孔缩小）.5.TreatmentofAcuteIntoxication

①Terminateexposure②Maintainairway

③Atropine

④cholinesterasereactivator

⑤othertreatmentAtropine(阿托品）“及早、足量、反复”--阿托品化（大、红、快、干、净）①Atropineblocksacetylcholinereceptors(M-R)andhaltsthecholinergicstimulation；②Verylargedosesofatropineareusuallyrequired；③Thepatientshouldbekeptatropinelized（阿托品化）bygivingatropineeveryhour.Ⅲ.CholinesteraseReactivator（胆碱酯酶复活药）

①Compoundscalledoximes（肟）cancausedephosphorylation（脱磷酸）.

②OximeshavethegeneralstructureR-CH=N-OH（肟基）.

③Reactivateacetylcholinesteraseandiseffectiveinrestoringskeletalmusclefunction.④Butseemslesseffectiveatreversingmuscarinicorcentralsigns.Pralidoximeiodide(碘解磷定，派姆，PAM）1.Pharmacologicaleffects①Dephosphorylation

Phosphorylatedcholinesterase+PAM--→phosphorylatedPAM+reactivatedAChE

②Directandminoreffect

PAM+organophosphate--→phosphorylatedPAM2.Improvethesymptoms①stopmusclefasciculation（肌束颤动）②improveCNSsymptoms--awakethepatients--stopconvulsion（躁动不安）3.SideEffects

Generalmalaise（不适）,blurredvision（视力模糊）,dizziness,nausea（恶心）,Vomiting,tachycardia（心动过速）Pralidoximechloride,PAM-Cl(氯解磷定）SimilartoP