抗膽堿酯酶藥和膽堿酯酶復(fù)活藥課件1

抗膽堿酯酶藥和膽堿酯酶復(fù)活藥(1)幻燈片本課件PPT僅供大家學(xué)習(xí)使用學(xué)習(xí)完請(qǐng)自行刪除，謝謝！本課件PPT僅供大家學(xué)習(xí)使用學(xué)習(xí)完請(qǐng)自行刪除，謝謝！Cholinesterase（膽堿酯酶，AChE）acetylcholinesterase（乙酰膽堿酯酶）也稱真性膽堿酯酶：主要存在于膽堿能神經(jīng)末梢突觸間隙。Pseudocholinesterase（假性膽堿酯酶）：主要存在于血液及肝臟中。新斯的明抑制膽堿酯酶過(guò)程示意圖Neostigmine〔新斯的明〕1.Pharmacologicaleffects①cholinesteraseinhibitor②verystrongeffectonskeletalmuscle--directactivatingN2receptors--releaseAChatthemotornerveendings〔運(yùn)動(dòng)神經(jīng)〕③strongstimulatingeffectongastrointestinaltract〔胃腸道平滑肌〕andgallbladdersmoothmuscle〔膽囊平滑肌〕I.易逆性抗膽堿酯酶藥

2.ClinicalUses

①myastheniagravis（重癥肌無(wú)力）

②Postoperativeileus（術(shù)后腸梗阻）andurinaryretention（尿潴留）

③Paroxysmalsupraventriculartachycardia（陣發(fā)性室上性心動(dòng)過(guò)速）

④Overdosageofmusclerelaxants

⑤Atropineintoxication3.SideEffectslargedosage----nausea（惡心）,vomiting（嘔吐）,abdominalpain（腹痛）,HR,fibrillationofmusclefibers（肌束顫動(dòng)）,“cholinergiccrisis”（膽堿能危機(jī)）4.Contraindications

①M(fèi)echanicalintestinalobstruction(ileus)（機(jī)械性腸梗阻）②urinaryobstruction（尿路阻塞）③bronchialasthma（支氣管哮喘）Pyridostigmine〔吡斯的明〕1.Similarandweakerthanneostigmine2.Durationislonger3.ClinicalUses

①myastheniagravis

②postoperativeintestinaldistentionandurinaryretention

③lesssideeffectsPhysostigmine(毒扁豆堿，又稱Eserine〕ClinicalUses①glaucoma〔青光眼〕②awakeningoftraditionalChineseherbanesthesia〔中藥麻醉的催醒〕③atropineintoxication病例討論Ⅱ.難逆性抗膽堿酯酶藥

Organophosphates(有機(jī)磷酸酯類(lèi)，OPs）1.Classification①Organophosphorus--dipterex（敵百蟲(chóng)）,rogor（樂(lè)果）,DDVP,Parathion（對(duì)硫磷）,Malathion（馬拉硫磷）--usedasaninsecticide.--rapidlyabsorbed–skin,respiratory,GIetc.②Nervegases--tabun（塔崩）,sarin（沙林）,soman（梭曼）有機(jī)磷酸酯類(lèi)抑制膽堿酯酶過(guò)程示意圖2.Mechanismof

OrganophosphateIntoxication

①WithexposuretoOpsanticholinesteraseagents,theenzyme(AChE)isphosphorylated（使磷酸化）andbecomesunabletofunction.②Acetylcholinebuild-up,whichcausesinterfer-encewithnerveimpulsetransmissionatnerveendings.3.Acuteintoxication①M(fèi)uscarinicreceptors--pupil,vision,gland,respiration,gastrointestinaltract,bladder,etc.②Nicotinicreceptors--heartrate,bloodpressure--neuromuscularjunction③centralnervoussystem--excitement→inhibition

CholinesteraseAging(Onceagingoccurs,re-activationoftheenzymeisvirtuallyimpossible.)

Acutecholinergiccrisis（急性膽堿能危象）4.ChronicIntoxication

ReductionofAChE,headache,dizziness,fatigue（疲勞）,sometimesmusclefasciculation,miosis（瞳孔縮?。?5.TreatmentofAcuteIntoxication

①Terminateexposure②Maintainairway

③Atropine

④cholinesterasereactivator

⑤othertreatmentAtropine(阿托品）“及早、足量、反復(fù)”--阿托品化（大、紅、快、干、凈）①Atropineblocksacetylcholinereceptors(M-R)andhaltsthecholinergicstimulation；②Verylargedosesofatropineareusuallyrequired；③Thepatientshouldbekeptatropinelized（阿托品化）bygivingatropineeveryhour.Ⅲ.CholinesteraseReactivator（膽堿酯酶復(fù)活藥）

①Compoundscalledoximes（肟）cancausedephosphorylation（脫磷酸）.

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（肌束顫動(dòng)）②improveCNSsymptoms--awakethepatients--stopconvulsion（躁動(dòng)不安）3.SideEffects

Generalmalaise（不適）,blurredvision（視力模糊）,dizziness,nausea（惡心）,Vomiting,tachycardia（心動(dòng)過(guò)速）Pralidoximechloride,PAM-Cl(氯解磷定）SimilartoPAM,butreactivatingenzymeeffectmorestronger.Canbeusedim.oriv.病例討論某男，24歲。因20min前口服敵敵畏15mL而入院治療。體檢：嗜睡狀，大汗淋漓，嘔吐數(shù)次。全身皮膚濕冷，無(wú)肌肉震顫。雙側(cè)瞳孔直徑2～3mm對(duì)光反射存在。體溫、呼吸及血壓基本正常。雙肺呼吸音粗?；?yàn)：WBC14.2×109/L，中性93％，余未見(jiàn)異常。診斷為急性有機(jī)磷農(nóng)藥中毒。