神经系统药理魏尔清（传出药理概论 拟胆碱药课件

Part2Parasympathomimetics Cholinoceptoragonists M NAnticholinesteraseinhibitors AMuscarinicreceptoragonists AMuscarinicreceptoragonists 1 CholineEsters 胆碱酯类 Acetylcholine乙酰胆碱Carbachol卡巴胆碱Methacholine醋甲胆碱Bethanecholchloride氯贝胆碱2 NaturalAlkaloids 生物碱类 Pilocarpine毛果芸香碱 匹罗卡品 Muscarine毒蕈碱 Pilocarpine毛果芸香碱 匹罗卡品 Pilocarpine毛果芸香碱 AMuscarinicreceptoragonists 1 Pharmacologicaleffects 1 EyesMiosis 缩瞳 contractionofsphinctermuscleofirisLowingintraocularpressure 降低眼内压 enlargingangleofanteriorchamber increasingdrainageofaquoushumorSpasmofaccommodation 调节痉挛 contractionofciliarymuscle contractionfornearvision AMuscarinicreceptoragonists Iris cilliarymuscles andSchelemmcanal Aqueoushumordrainage Pilocarpine Atropine 2 Promotingsecretionofexocrineglands 外分泌腺体 especiallyinsweat salivaryandtearglands AMuscarinicreceptoragonists 2 Clinicaluses 1 OphthamologicalusesGlaucoma narrow orwide anglesIritis miotics mydriatics BOXGlaucomaAcutecongestiveglaucoma narrow angle Chronicsimpleglaucoma wide angle AMuscarinicreceptoragonists 2 SystemicuseDrymouth radiotherapyAntidoteforatropinepoisoning AMuscarinicreceptoragonists 3 Adverseeffects 1 Local eye pain tears 2 Systemic secretionofexocrineglands treatedwithatropine AMuscarinicreceptoragonists BAnticholinesterases 1 Reversibleanticholinesterases2 Irreversibleanticholinesterases anionicsiteesteraticsiteAcetylcholinesteraseisthemechanismofterminatingACheffects B 1Reversibleanticholinesterases Actionofacetylcholinesterase Acetylcholinese structureforinteractionwithsubstrate B 1Reversibleanticholinesterases Neostigmine新斯的明 Neostigmine新斯的明 1 PharmacologicaleffectsbindingtoAChE butslowlyhydrolysisinhibitingAChEactivityPropertiesofEffectsstrongereffectonskeletalmusclesAChE AChrelease stimulatingNMreceptoreffectiveonGItractandurinarybladdermorepolarandcannotenterCNSrelativelyineffectiveonCVS glands eye B 1Reversibleanticholinesterases EffectofneostigmineonAChE Actionofneostigmineonacetylcholinesterase 2 Clinicaluses 1 Myastheniagravis 重症肌无力 symptomatictreatment overdose cholinergiccrisis 2 Paralyticileusandbladder 手术后肠道及膀胱麻痹 postoperativeabdominaldistensionandurinaryretention 3 Antidotefornondepolarizingskeletalmusclerelaxantspoisoning 解除非除极化型肌松药中毒 4 Paroxysmalsuperventriculartachycardia 阵发性室上性心动过速 B 1Reversibleanticholinesterases 3 Adverseeffects 1 Cholinergiceffects muscarinicandnicotiniceffects treatedwithatropine muscarinic 2 Contraindications mechanicalileus 机械性肠梗阻 urinaryobstruction 尿路阻塞 bronchialasthma 支气管哮喘 poisoningofdepolarizingskeletalmusclerelaxants 除极化型肌松药中毒 B 1Reversibleanticholinesterases OtherreversibleanticholinesterasesPyridostigmine 吡斯的明 myastheniagravis paralyticileusandbladderPhysostigmine 毒扁豆碱 glaucomaEdrophoniumchloride 依酚氯铵 myastheniagravisGalantarmine 加兰他敏 myastheniagravis B 1Reversibleanticholinesterases AnticholinesterasesimprovingmemoryTacrine 他克林 improvingmemory hepatictoxicityDonepezil 多奈哌齐 andrivastigmine 利凡斯的明 improvingmenory usedinmild moderateAlzheimerpatientsHuperzine 哈伯因 石杉碱甲 myastheniagravis improvingmemory B 1Reversibleanticholinesterases B 2IrreversibleAnticholinesterasesandCholinesterasereactivators 1 Organophosphates 有机磷酸酯类 1 ToxicologyIrreversiblebindingtoestericsiteofAChEbycovalentattachment phosphorylatedAChE agingAChaccumulatedinthesynapticsites andcausedtoxiceffects IrreversiblybindingtoestericsiteofAChEbycovalentattachment phosphorylatedAChE 2 ToxicsymptomsAcuteintoxicationMuscarinicsymptomseye exocrineglands respiration GItract urinarytract CVSNicotinicsymptomsNN elevationofBP increaseofHR NM tremorofskeletalmusclesCentralsymptomsexcitation convulsion depression advancedphase B 2IrreversibleAnticholinesterasesandCholinesterasereactivators ChronicintoxicationusuallyoccupationalpoisoningplasmaChEactivity weakness restlessness anxiety tremor miosis B 2IrreversibleAnticholinesterasesandCholinesterasereactivators 3 DetoxicationEliminationofpoison SupportivetherapyAntidotesAtropine antagonizingmuscariniceffects early largerdose andrepeateduseCholinesterasereactivators reactivationofphosphorylatedAChE moderate severepatients earlyuse combinedwithatropine B 2IrreversibleAnticholinesterasesandCholinesterasereactivators 2 Cholinesterasereactivators Pyraloximemethoiodide碘解磷定 PAM RecognizingandbindingtoAChE oximegroupConjugatedwithorgano phosphates B 2IrreversibleAnticholinesterasesandCholinesterasereactivators 1 Pharmacologicaleffectsa RecognizingandbindingtoAChE conjugatingwithorganophosphatebyoximegroup 肟基 b Conjugationwithfreeorganophasphatesc RapidreactivationofAChEofneuromuscularjunctions B 2IrreversibleAnticholinesterasesandCholinesterasereactivators 1 2 2 Clinicalusesa Moderate severepatientsb Earlyuse ineffectiveforagingphosphorylatedAChEc Moreeffectiveontremord Combinationwithlargerdoseofatropine B 2IrreversibleAnticholinesterasesandCholinesterasereactivators 3 Adverseeffectsa Centralreactions i v 500mg minb Iodinetoxiceffectsc overdose inhibitingAChE B 2IrreversibleAnti