藥理學(xué)教學(xué)課件：擬副交感神經(jīng)藥

Parasympathomimetics

cholinergicagonistsanticholinesterases

Parasympathomimetics

cholinergicagonists

completecholinergicdrugs

◆acetylcholine(ACh)

◆carbacholM-cholinoceptoragonist

◆pilocarpineN-cholinoceptoragonist

◆nicotineAcetylcholine(ACh)Meffects:1.CardiovascularsystemvasodilationdecreaseheartratenegativedromotropiceffectnegativeinotropiceffectshortenatrialrefractoryperiodAChhasbothM-RandN-Ractivity2.stimulatevisceralsmoothmuscle3.increaseintestinalsecretionsandsalivary，

bronchiolar4.miosis5.contractskeletalmuscleAcetylcholine(ACh)Pilocarpine(毛果蕓香堿,匹魯卡品)OriginoftheDrug -SouthAmerican -Pilocarpusjaborandi -Isolatedin1875ChemicalStructureParasympathomimetic（Cholinergic

agonist)ActionsM-receptoragonist1.Eye:miosis:constrictthepupillaesphinctermuscle,causingmiosis(markedconstrictionofthepupil).lowerintraocularpressureaccommodatespasm鞏膜靜脈竇角膜小梁網(wǎng)（濾簾）虹膜晶狀體睫狀體前房EyeFluidProductionandPressureTypesofGlaucomaOpen-AngleGlaucomaClosed-AngleGlaucomaAnteriorChamberangleclosureBlockeddrainageofaqueousBlockageattrabecularmeshworkAnteriorchamberopenBlockeddrainageofaqueousaccommodatespasmActions:2.Gland:

increaseglandsecretion,especiallysweatglandandsalivarygland.3.Smoothmuscle:

stimulateintestinalandairwaysmoothmuscle4.Cardiovascular:decreaseheartrateTherapeuticuseglaucoma(mainclosed-angleglaucoma)iritis:contractsthepupilstopreventtheadhesionofirisandlensXerostomiaNotice:pressesinnercanthus,preventsabsorptionofdrugsfromnasolacrimalcanal,otherwise,itcanenterthebrainandcauseCNSsymptoms,sweatingandsalivation.muscarine

(毒蕈堿)Anticholinesteraseagents

ACh在AChE作用下水解過程

AnticholinesteraseagentscaninhibitorinactivateAChE,causingtheaccumulationofAChatthecholinergicreceptors.ThesedrugscanthusprovokeMandNreceptorsresultinginMandNeffects.

Anticholinesterasesareclassifiedasreversibleandirreversibleinhibitors.Neostigmine(新斯的明)myastheniagravis(重癥肌無力):anautoimmunediseasecausedbyantibodiestothenicotinereceptorthatbindtotheACh-Rofneuromuscularjunctions.NeostigminehasadirectandindirectactionsonNM-R(end-plate).ItcanreversiblyinhibitAChEflatulenceanduroschesisafteroperationantidotestopoisoningfromskeletalmusclerelaxantsuchastubocurarineparoxysmal

ventricular

tachycardiaglaucomaAdverseeffects:includetheactionsofgeneralizedcholinergicstimulation,suchassalivation,nausea,vomitting,diarrhea.

Physostigmine(毒扁豆堿,eserin)叔胺類可通過BBB季胺類不能通過BBBEye:1)miosis2)lowersintraocularpressure3)accommodatesspasm

mainlyusedinglaucomaPharmacologicalactionanduses:Whatisthedifferencebetweenphysostigmineandpilocarpine?Organophosphates

intoxicationandrescueTypes:Agriculturalinsectcides:

Dipterex（敵百蟲）

DDVP（敵敵畏）

Malathion（馬拉硫磷）

Parathion（對(duì)硫磷，1605）

Systox（內(nèi)吸磷，1059）

Rogor（樂果）Wargas:Sarin（沙林）Soman（梭曼）Tabun（塔崩）ItcanirreversiblyinhibitsAChEMechanismofintoxicationOrganophosphatesare“irre-versible”anticholinesterasedrugs.TheirphosphoratomcombineswithAChEbycovalentbondandformsphosphatedAChEthatisuneasytobehydrolyzed.TheactivityofAChEdiminishesmarkedlyandtheconcentrationofAChincreases.Administeringassoonaspossibleinordertopreventenzymefrom“aging”.

Thewayofintoxication:

skin;respiratorytract;gastrointestinaltract

Symptomsofpoisoning1)M-R:Glands,Eye,Bronchial,GItractN1-R:bothSymptheticandPara.2)N-RN2-R:Skeletalmuscletremor3)CNSexcitinginhibition1)Removalanyingestedpoison(lavage)Dipterex----don’tgastriclavagewith

alkalinesolutionDDVPParathion（1605）----don’tgastriclavagewithKMnO4solutionMintacol（1600）2)Rescuingwithdrugs

AtropineantimuscarinceffectsCholinesterasereactivatorEmergencytreatmentPAM(pralidoximeiodide)Cholinesterasereactivator

Actionanduses:reactivatingthecholinesterase:effectivegroups:quaternarynitrogencombineswithphosphatedAChEoximecombineswithphosphorylphosphated-PAMdecomposesAChEdissociatesItdirectlycombineswithfree-organophosphates

preventsthemfurthercombinewithAChEIthasmarkedactiononneuromuscularjunctionsandpromptlyinhibitsfasciculation.ImprovesCNSsymptoms

Itcan’tdirectlyantagonizethe