Chpt-07-Cholinoceptor-activating-drugs膽堿受體激動劑

Chapter7CholinoceptoragonistsPharmacologyInstructor:LeiLinsheng雷林生Chapter7Cholinoceptoragoni1Cholinoceptoragonistsarealargegroupofdrugsthatmimicacetylcholineandclassifiedpharmacologicallybytheirspectrumofactiondependingonthetypeofreceptorthatisactivated.Cholinoceptoragonistsarea2Classification1.MCholinoceptoragonists1)Cholineesters

methacholine

carbacholbethanechol2)Alkaloids

pilocarpine2.NCholinoceptoragonists

nicotineClassification3

AcetylcholineA.Muscariniceffect(M-effect)ivsmalldosagedecreasesheartrateandcontractilitydilationofbloodvessels,declineofbloodpressureconstrictionofbronchialmuscle,gastrointestinal,urinarytract,uterussmoothmuscleandpupil

Acetylcholine4

SLUDresponse---Salivation---Lacrimation---Urination---

Defecation

increasesthesecretionofgland(sweat,salivary,lacrimal,nasopharyngeal)increasesthesecretionofgl5B.Nicotiniceffects(N-effect)LargerdosageactivatesN1--producesandactivatesalltheautonomicganglia--resemblessimultaneousdischargeofboththeparasympatheticandsympatheticnervoussystemsB.Nicotiniceffects(N-effect6activatesN1receptorofpheochromecellsofadrenalmedulla---releasesadr.activatesN2,constrictionofskeletalmuscleC.Therapeuticuse

None---actionistootransientNoteffectiveorallyDurationafterIV-2minutesactivatesN1receptorofphe7Methacholine醋甲膽堿

SelectiveforMreceptornot

easilyhydrolyzedbycholinesterase---

effectsarelongerusedtotreatxerostomiaMeasurementofbronchialhyperactivity(hyperresponsiveness)(methacholinechallenge激發(fā)test)Methacholine醋甲膽堿82.1Themethacholinechallengetestisonemethodofassessingairwayresponsiveness.Inthistest,thepatientinhalesanaerosolofoneormoreconcentrationsofmethacholine.Resultsofpulmonaryfunctiontests(eg,spirometry,specificconductance)performedbeforeandaftertheinhalationsareusedtoquantitateresponse.Thisguidelineappliestoadultsandchildrencapableofadequatelyperformingspirometryorbodyplethysmographyandofcooperatingduringthecourseofthechallenge.2.2Apositivetestisdefinedasadecreasefromthebaselineforcedexpiratoryvolumeinthefirstsecond(FEV1)orofthepostdiluentFEV1valueof20%,orofadecreaseinspecificconductanceof35-45%fromthebaselineorpost-diluentvalue.Cardiacarrhythmiascausedbymethacholineareparticularlypronetooccurinpatientswithhyperthyroidism

2.1Themethacholinechallenge9Carbachol卡巴膽堿

similartoAch(verypotentNandM-directeffect)hasmanysideeffectsusedtotreatglaucomaCarbachol卡巴膽10Bethanechol貝膽堿Effectivebybothoralandparenteraladministration

clinicalusePostoperativeileus,Flatulence,Gastricatonia,Gastricretention,Urinaryretention

Bethanechol貝膽堿11Contraindicationsintheuseofcholineesters?Bronchialasthma:Precipitationofbronchospasm?Hyperthyroidism:Precipitationofcardiacarrhythmias?Myocardialinfarction:Precipitationofhypotensionandconductionblock?Pepticulcer:IncreasegastricacidsecretionContraindicationsintheuseo12Pilocarpine毛果蕓香堿A.Pharmacologiceffects--stimulatesM-receptor1.Eyesa.miosis

contractionofirissphinctersmoothmuscle(circularmuscle)Pilocarpine13Chpt-07-Cholinoceptor-activating-drugs膽堿受體激動劑14Parasympathetic-constricts

pupil

thusatropinecausesrelaxation

ofcircularmuscleM

circularmuscleRadialmuscleParasympathetic-constrictspup15bDecreasesintraocularpressure--asaresultofcontractionof

irissphincterandciliarymuscleCiliarymusclecontractionputstensiononthetrabecularmeshwork,openingitsporesandfacilitatingoutflowoftheaqueoushumorintothecanalofSchlemn,increasedoutflowreducesintraocularpressure.bDecreasesintraocularpress16房水:睫狀體產(chǎn)生→眼后房→瞳孔→眼前房→虹膜角膜角→虹膜角膜角隙→鞏膜靜脈竇→睫前靜脈→眼靜脈鞏膜靜脈竇(sinusvenosussclerae)是一環(huán)形管道,管壁由內(nèi)皮、不連續(xù)的基膜和薄層結(jié)締組織構(gòu)成。鞏膜靜脈竇,即Schlemn管,是一個圍繞前房角一周的環(huán)行管。位于鞏膜突稍前的鞏膜內(nèi)溝中,表面由小梁網(wǎng)所復(fù)蓋,向外通過鞏膜內(nèi)靜脈網(wǎng)或直接經(jīng)房水靜脈將房水運(yùn)出球外,向內(nèi)與前房交通。房水:睫狀體產(chǎn)生→眼后房→瞳孔→眼前房→虹膜角膜角→虹膜角17小梁網(wǎng)(trabecularmeshwork),為位于鞏膜靜脈竇內(nèi)側(cè)、Schwalbe線和鞏膜突之間的結(jié)構(gòu)。房水產(chǎn)生后，進(jìn)入前房，通過小梁細(xì)胞和內(nèi)層Schlemm管壁離開眼球而進(jìn)入靜脈系統(tǒng)。睫狀肌緊鄰睫狀上皮和小梁網(wǎng)。一旦睫狀肌收縮，晶狀體調(diào)節(jié)力增加，小梁網(wǎng)的構(gòu)型發(fā)生變化，房水流出易度增加。小梁網(wǎng)(trabecularmeshwork),為位于鞏膜18iriscorneaciliarymusclesuspensoryligamentsCanalofSchlemnlensiriscorneaciliarymusclesuspen19corneaCiliarymuscleirisCanalofSchlemnsuspensoryligamentslenscorneaCiliarymuscleirisCanal20Trabecularmeshwork

SchlemncanalirisCiliarymuscleTrabecularmeshworkSchlemnca21Chpt-07-Cholinoceptor-activating-drugs膽堿受體激動劑22c.

cyclospasmspasmofaccommodationciliarymusclecontractionrelaxationofsuspensoryligament---lensbecomesmoreconvex---myopia(shortsight)c.cyclospasm23iriscorneaciliarymusclesuspensoryligamentsCanalofSchlemnlensiriscorneaciliarymusclesuspen24Glandsincreasessecretionofsweatgland,salivarygland,etc.Glands25B.ClinicalUses1.

Glaucoma

eye-drops,ointmenteffectonpupilreducedintraocularpressure2.

IritisPreventtheadhesionofiristolensUsewithmydriaticsalternativelyB.ClinicalUses26N膽堿受體激動藥煙堿(nicotine,尼古丁)

液態(tài)生物堿，脂溶性極強(qiáng)，可經(jīng)皮膚吸收興奮自主神經(jīng)節(jié)和神經(jīng)肌肉接頭的N受體，作用呈雙相性作用廣泛、復(fù)雜，故無臨床實用價值N膽堿受體激動藥煙堿(nicotine,尼古丁)液態(tài)27TobaccosmokehasbeenshowntocontaincompoundscapableofinhibitingMAO.Monoamineoxidaseisresponsibleforthedegradationofdopamineinthehumanbrain.WhendopamineisbrokendownbyMAO-B,neurotoxicby-productsareformed,possiblycontributingtoParkinson'sandAlzheimersdisease.ManysuchpapersregardingAlzheimer'sdiseaseandParkinson'sDiseasehavebeenpublished.Tobaccosmokehasbeenshownt28RecentstudiesfindnobeneficiallinkbetweensmokingandAlzheimer'sdiseaseandinsomecases,suggestitmayactuallyresultinanearlieronsetofthedisease.However,nicotinehasbeenshowntodelaytheonsetofParkinson'sdis