Chpt-07-Cholinoceptor-activating-drugs胆碱受体激动剂

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醋甲胆碱

SelectiveforMreceptornot

easilyhydrolyzedbycholinesterase---

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

2.1Themethacholinechallenge9Carbachol卡巴胆碱

similartoAch(verypotentNandM-directeffect)hasmanysideeffectsusedtotreatglaucomaCarbachol卡巴胆10Bethanechol贝胆碱Effectivebybothoralandparenteraladministration

clinicalusePostoperativeileus,Flatulence,Gastricatonia,Gastricretention,Urinaryretention

Bethanechol贝胆碱11Contraindicationsintheuseofcholineesters•Bronchialasthma:Precipitationofbronchospasm•Hyperthyroidism:Precipitationofcardiacarrhythmias•Myocardialinfarction:Precipitationofhypotensionandconductionblock•Pepticulcer:IncreasegastricacidsecretionContraindicationsintheuseo12Pilocarpine毛果芸香碱A.Pharmacologiceffects--stimulatesM-receptor1.Eyesa.miosis

contractionofirissphinctersmoothmuscle(circularmuscle)Pilocarpine13Chpt-07-Cholinoceptor-activating-drugs胆碱受体激动剂14Parasympathetic-constricts

pupil

thusatropinecausesrelaxation

ofcircularmuscleM

circularmuscleRadialmuscleParasympathetic-constrictspup15bDecreasesintraocularpressure--asaresultofcontractionof

irissphincterandciliarymuscleCiliarymusclecontractionputstensiononthetrabecularmeshwork,openingitsporesandfacilitatingoutflowoftheaqueoushumorintothecanalofSchlemn,increasedoutflowreducesintraocularpressure.bDecreasesintraocularpress16房水:睫状体产生→眼后房→瞳孔→眼前房→虹膜角膜角→虹膜角膜角隙→巩膜静脉窦→睫前静脉→眼静脉巩膜静脉窦(sinusvenosussclerae)是一环形管道,管壁由内皮、不连续的基膜和薄层结缔组织构成。巩膜静脉窦,即Schlemn管,是一个围绕前房角一周的环行管。位于巩膜突稍前的巩膜内沟中,表面由小梁网所复盖,向外通过巩膜内静脉网或直接经房水静脉将房水运出球外,向内与前房交通。房水:睫状体产生→眼后房→瞳孔→眼前房→虹膜角膜角→虹膜角17小梁网(trabecularmeshwork),为位于巩膜静脉窦内侧、Schwalbe线和巩膜突之间的结构。房水产生后，进入前房，通过小梁细胞和内层Schlemm管壁离开眼球而进入静脉系统。睫状肌紧邻睫状上皮和小梁网。一旦睫状肌收缩，晶状体调节力增加，小梁网的构型发生变化，房水流出易度增加。小梁网(trabecularmeshwork),为位于巩膜18iriscorneaciliarymusclesuspensoryligamentsCanalofSchlemnlensiriscorneaciliarymusclesuspen19corneaCiliarymuscleirisCanalofSchlemnsuspensoryligamentslenscorneaCiliarymuscleirisCanal20Trabecularmeshwork

SchlemncanalirisCiliarymuscleTrabecularmeshworkSchlemnca21Chpt-07-Cholinoceptor-activating-drugs胆碱受体激动剂22c.

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

Glaucoma

eye-drops,ointmenteffectonpupilreducedintraocularpressure2.

IritisPreventtheadhesionofiristolensUsewithmydriaticsalternativelyB.ClinicalUses26N胆碱受体激动药烟碱(nicotine,尼古丁)

液态生物碱，脂溶性极强，可经皮肤吸收兴奋自主神经节和神经肌肉接头的N受体，作用呈双相性作用广泛、复杂，故无临床实用价值N胆碱受体激动药烟碱(nicotine,尼古丁)液态27TobaccosmokehasbeenshowntocontaincompoundscapableofinhibitingMAO.Monoamineoxidaseisresponsibleforthedegradationofdopamineinthehumanbrain.WhendopamineisbrokendownbyMAO-B,neurotoxicby-productsareformed,possiblycontributingtoParkinson'sandAlzheimersdisease.ManysuchpapersregardingAlzheimer'sdiseaseandParkinson'sDiseasehavebeenpublished.Tobaccosmokehasbeenshownt28RecentstudiesfindnobeneficiallinkbetweensmokingandAlzheimer'sdiseaseandinsomecases,suggestitmayactuallyresultinanearlieronsetofthedisease.However,nicotinehasbeenshowntodelaytheonsetofParkinson'sdis