第17章 作用于膽堿受體的藥物(傳出神經(jīng)藥理)

第十七章

作用于膽堿受體的藥物I.DefinitionDrugscancombinewithcholinoceptorandactlikeACh.II.Classfication1.M-cholinoceptoragonists膽堿酯類：acetylcholine（乙酰膽堿）,methacholine（醋甲膽堿）,carbachol（卡巴膽堿）,bethanechol（貝膽堿）擬膽堿生物堿：Pilocarpine（毛果蕓香堿）,arecoline（檳榔堿）,musarine（毒蕈堿）

2.N-cholinoceptoragonistsnicotine（尼古丁，煙堿）Acetylcholine（乙酰膽堿）

1.Muscariniceffect(M-effect):iVsmalldosage

①decreaseheartrateandcontractility

②dilation（擴張）

ofbloodvessels,declineofbloodpressure

③constriction（收縮）

ofbronchialmuscle,gastrointestinal,urinarytract,uterussmooth

muscle（子宮平滑肌）andpupil（瞳孔）

④increasethesecretionofgland(sweat,salivary,lacrimal,nasopharyngeal)

⑤SLUDresponse--Salivation,Lacrimation,Urination,Defecation（流涎、流淚、大小便失禁）2.Nicotiniceffects(N-effect):Largerdosage①activatesN1

a.produceandactivatealltheautonomicganglia（神經(jīng)節(jié)）b.resemblessimultaneousdischargeofboththeparasympatheticandsympatheticnervoussystems②activatesN2

a.constrictionofskeletalmuscleb.activatesN1receptorofpheochrome（嗜鉻細胞瘤）cellsofadrenalmedulla（腎上腺髓質(zhì)）--releaseadr.3.TherapeuticuseNone---actionaretootransient

Pilocarpine

（匹魯卡品，即毛果蕓香堿）

1.Pharmacologicaleffects：stimulatesM-receptor(1)Eyea.miosis（縮瞳）

b.Decreaseintraocularpressurec.cyclospasm（調(diào)節(jié)痙攣）(2)Glandsincreasesecretionofsweatgland,salivarygland（唾液腺）M受體激動藥和阻斷藥對眼的作用示意圖房水循環(huán)2.ClinicalUsesa.Glaucoma（青光眼：閉角型青光眼、開角型青光眼）b.Iritis（虹膜炎：與擴瞳藥交替應(yīng)用）I.Definition&classificationcholinoceptorblockingdrugs

（膽堿受體阻斷藥）的概念分類1.按受體

M-cholinoceptorblockingdrugsM1,M2,M3N-cholinoceptorblockingdrugsN1,N2

2.按用途

平滑肌解痙藥，神經(jīng)節(jié)阻斷藥，骨骼肌松弛藥和中樞性抗膽堿藥第二節(jié)M膽堿受體阻斷藥Ⅱ.M-cholinoceptorblockingdrugsAtropoineandrelatedalkaloid（生物堿）阿托品類生物堿及其來源植物名稱主要生物堿

顛茄（Atropabelladonna)莨菪堿曼陀羅（Daturastramonium)莨菪堿洋金花（Daturasp.)東莨菪堿莨菪（Hyoscyamusniger)莨菪堿唐古特莨菪（Scopoliatangutica)山莨菪堿Atropine（阿托品）,Analkaloidthataffectsthenervoussystem1.MechanismofAction①Competitiveantagonism（對抗）ofAChtomuscarinicreceptors②NotdistinguishamongM1,M2,M3

③Mostsensitivetissues:salivary,bronchialandsweatglands④Lesssensitive:gastricparietalcells（壁細胞）(gastricacidsecretion)⑤Intermediate:smoothmuscleeffectorsandtheheart2.PharmacologicalEffects

①Inhibitionthesecretionofgland

a.salivarygland(drymouth)b.sweatgland(dryskin)c.bronchialsecretaryglandd.largedosage---inhibitsthesecretaryfunctionofthestomach②Visual

a.mydriasis（散瞳）b.cycloplegia（睫狀肌麻痹）--can`tfocusfornearvisionc.increasesintraocular（眼內(nèi)的）pressureM-R阻斷藥M-R激動藥③Relaxationofvisceral（內(nèi)臟的）smoothmusclea.stomachintestine(reducedtoneandmotility)b.bronchialmuscle,detrusor（逼尿?。﹐fbladder,urinarytractc.biliarytract–gallbladder（膽囊）andbileducts（膽管）--mildantispasmodicactiond.uterus（子宮）--veryweakeffect④Heart

a.smalldosage:decreasesheartrate(M1-Rblocker)b.largedosage:increasestheheartrate(M2-Rblocker)c.influenceismostnoticeableinthepeoplewhomvagal（迷走神經(jīng)）toneisconsiderable.⑤Dilate（擴張）bloodvesselsandimprove（改善）microcirculationa.therapeuticdosage---nosignificanteffectb.largedosage--dilatescutaneous（皮膚的）bloodvessels(faceandneck)improvemicrocirculation,recoverthebloodsupplytotheimportantorgans,relieveanoxia（缺氧癥）ofthetissues.?CNSstimulatingeffecta.therapeuticdoses(0.5~1.0mg)--mildexcitationb.toxicdoses--restlessness,irritability,disorientation,hallucination（幻覺）,delirium（譫妄）

c.continuallargerdoses--CNSdepression---circulatorycollapseandrespiratoryfailure3.ClinicalUses

①Relaxationofsmoothmusclespasm（痙攣）--visceral（內(nèi)臟的）colicpain（絞痛）a.gastricandintestinalcolicpainb.bladderirritatingsymptomsc.gallbladdercolicpain(lesseffect)d.renalcolicpain(lesseffect)②Inhibitionofthesecretaryglandsecretion

a.preanaestheticmedicationforcontrollingthesideeffectofaether（乙醚）b.adjunctivetherapyforpepticulcers③Ophthalmology（眼科學(xué)）

a.examiningopticfundus（底）b.examiningretina（視網(wǎng)膜）c.preventadhesionformationinuveitis（葡萄膜炎）andiritis(relaxtheirisandciliarybody)④Cardiovascular（心臟血管的）disorder

--severearrhythmia(bradycardia（心動過緩）:SAblock,A-Vblock)⑤Anti-shock（抗休克）--infectiousshock⑥Organophosphateintoxication4.SideEffectsdependingonthedoseofdrugemployed;mayhave:drymouth（口干）,blurredvision（視物模糊）,tachycardia（心動過速）,drynessofskin（皮膚干燥）,flush（面色潮紅）,dizziness（頭昏）,difficultyinurination（排尿困難）,constipation（便秘）5.Toxiceffects

hyperthermia（高熱）,restlessness（煩躁）,delirium（譫妄）,hallucination（幻覺）,coma（昏迷）etc.6.Contraindications（禁忌癥）①glaucoma（青光眼）②pyloricobstruction（幽門梗阻）③prostatichypertrophy（前列腺肥大）7.Usewithcaution（慎用）

①myocardialinfarction（心肌梗塞）,tachycardia（心動過速）②elderlyAnisodamine（山莨菪堿，654-2）

①peripheralanticholinergiceffect（外周抗膽堿作用）②Uses--colicpain(gastrointestinaltract)--infectiousshock（感染中毒性休克）Scopolamine（東莨菪堿）likeatropine,butwithcentralsedative（鎮(zhèn)靜）effect1.Uses

①preanaesthetic（麻醉前）medication--sedation&inhibitsecretion②motion(travel)sickness2.Sideeffects:similartoatropineSyntheticmydriatic幾種擴瞳藥滴眼作用的比較藥物濃度(%)

擴瞳作用高峰(min)消退(d)

調(diào)節(jié)麻痹作用高峰(min)消退(d)硫酸阿托品1.030-407-101-37-12后馬托品1.0-2.040-601-20.5-11-2托比卡胺0.5-1.020-400.250.5<0.25環(huán)噴托酯0.530-50110.25-1尤卡托品2.0-5.0301/12-1/4----SyntheticspasmolyticagentsPropanthelinebromide（溴丙胺太林）inhibitsgastrointestinaltractcontractionandinhibitsgastricacidsecretion.Uses①pepticulcerasanadjuvant（輔佐劑）②gastricspasm③pregnantvomiting（妊娠嘔吐）④bed-wetting（遺尿癥）抗膽堿酯酶藥和膽堿酯酶復(fù)活藥第三節(jié)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程示意圖Neostigmine（新斯的明）1.Pharmacologicaleffects

①cholinesteraseinhibitor

②verystrongeffectonskeletalmuscle--directactivatingN2receptors--releaseAChatthemotornerveendings（運動神經(jīng)）

③strongstimulatingeffectongastrointestinaltract（胃腸道平滑?。゛ndgallbladdersmoothmuscle（膽囊平滑肌）I.易逆性抗膽堿酯酶藥

2.ClinicalUses

①myastheniagravis（重癥肌無力）

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

③