8 第八章 胆碱受体阻断药

Chapter8Cholinoceptorblockingdrugs,胆碱受体阻断药,Cholinoceptorblockingdrugs：Anticholinergicdrugs(抗胆碱药)cancombinewithcholinergicreceptorsandinhibitAchorcholinergicdrugstocombinewiththereceptors.,TheyaredividedintoM-cholinoceptorblockingdrugsandN-cholinoceptorblockingdrugs.,1M-cholinoceptorblockingdrugs：Atropineandatropinelikebiologicalalkaloid(阿托品和阿托品类生物碱),Atropine阿托品(存在于颠茄、曼陀罗、莨菪中),颠茄,曼陀罗,belladonna,1、（）M-R（阻断M-受体）2、largedose,toxicdose:（）N1-R,（）CNS选择性：（）M-R（）N1-R,mechanismofaction,glandeyesmoothmuscleheartCNS,sweatgland汗腺、salivarygland唾液腺lachrymal泪腺、bronchialgland呼吸道腺体gastricparietalcells胃壁细胞,PharmacologicalEffects,一、glands：decreasethesecretion,二、eye1)mydriasis扩瞳,atropine（）瞳孔括约肌M-R开大肌功能占优势瞳孔扩大,atropine（）瞳孔括约肌M-R扩瞳虹膜退向外缘前房角间隙变小房水回流眼内压,2)increaseintraocularpressure升高眼压,3）paralysisofaccommodation调节麻痹,Atropine：睫状肌M-R睫状肌松驰悬韧带拉紧晶状体扁平屈光度视远物清、近物模糊,characteristics1)作用强度与SM紧张度成正比对痉挛的SM作用最强selectivitytosmoothmuscle：gastrointestinaltracturinarybladder膀胱、尿道Biliarytract胆管、ureter输尿管、bronchia支气管、uterus子宫,三、smoothmuscle：relaxation,1、HR：1)therapeuticdoseHR（）突触前膜M1-R负反馈Ach释放特点：a.短时、轻度(每分钟减少4-8次)b.部分病人出现,四、Cardiovascularsystem：,（一）Heart,2、A(atria)-V(ventricle)conduction（房室传导）：atropine(一)M-Rconduction,2)largerdoseHR（）窦房结起搏点M2-R解除了迷走神经对心脏的抑制，强度与迷走神经张力水平有关。因此年青人心率变化明显。,Therapeuticdose-nosignificanteffect原因：多数血管缺乏胆碱能神经支配,（二）Vesselandbloodpressure血管和血压,Largerdose-dilatecutaneousvessel(皮肤血管扩张)，warmandflush(热，潮红)机理：不明，与（）M-R无关possiblereason：1)atropinesecretionofsweatglandT代偿性散热反应2)atropinedilatethebloodvesseldirectly,0.5-1.0mg-increasethefrequencyofrespiration1.0-5.0mg-stimulatecerebrum(大脑)-restlessness(焦躁不安)10mg-hallucination(幻觉),delirium(精神错乱)andconvulsion(惊厥),五、CNS,excitationdepression,1、Relaxationofsmoothmusclespasm:Atropineisusedtotreatvisceralcolicpain(内脏绞痛),【ClinicalUses】,胃肠绞痛膀胱刺激症状胆、肾绞痛,也可用于遗尿症，因Atropine可松弛膀胱逼尿肌,治疗时要与哌替啶合用,1)Iridocyclitis(虹膜睫状体炎)：虹膜括约肌和睫状肌休息充分，有助于炎症消退与缩瞳药合用：防止粘连2)Opticalexamination验光配镜：准确测定屈光度特点：调节麻痹作用持久(2-3天)成人少用小儿验光用：睫状肌调节功能强,3、eye：,2、Inhibitionofthesecretionoftheglands制止腺体分泌：,1)preanestheticmedication全麻前给药：decreasetherespiratoryandsalivatory(唾液)glandsecretionpreventthesideeffectofgeneralanesthetics(防止分泌物阻塞呼吸道及吸入性肺炎),2)severenightsweatandsalivation(严重盗汗和流涎),Bradycardia(心动过缓)，S-Ablockade，A-Vblockadebyhyperfunction(机能亢进)ofvagalnerves（迷走神经）,4、Cardiovasculardisorder,Attention:toolargedose：inducetheincreaseofHRandoxygenconsumptionandincreasetheriskofventricular(心室）fibrillation（纤维颤动）.,5.Antishock:infectiousshock暴发型流行性脑脊髓膜炎、中毒性菌痢、中毒性肺炎,Largedoseofatropine-abolishthevesselspasm,dilateperipheralvessel,improvemicrocirculation(微循环),Attention:Atropineisnotusedtotheshockpatientaccompanywithfeverandtachycardia(心动过速).,AsearlyaspossibleAtropinization（阿托品化）RepeatedlyCombinationwithreactivators,6.Organophosphateintoxication,Sideeffect（0.4-0.6mg）：drymouth、blurredvision视力模糊、tachycardia、mydriasis、drynessofskinandflush，difficultyinurination,constipation(便秘).,adverseaction,Toxiceffects：actionofcardiovascularsystem,（）CNS,contraindication:Glaucoma，prostatauxe(前列腺肥大),anisodamine(山莨菪碱，654-2),1.similareffectstothatofatropine,buttheintensityisonly1/20-1/10tothatofatropine2.cantpasstheBBB,noeffectsonCNS3.relievethespasmofthesmoothmuscle,especiallytoGItracts4.clinicalUses:colicpain绞痛(gastrointestinal)andinfectioustoxicshock感染中毒性休克,scopolamine（东莨菪碱）,Peripheral(外周)effectissimilartoatropinegland,eyeatropinecardiovascularsystematropine,2.depressCNSlowdosage:sedation镇静largedosage:hypnotic催眠,3.ClinicalUses1)preanesthesia2)motionsickness(晕动病)3)Parkinsonism,substitutiveatropine阿托品的合成代用品,合成扩瞳药homatropine后马托品、tropicamide托吡卡胺合成解痉药propanthelinebromide溴丙胺太林（普鲁本辛）选择性M受体亚型阻断剂pirenzepine哌仑西平(M1-R),2CholinoceptorblockingdrugsN-Rblockingdrugs,ganglionblockade神经节阻滞药,(-)N1-R(-)postganglialfibresofsympatheticandparasympatheticnerves,Mecamylamine美加明Trimethaphancamsylate樟磺咪芬,mechanism,clinicalusage控制性降压:麻醉时控制性降压，以减少手术区出血。,adverseeffect多、严重,skeletalmuscularrelaxants骨骼肌松驰药(肌松药),Depolarizingmuscularrelaxants除极化型肌松药Nondepolarizingmuscularrelaxants非除极化型肌松药,classification,一、Depolarizingmuscularrelaxants除极化型肌松药（非竞争性肌松药）,suxamethonium琥珀胆碱,又名scoline司可林,mechanismsuxamethonium（）N2-R后膜持久去极化N2-R不能对ACh起反应肌松,Characteristics,2、骨骼肌先收缩后放松Relaxationorder:neck（颈）shoulderabedomenlimbs,3、itishydrolyzedbypseudocholinesterase（假胆碱酯酶）intheblooda)过量中毒时不可用新斯的明解救(人工呼吸机)b)遗传性ChE缺陷，有机磷中毒不可使用该药,1、iv，theeffectisquick,strongandshort,4.对喉肌松弛作用强，用于气管镜、食道镜操作。,5.青光眼、高钾血症禁用。,肌肉持久去极化，K+释放增加,眼外骨骼肌收缩，升高眼内压,mechanismd-tubocurarine(-)N2-R竞争性对抗ACh的作用肌松,二、nondepolarizingmuscularrelaxants非除化型肌松药（竞争性肌松药）d-tubocurarine筒箭毒碱,1、pocannotbeabsorbedivtheeffectisquick,strong,short2、R