第八章受体阻断药

思考：1、去神经的眼分别滴加毛果芸香碱、毒扁豆碱，瞳孔各有何反应？2、去神经的骨骼肌分别滴加新斯的明、毒扁豆碱，骨骼肌反应是否一样？2Chapter8Cholinoceptorblockingdrugs－M-Rblockingdrugs胆碱受体阻断剂（I）－M-R阻断剂3AnticholinergicdrugscancombinewithcholinergicreceptorsandinhibitAchorcholinergicdrugstocombinewiththereceptors.TheyaredividedintoM-cholinoceptorblockingdrugsandN-cholinoceptorblockingdrugs.4§1Atropineandatropinelikebiologicalalkaloid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belladonna51、（－）M-R2、largedose,toxicdose:（－）N1-R,（＋）CNS选择性：（－）M-R（－）N1-Rmechanismofaction6glandeyesmoothmuscleheartCNSsweatgland汗腺、salivarygland唾液腺lachrymal泪腺、bronchialgland呼吸道腺体gastricparietalcells胃的壁细胞PharmacologicalEffects一、glands：decreasethesecretion7二、eye1)mydriasis扩瞳atropine→（－）瞳孔括约肌M-R→开大肌功能占优势→瞳孔扩大8atropine→（－）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93）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10characteristics1)作用强度与SM紧张度成正比对痉挛的SM作用最强2)selectivitytosmoothmuscle：gastrointestinaltracturinarybladder膀胱、尿道Biliarytract胆管、ureter输尿管、bronchia支气管、uterus子宫三、smoothmuscle：relaxation111、HR：1)therapeuticdoseHR（－）突触前膜M1-R→负反馈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）Heart122、A(atria)-V(ventricle)conduction：atropine→(一)M-R→conduction↑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。13Therapeuticdose---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，warmandflush机理：不明，与（－）M-R无关possiblereason：1)atropinesecretionofsweatglandT代偿性散热反应2)atropinedilatethebloodvesseldirectly140.5-1.0mg----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、CNSexcitationdepression151、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161)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：172、Inhibitionofthesecretionoftheglands制止腺体分泌：1)preanestheticmedication全麻前给药：decreasetherespiratoryandsalivatory(唾液)glandsecretion→preventthesideeffectofgeneralanesthetics(防止分泌物阻塞呼吸道及吸入性肺炎)2)severenightsweatandsalivation：18Bradycardia(心动过缓)，S-Ablockade，A-Vblockadebyhyperfunction(机能亢进)ofvagalnerves4、CardiovasculardisorderAttention:toolargedose：inducetheincreaseofHRandoxygenconsumptionandincreasetheriskofventricular(心室）fibrillation（纤维颤动）.195.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).20AsearlyaspossibleAtropinization（阿托品化）RepeatedlyCombinationwithreactivators6.Organophosphateintoxication21Sideeffect（0.4-0.6mg）：drymouth、blurredvision视力模糊、tachycardia、mydriasis、drynessofskinandflush，difficultyinurination,constipation(便秘).adverseactionToxiceffects：actionofcardiovascularsystem,（＋）CNScontraindication:Glaucoma，prostatauxe(前列腺肥大)22anisodamine(山莨菪碱654-2)1.similareffectstothatofatropine,buttheintensityisonly1/20-1/10tothatofatropine2.can’tpasstheBBB,noeffectsonCNS3.relievethespasmofthesmoothmuscle,especiallytoGItracts4.clinicalUses:colicpain绞痛(gastrointestinal)andinfectioustoxicshock感染中毒性休克23scopolamine（东莨菪碱）1.Peripheral(外周)effectissimilartoatropinegland,eyeatropinecardiovascularsystematropine2.depressCNSlowdosage:sedation镇静largedosage:hypnotic催眠3.ClinicalUses1)preanesthesia2)motionsickness(晕动病)3)Parkinsonism24§2substitutiveatropine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)25chapter9Cholinoceptorblockingdrugs－N-Rblockingdrugs胆碱受体阻断剂（II）－N-R阻断剂26§1ganglionblockade神经节阻滞药(-)N1-R→(-)postganglialfibresofsympatheticandparasympatheticnervesMecamylamine美加明Trimethaphancamsylate樟磺咪芬mechanismclinicalusage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27§2skeletalmuscularrelaxants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classification28一、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29Characteristics2、骨骼肌先收缩后放松Relaxationorder:neckshoulderabdomenlimbs3、itishydrolyzedbypseudocholinesteraseintheblooda)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,strongandshort304.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31mechanismd-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321、pocannotbeabsorbedivtheeffectisquick,strong,short2、Relaxationorder:head,neck→shoulder,limbs→intercostalmuscle(肋间肌)→diaphragm(膈肌)出现呼吸肌麻痹，人工呼吸+新斯的明3、禁用于重症肌无力、支气管哮喘、严重休克。儿童不宜使用(发生高敏反应较多)。Characteristics促进组胺释放33思考：1、阿托品解救有机磷酸酯类中毒时过量，能否用新斯的明、毒扁豆碱、毛果芸香碱解救？2、试比较两类肌松药的不同