膽堿受體阻斷藥課件

Chapter8

Cholinoceptorblockingdrugs膽堿受體阻斷藥Cholinoceptorblockingdrugs：

Anticholinergicdrugs(抗膽堿藥)cancombinewithcholinergicreceptorsandinhibitAchorcholinergicdrugstocombinewiththereceptors.

TheyaredividedintoM-cholinoceptorblockingdrugsandN-cholinoceptorblockingdrugs.

§1M-cholinoceptorblockingdrugs：

Atropineandatropinelikebiologicalalkaloid(阿托品和阿托品類生物堿)Atropine阿托品(存在于顛茄、曼陀羅、莨菪中)顛茄曼陀羅belladonnagland>eye

>smoothmuscle

>heart>CNS

sweatgland汗腺、salivarygland唾液腺>lachrymal淚腺、bronchialgland呼吸道腺體>gastricparietalcells

胃壁細(xì)胞PharmacologicalEffects一、glands↓：

decreasethesecretion二、eye1)mydriasis

擴(kuò)瞳

atropine→（－）瞳孔括約肌M-R→開大肌功能占優(yōu)勢(shì)→瞳孔擴(kuò)大atropine→（－）瞳孔括約肌M-R→擴(kuò)瞳→虹膜退向外緣→前房角間隙變小→房水回流↓→眼內(nèi)壓2)increaseintraocularpressure

升高眼壓3）paralysisofaccommodation調(diào)節(jié)麻痹Atropine：睫狀肌M-R↓→睫狀肌松馳→懸韌帶拉緊→晶狀體扁平→屈光度→視遠(yuǎn)物清、近物模糊1、HR：

1)therapeuticdoseHR

（－）突觸前膜M1-R→負(fù)反饋→Ach釋放↑特點(diǎn)：a.短時(shí)、輕度(每分鐘減少4-8次)

b.部分病人出現(xiàn)

四、Cardiovascularsystem：（一）Heart2、A(atria)-V(ventricle)conduction（房室傳導(dǎo)）：

atropine→(一)M-R→conduction↑2)largerdoseHR↑

（－）竇房結(jié)起搏點(diǎn)M2-R→解除了迷走神經(jīng)對(duì)心臟的抑制，強(qiáng)度與迷走神經(jīng)張力水平有關(guān)。因此年青人心率變化明顯。0.5-1.0mg----

increasethefrequencyofrespiration1.0-5.0mg---stimulatecerebrum(大腦)---restlessness(焦躁不安)

>10mg---hallucination(幻覺),delirium(精神錯(cuò)亂)andconvulsion(驚厥)五、CNSexcitationdepression1、Relaxationofsmoothmusclespasm:Atropineisusedtotreatvisceralcolicpain

(內(nèi)臟絞痛)【ClinicalUses】胃腸絞痛>膀胱刺激癥狀>膽、腎絞痛也可用于遺尿癥，因Atropine可松弛膀胱逼尿肌治療時(shí)要與哌替啶合用1)Iridocyclitis(虹膜睫狀體炎)：虹膜括約肌和睫狀肌休息充分，有助于炎癥消退與縮瞳藥合用：防止粘連2)

Opticalexamination

驗(yàn)光配鏡：準(zhǔn)確測(cè)定屈光度特點(diǎn)：調(diào)節(jié)麻痹作用持久(2-3天)成人少用小兒驗(yàn)光用：睫狀肌調(diào)節(jié)功能強(qiáng)

3、eye：Bradycardia(心動(dòng)過緩)，S-Ablockade，A-Vblockadebyhyperfunction(機(jī)能亢進(jìn))ofvagalnerves（迷走神經(jīng)）4、CardiovasculardisorderAttention:toolargedose：inducetheincreaseofHRandoxygenconsumptionandincreasetheriskofventricular(心室）

fibrillation（纖維顫動(dòng)）.5.Antishock:infectiousshock

暴發(fā)型流行性腦脊髓膜炎、中毒性菌痢、中毒性肺炎

Largedoseofatropine-----abolishthevesselspasm,dilateperipheralvessel,improvemicrocirculation(微循環(huán))Attention:

Atropineisnotusedtotheshockpatientaccompanywithfeverandtachycardia(心動(dòng)過速).AsearlyaspossibleAtropinization（阿托品化）RepeatedlyCombinationwithreactivators

6.Organophosphateintoxicationanisodamine(山莨菪堿，654-2)1.similareffectstothatofatropine,buttheintensityisonly1/20-1/10tothatofatropine2.can’tpasstheBBB,noeffectsonCNS3.relievethespasmofthesmoothmuscle,especiallytoGItracts4.clinicalUses:colicpain絞痛

(gastrointestinal)andinfectioustoxicshock感染中毒性休克scopolamine（東莨菪堿）Peripheral(外周)effectissimilartoatropinegland,eye>atropinecardiovascularsystem<atropine2.depressCNSlowdosage:sedation鎮(zhèn)靜

largedosage:hypnotic催眠3.ClinicalUses1)preanesthesia2)motionsickness(暈動(dòng)病)3)Parkinsonismsubstitutiveatropine

阿托品的合成代用品合成擴(kuò)瞳藥

homatropine后馬托品、

tropicamide托吡卡胺合成解痙藥

propanthelinebromide

溴丙胺太林（普魯本辛）選擇性M受體亞型阻斷劑

pirenzepine哌侖西平(M1-R)ganglionblockade

神經(jīng)節(jié)阻滯藥(-)N1-R→(-)postganglialfibresofsympatheticandparasympatheticnervesMecamylamine美加明Trimethaphancamsylate樟磺咪芬mechanismclinicalusage控制性降壓:麻醉時(shí)控制性降壓，以減少手術(shù)區(qū)出血。adverseeffect

多、嚴(yán)重

skeletalmuscularrelaxants

骨骼肌松馳藥(肌松藥)Depolarizingmuscularrelaxants

除極化型肌松藥Nondepolarizingmuscularrelaxants

非除極化型肌松藥classification4.對(duì)喉肌松弛作用強(qiáng)，用于氣管鏡、食道鏡操作。5.青光眼、高鉀血癥禁用。肌肉持久去極化，K+釋放增加眼外骨骼肌收縮，升高眼內(nèi)壓mechanismd-tubocurarine→(-)N2-R競(jìng)爭(zhēng)性對(duì)抗ACh的作用肌松二、nondepolarizingmuscularrelaxants

非除化型肌松藥（競(jìng)爭(zhēng)性肌松藥）

d-tubocurarine筒箭毒堿1、pocannotbeabsorbedivtheeffectisquick,strong,short2、Relaxationorder:head,neck→shoulder,limbs→intercos