药理第9章--胆阻.ppt

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1、胆碱受体阻断药的分类胆碱受体阻断药的分类n nM M cholinoceptorcholinoceptor blocking drugs blocking drugsn nN N1 1 CholinoceptorCholinoceptor Blocking Drugs Blocking Drugs(ganglionicganglionic blocking drugs blocking drugs）n nN N2 2 CholinoceptorCholinoceptor Blocking Drugs Blocking Drugs(Skeletal muscle relaxants)(Skele

2、tal muscle relaxants)第一节第一节 M-M-CholinoceptorCholinoceptor Blocking Blocking DrugsDrugsn n 阿托品阿托品(Atropine)(Atropine)n nA belladonna alkaloid,has a high A belladonna alkaloid,has a high affinity for M receptors,where it binds affinity for M receptors,where it binds competitively,preventing acetylcho

3、line competitively,preventing acetylcholine from binding to that site.from binding to that site.n n竞争性拮抗竞争性拮抗AchAch对对M M受体的激动作用，大剂量阻受体的激动作用，大剂量阻断断N N受体。受体。Pharmacological effects Pharmacological effects n n1 1、解除平滑肌痉挛：松驰多种内脏平滑肌、解除平滑肌痉挛：松驰多种内脏平滑肌n n特点特点:n n(1)(1)对过度活动或痉挛的平滑肌松驰作用较对过度活动或痉挛的平滑肌松驰作用较显著。显

4、著。n n (2)(2)胃肠胃肠 膀胱膀胱 胆囊胆囊,胆管胆管,输尿管输尿管,支气管支气管,子宫子宫n n2.2.抑制腺体分泌抑制腺体分泌 唾液腺唾液腺(口干口干),),汗腺汗腺(皮肤干燥皮肤干燥)呼吸道呼吸道腺体腺体 胃腺。大剂量也抑制胃的分泌机能胃腺。大剂量也抑制胃的分泌机能 Salivary gland(dry mouth),sweat Salivary gland(dry mouth),sweat gland(dryness of the skin)bronchial gland(dryness of the skin)bronchial secretorysecretory glan

5、d gland(discharge decreased)(discharge decreased)stomach gland(Large dosage may stomach gland(Large dosage may inhibit the inhibit the secretorysecretory function of the function of the stomach)stomach)n n3.Eye:it blocks all cholinergic 3.Eye:it blocks all cholinergic activity on the eye,resulting i

6、n activity on the eye,resulting in dilation of pupil,unresponsiveness dilation of pupil,unresponsiveness to light and inability to focus for to light and inability to focus for near vision.In patients with near vision.In patients with glaucoma,intraocular pressure may glaucoma,intraocular pressure m

7、ay rise dangerously.rise dangerously.n n(1)(1)散瞳散瞳(mydriasismydriasis)：?n n(2)(2)眼内压升高：眼内压升高：?n n(3)(3)调节麻痹调节麻痹(cycloplegiacycloplegia)：?n n睫状肌松弛，拉紧悬韧带，使晶状体睫状肌松弛，拉紧悬韧带，使晶状体变扁平，屈光度降低，以致视近物模变扁平，屈光度降低，以致视近物模糊，视远物清楚。糊，视远物清楚。n4.Cardiovascular system:4.Cardiovascular system:nAtropine produces Atropine pro

8、duces divergentdivergent effects on the cardiovascular effects on the cardiovascular system,depending on the dose.system,depending on the dose.n n（1 1）At low dose(0.4-0.6mg),it At low dose(0.4-0.6mg),it results in the blockade of results in the blockade of 突触前膜突触前膜(presynaptic membrane)的的M1M1受体，受体，t

9、hus thus permitting increased Ach release.permitting increased Ach release.心率减慢。心率减慢。n n（2 2）With higher dose of atropine With higher dose of atropine(at least of 1mg),the cardiac M-(at least of 1mg),the cardiac M-receptors on the SAreceptors on the SA（sinoatrial）nodenode窦房结窦房结are blocked,and the ca

10、rdiac are blocked,and the cardiac rate increases moderately.rate increases moderately.n n迷走神经张力高的青年，心率加快作用迷走神经张力高的青年，心率加快作用显著，对婴幼儿和老年人的心率影响很显著，对婴幼儿和老年人的心率影响很小。小。n n(3)(3)扩张血管，改善微循环扩张血管，改善微循环：治疗量对血管和：治疗量对血管和血压无明显影响，大剂量解除小血管痉挛，血压无明显影响，大剂量解除小血管痉挛，改善微循环和重要器官的血流供应，减轻组改善微循环和重要器官的血流供应，减轻组织缺氧。织缺氧。n nThe mec

11、hanism of dilation of blood The mechanism of dilation of blood vessel is not related to the vessel is not related to the blockage of M receptor.blockage of M receptor.n n5.CNS5.CNSn n(1)(1)治疗量（治疗量（0.50.51mg)1mg)：可轻度兴奋延可轻度兴奋延脑和大脑皮层。脑和大脑皮层。n n (2)(2)较大剂量（较大剂量（5mg)5mg)：中枢兴奋明显中枢兴奋明显加强，可由兴奋转入抑制、死亡。加强，可由兴

12、奋转入抑制、死亡。In In high doses,it causes agitation,high doses,it causes agitation,seizures,hallucinations and coma.seizures,hallucinations and coma.Clinical uses Clinical uses n1.Atropine is used as an 1.Atropine is used as an antispasmodic agent to relax antispasmodic agent to relax the gastrointestinal

13、 tract and the gastrointestinal tract and bladder.bladder.n解除平滑肌痉挛：胃肠绞痛解除平滑肌痉挛：胃肠绞痛 膀胱刺膀胱刺激症激症 胆绞痛和肾绞痛（胆、肾绞痛胆绞痛和肾绞痛（胆、肾绞痛常与镇痛药哌替啶合用）。常与镇痛药哌替啶合用）。n n2.2.眼科：眼科：n n（1 1）虹膜睫状体炎）虹膜睫状体炎:it may be also be:it may be also be used to topically in used to topically in iritisiritis as a as a mydriaticmydriatic

14、agent,to prevent the agent,to prevent the formation of adhesions between the iris formation of adhesions between the iris and the cornea.and the cornea.n n(2)(2)扩瞳扩瞳:检查眼底。检查眼底。n n(3)(3)验光配镜：使调节麻痹，晶状体固定，验光配镜：使调节麻痹，晶状体固定，准确地测定屈光度。仅儿童验光时用。准确地测定屈光度。仅儿童验光时用。n3.This drug is sometimes used 3.This drug is s

15、ometimes used as an as an antisecretoryantisecretory agent to agent to block secretions in the upper block secretions in the upper and lower respiratory tracts and lower respiratory tracts prior to surgery.prior to surgery.全身麻醉前给药抑制腺体分泌全身麻醉前给药抑制腺体分泌n n4.4.缓慢型缓慢型心律失常：心律失常：窦性心动过缓窦性心动过缓(bradycardiasbra

16、dycardias)，I,III,II度房室度房室传导阻滞等。传导阻滞等。n n心肌梗死引起的窦性或房室结性心动过缓时，心肌梗死引起的窦性或房室结性心动过缓时，大剂量增加心率而加重心肌缺血。大剂量增加心率而加重心肌缺血。n n5.5.抗休克抗休克:？n n暴发型流脑、中毒性菌痢、中毒性肺炎暴发型流脑、中毒性菌痢、中毒性肺炎等所致的休克。等所致的休克。n n伴高热不用。？伴高热不用。？n6.Atropine can be used for the 6.Atropine can be used for the treatment of overdose of treatment of overdo

17、se of organophosphate and some types organophosphate and some types of mushroom poisoning.of mushroom poisoning.nMechanism?Mechanism?nIts ability to enter the CNS is Its ability to enter the CNS is one of particular importance.one of particular importance.Adverse effects Adverse effects n nSide Effe

18、cts:dry mouth,Side Effects:dry mouth,tachycardia,blurred vision,tachycardia,blurred vision,dryness of skin and flush,dryness of skin and flush,difficulty in urination,difficulty in urination,constipation.constipation.口干口干,心悸心悸,视力模糊视力模糊,皮肤干燥潮红，排尿困难、便秘。皮肤干燥潮红，排尿困难、便秘。n nToxic reactions:CNS Toxic react

19、ions:CNS 过度兴奋烦躁、过度兴奋烦躁、定向障碍、幻觉；中枢抑制出现昏迷，循定向障碍、幻觉；中枢抑制出现昏迷，循环、呼吸衰竭。环、呼吸衰竭。n nEffects on the CNS include Effects on the CNS include restlessnessrestlessness兴奋烦躁、坐立不安兴奋烦躁、坐立不安,confusionconfusion（disorientationdisorientation）定向障碍定向障碍,hallucinationhallucination幻觉幻觉,which may which may progress to depress

20、ion,collapse progress to depression,collapse（衰竭）（衰竭）of the circulatory and of the circulatory and respiratory systems and death.respiratory systems and death.中毒解救中毒解救n n解毒药解毒药:毒扁豆碱，毛果芸香碱，新斯的明毒扁豆碱，毛果芸香碱，新斯的明.当解救当解救有机磷酸酯类中毒而用阿托品过量时，不宜有机磷酸酯类中毒而用阿托品过量时，不宜用胆碱酯酶抑制剂：新斯的明和毒扁豆碱用胆碱酯酶抑制剂：新斯的明和毒扁豆碱.n n其他方法：催吐、洗

21、胃、导泻、输液、利尿其他方法：催吐、洗胃、导泻、输液、利尿等。等。禁忌症或慎用禁忌症或慎用n nGlaucomaGlaucoma青光眼、青光眼、prostaticprostatic hypertrophyhypertrophy前列腺肥大、前列腺肥大、tachycardiatachycardia心动过速、心动过速、the agedthe aged老年人老年人 ScopolamineScopolamine东莨菪碱东莨菪碱n nAnother belladonna alkaloidAnother belladonna alkaloid，produces produces peripheral eff

22、ects similar to those of peripheral effects similar to those of atropine.However,it has greater atropine.However,it has greater action on the CNS and a longer duration action on the CNS and a longer duration of action in comparison to those of of action in comparison to those of atropine.atropine.n

23、n对对CNSCNS的作用特点、表现？的作用特点、表现？n n（1 1）主要抑制作用：镇静，）主要抑制作用：镇静，应用？应用？n n原因是化学结构中有一特殊的原因是化学结构中有一特殊的“氧桥氧桥”结构。结构。n n（2 2）抗晕动作用，）抗晕动作用，It is one of the It is one of the most effective anti-motion sickness most effective anti-motion sickness drugs available.drugs available.原理？原理？应用？应用？n n（3 3）It also has the un

24、usual effect It also has the unusual effect of blocking short-term memory.of blocking short-term memory.应用？应用？n n（4 4）抗帕金森病（）抗帕金森病（震颤麻痹）震颤麻痹）AnisodamineAnisodamine山莨菪碱山莨菪碱n n与与atropineatropine比较：比较：n n不易通过血脑屏障，无明显中枢作用不易通过血脑屏障，无明显中枢作用n n外周作用有一定的选择性：对内脏平滑肌解外周作用有一定的选择性：对内脏平滑肌解痉和抑制心血管作用相似，对腺体、眼作用痉和抑制心血管

25、作用相似，对腺体、眼作用弱。弱。选择性？选择性？n n降低血粘度，抑制血小板聚集，有较强改改降低血粘度，抑制血小板聚集，有较强改改善微循环作用。善微循环作用。n n应用？应用？Atropine Atropine 合成代用品合成代用品n n目的？目的？n n1 1、扩瞳药：有后马托品、托吡卡胺等。、扩瞳药：有后马托品、托吡卡胺等。n n2 2、解痉药：有普鲁本辛、胃复康等。、解痉药：有普鲁本辛、胃复康等。n n3 3、M M受体阻断药：哌仑西平等，主要用于受体阻断药：哌仑西平等，主要用于消化性溃疡。消化性溃疡。常用药物的比较常用药物的比较 药物药物 外周外周 扩张扩张 中枢中枢 临床应用临床应用

26、 抗胆碱抗胆碱 血管血管 作用作用阿托品阿托品阿托品阿托品 +兴奋兴奋 Atropine Atropine 或抑制或抑制山莨菪碱山莨菪碱山莨菪碱山莨菪碱 +感染性休克感染性休克 AniAnisosodaminedamine 内脏绞痛内脏绞痛 东莨菪碱东莨菪碱东莨菪碱东莨菪碱 +抑制抑制 麻醉前给药麻醉前给药ScoScopopolamine lamine 晕动病晕动病 震颤麻痹震颤麻痹第二节第二节 N N胆碱受体阻断药胆碱受体阻断药n n N N胆碱受体阻断药胆碱受体阻断药(1)N(1)N1 1胆碱受体阻断药胆碱受体阻断药 (神经节阻滞药神经节阻滞药)(2)N(2)N2 2胆碱受体阻断药胆碱受体

27、阻断药 (骨骼肌松弛药骨骼肌松弛药)神经节阻滞药神经节阻滞药 (ganglionicganglionic blocking drugs)blocking drugs)n n美卡拉美卡拉明明(美加明，美加明，mecamylaminemecamylamine)n n樟磺咪芬樟磺咪芬(trimetaphantrimetaphan camsilatecamsilate)n n本类药物能选择性阴断神经的本类药物能选择性阴断神经的N N1 1受体，阻滞受体，阻滞AchAch与与N N1 1受体的结合，从而阻滞了神经节的受体的结合，从而阻滞了神经节的冲动传递作用。冲动传递作用。n n药物对神经节的阻滞作用无

28、选择性，交药物对神经节的阻滞作用无选择性，交感和副交感神经节均阻断。感和副交感神经节均阻断。n n1.1.阻断交感神经节，产生药理效应。阻断交感神经节，产生药理效应。n n小动脉扩张，外周阻力降低；静脉血管小动脉扩张，外周阻力降低；静脉血管扩张，回心血量减少，血压明显降低。扩张，回心血量减少，血压明显降低。n n临床曾用于高血压危象的治疗。降压作临床曾用于高血压危象的治疗。降压作用强大而可靠，维持时间短。用强大而可靠，维持时间短。n n目前临床主要用于麻醉时控制血压，以目前临床主要用于麻醉时控制血压，以减少手术区的出血。也用于主动脉瘤手减少手术区的出血。也用于主动脉瘤手术。术。n n2.2.阻

29、断副交感神经节，产生不良反应。阻断副交感神经节，产生不良反应。n n如口干、便秘、扩瞳及尿潴留等。如口干、便秘、扩瞳及尿潴留等。骨骼肌松弛药骨骼肌松弛药 (skeletal(skeletal muscular relaxants)muscular relaxants)n n 除极化型肌松药除极化型肌松药 n n骨骼肌松弛药骨骼肌松弛药n n 非除极化型肌松药非除极化型肌松药 除极化型肌松药除极化型肌松药除极化型肌松药除极化型肌松药 (depolarizing muscular(depolarizing muscular(depolarizing muscular(depolarizing mu

30、scular relaxants)relaxants)relaxants)relaxants)n n作用机制：作用机制：作用机制：作用机制：nIt attaches to the N receptor and acts like It attaches to the N receptor and acts like Ach to depolarize the junction.Ach to depolarize the junction.nUnlike Ach,which is instantly destroyed by Unlike Ach,which is instantly destr

31、oyed by AchEAchE,the depolarizing agent persist at high,the depolarizing agent persist at high concentrations in the synaptic cleft,concentrations in the synaptic cleft,remaining attached to the receptor for a remaining attached to the receptor for a relatively long time,and providing a relatively l

32、ong time,and providing a constant stimulation of the receptor.constant stimulation of the receptor.n n药物与神经肌接头后膜药物与神经肌接头后膜N N2 2受体结合，产生与受体结合，产生与AchAch相似的，较持久的除极作用，使相似的，较持久的除极作用，使N N2 2受体对受体对AchAch不起反应而使骨骼肌松弛。不起反应而使骨骼肌松弛。n n作用特点：作用特点：n n1.1.药物作用的开始，常出现短暂的肌束药物作用的开始，常出现短暂的肌束颤动。颤动。n n2.2.快速耐受性。快速耐受性。n n

33、3.3.抗抗AchEAchE药新斯的明不能解除其肌松药药新斯的明不能解除其肌松药的中毒作用，反能加强中毒作用。因新的中毒作用，反能加强中毒作用。因新斯的明抑制斯的明抑制AchEAchE，减少琥珀胆碱的代谢。减少琥珀胆碱的代谢。n n4.4.治疗量无神经节阻滞作用。治疗量无神经节阻滞作用。n n琥珀胆碱琥珀胆碱(succinylcholinesuccinylcholine,司可林司可林,scolinescoline)n n 药理作用药理作用 n n1.1.肌松作用肌松作用n n作用快、短，易于控制。静脉注射作用快、短，易于控制。静脉注射10301030 mg mg琥珀胆碱后，琥珀胆碱后，1min

34、1min出现作用，出现作用，2min2min达高达高 峰，峰，5min5min作用消失。琥珀胆碱在体内被血作用消失。琥珀胆碱在体内被血浆浆AchEAchE水解。水解。n n2.2.肌松作用顺序及恢复顺序肌松作用顺序及恢复顺序n n颈部颈部 肩胛肩胛 腹部腹部 四肢四肢 面部面部 舌舌 咽喉咽喉 咀嚼肌咀嚼肌 呼吸肌呼吸肌 n n3.3.肌松作用强度肌松作用强度n n以颈部以颈部 及四肢松弛最明显及四肢松弛最明显,其次为面部、舌、其次为面部、舌、咽喉、咀嚼肌咽喉、咀嚼肌 。n n 临床应用临床应用 n n1.1.松弛咽喉肌，以利于插管。支气管镜、松弛咽喉肌，以利于插管。支气管镜、食管镜检查。食管

35、镜检查。n n2.2.浅麻醉辅助用药，以利于肌肉松弛，浅麻醉辅助用药，以利于肌肉松弛，有利于手术的进行。有利于手术的进行。n n 不良反应不良反应 n n1.1.窒息窒息 过量呼吸麻痹过量呼吸麻痹n n2.2.肌束颤动、高血钾肌束颤动、高血钾n n 药物相互作用药物相互作用 n n1.1.本品不能与本品不能与AchEAchE抑制剂合用，合用时会增抑制剂合用，合用时会增本药的毒性，如新斯的明，环磷酰胺，氮芥，本药的毒性，如新斯的明，环磷酰胺，氮芥，普鲁卡因，可卡因等。普鲁卡因，可卡因等。n n2.2.本品不能与骨骼肌松弛药合用，合用时会本品不能与骨骼肌松弛药合用，合用时会增本药的呼吸麻痹，如氨基

36、甙类抗生素，多增本药的呼吸麻痹，如氨基甙类抗生素，多粘菌素粘菌素B B，呋塞米利尿药。呋塞米利尿药。非非除极化型肌松药除极化型肌松药 (竞争型肌松药竞争型肌松药,competitive muscular relaxants)competitive muscular relaxants)n n作用机制作用机制n n本类药物与本类药物与AchAch竞争神经肌接头的竞争神经肌接头的N2N2受体，阻受体，阻断断AchAch对对N N2 2受体的激动作用而使骨骼肌松弛。受体的激动作用而使骨骼肌松弛。The drugs combine with the N receptor The drugs combi

37、ne with the N receptor and prevent the binding of Ach.and prevent the binding of Ach.n n特点：抗特点：抗AchEAchE药新斯的明能解除其肌松作用。药新斯的明能解除其肌松作用。因本类药物代谢不受因本类药物代谢不受AchEAchE的的影响。影响。n n 筒筒箭毒箭毒碱碱(d-tubocurarined-tubocurarine)n n肌松顺序及恢复顺序肌松顺序及恢复顺序眼部肌肉眼部肌肉 四肢肌四肢肌 躯干肌躯干肌肋间肌肋间肌 膈肌膈肌n n特点：特点：n n1.1.本药静注后本药静注后3-6min3-6min起效，持起效，持20-40min20-40min。n n2.2.安全性比较小，因作用时间较长，其作安全性比较小，因作用时间较长，其作用不易逆转用不易逆转(呼吸肌松弛呼吸肌松弛)，目前临床少用。，目前临床少用。