1. Cholinoceptor Blocking Drugs 成都大学医护学院 药理教研室 王跃锜 原创

2. 1 Muscarinic Cholinoceptor Blocking Drugs 毒蕈碱型受体阻断药， M 受体阻断药 2 Nicotinic Cholinoceptor Blocking Drugs 烟碱型受体阻断药， N 受体阻断药

3. Receptor Type Other NamesLocation 部位 M1M1 Nerves 神经 M2M2 Cardiac M 2 Heart, nerves, smooth muscle 心脏， 神经，平滑肌 M3M3 Glands, smooth muscle, endothelium 腺体，平滑肌，内皮细 胞 M4M4 CNS 中枢神经系统 M5M5 CNS NMNM Muscle type, end plate receptor 肌肉型，终板受体 Skeletal muscle neuromuscular junction 骨骼肌神经肌肉接头 N Neuronal type, ganglion receptor 神经元型，神经节受体 postganglionic cell body, dendrites 突触后细胞，树突

4. tertiary amine alkaloid esters of tropic acid 莨菪酸的叔胺生 物碱酯 Propantheline 丙胺太林, 普鲁本辛 Quaternary amine antimuscarinic agents 季胺类化合物

5. Most tertiary antimuscarinic drugs （叔胺类抗胆碱 药） are well absorbed from the gut （消化道） and conjunctival membranes （结膜）. In contrast, only 10–30% of a dose of a quaternary antimuscarinic drug （季胺类抗胆碱药） is absorbed after oral administration （口服）, reflecting the decreased lipid solubility of the charged molecule （带电荷的分子）.

6. Atropine and the other tertiary agents( 叔胺类抗胆碱药 ) are widely distributed in the body. Significant levels are achieved in the CNS( 中枢神经系统 ) within 30 minutes to 1 hour, and this can limit the dose tolerated when the drug is taken for its peripheral effects. Scopolamine （东莨菪碱） is rapidly and fully distributed into the CNS where it has greater effects than most other antimuscarinic drugs. In contrast, the quaternary derivatives （ 季胺类抗胆碱药 ） are poorly taken up by the brain and therefore are relatively free—at low doses—of CNS effects.

7. After administration, the elimination 消除 of atropine from the blood occurs in approximately 15 hours. About 50% of the dose is excreted unchanged in the urine 尿. Most of the rest appears in the urine as hydrolysis 水解 and conjugation products 结合物. The drug‘s effect on parasympathetic 副交感 function declines rapidly in all organs except the eye. Effects on the iris 瞳孔 and ciliary muscle 睫状肌 persist for more than 72 hours.

8. Atropine causes reversible (surmountable 可逆的 ) blockade at muscarinic receptors; that is, blockade by a small dose of atropine can be overcome by a larger concentration of acetylcholine 乙酰胆碱 or equivalent muscarinic agonist M 受体阻 断药. Tissues 组织 most sensitive to atropine are the salivary 唾液腺, bronchial 支气管, and sweat glands 汗腺. Secretion of acid by the gastric parietal cells 胃壁细胞 is the least sensitive.

9. Atropine is highly selective 选择性 for muscarinic receptors M 型受体. Its potency 效力 at nicotinic receptors N 型受体 is much lower. Atropine does not distinguish 区分 among the M 1, M 2, and M 3 subgroups 亚型 of muscarinic receptors. In contrast, other antimuscarinic drugs are moderately selective for one or another of these subgroups.

10.  Central Nervous System 中枢神经系统 In the doses usually used, atropine 阿托品 has minimal stimulant effects 兴奋效应 on the CNS, and a slower, longer-lasting sedative 镇静 effect on the brain. Scopolamine 东莨菪碱 has more marked central effects, producing drowsiness 嗜睡 when given in recommended dosages and amnesia 失忆 in sensitive individuals. In toxic doses 中毒剂量, scopolamine, and to a lesser degree atropine, can cause excitement 兴奋, agitation 焦躁, hallucinations 幻觉, and coma 昏迷.

11.  Eye 眼 前房角变窄 睫状肌松弛 扩瞳 畏光，调节麻痹 房水回流受阻 泪腺分泌减少，眼干涩

12. Cardiovascular System 心血管系统 心率上升，房室传导加快

13.  Respiratory System 呼吸系统 支气管分泌减少，支气管扩张

14.  Gastrointestinal Tract 消化道 Blockade of muscarinic receptors has dramatic effects on motility 运动 and some of the secretory 分泌 functions of the gut 肠道. Antimuscarinic drugs M 型抗胆碱药 have marked effects on salivary secretion 唾液分泌 ; dry mouth occurs frequently in patients taking antimuscarinic drugs. Gastric secretion 胃酸 分泌 is blocked less effectively. Gastrointestinal smooth muscle motility 胃肠平滑肌运动 is affected from the stomach 胃 to the colon 结肠. In general, the walls of the viscera 内脏 are relaxed, and both tone 张力 and propulsive movements 蠕动 are diminished. Therefore, gastric emptying time 胃排空时间 is prolonged, and intestinal transit time is lengthened.

15.  Genitourinary Tract  泌尿道 The antimuscarinic action of atropine and its analogs 同 类药 relaxes smooth muscle of the ureters 输尿管 and bladder wall 膀 胱壁 and slows voiding 排尿. Sweat Glands 汗腺 体温上升，皮肤 血流增加 散热降低 皮肤变干 汗液减少

16.  Ophthalmologic Disorders 眼科 Accurate measurement of refractive error 屈光不正 in uncooperative patients, eg, young children, requires ciliary paralysis 睫状肌麻痹. Also, ophthalmoscopic examination 眼底 镜检查 of the retina 视网膜 is greatly facilitated by mydriasis 散瞳. Therefore, antimuscarinic agents, administered topically as eye drops 眼药水 or ointment 眼膏, are very helpful in doing a complete examination. For adults and older children, the shorter-acting drugs are preferred （如 后马托品，托吡卡胺）. For younger children, the greater efficacy of atropine is sometimes necessary. A second ophthalmologic use is to prevent synechia (adhesion 粘 连 ) formation in uveitis 葡萄膜炎 and iritis 虹膜炎.

17. DrugDuration of Effect (days) 作用持续时间 Usual Concentration (%) 常用浓度 Atropine 阿托品 7–100.5–1 Scopolamine 东莨菪碱 3–70.25 Homatropine 后马托品 1–32–5 Tropicamide 托吡卡胺 0.250.5–1

18.  Respiratory Disorders 呼吸系统 The use of atropine 阿托品 became part of routine preoperative medication 术前给药 when anesthetics 麻醉 such as ether 乙醚 were used, because these irritant 刺激性 anesthetics markedly increased airway secretions 分泌 and were associated with frequent episodes of laryngospasm 喉痉挛. Preanesthetic 麻醉前 injection of atropine 阿托品 or scopolamine 东莨菪 碱 could prevent these hazardous effects.

19.  Cardiovascular Disorders 心血管系统 Marked reflex vagal discharge 迷走神经反射性兴奋 sometimes accompanies the pain of myocardial infarction 心肌梗塞 (eg, vasovagal attack 血管迷走神经性发作 ) and may impair cardiac output 心输出. Parenteral 注射 atropine or a similar antimuscarinic drug is appropriate therapy in this situation. Rare individuals without other detectable cardiac disease have hyperactive carotid sinus reflexes 颈动脉窦反射 and may experience faintness 眩晕 or even syncope 昏厥 as a result of vagal discharge 迷走兴奋 in response to pressure on the neck, eg, from a tight collar. Such individuals may benefit from the use of atropine or a related antimuscarinic agent.

20.  Gastrointestinal Disorders 消化道 Antimuscarinic agents can provide some relief in the treatment of mild or self-limited conditions of hypermotility 胃肠平滑肌过度兴奋.  Urinary Disorders 泌尿系统 Atropine and other antimuscarinic drugs have been used to provide symptomatic relief in the treatment of urinary urgency 尿急 caused by minor inflammatory bladder disorders 膀胱炎.

21.  Cholinergic Poisoning 胆碱能中毒 Severe cholinergic excess is a medical emergency, especially in rural communities where cholinesterase inhibitor insecticides 杀虫剂 are commonly used and in cultures where wild mushrooms 毒蘑菇 are commonly eaten. The potential use of cholinesterase inhibitors as chemical warfare “nerve gases“ 神经毒气 also requires an awareness of the methods for treating acute poisoning.

22. Overdoses 过量 of atropine or its congeners 同类药 are generally treated symptomatically 对症治疗. Poison control experts discourage the use of physostigmine 毒扁豆碱 or another cholinesterase inhibitor 胆碱酯酶抑制药 to reverse the effects of atropine overdose because symptomatic management is more effective and less dangerous. Symptomatic treatment may require temperature control with cooling blankets and seizure 癫痫 control with diazepam 安定.Artificial respiratory support is needed in respiratory depression.

23. Contraindications to the use of antimuscarinic drugs are relative 相对禁忌, not absolute. Obvious muscarinic excess, especially that caused by cholinesterase inhibitors 胆碱酯酶抑制药, can always be treated with atropine. Antimuscarinic drugs are contraindicated in patients with glaucoma 青光眼, especially angle-closure glaucoma 急性闭角型青光 眼. In elderly men, antimuscarinic drugs should always be used with caution and should be avoided in those with a history of prostatic hyperplasia 前列腺肥大.

24. 1 Ganglionic blocking drugs 神经节阻断药 2 Skeletal muscular relaxants 骨骼肌松弛剂

25. Ganglion Preganglionic fiber Postganglionic fiber

26.  Mecamylamine 美加明 and trimethaphan 咪噻吩 is occasionally used in the treatment of hypertensive emergencies 高血压危象 and dissecting aortic aneurysm 主动脉夹层动脉瘤 ; in producing hypotension 低血压, which can be of value in neurosurgery 神经手术 to reduce bleeding in the operative field.

27.  Neuromuscular blocking drugs interfere with transmission at the neuromuscular end plate 终板. These compounds are used primarily as adjuncts 辅助用药 during general anesthesia 全身麻醉 to facilitate tracheal intubation 气管插管 and optimize surgical conditions while ensuring adequate ventilation 通气.

29. 1 Nondepolarizing muscular relaxants (d -tubocurarine 筒箭毒碱 ) 非除极化肌松药 2 Depolarizing muscular relaxants (succinylcholine 琥珀酰胆碱 ) 除极化肌松药

30. 筒箭毒碱

32.  During anesthesia 麻醉, administration of tubocurarine 筒箭毒 碱 initially causes motor weakness, followed by the skeletal muscles becoming flaccid 松弛的 and inexcitable to electrical stimulation. In general, larger muscles (eg, abdominal 腹肌, trunk 躯干, diaphragm) 横隔膜 are more resistant to neuromuscular blockade and recover more rapidly than smaller muscles (eg, facial 面部, foot, hand). The diaphragm 膈 肌 is usually the last muscle to be paralyzed 麻痹. When administration of muscle relaxants is discontinued, recovery of muscles usually occurs in reverse order, with the diaphragm regaining function first.

33. 乙酰胆碱 琥珀酰胆碱

35.  Following the administration of succinylcholine 琥珀酰胆 碱, transient muscle fasciculations 肌束震颤 occur over the chest 胸部 and abdomen 腹部 within 30 seconds. As paralysis 麻痹 develops rapidly (< 90 seconds), the arm, neck, and leg muscles are initially relaxed followed by the respiratory muscles 呼吸肌. As a result of succinylcholine‘s rapid hydrolysis 水解 by cholinesterase in the plasma 血浆 (and liver), the duration of neuromuscular block typically lasts less than 10 minutes.

36. Tubocurarine 筒箭毒碱 Succinylcholine 琥珀酰胆碱 Phase IPhase II Effect of neostigmine 新斯的明的影响 AntagonisticAugmented 1 Antagonistic Initial excitatory effect on skeletal muscle 骨骼肌初始的表现 NoneFasciculations 肌束震颤 None

37.  A 63-year-old architect, complains of urinary symptoms to his family physician. He has hypertension and the last 8 years, he has been adequately managed with a thiazide diuretic 噻嗪类 利尿药 and an angiotensin-converting enzyme inhibitor. During the same period, he developed the signs of benign prostatic hypertrophy, which eventually required prostatectomy 前列腺切除 to relieve symptoms. He now complains that he has an increased urge to urinate as well as urinary frequency, and this has disrupted the pattern of his daily life.  What treatment steps would you initiate?

38.  A 53-year-old woman comes to see you for a consultation. She is scheduled to take a Caribbean cruise in 2 weeks but is concerned about sea sickness. She has been on boats before and is very sensitive to motion sickness. A friend mentioned to her that there is a patch that is effective for this problem. She is in good health and takes no medications regularly. Her examination is normal. You prescribe a scopolamine transdermal patch for her.  · What is the mechanism of action of scopolamine?  · What are the common side effects of this medication?  · What are some relative contraindications to its use?

39.  Mechanism of action of scopolamine: Competitive antagonist of muscarinic cholinoreceptors in the vestibular system and the central nervous system (CNS).  Common side effects: Mydriasis, dry mouth, tachycardia, urinary retention, confusion, drowsiness.  Relative contraindications: Glaucoma, urinary obstruction, heart disease.