Chpt 09 Cholinoceptor-blocking drugs中胆碱受体阻断药.pptVIP

Chapter 9 Cholinoceptor- Blocking Drugs Pharmacological Action highly selective for muscarinic receptors acts by competitive antagonism of ACh binding to muscarinic receptors Not distinguish between M1, M2, M3 Organ Selectivity Most sensitive tissues: salivary, bronchial and sweat glands Less sensitive: gastric parietal cells (gastric acid secretion) Intermediate: smooth muscle autonomic effectors and the heart rapid hydrolysis by pseudocholin-esterase in the plasma and liver. the duration of neuromuscular block typically lasts 5–10 minutes. transient muscle fasciculations. Depolarizing Drug succinylcholine 琥珀胆碱 As skeletal muscle relaxant for tracheal intubation, bronchoscopy, esophagoscopy, etc. it is perennially popular in emergency medicine because it arguably has the fastest onset and shortest duration of action of all muscle relaxants. Adjunct for general anesthesia. Clinical use succinylcholine 1. Asphyxia 窒息 or apnea 呼吸暂停 respirator prepared. 2. Muscle pain unsynchronized contraction. 3. Hyperkalemia patients with burns, nerve damage or neuromuscular disease, closed head injury and other trauma, peritoneal infections, and renal failure are especially susceptible. Adverse reaction succinylcholine 4. 恶性高热 (malignant hyperthermia) 现象:全身麻醉时个别病人表现为琥珀酰胆碱的肌松作用失效，不明原因的心动过速，体温升高，并迅速上升到极点。 后果：早期死于心力衰竭，晚期死于肌红蛋白血症引起的肾功能衰竭。 恶性高热 原因: 兰尼丁受体 (RYRl，ryanodine receptor) 蛋白等位基因发生突变. 兰尼丁受体功能: Ca2+ 释放通道蛋白, 含Ca2+通道，其功能是释放Ca2+，同时也作为骨骼肌内肌浆网和T小管的桥梁结构。 恶性高热 病理机制: 乙醚、氧化亚氮、氟烷、环丙烷等全身麻醉药可能作用于突变的兰尼丁受体使肌浆网过量释放Ca2+ ，高浓度的Ca2+ 通过肌动蛋白、内质网、线粒体而使ATP酶活性增高，引起肌肉收缩和代谢过旺，从而产生高热。 治疗措施: 立即停止手术和麻醉、冷冻处理、纠正酸中毒等。 静脉输注肌松药硝苯呋海因(丹曲林dantrolene)可阻断肌浆网对Ca2+ 的释放，从而减少肌张力和产热，以终止发作，挽救生命。 恶性高热 Initial transient muscle fasciculations Tachyphylaxis (acute tolerance) Anticholinesterase agents are unable to reverse their muscular relaxant effect. Neostigmine ineffective. No ganglion-blocking effect at therapeutic dose. Characteristics (