Cholinoceptor Blocking Drugs

Classification Base on specific receptor affinities Antimuscarinic agents Antinicotinic agents( consist of ganglion-blockers and neuromuscular junction blockers)

Atropine and its alkaloids Anisodamine Acopolamine

chemistry and pharmacokinetics Tertiary amine alkaloid esters of tropic acid Well absorbed from the gut and across the conjunctival membrane Widely distributed Metabolism and excretion

Pharmacological Effects Glands Sweat, salivary gland secretion are greatly reduced Bronchial secretion decreased Reduction in gastric secretion and total acid content, especially at doses greater than 1 mg

Pharmacological Effects Eye Mydriasis ocular pressure increase cycloplegia

毛果芸香碱的缩瞳作用 动眼神经的副交感神经支配 毛果芸香碱激动 瞳孔括约肌 M受体 缩瞳 阿托品阻断 占优 瞳孔开大肌 扩瞳 瞳孔开大肌 扩瞳 激动 去甲状腺素能神经支配 虹膜(包括瞳孔括约肌和瞳孔开大肌 ) 毛果芸香碱的缩瞳作用

毛果芸香碱的降低眼内压作用 睫状体上皮 细胞分泌 血管渗出 狭窄时眼内压增高，闭角型青光眼（急，慢型充血性青光眼） 房水 瞳孔 睫状体上皮 细胞分泌 血管渗出 狭窄时眼内压增高，闭角型青光眼（急，慢型充血性青光眼） 房水 瞳孔 毛果芸香碱收缩瞳孔括约肌 前房角间隙 前房 缩瞳虹膜拉紧 间隙扩大,房水入循环 虹膜根部变薄 降低眼内压 变性或硬化时眼内压增高 开角性青光眼（慢性单纯性青光眼） 小梁网 收缩睫状肌 扩张小血管 毛果芸香碱 巩膜静脉窦 阿托品扩瞳，虹膜退向四周，前房角 间隙变窄，房水回流受阻，眼内压升高 血流 毛果芸香碱的降低眼内压作用

毛果芸香碱的调节痉挛作用 正常时晶体较扁平 (瞳孔括约肌) 受睫状肌控制 环状肌 辐射状肌 (瞳孔开大肌) 去甲肾上腺素能 睫状肌起点 去甲肾上腺素能 神经支配 对眼调节无重要意义 阿托品 动眼神经兴奋或毛果芸香碱 动眼神经胆碱能神经 悬韧带 向瞳孔中心收缩悬韧带，睫状小带放松 睫状肌松弛而退向外缘，悬韧带拉紧 外界 晶状体变凸屈光度增加 晶状体变扁屈光度降低 只视近物(调节痉挛) 只视远物(调节麻痹) 毛果芸香碱的调节痉挛作用

Pharmacological Effects Smooth muscle Gastrointestinal tract: relax Genitourinary tract: relax, void slowly

Pharmacological Effects Cardiovascular system: Heart rate:Lower doses: Presynaptic receptor blocked bradycardia At moderate to high therapeutic doses: tachycardia Atrioventricular conduction In toxic concentrations: intraventricular conduction block

Pharmacological Effects blood vessel and pressure Vasodilation and hypopiesis caused by cholinnergic nerve can be blocked At toxic doses, cutaneous vasodilation

Pharmacological Effects CNS At normal doses, minimal stimulant effect In toxic doses, excitement, agitation, hallucinations and coma

Clinical uses Relieve hyperkinesia Inhibit secretion Ophthalmology: iritis, optometry Arrhythmia shock Cholinergic poisoning

Clinical uses 2001年 1月11日 羊城晚报（成都消息） 37岁男性，因家庭纠纷喝乐果中毒。昏迷，每30分钟用5支阿托品，无效 每10分钟用5支，无效 每5分钟用10支，连续使用72小时，总共用了1700支，850 mg 病人清醒，生命体征趋向平稳。（阿托品的 最低致死量为成人80-130 mg ，儿童10 mg ）。

Adverse effects Dry mouth, mydriasis, tachycardia, hot and flushed skin, agitation and delirium Hyperthermic effects: dangerous when overdose in infants/children CNS: hallucinations, coma

Rescue Catharsis Physostigmine CNS: diazepam

Anisodamine Pharmacodynamics: similar to atropine Clinical uses: shock

Scopolamine CNS: inhibited Take before anaesthesia motion sickness Parkinson’s disease

mydriatic 药　物 扩 瞳 作 用 调 节 麻 痹 作 用 浓 度（%） 高 峰 （分） 消 退 （日） （小时） 消 退（日） 硫酸阿托品 1.0  30～40 7～10 1～3 7～12 氢溴酸 后马托品 1.0 40～60 1～2 0.5～1 托吡卡胺  0.5～1.0  20～40 1/4 1/2 <1/4

Quaternary antimuscarinic drug: propantheline bromide Triple antimuscarinic drug: Pakinson’s disease benactyzine

Pirenzepin Block M1, M4 receptor selectively Ulcer, chronic bronchitis

NN Cholinoceptor Blocking Drugs ganglionic blocking drugs Mecamylamine, trimetaphan camsilate

pharmacodynamics Block N1-receptors in ganglion competitively, decrease blood pressure Small artery Relax, decrease blood vessle resistance Venulae relax, decrease blood volume returing to heart

Clinical use Decompression in anesthesia and operation of aortic aneurysm

Adverse response Much and severe adverse responses：postural hypotension, retention of urine, etc.

N2 Cholinoceptor Blocking Drugs Skeletal muscle relaxants It combines with N2-receptor of motor end-plate on postsynaptic membrane, the transmission of nerve impulse is blocked, leading to skeletal muscle relaxation.

divide into two classes on the basis of their mechanism of action Depolarizing muscular relaxants: succinylcholine Nondepolarizing muscular relaxants: d-tubercurarine

Depolarizing muscular relaxants Mechnism Binds to Nm receptor Depolarize longer than Ach Depolarization nondepolarization

Depolarizing muscular relaxants Quiver before relaxation Acute tolerance Cholinesterase inhibitors can strength its effects Can not block NN-receptors in ganglion

Succinylcholine Clinical uses: Guttural muscle are more sensitive to succinylcholine Bronchoscope examination, esophagoscope examination

Adverse responses Asphyxia Fascicle quiver blood plasma Idiosyncratic reaction

Nondepolarizing muscular relaxants d-tubercurarine