《英新模板拟副交感神经药》由会员分享，可在线阅读，更多相关《英新模板拟副交感神经药（27页珍藏版）》请在金锄头文库上搜索。
1、Zhi-guo Song,Department of Pharmacology,Parasympathomimetics,cholinergic agonistsanticholinesterases,Parasympathomimetics,cholinergic agonists,complete cholinergic drugs acetylcholine ( ACh ) carbacholM-cholinoceptor agonist pilocarpineN-cholinoceptor agonist nicotine,Acetylcholine (ACh),M effects:
2、1. Cardiovascular system vasodilation decrease heart rate negative dromotropic effect negative inotropic effect shorten atrial refractory period,ACh has both M-R and N-R activity,2. stimulate visceral smooth muscle 3. increase intestinal secretions and salivary ， bronchiolar 4. miosis 5. contract sk
3、eletal muscle,Acetylcholine (ACh),Pilocarpine (毛果芸香碱, 匹鲁卡品),Origin of the Drug-South American- Pilocarpus jaborandi-Isolated in 1875,Chemical Structure,Parasympathomimetic （Cholinergic agonist),Actions M-receptor agonist 1. Eye: miosis: constrict the pupillae sphincter muscle, causing miosis (marked
4、 constriction of the pupil). lower intraocular pressure accommodate spasm,Eye Fluid Production and Pressure,Types of Glaucoma,Open-Angle Glaucoma,Closed-Angle Glaucoma,Anterior Chamber angle closure,Blocked drainage of aqueous,Blockage at trabecularmeshwork,Anterior chamber open,Blocked drainage of
5、aqueous,accommodate spasm,Actions: 2.Gland: increase gland secretion , especially sweat gland and salivary gland . 3.Smooth muscle: stimulate intestinal and airway smooth muscle 4.Cardiovascular: decrease heart rate,Therapeutic use,glaucoma (main closed-angle glaucoma) iritis: contracts the pupils t
6、o prevent the adhesion of iris and lens XerostomiaNotice: presses inner canthus, prevents absorption of drugs from nasolacrimal canal, otherwise, it can enter the brain and cause CNS symptoms, sweating and salivation.,muscarine (毒蕈碱),Anticholinesterase agents,ACh在AChE作用下水解过程,Anticholinesterase agent
7、s can inhibit or inactivate AChE, causing the accumulation of ACh at the cholinergic receptors. These drugs can thus provoke M and N receptors resulting in M and N effects.Anticholinesterases are classified as reversible and irreversible inhibitors.,Neostigmine (新斯的明),myasthenia gravis(重症肌无力): an au
8、toimmune disease caused by antibodies to the nicotine receptor that bind to the ACh-R of neuromuscular junctions.Neostigmine has a direct and indirect actions on NM-R (end-plate).,It can reversibly inhibit AChE,flatulence and uroschesis after operation antidotes to poisoning from skeletal muscle rel
9、axant such as tubocurarine paroxysmal ventricular tachycardia glaucoma Adverse effects:include the actions of generalized cholinergic stimulation, such as salivation, nausea, vomitting, diarrhea.,Physostigmine (毒扁豆碱, eserin),Eye: 1) miosis2) lowers intraocular pressure 3) accommodates spasmmainly us
10、ed in glaucoma,Pharmacological action and uses:,What is the difference between physostigmine and pilocarpine?,Organophosphates intoxication and rescue,Types:Agricultural insectcides:Dipterex （敌百虫）DDVP （敌敌畏）Malathion （马拉硫磷）Parathion （对硫磷，1605）Systox （内吸磷，1059）Rogor （乐果）War gas:Sarin （沙林）Soman （梭曼）Tab
11、un （塔崩）,It can irreversibly inhibits AChE,Mechanism of intoxication,Organophosphates are “ irre-versible ” anticholinesterase drugs . Their phosphor atom combines with AChE by covalent bond and forms phosphated AChE that is uneasy to be hydrolyzed. The activity of AChE diminishes markedly and the co
12、ncentration of ACh increases. Administering as soon as possible in order to prevent enzyme from “aging”.,The way of intoxication:skin; respiratory tract; gastrointestinal tract,Symptoms of poisoning 1)M-R: Glands, Eye, Bronchial, GI tractN1-R: both Sympthetic and Para. 2)N-RN2-R: Skeletal muscle tre
13、mor3)CNS exciting inhibition,1) Removal any ingested poison (lavage)Dipterex - dont gastric lavage withalkaline solution DDVPParathion（1605） - dont gastric lavage with KMnO4 solution Mintacol（1600）,2) Rescuing with drugsAtropine anti muscarinc effectsCholinesterase reactivator,Emergency treatment,PA
14、M (pralidoxime iodide) Cholinesterase reactivator,Action and uses: reactivating the cholinesterase :effective groups: quaternary nitrogen combines with phosphated AChE oxime combines with phosphoryl phosphated-PAM decomposes AChE dissociates,It directly combines with free- organophosphates prevents
15、them further combine with AChE It has marked action on neuromuscular junctions and promptly inhibits fasciculation.Improves CNS symptomsIt cant directly antagonize the accumulated ACh, therefore, it should be used with atropine,PAM-CL Obidoxime (双复磷) administered by iv. and im. power and longer than PAM,Question: What are the different results between using atropine and PAM for organophosphate poisoning? Why?,
