英新模板擬副交感神經(jīng)藥

1、Zhi-guo Song,Department of Pharmacology,Parasympathomimetics,cholinergic agonists anticholinesterases,Parasympathomimetics,cholinergic agonists,complete cholinergic drugs ◆ acetylcholine ( ACh ) ◆

2、carbachol M-cholinoceptor agonist ◆ pilocarpine N-cholinoceptor agonist ◆ nicotine,Acetylcholine (ACh),M effects:1. Cardiovascular systemvasodilationdecrease heart ratenegative dromot

3、ropic effect negative inotropic effectshorten atrial refractory period,ACh has both M-R and N-R activity,2. stimulate visceral smooth muscle3. increase intestinal secretions and salivary ， bronchiolar4. miosis5

4、. contract skeletal muscle,Acetylcholine (ACh),Pilocarpine(毛果蕓香堿, 匹魯卡品),Origin of the Drug-South American- Pilocarpus jaborandi-Isolated in 1875,Chemical Structure,Parasympathomimetic （Cholinergic agonist),Actions

5、M-receptor agonist1. Eye:miosis: constrict the pupillae sphincter muscle, causing miosis (marked constriction of the pupil).lower intraocular pressureaccommodate spasm,Eye Flu

6、id Production and Pressure,Types of Glaucoma,Open-Angle Glaucoma,Closed-Angle Glaucoma,Anterior Chamberangle closure,Blocked drainage of aqueous,Blockage at trabecular meshwork,Anterior chamber open,Blocked drai

7、nage of aqueous,accommodate spasm,Actions:2.Gland: increase gland secretion , especially sweat gland and salivary gland .3.Smooth muscle: stimulate intestinal and airway smooth muscle4.Cardiovascular: decrease h

8、eart rate,Therapeutic use,glaucoma (main closed-angle glaucoma)iritis: contracts the pupils to prevent the adhesion of iris and lensXerostomiaNotice: presses inner canthus, prevents absorption of dr

9、ugs from nasolacrimal canal, otherwise, it can enter the brain and cause CNS symptoms, sweating and salivation.,muscarine (毒蕈堿),Anticholinesterase agents,ACh在AChE作用下水解過程,Antich

10、olinesterase agents 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. Anticholineste

11、rases are classified as reversible and irreversible inhibitors.,Neostigmine (新斯的明),myasthenia gravis(重癥肌無力): an autoimmune disease caused by antibodies to the nicotine receptor that bind to the ACh-R of neuromuscula

12、r junctions.Neostigmine has a direct and indirect actions on NM-R (end-plate).,It can reversibly inhibit AChE,flatulence and uroschesis after operationantidotes to poisoning from skeletal muscle relaxant such as t

13、ubocurarineparoxysmal ventricular tachycardiaglaucomaAdverse effects: include the actions of generalized cholinergic stimulation, such as salivation, nausea, vomitting, diarrhea.,Physostigmine (毒扁豆堿,

14、 eserin),Eye: 1) miosis 2) lowers intraocular pressure 3) accommodates spasm mainly used in glaucoma,Pharmacological action and uses:,What is the difference between physostigmine and pilocarp

15、ine?,Organophosphates intoxication and rescue,Types: Agricultural insectcides: Dipterex （敵百蟲） DDVP （敵敵畏） Malathion （馬拉硫磷） Parathion （對硫磷，1605） Systox （內(nèi)吸磷，1059） Rogor

16、 （樂果） War gas: Sarin （沙林） Soman （梭曼） Tabun （塔崩）,It can irreversibly inhibits AChE,Mechanism of intoxication,Organophosphates are “ irre-versible ” anticholinesterase drugs . Their phosphor

17、 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 concentration of ACh increases.Administering as soon as possi

18、ble in order to prevent enzyme from “aging”.,,The way of intoxication: skin; respiratory tract; gastrointestinal tract,Symptoms of poisoning1)M-R: Glands, Eye, Bronchial, GI tract N1-R: both Sym

19、pthetic and Para.2)N-R N2-R: Skeletal muscle tremor3)CNS exciting inhibition,,,1) Removal any ingested poison (lavage) Dipterex ---- don’t gastric lavage with alkaline s

20、olution DDVP Parathion（1605） ---- don’t gastric lavage with KMnO4 solution Mintacol（1600）,2) Rescuing with drugs Atropine anti muscarinc effects Cholinesterase reactivator,,,Eme

21、rgency treatment,PAM (pralidoxime iodide) Cholinesterase reactivator,Action and uses: reactivating the cholinesterase : effective groups: quaternary nitrogen combines with phosphated AChE oxime combines with p

22、hosphoryl phosphated-PAM decomposes AChE dissociates,It directly combines with free- organophosphates prevents them further combine with AChE It has marked action on neuromuscular junctions and promp

23、tly inhibits fasciculation. Improves CNS symptoms It can’t directly antagonize the accumulated ACh, therefore, it should be used with atropine,PAM-CLObidoxime (雙復(fù)磷) administered by iv. and im. power