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Section 10. Nervous system Chapter 5. Drugs acting on nervous system

Section 10. Nervous system Chapter 5. Drugs acting on nervous system. Chapter 5. Drugs acting on nervous system Including: Drugs acting on efferent nervous Drugs acting on afferent nervous Drugs acting on central nervous. Drugs acting on efferent nervous:

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Section 10. Nervous system Chapter 5. Drugs acting on nervous system

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  1. Section 10. Nervous systemChapter 5.Drugs acting on nervous system

  2. Chapter 5. Drugs acting on nervous system Including: Drugs acting on efferent nervous Drugs acting on afferent nervous Drugs acting on central nervous

  3. Drugs acting on efferent nervous: Part 1. General consideration of eff-erent nervous pharmacology Part 2. Parasympathomimetics Part 3. Cholinoceptor blocking drugs Part 4. Adrenoceptor agonists Part 5. Adrenoceptorantagonists Drugs acting on afferent nervous: Part 6. Local anesthetics

  4. Drugs acting on central nervous: Part 7. Sedative-hypnotics Part 8. CNS stimulatants Part 9. Anti-epileptic drugs and anticonvulsant drugs Part 10. Drugs of anti-Parkinson’s disease Part 11. Drugs treated psychiatric disorders Part 12. Analgesics Part 13. Antipyretic, analgesic and anti-inflammatory drugs Part 14. General anesthetics

  5. Part 1. General consideration of efferent nervous pharmaco-logy(传出神经系统药理概论) 1. Classification of efferent nerves 2. Metabolism of neurotransmitters of efferent nerves 3. Receptors and responses 4. Mechanism of the drugs action 5. Classification of the drugs

  6. General consideration 1. Classification of efferent nerves: (1)Classification according to anatomy: Sympathetic n. Autonomic n. Efferent n.Parasymthetic n. Somatic motor n.

  7. General consideration (2)Classification according to neuro-transmitters: ▲ Most of sympatheticpostganglionic fibers. ①Noradrenergic nerves:Noradrenaline(NA) ②Cholinergic nerves:Acetylcholine(ACh) ▲ All sympathetic and parasympathetic preganglionic fibers; ▲All parasympathetic postganglionic fibers; ▲A few of sympathetic postganglionic fibers; ▲Somatic motor nerve fibers.

  8. 1.●<ACh●<NA <ACh 2. ●<ACh●<ACh 3. ●<ACh CNS 1.Sympathetic nerve; 2.Parasympathetic nerve;3. Somatic motor nerve. effectors

  9. General consideration 2. Metabolism of neurotransmitters of efferent nerves: (1)Metabolism of ACh: Acetyl-CoA+CholineAChrelease CoA AChE AChAcetic acid+Choline hydrolysis

  10. General consideration (2)Metabolism of NA: HO- -CH2-CH-NH3HO- -CH-CH2-NH3 COOHHO COOH (Tyrosine)(Dopa) HO- -CH2-CH-NH3 HO- -CH-CH2-NH3 HO HO OH (Dopamine)(NA) NA Release uptake1(vesicle/MAO) uptake2(extraneuronal cell/COMT)

  11. General consideration 3. Receptors and responses: (1)Cholinoceptors: ①Muscarinic receptor(M-receptor): M1receptor:gastric parietal cell, secretion M2receptor:heart, inhibition M3receptor: smooth muscle, contraction M4receptor:exocrine glands, secretion M5receptor: CNS, excitation ②Nicotinic receptor(N-receptor): NNreceptor:ganglion, excitation NMreceptor:skeletal muscles, contraction

  12. General consideration (2)Adrenoceptors: 1receptors:vascular smooth muscle and pupillary dilator —— vasoconstriction, mydriasis. 2receptors:CNS, presynaptic m. —— vasodilatation. ①receptors: ② receptors: 1receptors:heart —— excitement. 2 receptors:bronchial smooth muscle —— relaxation.

  13. General consideration 4. Mechanism of the drugs action: ①agonist: pilocarpine(毛果芸香碱),adrenaline(肾上腺素) (1)Directly action on receptors: ②antagonist:atropine(阿托品), phentolamine(酚妥拉明), propranolol(普萘洛尔) (2)Influencing neurotransmitters release(indirect action): ①destruction:anti-AChE: neostigmine (新斯的明) ②release:ephedrine(麻黄碱) ③depleting store:reserpine(利舍平)

  14. General consideration 5. Classification of the drugs: (1)Cholinomimetics(拟胆碱药); (2)Anti-choline drugs(抗胆碱药); (3)Adrenoceptor angonist(肾上腺素受体激动药); (4)Adrenoceptor blocking drugs(肾上腺素受体阻断药).

  15. General consideration (1)Cholinomimetics(拟胆碱药): ①Cholinoceptor agonist: M, N receptor:Acetylcholine(乙酰胆碱) M receptor: Pilocarpine(毛果芸香碱) N receptor:Nicotine(烟碱) ②Anticholinesterase(抗胆碱酯酶药): Neostigmine(新斯的明) ③Promoting ACh release(促ACh释放药): Fampridine(法普利定)

  16. General consideration (2)Anti-choline drugs(抗胆碱药): M receptor:atropine(阿托品) M1 receptor:pirenzepine(哌仑西平) M2receptor:gallamine triethiodide (戈拉碘铵) M3 receptor:hexahydrosiladifenidol (六氢硅杂二苯哌丁醇) ① Cholinoceptor blocking drugs: N receptor: NN receptor:mecamylamine(美卡拉明) NM receptor:tubocurarine(筒箭毒碱) ②Cholinesterase reactivators (胆碱酯酶复活药): PAM (碘解磷定), PAM-Cl(氯解磷定)

  17. General consideration (3)Adrenoceptor angonist: 1,2 receptoragonist: noradrenaline(去甲肾上腺素) 1 receptoragonist: phenylephrine(去氧肾上腺素) 2 receptoragonist:clonidine(可乐定) ① receptoragonist: ②,  receptoragonist: adrenaline(肾上腺素) ③ receptoragonist: 1, 2 receptoragonist: isoprenaline(异丙肾上腺素) 1 receptoragonist: dobutamine(多巴酚丁胺) 2 receptoragonist: sabutamol(沙丁胺醇)

  18. General consideration (4)Adrenoceptor blocking drugs: 1,2:phentolamine(酚妥拉明) 1:prazosin(哌唑嗪) 2:yohimbine(育亨宾) ① blocking drugs: ②blocking drugs: 1, 2:propranolol(普萘洛尔) 1:atenolol(阿替洛尔) 2:butasamine(布他沙明) ③ , blocking drugs: labetalol(拉贝洛尔)

  19. Part 2. Parasympathomimetics (拟副交感神经药)

  20. Parasympathomimetics can be divided into: (A)Mcholinoceptor agonists ●Cholinergic agonists(胆碱能激动药) —— cholinomimetics(拟胆碱药): Ⅰ. Choline esters(胆碱酯类) Methacholine(醋甲胆碱), Ⅱ. Alkaloids(生物碱类) Pilocarpine(毛果芸香碱) (B)Ncholinoceptoragonists: Nicotine(烟碱) ●Anticholinesterase agents(抗胆碱酯酶药): (A)Reversible anti-AChE agents: Neostigmine(新斯的明), (B)Irreversible anti-AChE agents: Organophosphates(有机磷酸酯类).

  21. ●Cholinergic agonists(胆碱能激动药) —— cholinomimetics(拟胆碱药): (A)M cholinoceptor agonists: Ⅰ. Choline esters(胆碱酯类) Acetylcholine(乙酰胆碱); Methacholine(醋甲胆碱): Xerostomia(口腔干燥症) Carbachol(卡巴胆碱): Glaucoma(青光眼) Bethanechol chloride(氯贝胆碱): Post-operativeabdominal distension (腹胀) and uroschesis(尿潴留); Xerostomia.

  22. Ⅱ. Alkaloids(生物碱类): Pilocarpine(毛果芸香碱, 匹鲁卡品) 1. Pharmacological effects: It can excite M receptor directly, the sensitivity for eye and exocrine glands. (1)Eye: ①Pupillaryconstriction ②Intraocular pressure(降低眼内压); ③Constrict ciliary muscle(睫状肌) —— spasm of accommodation. ②;

  23. Pilocarpine

  24. Pilocarpine (1)Eye ▲ pupillary constriction(myosis) ▲ Fall in intraocular pressure ▲ Spasm of accommodation ——constrict ciliary muscle (2)Exocrine glands promoting glands secreting (3)Smooth muscle constriction: GI, biliary tract, bronchus, womb, bladder (4)Cardiovascular system heart rate↓

  25. Pilocarpine 2. Clinical Uses: (1)Glaucoma(青光眼): Angle-closure type(闭角型) (acute congestive type, 急性充血型) Open-angle type(开角型) (chronic simple type, 慢性单纯型) (2)Iritis(虹膜炎): myotics(缩瞳药)/mydriatics(扩瞳药) (3)Xerostomia(口腔干燥症): po

  26. (B)N cholinoceptor agonists Nicotine(烟碱)

  27. ● Anticholinesterase agents: (A)Reversible anti-AChE agents:Neostigmine(新斯的明),Physostigmine(毒扁豆碱) (B)Irreversible anti-AChE agents: Organophosphates(有机磷酸酯类)

  28. (A)Reversible anti-AChE agents: Main pharmacological effects: inhibit AChE  ACh (1)Increasing contraction strength of skeletal muscle; (2)Enhancing contraction of smooth muscle of GI / bladder / branchus; (3)Myosis,  intraocular pressure ; (4)Exocrine glands secretion.

  29. Neostigmine(新斯的明) 1. Pharmacokinetics: (1)Absorbed poorly after oral adminis-tration:It is a chemical compound ofquarternary ammonium(季铵类化合物), im or sc: 0.5mg～2mg/once; po: 15mg～30mg/once (2)It is destroyed by plasma esterase. (3)t½: 1～2 hr.

  30. Neostigmine 2. Pharmacological effects: (1)Increasing contraction strength of skeletal muscle:  inhibit AChE; direct stimulate NM receptor. (2)Enhancing contraction of smooth muscle of GI /bladder/branchus.

  31. Neostigmine 3. Clinical uses: (1)Myasthenia gravis(重症肌无力); (2)Post-operative abdominal disten-tion or urinary retention(手术后腹胀气和尿潴留); (3)Paroxysmal atrial tachycardia (阵发性室上性心动过速); (4)Overdose of tubocurarine(筒箭毒碱): 对抗竞争性肌松药过量时的中毒.

  32. Neostigmine 4. Adverse reaction: (1)Overdose: Cholinergic crisis(胆碱能危象). (2)Contraindications(禁忌证): mechanical ileus(机械性肠梗阻); urinary obstruction(尿道梗阻); bronchial asthma(支气管哮喘).

  33. Physostigmine(毒扁豆碱) 1. Pharmacokinetics: It is achemical compound of tertiary amine(叔胺类化合物). (1)easy to be absorbed by po; (2)easy to cross cornea; (3)easy to cross blood brain barrier. 2. Clinical use: glaucoma, the effect is longer and stronger than pilocarpine.

  34. (B)Irreverible anti-ChE agents: Organophosphates (有机磷酸酯类) Organophosphates+AChE phosphorylated AChE 1. Symptoms of acute intoxication of organophosphates: (1)Muscarinic effects(M样作用); (2)Nicotinic effects(N样作用); (3)Central effects(中枢作用)

  35. 东京地铁毒气事件 时间: 1995年3月20日; 地点:日本东京地铁(3条线路11个车厢); 毒剂:沙林(Sarin)——甲氟磷异丙酯; 主犯: 奥姆(AUM)真理教教主麻原彰晃; 后果: 5500多人中毒, 其中12人死亡, 另有14人终身残疾; 判决: 2004年2月27日日本东京最高法院判处麻原彰晃死刑.

  36. 2.Prevention and treatment of organophosphate intoxication: (1)Prevention of intoxication (2)Treatment of intoxication: ①Clear away organophosphate; ②Treatment with large dose of atropine; ③Treatment with Cholinesterase reactivators(PAM or PAM-Cl)

  37. Cholinesterase reactivators Pyraloxime methoiodide (PAM, 碘解磷定) 1. Pharmacological effects: (1)ReactivatingphosphorylatedAChE PAM +Phosphorylated AChE  Complex  AChE(reactivition) + PAM-phosphoate(nontoxic).

  38. PAM (2)Conjugation with free organo-phosphates: PAM+Freeorganophosphates PAM-phosphoate. (3)Remarkably rapid reactivation of AChE of neuromuscular junction.

  39. PAM 2. Clinical uses: Moderate-severe intoxication of organophosphates and combination withatropine. 3. Adverse reaction: (1)Centralsymptoms, whenivspeed > 0.5 g/min (2)Inhibition of AChE/when PAM overdose(> 2 g/once).

  40. Pyraloxime methylchloride (PAM-Cl, 氯解磷定) The characteristics: (1)Solubility in water is high; (2)Solution of water is stable; (3)Used with iv or im, and the effect of either is the same asPAM.

  41. 应颂敏 yings@zju.edu.cn

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