1. Section 10. Nervous system Chapter 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. Adrenoceptor antagonists
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. General consideration of efferent nervous pharmaco-logy(传出神经系统药理概论)
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. 1. Classification of efferent nerves:
General consideration
(1)Classification according to anatomy:
Sympathetic n.
Autonomic n.
Efferent n Parasymthetic n.
Somatic motor n.

7. (2)Classification according to neuro-transmitters:
General consideration
①Noradrenergic nerves: Noradrenaline(NA)
▲ Most of sympathetic postganglionic fibers.
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 2. ● <ACh● <ACh 3. ● <ACh
CNS
1. Sympathetic nerve;
2. Parasympathetic nerve; Somatic motor nerve.
effectors

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

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

11. 3. Receptors and responses:
General consideration
(1)Cholinoceptors:
①Muscarinic receptor(M-receptor):
M1 receptor: gastric parietal cell, secretion
M2 receptor: heart, inhibition
M3 receptor: smooth muscle, contraction
M4 receptor: exocrine glands, secretion
M5 receptor: CNS, excitation
②Nicotinic receptor(N-receptor):
N N receptor: ganglion, excitation
N M receptor: skeletal muscles, contraction

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

13. 4. Mechanism of the drugs action:
General consideration
(1)Directly action on receptors:
①agonist: pilocarpine(毛果芸香碱), adrenaline(肾上腺素)
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. 5. Classification of the drugs:
General consideration
(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. (1)Cholinomimetics(拟胆碱药):
General consideration
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. (2)Anti-choline drugs(抗胆碱药):
General consideration
① Cholinoceptor blocking drugs:
M receptor: atropine(阿托品)
M1 receptor: pirenzepine(哌仑西平)
M2 receptor: gallamine triethiodide
(戈拉碘铵)
M3 receptor: hexahydrosiladifenidol
(六氢硅杂二苯哌丁醇)
N receptor:
NN receptor: mecamylamine(美卡拉明)
NM receptor: tubocurarine(筒箭毒碱)
② Cholinesterase reactivators (胆碱酯酶复活药):
PAM (碘解磷定), PAM-Cl(氯解磷定)

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

18. (4)Adrenoceptor blocking drugs:
General consideration
①  blocking drugs:
1, 2: phentolamine(酚妥拉明)
1: prazosin(哌唑嗪)
2: yohimbine(育亨宾)
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. Parasympathomimetics
Part 2.
Parasympathomimetics
(拟副交感神经药)

20. Parasympathomimetics can be divided into:
●Cholinergic agonists(胆碱能激动药)
—— cholinomimetics(拟胆碱药):
(A)M cholinoceptor agonists
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)N cholinoceptor agonists:
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. (A)M cholinoceptor agonists:
●Cholinergic agonists(胆碱能激动药)
—— cholinomimetics(拟胆碱药):
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-operative abdominal distension (腹胀) and uroschesis(尿潴留);
Xerostomia.

22. Pilocarpine(毛果芸香碱, 匹鲁卡品)
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:
①Pupillary constriction
② Intraocular pressure(降低眼内压);
③Constrict ciliary muscle(睫状肌)
—— spasm of accommodation. ②;

23. Pilocarpine

24. (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↓
Pilocarpine

25. (acute congestive type, 急性充血型) (chronic simple type, 慢性单纯型)
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
Pilocarpine

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

27. (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)
● Anticholinesterase agents:

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 of quarternary 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. 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.
Neostigmine

31. 3. Clinical uses: Neostigmine
(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.
Neostigmine

32. Cholinergic crisis(胆碱能危象). mechanical ileus(机械性肠梗阻);
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).
Neostigmine

33. Physostigmine(毒扁豆碱) 1. Pharmacokinetics: 2. Clinical use:
It is a chemical 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. Organophosphates (有机磷酸酯类)
(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)Reactivating phosphorylated AChE
PAM + Phosphorylated AChE
 Complex  AChE(reactivition)
+ PAM-phosphoate(nontoxic).

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

39. PAM 2. Clinical uses: 3. Adverse reaction:
Moderate-severe intoxication of organophosphates and combination with atropine.
3. Adverse reaction:
(1)Central symptoms, when iv speed
> 0.5 g/min
(2)Inhibition of AChE/when PAM
overdose(> 2 g/once).
PAM

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 as PAM.

41. 应颂敏