药理学基本概念

1. 药理学基本概念

2. 各系统疾病的药物治疗 按药物作用特点分类 传出神经系统药物 化学治疗药物（化疗药） 按疾病系统分类 中枢神经系统药物 心血管系统药物 其他各系统药物

3. 各系统疾病的药物治疗 学习要点  理解疾病的病理生理特点及用药理由  掌握典型的代表药主要药理作用、药动学特点、临床应用、不良反应及注意事项  了解其他同类药物的主要特点

4. 各系统疾病的药物治疗 Example Aspirin 阿司匹林 Acetylsalicylic acid 乙酰水杨酸 Aspirin 阿司匹林

5. 各系统疾病的药物治疗 Aspirin能抑制环氧合酶（COX），减少PG合成；大剂量解热镇痛抗炎，小剂量抗血小板 相关疾病的病理生理： 1. 发热、炎症及炎症性疼痛与PG合成有关 2. 血小板聚集的重要调节因素之一是花生四烯酸经COX途径合成TXA2

6. 各系统疾病的药物治疗 • 1. ADME • transformed to salicylic acid form in the body • hepatic metabolism is primarily conjugation. • Excretion from urine, the excretion of unchanged forms of aspirin is increased in the alkalinized urine. • larger doses ( > 1 g/d):non-linear elimination, zero order kinetic process, easier to accumulation and intoxication.

7. 各系统疾病的药物治疗 • 2. Pharmacological effects and clinical uses • (1) Antipyretic, analgesic and anti-inflammatory effects • moderate doses (0.3～0.6 g):antipyretic and analgesic effects • larger doses (3～5 g/d):anti-inflammatory and anti-rheumatic effects; only relieves symptoms. • to treat acute rheumatic fever(急性风湿热), • to abate pain and symptoms of rheumatic & rheumatoid arthritis (风湿性和类风湿性关节炎).

8. 各系统疾病的药物治疗 • (2) Inhibition of platelet aggregation • small doses (30～100 mg/d):inhibiting TXA2 synthesis, preventing thrombosis. • used to treat ischemic heart disease, reduce the mortality of myocardiac infarction, and prevent cerebral thrombosis. • larger doses:inhibiting PGI2 synthesis, promoting thrombosis. PGI2:vasodilation and platelet depolymerization (血小板解聚).

9. The mechanism of aspirin: Target enzymes acetylated

10. 各系统疾病的药物治疗 • 3. Adverse effects • (1) GI reactions • stimulating gastric mucosa and CTZ (larger doses); • inhibiting PG synthesis in GI tract • irritant symptoms; gastric bleeding; ulcerous disorders Contraindications: ulcerous disorders

11. 各系统疾病的药物治疗 • (2) Prolongation of bleeding time • small doses:inhibiting platelet aggregation • larger doses:inhibiting synthesis of thrombogen Contraindications: one week prior to surgery; severe hepatic damage; vitamin K deficiency; prothrombinopenia (凝血酶原减少症).

12. 各系统疾病的药物治疗 • (3) Allergic reactions • urticaria (荨麻疹), • angioneurotic edema, • aspirin-induced asthma, • occasionally anaphylactic shock. • Contraindications:bronchial asthma

13. 各系统疾病的药物治疗 • (4) Salicylism （水杨酸反应） dose > 5 g/d:CNS symptoms, including mental confusion; hyperventilation. i.v. NaHCO3can promote the excretion of aspirin. • (5) Hepatic damage • Overdose: hepatic damage Reye’s syndrome (瑞夷综合征):in children, severe hepatic damage (严重肝损害) and encephalopathy (脑病)

14. 各系统疾病的药物治疗 4. Drug interactions

15. 各系统疾病的药物治疗 • Acetaminophen （对乙酰氨基酚）： • antipyretic and analgesic effects are mild and lasting, but almost no anti-inflammatory effects, - not aNSAID • higher selectivity to COX in CNS. mainly used in cold, fever, and headache, etc. overdose can damage liver and kidney.

16. 各系统疾病的药物治疗 • indomethacin 吲哚美辛：stronger efficacy, controlling special types of fever; severe adverse effects • ibuprofen 布洛芬（芬必得）：stronger antipyretic, analgesic and anti-inflammatoryeffects; weaker GI reactions; vision damage • piloxicam 吡罗昔康:long-acting anti-inflammatory and analgesic agent; long-term use induces hemorrhage and ulcers in GI tract

17. 各系统药理学

18. Chapter 3The nervous system pharmacology

19. Part 1Pharmacology of the Efferent Nervous System

20. Sympathetic nerves Parasympathetic nerves Motor nerve

21. NE ACh Autonomic nervous system Sympathetic Ganglia Parasympathetic ACh ACh Somatic motor nervous system Motor nerves ACh Overview of efferent nervous system

22. Overview of autonomic nervous system

23. Synapse

24. Neurotransmitters

25. Termination of neurotransmitter actions Enzymatic degradation: acetylcholinesterase Neurotransmitter transporters

26. 1Transmitters and Receptors • 1.1 Transmitters • (1) Acetylcholine (ACh) • Cholinergic nerves • a. pre-ganglionic fibers of sympathetic and parasympathetic nerves • b. post-ganglionic fibers of parasympathetic, and part of sympathetic nerves • c. motor nerves

27. Acetylcholinesterase (AChE) • Terminating ACh effects AChE

28. (2) Norepinephrine (NE) • ornoradrenaline (NA) • Adrenergic nerves • most of post-ganglionic fibers of sympathetic nerves

30. Termination of norepinephrine effects • Uptake • neurotransmitter transporters • uptake 1: neuronal uptake • uptake 2: non-neuronal uptake • Enzymatic degradation • monoamine oxidase (MAO) • catechol-O-methyltransferease (COMT)

31. 2 Receptors • 2.1 Acetycholine receptors • (cholinoceptors, cholinergic receptors) • Muscarinic receptors (M receptors) • Nicotinic receptors (N receptors)

32. Mucarinicreceptors: 7-transmembrane G protein-coupled receptor Nicotinic receptors: ligand-gated ion channel

33. Mucarinic receptors • Depression of the heart: heart rate, conduction • Contraction of smooth muscles: • sensitive: GI tract, bronchial, urinary bladder • insensitive:uterine, blood vessels • Exocrine glands: sensitive: sweat, tears, salivary • insensitive: GI tract • Eye: miosis: contraction of sphincter muscle of iris • contraction for near vision: contraction of ciliary muscle

34. Nicotinic receptors • NN receptors（ N1 receptors） • Sympathetic and parasympathetic ganglia • Adrenal medulla (hypotesion, rare uses) • NM receptors （N2 receptors） • Contraction of skeletal muscles • (skeletal muscle relaxants)

35. Cholinomimetics: M receptor agonist: pilocarpine 毛果芸香碱 AChE inhibitors (anticholinesterases) Reversible:neostigmine 新斯的明 Irreversible:organophosphates有机磷酸酯类 Cholinergic antagonists: M receptor antagonist: atropine阿托品 NM receptor antagonists: succinylcholine 琥珀胆碱 Cholinesterase reactivators： pralidoxime iodide碘解磷定

36. 2.2 Adrenoceptors (adrenergic receptors) •  receptors • 1 receptors: • contraction of vascular smooth muscles: BP↑ • contraction of radial muscle of iris: mydriasis • 2 receptors:CNS, presynaptic membranes of adrenergic nerves: vasodilatation

37.  receptors • 1 receptors: contractility, automaticity, conduction, oxygen-consumption, cardiac output: heart stimulation • 2 receptors: relaxation of bronchial smooth muscles

38. Adrenoceptor agonists:  : epinephrine 12: norepinephrine 1: phenylephrine; 2: clonidine 12: isoproterenol 1: dobutamine; 2: dobutamine Adrenoceptor antagonists:  :labetalol 12: phentolamine 1: prazosin; 2: yohimbine 12: propranolol 1:atenolol; 2:butoxamine

39. 2 Drug actions and classification • 1. Mechanisms of drug actions • 1.1 Direct actions on the receptors • Agonists • Antagonists

40. 1.2 Indirect actions via affecting • transmitters • (1) Synthesis: L-dopa 左旋多巴 • (2) Inactivation: AChEI, MAOI • (3) Release: neostigmine 新斯的明, ephedrine 麻黄碱, amphetamine 苯丙胺 • (4) Transport and storage: imipramine 丙咪嗪, reserpine 利血平（利舍平）

41. 1.3 Mimetics and antagonists • (1) Mimetics • direct-acting: receptor agonists • indirect-acting: increasing amounts and/or effects of transmitters • (2) Antagonists • direct-acting: receptor antagonists • indirect-acting: decreasing amounts and/or effects of transmitters

42. 2. Drug classification • 2.1 Cholinomimetics • (1) Cholinoceptor agonists (as tools for research) • M, N receptor agonists:carbachol 卡巴胆碱 • M receptor agonists:pilocarpine 毛果芸香碱 • N receptor agonists:nicotine 烟碱 • (2) Cholinesterase inhibitors (Anticholinesterases) • Reversible:neostigmine 新斯的明 • Irreversible:organophosphates 有机磷酸酯类

43. 2.2 Cholinergic antagonists • (1) Cholinoceptor antagonists • M cholinoceptor antagonists • non-selective:atropine 阿托品 • M1 cholinoceptor-selective: parenzepine • 哌仑西平

44. N cholinoceptor antagonists • NN cholinoceptor antagonists:mecamylamine • 美加明 • NM cholinoceptor antagonists:succinylcholine • 琥珀胆碱 • (2) Cholinesterase reactivators • pralidoxime iodide 碘解磷定

45. 2.3 Adrenoceptor agonists • (1)  receptor agonists • 12 receptor agonists:norepinephrine 去甲肾上腺素 • 1 receptor agonists:phenylephrine 去氧肾上腺素 • 2 receptor agonists:clonidine 可乐定 • (2) ,  receptor agonists • epinephrine, adrenaline 肾上腺素

46. (3)  receptor agonists： • 12 receptor agonists:isoproterenol • 异丙肾上腺素 • 1 receptor agonists:dobutamine 多巴酚丁胺 • 2 receptor agonists:dobutamine 沙丁胺醇

47. 2.4 Adrenoceptor antagonists • （1） receptor antagonists • 12 receptor antagonists: • short-acting: phentolamine 酚妥拉明 • long-acting: phenoxybenzamine 酚苄明 • 1 receptor antagonists: prazosin 哌唑嗪 • 2 receptor antagonists: yohimbine育亨宾

48. （2） receptor antagonists • 12 receptor antagonists:propranolol 普萘洛尔 • 1 receptor antagonists:atenolol 阿替洛尔 • 2 receptor antagonists:butoxamine 布他沙明 • （3）,  receptor antagonists • labetalol 拉贝洛尔

49. Part 2Pharmacology of the Central Nervous System