解热镇痛抗炎药Chapter 20Antipyretic-analgesic and anti-inflammatory drugs1Teaching goals1、简述阿司匹林的作用、用途、不良反应。2、简述对乙酰氨基酚的作用特点。3、比较解热镇痛药与氯丙嗪在降温方面的作用和应用。4、比较解热镇痛药与镇痛药在镇痛方面的作用和应用。21 Introduction【Definition】1. - 1. -have strong antipyretic effects2. - 2. -have analgesic effects3. -some have anti-inflammatory andanti-rheumatic effects.(一类具有解热、镇痛，且大多数还有抗炎、抗风湿作用的药物)3膜 磷 脂PLA2花 生 四 烯 酸白三烯等环内 过氧 化物环氧化酶糖皮质激素(-)解热镇痛抗炎药(-)甾体抗炎药SAIDs非甾体抗炎药NSAIDs【mechanism】vessalPGI2PGF, PGE等plateletTXA2non-steroidal anti-inflammatory drugs4PG: a group of autacoids - lead to inflammation, pain and fever.NSAIDs 环氧化酶（COX） 前列腺素（PG）合成 解热、镇痛、抗炎(是自体活性物质，可致炎、致痛、致热)5细菌毒素 病毒等粒细胞 吞噬、处理产生 释放内热原CNS PG合成与释放体温调定点370C发热NSAIDs COX (-)PG合成【common pharmacological actions】一. Antipyretic action (解热作用)6Properties : 1. temperature temperature of of patients with feverpatients with fever (只降发热者体温)2. independent of environment temperatureindependent of environment temperature (降温作用与环境温度无关)3. increase heat dissipation mainly.(主要增加散热)7Meaning of pyretic pyretic (发热利弊) : Advantages : 1. -enhance the defense function.(提高机体防御功能)2. diagnosis of diseases (热型是诊断的依据).8040 0c37 0c1 2 3 4 5day低热稽留热弛张热T9disadvantages ：high fever CNS function disorders CNS function disorders e.g. e.g. convulsion(惊厥)durative fever durative fever consume consume physical energy(持续发热，消耗体能)10Uses notes1. T 39c (especially for children)2. durativedurative fever that has been diagnosed clearly.(诊断明确的持久发热)3. fever with obvious pain.(发热伴明显疼痛者)4. symptomatic treatment only (仅为对症治疗)11组织损伤 局部炎症局部释放致痛物质 BK、PG等（+）痛觉 感受器疼痛痛觉增敏 NSAIDsNSAIDs COX PG synthesis PG致痛及痛觉增敏analgesia (镇痛)二. Analgesic action (镇痛作用)12Properties :1）moderate analgesics moderate analgesics (镇痛作用中等 )2）-be wellwell for chronic pain and inflammatory inflammatory pain pain （炎性疼痛及慢性钝痛效佳）3）no addiction and no respiratory depression (不成瘾，不抑制呼吸)13三. Anti-inflammatory action (抗炎作用)Prostaglandins (PG) ：1. - dilate blood vessels. (扩血管)2. vascular permeability (血管的通透性)e.g. tissue edematissue edema3. synergy with other inflammatory mediators.(协同其它炎症介质的作用 ) NSAIDs COX PG antiinflammation14Properties :1. symptomatic treatment only e.g. relieve redness, swelling, heat and pain (对症治疗，可明显改善红、肿、热、痛)2. -do not arrest the progression of pathological injury to tissue and occurrence of complications.(不能阻止病程进展及合并症的发生)3. Acetaminophen has no anti-inflammatory action. (苯胺类药无抗炎作用)15COX：COXCOX-1：COX-2：结构型，血管、胃、肾等诱导型，损伤性刺激诱导其作用NSAIDs非选择性环氧酶抑制药选择性环氧酶抑制药16Classification of drugs:水杨酸类： aspirin(阿司匹林）苯胺类：acetaminophen（对乙酰氨基酚）吲哚类：indomethacin(吲哚美辛）芳基丙酸类：ibuprofen（布洛芬）其它类：双氯芬酸、保太松等2 Non-selective COX inhibitors17I. Salicylates (水杨酸类)Aspirin (阿司匹林) Acetylsalicylic acid（乙酰水杨酸）18【pharmacokinetics 】 1. 1. -be absorbed rapidly-be absorbed rapidly. 2. 2. distribution wide - distribution wide - salicylate(水杨酸盐分布广泛） 3. elimination(消除) :doses 1g : zero order kinetics4. urine pH influence its excretion.urine pH influence its excretion.urine pH , the excretion of aspirin （尿液 pH , aspirin 排泄）191. Antipyretic, analgesic and antirheumatic actions(解热、镇痛、抗风湿)【 actions and uses】1. common cold and fever (感冒、发热)2. chronic pain：headache, toothache, muscular pain, dysmenorrhea (头痛、牙痛、肌肉痛、痛经等)3. rheumaticand and rheumatoid arthritis(风湿性、类风湿性关节炎)202. Anti-platelet effect (抗血小板作用) PG synthetase in platelet thromboxane (TXA2) synthesis prevents platelet aggregation (抑制PG合成酶 TXA2抑制血小板聚集）Uses: Prevention and treatment of thromboembolicdiseases（防治血栓性疾病）at low doses21Note ：aspirin环氧酶TXA2抗血小板聚集低浓高浓血小板血管壁环氧酶PGI2促血小板聚集TXA2：血栓素-促血栓形成PGI2 ：前列环素-抗血栓形成3. 儿科用于皮肤粘膜淋巴结综合征（川崎病）治疗22nausea(恶心) vomiting(呕吐) bleeding(出血)1. Gastrointestinal reactions: gastric ulcer (胃溃疡)Stimulates gastric mucosa directly (直接刺激胃粘膜) 【 Adverse reactions】（ ）CTZ（）PG synthesisPrevention ：餐后服、同服抗酸药、肠溶片232. Disturbance of blood coagulation(凝血障碍)1)（）TXA2 synthesis（）platelet aggregation (抑制血小板聚集)2）at high doses （-）prothrombin formation (大剂量抑制凝血酶原形成)Prevention and treatment (防治)：Vitamin K243. Allergic reactions (过敏反应)花生四烯酸环氧酶PG支气管扩张脂氧酶白三烯支气管收缩Aspirin(-)urticaria(荨麻疹), angioedema(血管神经性水肿), allergic shock , aspirin asthma(“阿司匹林哮喘”) 肾上腺素 无效254. Salicylism (水杨酸中毒)头晕、耳鸣、听力下降、精神错乱 如何加速 排泄？5. Reyes syndrome ( 瑞夷综合征 ）病毒性感染儿童肝衰竭合并脑病6.renal damage老人，伴心、肝、肾功能损害者26胃溃疡 严重肝病 低凝血酶原血症 Vk缺乏 有出血倾向者 哮喘 【 Contraindications】27二. 苯胺类Acetaminophen（对乙酰氨基酚） (扑热息痛)1. antipyretic and analgesic aspirin.(解热镇痛作用同aspirin）2. without antiinflammation（无抗炎作用）3. 对血液系统影响小3. week GI reaction 4. 长期或过量用药可致肝、肾损害282930（三）吲哚类Indomethacin(吲哚美辛) （消炎痛）1. One of the most potent COX inhibitors.2. Antiinflammatory,antipyretic and analgesic effects are remarkable.3. severe adverse reactions.（最强COX抑制剂之一解热、镇痛、抗炎作用均强不良反应发生率高且严重）31（四）芳基丙酸类 1. 吸收少受食物影响.2.