神经系统药理—吴希美解热镇痛药.ppt

1、Chapter 27Antipyretic-Analgesic and Antiinflammatory Drugs,A. General Pharmacological properties,1. Inhibition of prostaglandin synthesis inhibiting cyclooxygenase (COX，环氧酶), decreasing the synthesis of PGs and TXA2, resulting antipyretic, analgesic, and anti-inflammatory effects non-steroidal anti-

2、inflammatory drugs (NSAIDs, 非甾体抗炎药）。,2. Antipyretic effects Inhibition of PGE2 production in the hypothalamus induced by endogenous pyregens after pathological stimuli temperature notes: symptomatic control only, not be indicated in all patients with fever. The effect on body temperature is differen

3、t from that of chlorpromazine.,A. General Pharmacological properties,Comparison of properties of two types of drugs,3. Analgesic effects Analgesic effect is resulted from inhibition of PGE2 production. Effective on the pain of low to moderate intensity related to inflammatory responses. PGE2: a pain

4、 stimulant and hyperalgesic agent The analgesic effect is different from opioid analgesics.,A. General Pharmacological properties,Comparison of properties of two types of drugs,4. Anti-inflammatory effects PGs induce inflammatory responses. Inhibition of PG production can relieve inflammatory respon

5、ses, such as congestion, exudation, pain. The effect is different from that of glucocorticosteroids.,A. General Pharmacological properties,Comparison of properties of two types of drugs,5. COX-1 / COX-2 and selectivity of the drugs COX-1: constructive; involved in physiologic regulatory functions in

6、 GI tract, kidney, etc.; inhibition of COX-1 is related to the adverse effects. COX-2: inducible; involved in pathological responses such as inflammation, and pregnancy; inhibition of COX-2 is related to the therapeutic effects.,A. General Pharmacological properties,（）,（）,（）,（）,B. Salicylates,Aspiri

7、n 阿司匹林 Acetylsalicylic acid 乙酰水杨酸,Aspirin 阿司匹林,Salicylic acid 水杨酸,Salicylic sodium 水杨酸钠,Aspirin 阿司匹林 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 u

8、rine. larger doses ( 1g/d): non-linear elimination, zero order kinetic process, easier to accumulation and intoxication.,B. Salicylates,2. Pharmacological effects and clinical uses (1) Antipyretic, analgesic and anti-inflammatory effects moderate doses (0.30.6 g): antipyretic and analgesic effects l

9、arger doses (35 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 inhibiting PG synthesis in GI tract irritant symptoms; gastric bleeding; ulcerous disorders Contraindications: ulcerous disorders

10、,B. Salicylates,(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).,B. Salicylates,(3) Allergic reactio

11、ns urticaria(荨麻疹), angioneurotic edema, aspirin-induced asthma, occasionally anaphylactic shock. Contraindications: bronchial asthma,B. Salicylates,Aspirin-induced asthma: Phospholipids of cell menbrane Aspirin Phospholipase A2 (PLA2) (-) Arachidonic acid Cyclooxygenase Lipoxygenenase (环氧酶) PGH2 5-H

12、PETE (脂氧酶) Prostaglandins (PGs) Leukotrienes (LTs) (前列腺素) (白三烯),(4) Salicylism dose 5g/d: CNS symptoms, including mental confusion; hyperventilation. i.v. NaHCO3 can promote the excretion of aspirin. (5) Hepatic damage Overdose: hepatic damage Reyes syndrome(瑞夷综合征): in children, severe hepatic damag

13、e (严重的肝损害) and encephalopathy (脑病),B. Salicylates,Dose-response relationship of aspirin: therapeutic effects; adverse effects,4. Drug interactions,B. Salicylates,C. Para-aminophenol derivatives,Acetaminophen 对乙酰氨基酚 Paracetamol 扑热息痛,Acetaminophen （对乙酰氨基酚）： antipyretic and analgesic effects are mild a

14、nd lasting, but almost no anti-inflammatory effects, - not a NSAID higher selectivity to COX in CNS. mainly used in cold, fever, and headache, etc. overdose can damage liver and kidney.,C. Para-aminophenol derivatives,Differences between NSAIDs and Acetaminophen,Toxic metabolites of acetaminophen,D.

15、 Other anti-inflammatory drugs,Salicylates: aspirin Para-aminophenol derivatives: acetaminophen Indole and indene acetic acid derivatives: indomethacin, sulindac Propionic acid derivatives: ibuprofen, naproxen, fenopofen, ketoprofen COX-2 selective inhibitors: meloxicam, celecoxide, rofenxid Others:

16、 phenylbutazone, diclofenac,indomethacin 吲哚美辛,piloxicam 吡罗昔康,ibuprofen 布 洛 芬,D. Other anti-inflammatory drugs,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-inflammatory effects; weaker GI reactions; vision damage pilo