Antipyretic-analgesic and Antiinflammatory Drugs non-steroidal anti-inflammatory drugs ( NSAIDS)

1. Chapter 27 Antipyretic-analgesic and Antiinflammatory Drugsnon-steroidal anti-inflammatory drugs (NSAIDS)

2. Pharmacological effect • antipyreticaction: inhibit PG biosynthesis in hypothalamic region, lower the set-point; reduce elevated temperature, normal body temperature is only slightly affected. • analgesia: moderate • anti-inflammatory effects: • inhibit PG biosynthesis • inhibition of leukocyte and platelet adhesion

3. 通过抑制环氧酶（PG合成酶）发挥作用 作 用 机 制

4. COX-1 COX-2 Origin Physiologic Inflammatory stimulus Function • physiological： pregnant PG • pathological： inflammatory factor • Physiological function Platelet function Kidney function (PGE2) Gastric mucus secretion (PGI2) Cyclooxygenases(环氧酶，COX) : two isozymes COX1 and COX2 Comparison

5. 非选择性环氧酶抑制药 水杨酸类 阿司匹林 苯胺类 对乙酰氨基酚，非那西丁 吡唑酮类 保泰松 芳基乙酸类 双氯芬酸 有机酸类 吲哚衍生物 吲哚美辛 芳基丙酸类 萘普生 选择性环氧酶－2抑制药塞来昔布

6. Salicylates 水杨酸类Aspirin阿司匹林(Acetyl salicylic acid 乙酰水杨酸) Actions: • antipyretic and analgesic lower the body temperature of febrile patients manage low to moderate superficial pains, especially inflammationary • antirheumatic 抗风湿 obvious in acute rheumatic fever急性风湿热 and rheumatic arthritis风湿性关节炎

7. antithrombotic • low doses (40 mg/d) of aspirin can irreversibly inhibit TXA2 production in platelets without markedly affecting PGI2 production in the endothelial cells currently employed in the prophylactic and treatment of platelet highly-aggregated • large doses (more than 300 mg/d), PGI2 production in the endothelial cells can also be inhibited

8. Adverse effects of aspirin • GI tract: most common epigastric discomfort, gastric ulceration and bleeding • Allergic reaction nettle rash荨麻疹, angioneurotic edema血管神经性水肿 aspirin asthma ‘阿司匹林哮喘’ is rare • Disturbance of blood coagulation platelet aggregation inhibited and bleeding time prolonged

9. Salicylism水杨酸反应 (intoxication) headache, dizziness, tinnitus, nausea, vomiting, convulsions, coma. iv. sodium bicarbonate enhances the elimination of salicylate • Liver system Reye’s syndrome 瑞夷综合征 fulminating hepatitis with cerebropathy during viral infections, encountered in children

10. N H C O C H 3 O C H 2 5 N H N H C O C H 2 3 O C H O H 2 5 对氨苯乙醚 对乙酰氨基酚 Aniline 苯胺类Acetaminophen 对乙酰氨基酚 （paracetamol扑热息痛） 非那西丁 • analgesic and antipyretic effect is the same as aspirin, but no significant antiinflammatory effect • it dose not cause GI irritation • acute intoxication can cause damage of liver

11. Indomethacin 吲哚美辛(消炎痛) • powerful analgesic and antiinflammatory effect 12 times than aspirin • for treatment of acute arthritic and ankylosing spondylitis 强直性脊柱炎 • adverse effects • CNS: vertigo, frontal headache, mental confusion • GI: anorexia, nausea, abdominal pain, ulceration • Hypersensitivity reactions

12. Propionic acid derivatives 丙酸类 naproxen 萘普生 ibuprofen 布洛芬（芬必得） fenoprofen 非诺洛芬 • powerful antiinflammatory effect used for acute arthritic and ankylosing spondylitis • GI effects are generally less than that of aspirin and indomethacin

13. phenylbutazone 保泰松 powerful anti-inflammatory effects weak analgesic and antipyretic activities not a first line drug treatment of acute rheumatic disorders adverse effects include nausea, vomiting, hepatic and renal lesions, allergy, edema

14. COX-2 Selective Inhibitors Celecoxib 塞来昔布(西乐葆) • Indications: osteoarthritis 骨关节炎, rheumatoid arthritis 类风湿性关节炎, odontalgia 牙痛 • GI adverse effects and gastroduodenal ulcers are less