2. 解热镇痛抗炎药 Antipyretic analgesic and anti- inflammatory drugs 北京协和医学院基础医学院药理学系 叶菜英

3. Antipyretic analgesic and anti- inflammatory drugs  These drugs relieve the pain associated with inflammation, including that from arthritis and gout.  Antipyretic, analgesic, and antiinflammatory drugs.  They produce their anti-inflammatory action through a different mechanism, not as glucocorticoid.  Classed into non-steroidal anti-inflammatordrugs (NSAIDs) in 1974.

4. virus bacteria Bacterial product endotoxin TD Ag-Ab external feverendogenous pyrogen hypothalamus PL unsaturated fatty acid PGS PG TEMP SET cells febrile antipyretic analgesic inhibition Antipyretic action

5. Febrile: endogenous pyrogen →CNS→release PG↑ →thermotaxic center → Febrile Antipyretil: inhibit PG synthetase ， decrease synthesis of PG →hypothermy Antipyretic action

6. depression bradykinin pain sensor antipyretic analgesic painstimulus PG PG synthesis sensitization depression Analgesic action

7.  Mechanisms: Effect on periphery, inhibit the synthesis of prostaglandins and prevent bradykinin from stimulating pain receptors, also inhibit the recognition of pain impulses centrally and peripherally. Analgesic action

8. Anti-inflammatory action  Mechanisms: Inhibit a primary pathway in PG synthesis.  Summary: Inhibit the PG synthesis to antipyretil, analgesic and anti-inflammatory

9. 解热镇痛抗炎药分类 水杨酸类： 阿司匹林等 苯胺类： 对乙酰氨基酚（扑热息痛）等 吡唑酮类： 保泰松、羟基保泰松等 芳基烷酸类：布洛芬、炎痛喜康等

10. 阿斯匹林 解热镇痛消炎药 水杨酸类 阿斯匹林

11. Aspirin 【 physiological disposition 】 ： Oral, absorbed from gut → distribution, metabolism → kenosis (enter articular cavity, CSF)

12. 【 Pharmacological action 】 Atipyretic: temperature drop qiuckly Analgesic: medium intensity Anti-rheumatic: inhibit antigen-antibody reaction, antibody formation, antigen antibody union ， blood sedimentation↓, relieve flare of articulus. Aspirin

13. 【 Clinical Indications 】 Antipyretic analgesic and anti –inflammatory  Headache,toothache, algomenorrhea, neuralgiacourbature, arthralgia.  Fever  Acute rheumatism, rheumatoid arthritis Aspirin

14. 【 Pharmacological action & Clinical Indications 】 Effect on thrombosis ： Inhibit cycloxygenase cyclo-oxygenase ， reduce TXA 2 synthesis Inhibit PA effect on thromboxane synthesis aspirin TXA 2 synthetase PM phospholipid AA endoperoxide↓ TXA 2 ↓ thrombosis↓ PA↓ platelet releasion↓ Clinical Indications: low dose, long term use could prevent CHDthrombosis, cerebral thrombosis

15. Aspirin 【 Untoward reaction 】 Gastrointestinal tract reaction Block blood coagulation NS reaction: salicylism, nausea, vomiting, dizziness, tinnitus, acouesthesia↓ Anaphylactic response Nephrotoxicity

16. Paracetamol & Phenacetin   Strong antipyretic analgesic effect;   weak anti-rheumatic effect. (inhibition for center epoxidase is stronger than that for external epoxidase) Pharmacological action 【  Pharmacological action 】 Phenacetin Paracetamol P-aminophenetole Paracetamol Aniline Paracetamol

17. Phenacetin 【 Pharmacokinetics 】 Oral, absorb→hepatic metabolism →kenosis ↗ 60 ％ combine with GA de-ET （ 70 ％－ 80 ％） →Paracetamol→35 ％ combine with H2SO4,fail ↗ ↘ bare → hydroxide Phenacetin ↘ de-Ac→ P-aminophenetole → hydroxide → hemoglobin → oxidation metahemoglobin ↓ toxic metabolin

18. Paracetamol & Phenacetin 【 Untoward Reaction 】 Allergy occasionally: rash, drug fever, M.M damage Overdose (10~15g∕day)→acute poisoning→hepatonecrosis Overdose→methemoglobinemia, cyanosis, hypoxia, HA Kidney damage

19. Phenylbutazone ( 保泰松 ) Strong anti-inflammatory, effects, but weak effects. Strong anti-inflammatory, anti- rheumatic effects, but weak atipyretil, analgesic effects. 【 Pharmacologic action 】 Pyrazoketone Primary used to rheumatism and rheumatoid arthritis

20. 【 Physiological disposition 】 Oral to absorb, penetration synovia membrane→the concentration in synovia intermembrance space is 50% of that in blood (high concentration in joint tissue) Phenylbutazone ( 保泰松 ) Pyrazoketone

21. 【 Side effects 】 Stomach intestine reaction Water-sodium retention Anaphylactic respons Liver&kidney damage Thyromegaly and myxedema Phenylbutazone ( 保泰松 )

22. Indometacin 【 Untoward Reaction 】  One of the most potent inhibitors of COX isozymes;  Effects on inflammatory, atipyretil analgesic and rheumatism significantly;  Use to the cases which difficult to cure above-mentioned. Lots of untoward reaction, high incidence rate, Stomach intestine reaction (ulcer), CNS reaction, Inhibit hematopoietic system, anaphylactic response Organic acids

23. Brufen & Fenbid 【 Pharmacologic action 【 Pharmacologic action 】 Less stomach intestine reactions, good tolerance. 99% combine with plasma-albumin→enter synovial membrane tune slowly, keep high concentration. Effect is similar with aspirin, stronger than paracetamol. Used to rheumatism and rheumatoid arthritis. Light dyspepsia, rash occasionally.

24. Compound preparation (67 types)  Coldrine  Compound Aminopyrine Phenacetin Tablets  APC  Pseudoephedrine+Paracetamol+Dextromethorphan+ Chlorphenamine Maleate  Paracetamol  Compound Chlorphenamine Maleate 【 Essential component 】 APC: aspirin paracetamol caffeine Somedon: aminophenazone PAC caffeine

25. Thanks!