解热镇痛抗炎药 Antipyretic analgesic and anti-inflammatory drugs

1. 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

2. 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.

3. Antipyretic action hypothalamus antipyretic analgesic external fever endogenous pyrogen PL virus bacteria Bacterial product endotoxin TD Ag-Ab phagocyte （GC） inhibition unsaturated fatty acid PGS PG TEMP SET cells febrile

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

5. Analgesic action depression bradykinin painsensor antipyretic analgesic painstimulusPG PG synthesissensitization depression

6. Analgesic action • 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.

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

8. 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

9. 解热镇痛消炎药 水杨酸类 阿斯匹林 阿斯匹林

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

11. Aspirin 【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.

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

13. Aspirin 【Pharmacological action & Clinical Indications】 • Effect on thrombosis： Inhibit cycloxygenase cyclo-oxygenase，reduce TXA2 synthesis Inhibit PA effect on thromboxane synthesis aspirin TXA2synthetase PM phospholipid AA endoperoxide↓ TXA2↓ thrombosis↓ PA↓ platelet releasion↓ • Clinical Indications: low dose, long term use could prevent CHDthrombosis, cerebral thrombosis

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

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

16. 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 →oxidationmetahemoglobin ↓ toxic metabolin

17. 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

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

19. Pyrazoketone Phenylbutazone (保泰松) 【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)

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

21. Organic acids Indometacin • 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. 【Untoward Reaction】 Lots of untoward reaction, high incidence rate, Stomach intestine reaction (ulcer), CNS reaction, Inhibit hematopoietic system, anaphylactic response

22. Brufen & Fenbid 【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.

23. 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

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