解热镇痛抗炎药 ANTIPYRETIC ANALGESIC AND ANTI-INFLAMMATOGY DRUDS

解热镇痛抗炎药ANTIPYRETIC ANALGESIC ANDANTI-INFLAMMATOGY DRUDS 北京协和医学院基础医学院药理学系叶菜英

解热镇痛抗炎药antipyretic, analgesic, and antiinflammatory drugs These drugs relieve the pain associated with inflammation,including that from arthritis and gout. 称为解热镇痛抗炎药（antipyretic, analgesic, and antiinflammatory drugs)。 They produce their anti-inflammatory action through a different mechanism,not as glucocorticoid. 1974年国际上将这类药物归入非甾体类抗炎药类（non-steroidal anti-inflammatordrugs,NSAIDs) 。

解热镇痛抗炎药 hypothalamus antipyretic analgesic external fever endogenous pyrogen PL virus bacteria Bacterial product endotoxin TD Ag-Ab phagocyte （GC） • 解热作用Antipyretil action inhibition unsaturated fatty acid PGS PG TEMP SET cells febrile

解热镇痛抗炎药Antipyretic analgesic and anti –inflammatory drugs • 解热作用Antipyretil action • Febrile:endogenous pyrogen→CNS →release PG↑ →thermotaxic center → Febrile • Antipyretil ：inhibit PG synthetase，decrease synthesis of PG →hypothermy

解热镇痛抗炎药Antipyretic analgesic and anti –inflammatory drugs • 镇痛作用analgesic action depression bradykinin painsensor antipyretic analgesic painstimulusPG PG synthesissensitization depression

解热镇痛抗炎药Antipyretic analgesic and anti –inflammatory drugs • 镇痛作用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.

解热镇痛抗炎药Antipyretic analgesic and anti –inflammatory drugs • 抗炎作用Anti-inflammatory action Mechanisms：Inhibit a primary pathway in PG synthesis。 • Summary ：Inhibit the PG synthesis to antipyretil, analgesic and Anti-inflammatory

Classification • 水杨酸 (Salicylates) 类：阿司匹林aspirin等 • 苯胺类 (Aniline)：对乙酰氨基酚acetaminophen （扑热息痛）等 • 吡唑酮 (Pyrazoketone) 类：保泰松Phenylbutazone、羟基保泰松Oxyphenbutazone等 • 芳基烷酸类：布洛芬brufen、炎痛喜康Piroxicam等

解热镇痛消炎药水杨酸类阿斯匹林 阿斯匹林Aspirin

水杨酸类Salicylates：阿司匹林aspirin 【physiological disposition】： oral、absorbed from gut→distribution, metabolism→kenosis （enter articular cavity、CSF）

阿司匹林aspirin 【Pharmacological action】 • Atipyretil：temperature drop qiuckly • Analgesic： medium intensity • Anti-rheumatic：inhibit antigen-antibody reaction，antibody formation antigen antibody union，blood sedimentation↓，relieve flare of articulus.

阿司匹林aspirin Clinical Indications： Antipyretic analgesic and anti –inflammatory • headache,toothache,algomenorrhea, neuralgiacourbature,arthralgia。 • fever • acute rheumatism，rheumatoid arthritis

阿司匹林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

Salicylates：阿司匹林aspirin 【Untoward Reaction】 • Gastrointestinal tract reaction • Block blood coagulation • NS reaction：salicylism，nausea、vomiting、 dizziness、tinnitus、acouesthesia↓ • Anaphylactic response • Nephrotoxicity

解热镇痛消炎药苯胺类对乙酰氨基酚 对乙酰氨基酚 paracetamol （扑热息痛）非那西丁phenacetin Pharmacologic action Phenacetin strong antipyretil analgesic effect weak anti-rheumatic effect（inhibition for center epoxidase is stronger than that for external epoxidase） P-aminophenetole Paracetamol

非那西丁phenacetin 【Pharmacokinetics】 Oral,absorb→hepatic metabolism →kenosis ↗ 60％combine with GA de-ET（70％－80％）→Paracetamol→35％combine with H2SO4,fail ↗↘bare→hydroxide 非那西丁 ↘ de-Ac→P-aminophenetole→ hydroxide→hemoglobin →oxidationmetahemoglobin ↓ 溶血毒性代谢物

对乙酰氨基酚（扑热息痛），非那西丁phenacetin对乙酰氨基酚（扑热息痛），非那西丁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

解热镇痛消炎药吡唑酮类 保泰松 phenylbutazone Pharmacologic action Strong anti-inflammatory, anti-rheumatic effects ,but weak atipyretil,analgesic effects。 Primary used to rheumatism and rheumatoid arthritis

吡唑酮pyrazoketone类：保泰松phenylbutazone 【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 ）

保泰松phenylbutazone 【Side effrcts】 • Stomach intestine reaction • Water-sodium retention • Anaphylactic respons • Liver&kidney damage • Thyromegaly and myxedema

解热镇痛消炎药有机酸类 吲哚美辛 indometacin （消炎痛） 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）、C.N.S reaction、 Inhibit hematopoietic system、anaphylactic response

芳基烷酸类：布洛芬Brufen芬必得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

Compound preparation (67types) • Coldrine • Compound Aminopyrine Phenacetin Tablets • APC • Pseudoephedrine+Paracetamol+Dextromethorphan+ Chlorphenamine Maleate • Paracetamol • Compound Chlorphenamine Maleate Essential component • APC : aspirin paracetamol caffeine • 去痛片: aminophenazone PAC caffeine

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解热镇痛抗炎药 ANTIPYRETIC ANALGESIC AND ANTI-INFLAMMATOGY DRUDS