解热镇痛抗炎药 Antipyretic analgesic and antiinflammatory drugs 北京协和医学院基础医学院药理学系 叶菜英 Antipyretic analgesic and antiinflammatory 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. Antipyretic action hypothalamus ( GC ) endogenous pyrogen phagocyte external fever virus bacteria Bacterial product endotoxin TD Ag-Ab PL antipyretic analgesic unsaturated fatty acid PG TEMP SET cells febrile inhibition PGS Antipyretic action • Febrile: endogenous pyrogen →CNS→release PG↑ →thermotaxic center → Febrile • Antipyretil: inhibit PG synthetase, decrease synthesis of PG →hypothermy Analgesic action depression bradykinin antipyretic analgesic painstimulus PG PG synthesis depression pain sensor sensitization 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. Anti-inflammatory action Mechanisms: Inhibit a primary pathway in PG synthesis. Summary: Inhibit the PG synthesis to antipyretil, analgesic and anti-inflammatory 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 解热镇痛消炎药 阿斯匹林 水杨酸类 阿斯匹林 Aspirin 【physiological disposition】: Oral, absorbed from gut→distribution, metabolism→kenosis (enter articular cavity, CSF) 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. Aspirin 【 Clinical Indications 】 Antipyretic analgesic and anti –inflammatory Headache,toothache, algomenorrhea, neuralgiacourbature, arthralgia. Fever Acute rheumatism, rheumatoid arthritis 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 thrombosis↓ endoperoxide↓ PA↓ TXA2↓ platelet releasion↓ • Clinical Indications: low dose, long term use could prevent CHDthrombosis, cerebral thrombosis Aspirin 【Untoward reaction】 • Gastrointestinal tract reaction • Block blood coagulation • NS reaction: salicylism, nausea, vomiting, dizziness, tinnitus, acouesthesia↓ • Anaphylactic response • Nephrotoxicity Aniline Paracetamol Paracetamol & Phenacetin NHCOCH3 【 Pharmacological action 】 Strong antipyretic analgesic effect; weak anti-rheumatic effect. (inhibition for center epoxidase is stronger than that for external epoxidase) Phenacetin OC2H5 NHCOCH3 OH Paracetamol NH2 OC2H5 P-aminophenetole 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 metahemoglobin ↓ toxic metabolin → hydroxide→hemoglobin →oxidation 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 Pyrazoketone Phenylbutazone (保泰松) 【Pharmacologic action】 Strong anti-inflammatory, antiO rheumatic effects, but weak CH3(CH2)2CH2 atipyretil, analgesic effects. N N Primary used to rheumatism and rheumatoid arthritis O 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) Phenylbutazone (保泰松) 【Side effects】 • Stomach intestine reaction • Water-sodium retention • Anaphylactic respons • Liver&kidney damage • Thyromegaly and myxedema Organic acids Indometacin One of the most potent inhibitors of COX isozymes; H3CO CH2COOH Effects on inflammatory, atipyretil analgesic and rheumatism significantly; Use to the cases which difficult to cure N CH3 O C above-mentioned. 【Untoward Reaction】 In dom e tacin Lots of untoward reaction, high incidence rate, Stomach intestine reaction (ulcer), CNS reaction, Inhibit hematopoietic system, anaphylactic response Cl 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. 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 Thanks! Thanks!