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 • 解热作用 Antipyretil action

virusbacteriaBacterial productendotoxinTDAg-Ab

external fever

phagocyte

（GC

）

endogenous pyrogen

hypothalamus

PL

unsaturated fatty acid

PGS PG

TEMP SET cells

febrile

antipyretic analgesic

inhibition

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 pain sensor

antipyretic analgesic painstimulus PG

PG synthesis sensitization

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 synthesi

s 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 Oxyp

henbutazone 等• 芳基烷酸类：布洛芬 brufen 、炎痛喜康 Piroxic

am 等

阿斯匹林阿斯匹林 AspirinAspirin

O

COOH

C CH3

O

解热镇痛消炎药 水杨酸类 阿斯匹林

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 reacti

on ， 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 CHDthro

mbosis ， 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

对乙酰氨基酚 对乙酰氨基酚 paracetamol paracetamol （扑热息（扑热息痛）痛）非那西丁非那西丁 phenacetinphenacetin

strong antipyretil analgesic efstrong antipyretil analgesic effectfect weak weak anti-rheumaticanti-rheumatic effect effect（（ inhibition for center epoxidainhibition for center epoxidase is stronger than that for exterse is stronger than that for external epoxidasenal epoxidase ））

Pharmacologic actionPharmacologic action

NHCOCH3

OC2H5

NHCOCH3

OH

NH2

OC2H5

Phenacetin

Paracetamol P-aminophenetole

解热镇痛消炎药 苯胺类 对乙酰氨基酚

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 →oxidation metahemoglobin ↓

溶血毒性代谢物

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

保泰松 保泰松 phenylbutazonephenylbutazone

Strong anti-inflammatory, Strong anti-inflammatory, anti-rheumatic effects effects ,but weak ,but weak atipyretil,analgesic effects effects 。。

Pharmacologic actionPharmacologic action

NN

O

OCH3(CH2)2CH2

解热镇痛消炎药 吡唑酮类

Primary used to rheumatism and rheumatoid arthritis

吡唑酮 pyrazoketone 类：保泰松 phenylbutazone

【 Physiological disposition 】• Oral to absorb ， penetration synovia mem

brane→the concentration in synovia interm

embrance 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

吲哚美辛 吲哚美辛 indometacin indometacin （消炎（消炎痛）痛）

Untoward ReactionUntoward Reaction

N

CH2COOH

CH3

H3CO

CO

ClIndometacin

One of the most potent inhibitors of COX One of the most potent inhibitors of COX

isozymesisozymes

Effects on inflammatory,Effects on inflammatory,atipyretil analgesatipyretil analges

icic and and rheumatism significantlyrheumatism significantly

Use to the cases which difficult to cure aboUse to the cases which difficult to cure abo

ve-mentionedve-mentioned 。。

Lots of untoward reactionLots of untoward reaction ，， high incidence rate,high incidence rate, Stomach intestine reaction Stomach intestine reaction （（ ulcerulcer ）、）、 C.N.S reactionC.N.S reaction 、、Inhibit hematopoietic systemInhibit hematopoietic system 、、 anaphylactic responseanaphylactic response

解热镇痛消炎药 有机酸类

芳基烷酸类：布洛芬 Brufen 芬必得 fenbid

Pharmacologic actionPharmacologic action ：• Less sLess stomach intestine reactionstomach intestine reactions ，， good tolerancegood tolerance• 99% combine with 99% combine with plasma-albuminplasma-albumin→enter synovial m→enter synovial m

embrane embrane tune slowlytune slowly ，， keep high concentrationkeep high concentration• Effect is similar with aspirin,stronger thanEffect is similar with aspirin,stronger than

ParacetamolParacetamol• used to rheumatism and rheumatoid arthritisused to rheumatism and rheumatoid arthritis• light dyspepsialight dyspepsia ，， rash occasionallyrash 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

Thanks!Thanks!