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

解热镇痛抗炎药Antipyretic analgesic and anti-infl

ammatory drugs

北京协和医学院基础医学院药理学系 叶菜英

Antipyretic analgesic and anti-inflammatory drugs These drugs relieve the pain associated with inflammat

ion, 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 (NS

AIDs) in 1974.

virusbacteriaBacterial productendotoxinTDAg-Ab

external fever

phagocyte （GC

）endogenous pyrogen

hypothalamus

PL

unsaturated fatty acid

PGS PG

TEMP SET cells

febrile

antipyretic analgesic

inhibition

Antipyretic action

• Febrile: endogenous pyrogen →CNS→release PG↑

→thermotaxic center → Febrile• Antipyretil: inhibit PG synthetase ， decre

ase synthesis of PG →hypothermy

Antipyretic action

depression bradykinin pain sensorantipyretic analgesic painstimulus PG PG synthesis sensitization depression

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.

Analgesic action

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

阿阿阿阿

O

COOH

C CH3

O

解热镇痛消炎药 水杨酸类 阿斯匹林

Aspirin

【 physiological disposition 】： Oral, absorbed from gut→distribution, metabo

lism→kenosis (enter articular cavity, CSF)

【 Pharmacological action 】• Atipyretic: temperature drop qiuckly• Analgesic: medium intensity• Anti-rheumatic: inhibit antigen-antibody reaction, a

ntibody 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

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

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

Paracetamol & Phenacetin

Strong antipyretic analgesic effect; weak anti-rheumatic effect. (inhibition for center epoxidase is stronger than that for external epoxidase)

阿 PharmacologicPharmacologicalal action action 阿NHCOCH3

OC2H5

NHCOCH3

OH

NH2

OC2H5

Phenacetin

Paracetamol P-aminophenetole

Aniline ParacetamolParacetamol

Phenacetin【 Pharmacokinetics 】 Oral, absorb→hepatic metabolism →kenosis ↗ 60 ％ combine with GA

de-ET （ 70 ％－ 80 ％）→ Paracetamol→35 ％ combine with H2SO4,fail

↗ ↘bare→hydroxidePhenacetin ↘

de-Ac→P-aminophenetole → hydroxide→hemoglobin →oxidation metahemoglobin ↓

toxic metabolin

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

Phenylbutazone ( 保泰松 )

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

【【 Pharmacologic actionPharmacologic action 】】N

NO

OCH3(CH2)2CH2

Pyrazoketone

Primary used to rheumatism and rheumatoid arthritis

【 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

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

Phenylbutazone ( 保泰松 )

Indometacin

【 Untoward Reaction 】

N

CH2COOH

CH3

H3CO

CO

ClIndometacin

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

Brufen & Fenbid【【 Pharmacologic actionPharmacologic 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

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