Download Antipyretic analgesic and anti –inflammatory

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】
Indometacin
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
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