Antipyretic analgesic and anti –inflammatory
Download
Report
Transcript 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】
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!