??????? Antipyretic analgesic and anti-inflammatory drugs

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???????Antipyretic analgesic and
anti-inflammatory drugs

• ????????????????
• ???

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Antipyretic analgesic and anti-inflammatory 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.

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Antipyretic action
hypothalamus
antipyretic analgesic
external fever
endogenous pyrogen
PL
virus bacteria Bacterial product endotoxin TD Ag-A
b
phagocyte (GC)
inhibition
unsaturated fatty acid
PGS
PG
TEMP SET cells
febrile
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Antipyretic action

• Febrile
• endogenous pyrogen ?CNS?release PG?
  ?thermotaxic center ? Febrile
• Antipyretil inhibit PG synthetase,decrease
  synthesis of PG ?hypothermy

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Analgesic action

• depression
• bradykinin
  pain sensor
• antipyretic analgesic painstimulus PG
• PG synthesis
  sensitization
• depression

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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.

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• Anti-inflammatory action
• Mechanisms Inhibit a primary pathway
• in PG synthesis.
• Summary Inhibit the PG synthesis to antipyretil,
  
• analgesic and
  anti-inflammatory

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Aspirin

• ?physiological disposition?
• Oral, absorbed from gut?distribution,
  metabolism?kenosis (enter articular cavity, CSF)

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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.

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Aspirin

• ? Clinical Indications ?
• Antipyretic analgesic and anti inflammatory
• Headache,toothache, algomenorrhea,
• neuralgiacourbature, arthralgia.
• Fever
• Acute rheumatism, rheumatoid arthritis

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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

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Aspirin

• ?Untoward reaction?
• Gastrointestinal tract reaction
• Block blood coagulation
• NS reaction salicylism, nausea, vomiting,
• dizziness, tinnitus, acouesthesia?
• Anaphylactic response
• Nephrotoxicity

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Aniline Paracetamol
Paracetamol Phenacetin
? Pharmacological action ?

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

Phenacetin
P-aminophenetole
Paracetamol
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Phenacetin

• ?Pharmacokinetics?
• Oral, absorb?hepatic metabolism ?kenosis
• 
  ? 60combine with GA
• de-ET(70-80)?Paracetamol?35combine
  with H2SO4,fail
• ?
  ?bare?hydroxide
• Phenacetin
• ?
• de-Ac?P-aminophenetole ?
  hydroxide?hemoglobin ?oxidation metahemoglobin
  
  
  ?
• toxic metabolin
  

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Paracetamol Phenacetin

• ?Untoward Reaction?
• Allergy occasionally rash, drug fever, M.M
  damage
• Overdose (1015g/day)?acute poisoning?hepatonecros
  is
• Overdose?methemoglobinemia, cyanosis, hypoxia, HA
• Kidney damage

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Pyrazoketone
Phenylbutazone (???)
?Pharmacologic action?
Strong anti-inflammatory, anti-rheumatic effects,
but weak atipyretil, analgesic effects.
Primary used to rheumatism and rheumatoid
arthritis
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Pyrazoketone
Phenylbutazone (???)

• ?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)

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Phenylbutazone (???)

• ?Side effects?
• Stomach intestine reaction
• Water-sodium retention
• Anaphylactic respons
• Liverkidney damage
• Thyromegaly and myxedema

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Organic acids
Indometacin

• 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.

?Untoward Reaction?
Lots of untoward reaction, high incidence rate,
Stomach intestine reaction (ulcer), CNS
reaction, Inhibit hematopoietic system,
anaphylactic response
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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.

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Compound preparation (67 types)

• Coldrine
• Compound Aminopyrine Phenacetin Tablets
• APC
• PseudoephedrineParacetamolDextromethorphan
• Chlorphenamine Maleate
• Paracetamol
• Compound Chlorphenamine Maleate
• ?Essential component?
• APC aspirin paracetamol caffeine
• Somedon aminophenazone PAC caffeine

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