神经系统药理-吴希美解热镇痛药

Chapter27

Antipyretic-AnalgesicandAntiinflammatoryDrugs第一页，共四十页。编辑课件A.GeneralPharmacologicalproperties1.Inhibitionofprostaglandinsynthesisinhibiting

cyclooxygenase(COX，环氧酶),decreasingthesynthesisofPGsandTXA2,resultingantipyretic,analgesic,andanti-inflammatoryeffectsnon-steroidalanti-inflammatorydrugs(NSAIDs,非甾体抗炎药）。第二页，共四十页。编辑课件第三页，共四十页。编辑课件第四页，共四十页。编辑课件2.AntipyreticeffectsInhibitionofPGE2productioninthehypothalamusinducedbyendogenouspyregensafterpathologicalstimulitemperaturenotes:

symptomaticcontrolonly,notbeindicatedinallpatientswithfever.

Theeffectonbodytemperatureisdifferentfromthatofchlorpromazine.A.GeneralPharmacologicalproperties第五页，共四十页。编辑课件Comparisonofpropertiesoftwotypesofdrugs第六页，共四十页。编辑课件3.AnalgesiceffectsAnalgesiceffectisresultedfrominhibitionofPGE2production.Effectiveonthepainoflowtomoderateintensityrelatedtoinflammatoryresponses.PGE2:apainstimulantandhyperalgesicagentTheanalgesiceffectisdifferentfromopioidanalgesics.A.GeneralPharmacologicalproperties第七页，共四十页。编辑课件Comparisonofpropertiesoftwotypesofdrugs第八页，共四十页。编辑课件4.Anti-inflammatoryeffects

PGsinduceinflammatoryresponses.InhibitionofPGproductioncanrelieveinflammatoryresponses,suchascongestion,exudation,pain.Theeffectisdifferentfromthatofglucocorticosteroids.A.GeneralPharmacologicalproperties第九页，共四十页。编辑课件Comparisonofpropertiesoftwotypesofdrugs第十页，共四十页。编辑课件5.COX-1/COX-2andselectivityofthedrugsCOX-1:

constructive;

involvedinphysiologicregulatoryfunctionsinGItract,kidney,etc.;

inhibitionofCOX-1isrelatedtotheadverseeffects.COX-2:

inducible;involvedinpathologicalresponsessuchasinflammation,andpregnancy;

inhibitionofCOX-2isrelatedtothetherapeuticeffects.

A.GeneralPharmacologicalproperties第十一页，共四十页。编辑课件（－）（＋）（＋）（－）第十二页，共四十页。编辑课件第十三页，共四十页。编辑课件第十四页，共四十页。编辑课件第十五页，共四十页。编辑课件B.SalicylatesAspirin阿司匹林(āsīpǐlín)Acetylsalicylicacid乙酰水杨酸Aspirin阿司匹林(āsīpǐlín)Salicylicacid水杨酸Salicylicsodium水杨酸钠第十六页，共四十页。编辑课件Aspirin阿司匹林(āsīpǐlín)1.ADMEtransformedtosalicylicacidforminthebodyhepaticmetabolismisprimarilyconjugation.excretionfromurine,theexcretionofunchangedformsofaspirinisincreasedinthealkalinizedurine.largerdoses(>1g/d):

non-linearelimination,zeroorderkineticprocess,easiertoaccumulationandintoxication.B.Salicylates第十七页，共四十页。编辑课件第十八页，共四十页。编辑课件2.Pharmacologicaleffectsandclinicaluses(1)Antipyretic,analgesicandanti-inflammatoryeffects

moderatedoses(0.3～0.6g):antipyreticandanalgesiceffects

largerdoses(3～5g/d):anti-inflammatoryandanti-rheumaticeffects;onlyrelievessymptoms.

totreatacuterheumaticfever(急性(jíxìng)风湿热),toabatepainandsymptomsofrheumatic&rheumatoidarthritis(风湿性和类风湿性关节炎).B.Salicylates第十九页，共四十页。编辑课件(2)Inhibitionofplateletaggregation

smalldoses(30～100mg/d):inhibitingTXA2synthesis,preventingthrombosis.usedtotreatischemicheartdisease,reducethemortalityofmyocardiacinfarction,andpreventcerebralthrombosis.

largerdoses:inhibitingPGI2synthesis,promotingthrombosis.

PGI2:vasodilationandplateletdepolymerization(血小板解聚).

B.Salicylates第二十页，共四十页。编辑课件Themechanismofaspirin:Targetenzymesacetylated第二十一页，共四十页。编辑课件3.Adverseeffects(1)GIreactions

stimulatinggastricmucosaandCTZ(largerdoses);inhibitingPGsynthesisinGItractirritantsymptoms;gastricbleeding;ulcerousdisordersContraindications:ulcerousdisordersB.Salicylates第二十二页，共四十页。编辑课件(2)Prolongationofbleedingtimesmalldoses:inhibitingplateletaggregationlargerdoses:inhibitingsynthesisofthrombogen

Contraindications:oneweekpriortosurgery;severehepaticdamage;vitaminKdeficiency,;prothrombinopenia(凝血酶原减少(jiǎnshǎo)症).B.Salicylates第二十三页，共四十页。编辑课件(3)Allergicreactionsurticaria(荨麻疹),angioneuroticedema,aspirin-inducedasthma,occasionallyanaphylacticshock.Contraindications:

bronchialasthmaB.Salicylates第二十四页，共四十页。编辑课件Aspirin-inducedasthma:

Phospholipidsofcellmenbrane

Aspirin

PhospholipaseA2(PLA2)(-)Arachidonicacid

CyclooxygenaseLipoxygenenase

(环氧酶)PGH25-HPETE(脂氧酶)

↓Prostaglandins(PGs)

↑Leukotrienes(LTs)

(前列腺素)

(白三烯)第二十五页，共四十页。编辑课件(4)Salicylism

dose>5g/d:CNSsymptoms,includingmentalconfusion;hyperventilation.i.v.NaHCO3canpromotetheexcretionofaspirin.

(5)Hepaticdamage

Overdose:hepaticdamage

Reye’ssyndrome(瑞夷综合征):inchildren,severehepaticdamage(严重(yánzhòng)的肝损害)andencephalopathy(脑病)B.Salicylates第二十六页，共四十页。编辑课件Dose-responserelationshipofaspirin:therapeuticeffects;adverseeffects第二十七页，共四十页。编辑课件4.DruginteractionsB.Salicylates第二十八页，共四十页。编辑课件C.Para-aminophenolderivativesAcetaminophen对乙酰氨基酚Paracetamol

扑热息痛第二十九页，共四十页。编辑课件Acetaminophen（对乙酰氨基酚）：

antipyreticandanalgesiceffectsaremildandlasting,butalmostnoanti-inflammatoryeffects,-nota

NSAIDhigherselectivitytoCOXinCNS.

mainlyusedincold,fever,andheadache,etc.

overdosecandamageliverandkidney.C.Para-aminophenolderivatives第三十页，共四十页。编辑课件DifferencesbetweenNSAIDsandAcetaminophen第三十一页，共四十页。编辑课件Toxicmetabolitesofacetaminophen第三十二页，共四十页。编辑课件D.Otheranti-inflammatorydrugsSalicylates:aspirinPara-aminophenolderivatives:acetaminophenIndoleandindeneaceticacidderivatives:indomethacin,sulindacPropionicacidderivatives:

ibuprofen,naproxen,fenopofen,ketoprofenCOX-2selectiveinhibitors:meloxicam,celecoxide,rofenxidOthers:phenylbutazone,diclofenac第三十三页，共四十页。编辑课件第三十四页，共四十页。编辑课件indomethacin吲哚(yǐnduǒ)美辛piloxicam吡罗昔康ibuprofen布洛芬第三十五页，共四十页。编辑课件D.Otheranti-inflammatorydrugsindomethacin吲哚(yǐnduǒ)美辛：strongerefficacy,controllingspecial