神經系統(tǒng)藥理-吳希美解熱鎮(zhèn)痛藥

Chapter27

Antipyretic-AnalgesicandAntiinflammatoryDrugs第一頁，共四十頁。編輯課件A.GeneralPharmacologicalproperties1.Inhibitionofprostaglandinsynthesisinhibiting

cyclooxygenase(COX，環(huán)氧酶),decreasingthesynthesisofPGsandTXA2,resultingantipyretic,analgesic,andanti-inflammatoryeffectsnon-steroidalanti-inflammatorydrugs(NSAIDs,非甾體抗炎藥）。第二頁，共四十頁。編輯課件第三頁，共四十頁。編輯課件第四頁，共四十頁。編輯課件2.AntipyreticeffectsInhibitionofPGE2productioninthehypothalamusinducedbyendogenouspyregensafterpathologicalstimulitemperaturenotes:

symptomaticcontrolonly,notbeindicatedinallpatientswithfever.

Theeffectonbodytemperatureisdifferentfromthatofchlorpromazine.A.GeneralPharmacologicalproperties第五頁，共四十頁。編輯課件Comparisonofpropertiesoftwotypesofdrugs第六頁，共四十頁。編輯課件3.AnalgesiceffectsAnalgesiceffectisresultedfrominhibitionofPGE2production.Effectiveonthepainoflowtomoderateintensityrelatedtoinflammatoryresponses.PGE2:apainstimulantandhyperalgesicagentTheanalgesiceffectisdifferentfromopioidanalgesics.A.GeneralPharmacologicalproperties第七頁，共四十頁。編輯課件Comparisonofpropertiesoftwotypesofdrugs第八頁，共四十頁。編輯課件4.Anti-inflammatoryeffects

PGsinduceinflammatoryresponses.InhibitionofPGproductioncanrelieveinflammatoryresponses,suchascongestion,exudation,pain.Theeffectisdifferentfromthatofglucocorticosteroids.A.GeneralPharmacologicalproperties第九頁，共四十頁。編輯課件Comparisonofpropertiesoftwotypesofdrugs第十頁，共四十頁。編輯課件5.COX-1/COX-2andselectivityofthedrugsCOX-1:

constructive;

involvedinphysiologicregulatoryfunctionsinGItract,kidney,etc.;

inhibitionofCOX-1isrelatedtotheadverseeffects.COX-2:

inducible;involvedinpathologicalresponsessuchasinflammation,andpregnancy;

inhibitionofCOX-2isrelatedtothetherapeuticeffects.

A.GeneralPharmacologicalproperties第十一頁，共四十頁。編輯課件（－）（＋）（＋）（－）第十二頁，共四十頁。編輯課件第十三頁，共四十頁。編輯課件第十四頁，共四十頁。編輯課件第十五頁，共四十頁。編輯課件B.SalicylatesAspirin阿司匹林(āsīpǐlín)Acetylsalicylicacid乙酰水楊酸Aspirin阿司匹林(āsīpǐlín)Salicylicacid水楊酸Salicylicsodium水楊酸鈉第十六頁，共四十頁。編輯課件Aspirin阿司匹林(āsīpǐlín)1.ADMEtransformedtosalicylicacidforminthebodyhepaticmetabolismisprimarilyconjugation.excretionfromurine,theexcretionofunchangedformsofaspirinisincreasedinthealkalinizedurine.largerdoses(>1g/d):

non-linearelimination,zeroorderkineticprocess,easiertoaccumulationandintoxication.B.Salicylates第十七頁，共四十頁。編輯課件第十八頁，共四十頁。編輯課件2.Pharmacologicaleffectsandclinicaluses(1)Antipyretic,analgesicandanti-inflammatoryeffects

moderatedoses(0.3～0.6g):antipyreticandanalgesiceffects

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

totreatacuterheumaticfever(急性(jíxìng)風濕熱),toabatepainandsymptomsofrheumatic&rheumatoidarthritis(風濕性和類風濕性關節(jié)炎).B.Salicylates第十九頁，共四十頁。編輯課件(2)Inhibitionofplateletaggregation

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

largerdoses:inhibitingPGI2synthesis,promotingthrombosis.

PGI2:vasodilationandplateletdepolymerization(血小板解聚).

B.Salicylates第二十頁，共四十頁。編輯課件Themechanismofaspirin:Targetenzymesacetylated第二十一頁，共四十頁。編輯課件3.Adverseeffects(1)GIreactions

stimulatinggastricmucosaandCTZ(largerdoses);inhibitingPGsynthesisinGItractirritantsymptoms;gastricbleeding;ulcerousdisordersContraindications:ulcerousdisordersB.Salicylates第二十二頁，共四十頁。編輯課件(2)Prolongationofbleedingtimesmalldoses:inhibitingplateletaggregationlargerdoses:inhibitingsynthesisofthrombogen

Contraindications:oneweekpriortosurgery;severehepaticdamage;vitaminKdeficiency,;prothrombinopenia(凝血酶原減少(jiǎnshǎo)癥).B.Salicylates第二十三頁，共四十頁。編輯課件(3)Allergicreactionsurticaria(蕁麻疹),angioneuroticedema,aspirin-inducedasthma,occasionallyanaphylacticshock.Contraindications:

bronchialasthmaB.Salicylates第二十四頁，共四十頁。編輯課件Aspirin-inducedasthma:

Phospholipidsofcellmenbrane

Aspirin

PhospholipaseA2(PLA2)(-)Arachidonicacid

CyclooxygenaseLipoxygenenase

(環(huán)氧酶)PGH25-HPETE(脂氧酶)

↓Prostaglandins(PGs)

↑Leukotrienes(LTs)

(前列腺素)

(白三烯)第二十五頁，共四十頁。編輯課件(4)Salicylism

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

(5)Hepaticdamage

Overdose:hepaticdamage

Reye’ssyndrome(瑞夷綜合征):inchildren,severehepaticdamage(嚴重(yánzhòng)的肝損害)andencephalopathy(腦病)B.Salicylates第二十六頁，共四十頁。編輯課件Dose-responserelationshipofaspirin:therapeuticeffects;adverseeffects第二十七頁，共四十頁。編輯課件4.DruginteractionsB.Salicylates第二十八頁，共四十頁。編輯課件C.Para-aminophenolderivativesAcetaminophen對乙酰氨基酚Paracetamol

撲熱息痛第二十九頁，共四十頁。編輯課件Acetaminophen（對乙酰氨基酚）：

antipyreticandanalgesiceffectsaremildandlasting,butalmostnoanti-inflammatoryeffects,-nota

NSAIDhigherselectivitytoCOXinCNS.

mainlyusedincold,fever,andheadache,etc.

overdosecandamageliverandkidney.C.Para-aminophenolderivatives第三十頁，共四十頁。編輯課件DifferencesbetweenNSAIDsandAcetaminophen第三十一頁，共四十頁。編輯課件Toxicmetabolitesofacetaminophen第三十二頁，共四十頁。編輯課件D.Otheranti-inflammatorydrugsSalicylates:aspirinPara-aminophenolderivatives:acetaminophenIndoleandindeneaceticacidderivatives:indomethacin,sulindacPropionicacidderivatives:

ibuprofen,naproxen,fenopofen,ketoprofenCOX-2selectiveinhibitors:meloxicam,celecoxide,rofenxidOthers:phenylbutazone,diclofenac第三十三頁，共四十頁。編輯課件第三十四頁，共四十頁。編輯課件indomethacin吲哚(yǐnduǒ)美辛piloxicam吡羅昔康ibuprofen布洛芬第三十五頁，共四十頁。編輯課件D.Otheranti-inflammatorydrugsindomethacin吲哚(yǐnduǒ)美辛：strongerefficacy,controllingspecial