藥理學(xué)教學(xué)課件：Chapter 20 Antipyretic-analgesic and Anti-inflammatory Drugs

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Chapter20Antipyretic-analgesicandAnti-inflammatoryDrugs

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Non-SteroidalAnti-InflammatoryDrugs,NSAIDs)Thesedrugsrelievethepainassociatedwithinflammation,includingthatfromarthritisandgout.Theyproducetheiranti-inflammatoryactionthroughadifferentmechanism,notasglucocorticoid.Classedintonon-steroidalanti-inflammatorydrugs(NSAIDs)in1974.23Introduction

Non-SteroidalAnti-InflammatoryDrugs,NSAIDsAAntipyretic

（一）PGSynthetase（Cyclooxygenase）inthehypothalamicthermoregulatorycenter

Characteristics：MakingcoolingofbodytempratureoffeverBAnalgesic（一）PGSynthetase（Cyclooxygenase）intheperipheralpainpositionCAnti-Inflammatory（一）PGSynthetase（Cyclooxygenase）intheperipheralinflammatoryposition4AntipyreticActionFebrile:Endogenouspyrogen→CNS→ReleasePG↑→Thermoregulatorycenter→FebrileAntipyretic:

InhibitPGsynthetase，DecreasesynthesisofPG→Hypothermy5

depress

bradykininpain

sensorantipyreticanalgesicpainstimulus

PGsynthesis

sensitization

depress

Mechanisms:Inhibitthesynthesisofprostaglandinsandpreventbradykininfromstimulatingpainreceptors,alsoinhibittherecognitionofpainimpulsesperipherally.AnalgesicAction6Anti-InflammatoryActionMechanisms:

InhibitaprimarypathwayinPGsynthesis.

Summary:ByinhibitingthePGsynthesistoshowantipyretic,analgesicandanti-inflammatoryeffects.78NSAIDsshowdifferenteffectstoCOX-1andCOX-2：ThestrongertheinhibitingeffectstoCOX-1，themoreadversereactionthedrughas；

ThestrongertheinhibitingeffectstoCOX-2，themoreobvioustheantipyretic-analgesicandanti-inflammatoryeffectsthedrughas.9NonSelectivelyCyclooxygenaseInhibitingDrugsASalicylicAcidBAnilineCIndoleDArylAceticAcidEArylPropionicAcidFEnolicAcidGPyrazoleKetonesHAlkylKetonesIIbufenac(Yidingfensuan)

10ISalicylates1838，ExtractedfromPlant，1860，Synthesized，1875，Usedinclinic1899，Aspirinwasused.

Aspirin11【TheInVivoProcess】Absorption

MostabsorbedinsmallintestinebyP.O.，andhydrolyzedassalicylicacidquickly.DistributionPlasmaproteinbindingrateofsalicylatesis80~90%，

Distributedquicklytothewholebody,includearticularcavity、cerebro-spinalfluid、placentaMetabolismIntrahepaticoxidativemetabolism，Smalldoseofaspirin（below

1g）byP.O.willbeeliminatedasfirst-ordereliminationkinetics.12【PharmacologicalActionandUses】

Antipyretic

andAnalgesic

Mediumintensity

Temperaturedropqiuckly

Usedinheadache,toothache,

arthralgia,algomenorrhea,fever,musclepainetc.

Anti-rheumatic

Mediumintensity

Inhibitantigen-antibodyreaction,

Usedinacuterheumatism,rheumatoidarthritis,

13AnticoagulantEffect

Inhibitingplateletaggregation，

Preventingthrombosis。

Usedinthepreventationofcerebralthrombosisandmyocardialinfarction

14【AdverseReaction】AGastrointestinaltractreaction

Seenmostoften

nausea、vomitingetc.BBlockbloodcoagulation

VitKmaypreventCSalicylicacidreaction:

nausea,vomiting

dizziness

、tinnitus、acouesthesia

↓

severe→acid-basedisorders、insanityDAllergicResponse

Urticaria、Aspirinasthma、AllergicshockEReyeSyndrome→SevereliverdysfunctionFNephrotoxicity(ie:kidneytoxicity)15【DrugInteractions】

Competitivelycombinedwithplasmaprotein:

Dicoumarol(shuangxiangdousu)

Tolbutamide

(jiahuangdinniao)etc.

Competitivelyinsecretion:

Furosemide(promoteurine)16IIAniline

Phenacetin20～30％→Aminobenzeneether→

High-IronHband

Hemolyticpoisoningcompound70～80％→acetaminophen→60％combinedwithglucuronicacid→35％combined

withsulfuricacid→less→liverpoisoning

hydroxylcompound17

Acetaminophen

1949，F(xiàn)oundthatthedrughadobviousanti-pyreticandanalgesiceffects.Mostwidelyused.

Medicationforalongtime,maycauseliverandkidneydisorder.18IIIIndole

IndomethacinStronganti-pyreticandanalgesiceffects.Butmostadversereaction.19IVArylAceticAcid

Diclofenac

Strongeranti-pyretic、analgesicandanti-inflammatoryeffectsthanindomethacin．

Adversereactionissimilartoaspirin.RarelyseenliverfunctiondysorderandWBCreduced.

VArylPropionicAcid

Ibuprofen

Adversereactionofgastrointestinaltractislessthanaspirin.Widelyusedintreatingrheumatoidarthritisandosteoarthritis(bonearthritis)

20VIEnolicAcid

Piroxicam

Showeffectsquicklyandlasting.

Usedintreatingrheumatismandrheumatoidarthritis.21VIIPyrazoleKetones

Phenylbutazone

【PharmacologicAction】Stronganti-inflammatory,anti-rheumaticeffects,butweakatipyretic,analgesiceffects.Prototypeusedtorheumatismandrheumatoidarthritis.22【AdverseEffects】StomachintestinereactionWater-sodiumretentionAllergicresponseLiver&kidneydamageEtc.23VIIIAlkylKetones

NabumetoneIXIbufenacAcids

Sulindac

Effectintensityandadversereactionarelowerthanindomethacin.24SelectivelyInhibitingdrugsofCyclooxygenase

Nimesulide

ANewtypeofNSAID，higherselectivitytoinhibitCOX2.BStronganti-inflammaryeffects,lessadversereaction.CUse