解热镇痛抗炎药-北京协和医学院精品课程网站

解热镇痛抗炎药Antipyreticanalgesicandanti-inflammatorydrugs北京协和医学院基础医学院药理学系叶菜英Antipyreticanalgesicandanti-inflammatorydrugsThesedrugsrelievethepainassociatedwithinflammation,includingthatfromarthritisandgout.Antipyretic,analgesic,andantiinflammatorydrugs.Theyproducetheiranti-inflammatoryactionthroughadifferentmechanism,notasglucocorticoid.Classedintonon-steroidalanti-inflammatordrugs(NSAIDs)in1974.virusbacteriaBacterialproductendotoxinTDAg-Abexternalfeverphagocyte（GC）endogenouspyrogenhypothalamusPLunsaturatedfattyacidPGSPGTEMPSETcellsfebrileantipyreticanalgesicinhibitionAntipyreticaction•Febrile:endogenouspyrogen→CNS→releasePG↑→thermotaxiccenter→Febrile•Antipyretil:inhibitPGsynthetase，decreasesynthesisofPG→hypothermyAntipyreticactiondepressionbradykininpainsensorantipyreticanalgesicpainstimulusPGPGsynthesissensitizationdepressionAnalgesicactionMechanisms:Effectonperiphery,inhibitthesynthesisofprostaglandinsandpreventbradykininfromstimulatingpainreceptors,alsoinhibittherecognitionofpainimpulsescentrallyandperipherally.AnalgesicactionAnti-inflammatoryactionMechanisms:InhibitaprimarypathwayinPGsynthesis.Summary:InhibitthePGsynthesistoantipyretil,analgesicandanti-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、炎痛喜康等阿斯匹林解热镇痛消炎药水杨酸类阿斯匹林Aspirin【physiologicaldisposition】：Oral,absorbedfromgut→distribution,metabolism→kenosis(enterarticularcavity,CSF)【Pharmacologicalaction】•Atipyretic:temperaturedropqiuckly•Analgesic:mediumintensity•Anti-rheumatic:inhibitantigen-antibodyreaction,antibodyformation,antigenantibodyunion，bloodsedimentation↓,relieveflareofarticulus.Aspirin【ClinicalIndications】Antipyreticanalgesicandanti–inflammatoryHeadache,toothache,algomenorrhea,neuralgiacourbature,arthralgia.FeverAcuterheumatism,rheumatoidarthritisAspirinAspirin【Pharmacologicalaction&ClinicalIndications】•Effectonthrombosis：Inhibitcycloxygenasecyclo-oxygenase，reduceTXA2synthesisInhibitPAeffectonthromboxanesynthesisaspirinTXA2synthetasePMphospholipidAAendoperoxide↓TXA2↓thrombosis↓PA↓plateletreleasion↓•ClinicalIndications:lowdose,longtermusecouldpreventCHDthrombosis,cerebralthrombosisAspirin【Untowardreaction】•Gastrointestinaltractreaction•Blockbloodcoagulation•NSreaction:salicylism,nausea,vomiting,dizziness,tinnitus,acouesthesia↓•Anaphylacticresponse•NephrotoxicityParacetamol&PhenacetinStrongantipyreticanalgesiceffect;weakanti-rheumaticeffect.(inhibitionforcenterepoxidaseisstrongerthanthatforexternalepoxidase)【Pharmacologicalaction】NHCOCH3OC2H5NHCOCH3OHNH2OC2H5PhenacetinParacetamolP-aminophenetoleAnilineParacetamolPhenacetin【Pharmacokinetics】Oral,absorb→hepaticmetabolism→kenosis↗60％combinewithGAde-ET（70％－80％）→Paracetamol→35％combinewithH2SO4,fail↗↘bare→hydroxidePhenacetin↘de-Ac→P-aminophenetole→hydroxide→hemoglobin→oxidationmetahemoglobin↓toxicmetabolinParacetamol&Phenacetin【UntowardReaction】•Allergyoccasionally:rash,drugfever,M.Mdamage•Overdose(10~15g∕day)→acutepoisoning→hepatonecrosis•Overdose→methemoglobinemia,cyanosis,hypoxia,HA•KidneydamagePhenylbutazone(保泰松)Stronganti-inflammatory,anti-rheumaticeffects,butweakatipyretil,analgesiceffects.【Pharmacologicaction】NNOOCH3(CH2)2CH2PyrazoketonePrimaryusedtorheumatismandrheumatoidarthritis【Physiologicaldisposition】Oraltoabsorb,penetrationsynoviamembrane→theconcentrationinsynoviaintermembrancespaceis50%ofthatinblood(highconcentrationinjointtissue)Phenylbutazone(保泰松)Pyrazoketone【Sideeffects】•Stomachintestinereaction•Water-sodiumretention•Anaphylacticrespons•Liver&kidneydamage•ThyromegalyandmyxedemaPhenylbutazone(保泰松)Indometacin【UntowardReaction】NCH2COOHCH3H3COCOClIndometacinOneofthemostpotentinhibitorsofCOXisozymes;Effectsoninflammatory,atipyretilanalgesicandrheumatismsignificantly;Usetothecaseswhichdifficulttocureabove-mentioned.Lotsofuntowardreaction,highincidencerate,Stomachintestinereaction(ulcer),CNSreaction,Inhibithematopoieticsystem,anaphylacticresponseOrganicacidsBrufen&Fenbid【Pharmacologicaction】•Lessstomachintestinereactions,goodtolerance.•99%combinewithplasma-albumin→entersynovialmembranetuneslowly,keephighconcentration.•Effectissimilarwithaspirin,strongerthanparacetamol.•Usedtorheumatismandrheumatoidarthritis.•Lightdyspepsia,rashoccasionally.Compoundpreparation(67types)ColdrineCompoundAminopyrinePhenacetinTabletsAPCPseudoephedrine+Paracetamol+Dextromethorphan+ChlorphenamineMaleateParacetamolCompoundChlorphenamineMaleate【Essentialcomponent】•APC:aspirinparacetamolcaffeine•Somedon:aminophenazonePACcaffeineThanks!Thanks!