《药理学》课程PPT教学课件（Cardiovascular Sys）20 anti-inflammation drugs

NonsteroidalAnti-inflammatoryDrugs,Disease-Modifying Antirheumatic Drugs,Nonopioid Analgesics,and Drugs Used inGout

Nonsteroidal Anti-inflammatory Drugs, Disease-ModifyingAntirheumatic Drugs, Nonopioid Analgesics,and Drugs Used in Gout

theinflammatory responseWhat is Concepts ofinflammation?Inflammation describes the changesinseenresponse to tissue injury or insultThe hallmark ofinflammatory are:rednessswellingpainloss of function

the inflammatory response What is Concepts of inflammation? Inflammation describes the changes seen in response to tissue injury or insult. The hallmark of inflammatory are: redness swelling pain loss of function

inflammation is commonly divided intothreephases.acute inflammationthe immuneresponsechronic inflammationThe main cells and autacoids in inflammation are.neutrophil leucocytesmacrophageshistaminebradykininneuropeptides(substance-p,calcitonin,)cytokines(interleukins)the arachidonic acid metabolites(eicosanoids)

inflammation is commonly divided into three phases: acute inflammation the immune response chronic inflammation The main cells and autacoids in inflammation are: neutrophil leucocytes macrophages histamine bradykinin neuropeptides(substance-p, calcitonin, ) cytokines( interleukins) the arachidonic acid metabolites(eicosanoids)

Arachidonic acid metabolites: the eicosanoidsThe eicosanoids are of special importanceBiosyntheticpathway oftheeicosanoidsPhospholipids is mobilized by the enzyme PLA2arachidonic acid is metabolized, various eicosanoids aresynthesized.Theofarachidonatecyclooxygenasepathwayandmetabolism produces prostaglandins, thromboxanetheByproduceprostacyclintolipoxygenaseleukotrienes

Arachidonic acid metabolites: the eicosanoids The eicosanoids are of special importance Biosynthetic pathway of the eicosanoids Phospholipids is mobilized by the enzyme PLA2 arachidonic acid is metabolized, various eicosanoids are synthesized. The cyclooxygenase pathway of arachidonate metabolism produces prostaglandins, thromboxane and prostacyclin By lipoxygenase to produce the leukotrienes

Biosynthetic pathway of the eicosanoidMembranephospholipidPLA2|glucocorlicoidArachidonicacid-NSAIDSCOX+5-lipoxygenaseCyclicendoperoxides5-HPETEThromboxaneProstacyclin synthetaseLTA4LTB4synthetaseLTCPGE2PGF2TXA2PGl2TD→LTEA

Biosynthetic pathway of the eicosanoid LTA4 Membrane phospholipid Arachidonic acid PLA2 COX 5-HPETE Cyclic endoperoxides PGI2 PGE2 PGF2 TXA2 glucocorlicoid LTB4 LTD4 LTC4 LTE4 NSAIDS 5-lipoxygenase

The cyclooxygenase(COX) isoforms :COX-1is form tends to be homeostatic in functionCOX-2is induced during inflammation and tends tofacilitate the inflammatory response traumatictissue injury

The cyclooxygenase(COX) isoforms : COX-1 is form tends to be homeostatic in function COX-2 is induced during inflammation and tends to facilitate the inflammatory response traumatic tissue injury

ProstaglandinsA.role of prostaglandins as local mediatorsProstaglandins and related compounds areproduced in minute quantities by virtually alltissues.the prostaglandins do not circulate in the blood insignificant concentrationsB.synthesis ofprostaglandins

Prostaglandins A.role of prostaglandins as local mediators Prostaglandins and related compounds are produced in minute quantities by virtually all tissues. the prostaglandins do not circulate in the blood in significant concentrations. B.synthesis of prostaglandins

Biosynthetic pathway of the eicosanoidMembranephospholipidPLA2|glucocorlicoidArachidonicacid-NSAIDSCOX+5-lipoxygenaseCyclicendoperoxides5-HPETEThromboxaneProstacyclin synthetaseLTA4LTB4synthetaseLTCPGE2PGF2TXA2PGl2TD→LTEA

Biosynthetic pathway of the eicosanoid LTA4 Membrane phospholipid Arachidonic acid PLA2 COX 5-HPETE Cyclic endoperoxides PGI2 PGE2 PGF2 TXA2 glucocorlicoid LTB4 LTD4 LTC4 LTE4 NSAIDS 5-lipoxygenase

TABLE2-1.ThromboxaneProstaglandinProstaglandinProstaglandinProstacyclinPROSTANOIDLD,AIPTP,; TP,RECEPTORDP,;DP,EP,-EPFPA-FPBbrainendotheliumplateletsmast cellsuterusTARGETkidneybrainvascular smoothvascularsmoothvascular smoothORGANSmusclemusclemuscle&kidneysplateletsaiwaysairwaysmacrophagesTISSUESbrrainkidneyplateletseye

C.functions in the bodyeicosanoidActions in inflammationClassicalincreased vasodilatationprostaglandins:vascular permeabilityPGD2oedemaPGE2prostaglandins also sensitize nociceptivePGF2fibres to stimulation by otherinflammatory mediatorsThromboxane A2Platelet aggregation and vasoconstrictionProstacyclin(PGI2)Inhibition of platelet aggregation andvasodilatationLeukotrienes:IncreasevascularpermeabilityLTB4, LTC4promote leucocyle chemotaxis (and causecontractionofbronchial smoothmuscle

C.functions in the body eicosanoid Actions in inflammation Classical prostaglandins: PGD2 PGE2 PGF2 increased vasodilatation vascular permeability oedema prostaglandins also sensitize nociceptive fibres to stimulation by other inflammatory mediators Thromboxane A2 Platelet aggregation and vasoconstriction Prostacyclin(PGI2) Inhibition of platelet aggregation and vasodilatation Leukotrienes: LTB4, LTC4 Increase vascular permeability promote leucocyle chemotaxis (and cause contraction of bronchial smooth muscle)