藥理學(xué)英文版教學(xué)課件：Chapter 32 Adrenocorticosteroids

AdrenocorticosteroidsCorticosteroids(皮質(zhì)激素類(lèi))areaclassofsteroid（甾體類(lèi)）hormonesthatareproducedintheadrenalcortex(腎上腺皮質(zhì)).Corticosteroidsareinvolvedinawiderangeofphysiologicsystemssuchasstressresponse,immuneresponseandregulationofinflammation,carbohydratemetabolism,proteincatabolism,bloodelectrolytelevels,andbehavior.Glucocorticoids（糖皮質(zhì)激素）

suchascortisolcontrolcarbohydrate,fatandproteinmetabolismandareanti-inflammatorybypreventingphospholipidrelease,decreasingWBCactionandanumberofothermechanisms.Mineralocorticoids（鹽皮質(zhì)激素）

suchasaldosteronecontrolelectrolyteandwaterlevels,mainlybypromotingsodiumretentioninthekidney.AdrenalAnatomysmall,triangularglandslooselyattachedtothekidneysdividedintotwomorphologicallyanddistinctregionsadrenalcortex(皮質(zhì)outer)adrenalmedulla(髓質(zhì)inner)

Structure&functionofadrenalcortexzonaglomerulosa鹽皮質(zhì)激素zonafasciculata糖皮質(zhì)激素zonareticularis性激素

[Chemicalstructure]

基本結(jié)構(gòu)steroidnucleus(甾核)

C3酮基,C20羰基,C4-5雙鍵是保持生理功能所必需

glucocorticoids：C17-OH，C11=O或-OH

mineralocorticoids：C17無(wú)-OHC11無(wú)=O或有O與C18

相連

§1GlucocorticoidsStructural:

–OHinC17,-Oor–OHinC11PharmacokineticsLipidsoluble,p.oorinjectionadminis.Hydrocortisone80%boundtoplasmacorticosteroidbindingglobulin(CBG)CortisoneconvertedtohydrocortisoneinliverPharmacologicaleffects&mechanismI.onmetabolism:1.glycometabolism(糖代謝)promotesgluconeogenesis（糖異生）,decreasetheuseofbloodglucose,increasebloodglucoseconcentration2.proteinmetabolismpromotesbreakdownofproteininskeletonandmuscle—negativenitrogenbalance(負(fù)氮平衡);inhibitproteinsynthesis3.fatmetabolismenhancesfatbreakdown(lipolysis，脂解),redistributionoffat(centralobesity);4.mineralmetabolismNa+&waterretainingII.PermissiveactionSensitizetheresponseoftissuestosomehormonesIII.Anti-inflammatoryeffectsEarlystagedecreaseeffusion(滲出),edema,hot&feverandpainLatestageinhibitproliferationoffibroblasts（成纖維細(xì)胞）&capillarygrowth,affectthegranulation（肉芽）tissueformation.Mechanisms:geneeffectsandfasteffectsreducesphagocytic（噬菌）actionofwhitebloodcellsInducetheapoptosisofinflammatorycellsInducingtheproductionoflipocortin-1(脂質(zhì)素),inhibittheactivationofphospholipaseA2(PLA2),reducetheproductionofinflammatoryfactorssuchasprostaglandins,leukotriene（白三烯）,interleukin（白介素）andplatelet-activatingfactorsynthesis;（page336）alsoreducedtheexpressionofcyclooxygenaseII(COX2)andinhibitinducedNOsynthase.糖皮質(zhì)激素基因效應(yīng)機(jī)制示意圖

IV.immunosuppressive&antiallergiceffectsDecreaseorinhibitlymphocytes，inhibitthymus（胸腺）Anti-allergiceffect,inhibitproductionofallergicmediatorsV.Anti-shockeffectBenefitfromanti-inflammatoryeffectStabilizethemembraneoflysosome（溶酶體），reducetheamountofmyocardialdepressantfactor（心肌抑制因子）DilatespasmbloodvesselsIncreasethebody‘stolerancetoendotoxin（內(nèi)毒素）VI.OthereffectsAntipyreticeffectOnblood&bloodformingorgansOnCNS:stimulateOnbone:osteoporosis（骨質(zhì)疏松）,inhibitfunctionofosteoblasts（成骨細(xì)胞）,Ca++loseCardiovascularsystem:hypertensionDigestivesystem:increasesecretionofgastricacidsandpepsinClinicaluses1.severeinfectionAcuteinfection,accompaniedbyeffectiveantibacterialdrugusePreventinflammatorysequelae（后遺癥）2.autoimmununediseasea:systemiclupuserythematosus(系統(tǒng)性紅斑狼瘡),nephroticsyndrome(腎病綜合征)rheumatoidarthritis(類(lèi)風(fēng)濕性關(guān)節(jié)炎)antiorgantransplantationrejectionAllergicdiseases:bronchialasthma3.shocktreatment:infectiousshock4.bloodrelateddiseasesAcutelymphaticleukemiaAplasticanemia（再障）Thrombocytopenia(血小板減少癥)5.localapply:skindiseases,jointinjection6.substitutivetherapy:adrenocorticalinsufficiency7.stimulationoflungmaturationinthefetus:12mginjectiontwicetomotherin24hoursAdversereaction1.ADRafterlongterm&bigdoseusageDigestiveS/E:digestiveulcersInfectionHyperadrenocorticismCushing'ssyndromemoonshapedface,centralobesity,hypokalemia,glucosuriaCardiovasculardisorders:arthrosclerosis,hypertensionCNSdisorders:epilepsy,psychoticdisordersCushing'ssyndrome

Fatdepositscanformaroundstomachandupperback,butarmsandlegsstaythinanddon'tusuallygetfatter.skingetsthinnerandiseasilybruised.Cuts,scratchesandinsectbitestakealongtimetoheal.Pinkorpurplestretchmarksmayformonskin.facemaybecomeroundandpuffy.mayfeeltiredandhaveweakmuscles.mayfeeldepressed.Womenusuallyhaveirregularmenstrualperiodsandmaygrowthickormorevisiblebodyhair.Highbloodpressure,osteoporosis(weakandbrittlebones)andbloodsugarlevelsthatarehigherthannormaloftengetskininfectionsorotherinfections,andtheytakelongertoheal.2.WithdrawalreactionAdrenocorticalinsufficiencyRebound(反跳現(xiàn)象)Dosageschedule&periodoftreatmentMegadoseshortperiodaggressivelyuseforsevereinfectiousdiseases,3~5daysLargedosageprolongedperiodoftreatment,alternate-dayadministrationSmalldosesubstitutivetreatment§2MineralocorticoidsAldosterone(醛固酮)Desoxycorticosterone(去氧皮質(zhì)酮醛固酮前體）Substitutiveusageforadrenocorticalinsufficiency§3Adrenotrophin&corticalhormoneinhibitorsACTHcheckthefunctionofadrenalcortexSpironolactoneMitotane(米托坦):destroycellssecreteglucocorticoidandaldosterone,adrenalcortexcancertherapypractices1.commonlyusedglucocorticoidsdrugsinclude(),(),()and().2.themetabolismeffectsofhydrocortisoneare:()bloodglucoselevelby(),()and();(