(2)Systemiclupuserythematosus(SLE,系统红斑狼疮)

DrugsTreatingRheumatism1.Definitions•风湿病（rheumatism,rheumaticdiseases）是一组侵犯关节、骨骼、肌肉、血管及有关软组织或结缔组织为主的疾病，其中多数为自身免疫性疾病。发病多较隐蔽而缓慢，病程较长，且大多具有遗传倾向。包括：•1.弥漫性结缔组织病:类风湿关节炎(rheumatoidarthritis,RA)、系统红斑狼疮(systemiclupuserythematosus,SLE)、硬皮病、多肌炎、重叠综合征、血管炎•2.脊柱关节病:强制性脊柱炎、Reiter综合征、银屑病关节炎、未分化脊柱关节病等•3.退行性变:骨关节炎（osteoarthritis,OS）•4.与代谢和内分泌相关的风湿病:痛风、假性痛风、马方综合征、免疫缺陷病等•5.和感染相关的风湿病:反应性关节炎、风湿热（rheumaticfever,RF）等•6.肿瘤相关性风湿病:原发性(滑膜瘤、滑膜肉瘤等)；继发性(多发性骨髓瘤、转移瘤等)•7.神经血管疾病:神经性关节病、压迫性神经病变(周围神经受压、神经根受压等)、雷诺病等•8.骨与软骨病变:骨质疏松、骨软化、肥大性骨关节病、弥漫性原发性骨肥厚、骨炎等•9.非关节性风湿病:关节周围病变、椎间盘病变、特发性腰痛、其他痛综合征(如精神性风湿病)等•10.其他有关节症状的疾病:周期性风湿热、间歇性关节积液、药物相关的风湿综合征、慢性活动性肝炎等•2.Drugstreatingrheumatism•1.Non-steroidalanti-inflammatorydrugs(NSAIDs,非甾体抗炎药）antipyretic,analgesicandanti-inflammatorydrugs(解热镇痛抗炎药)•2.Glucocorticosteroids(糖皮质激素)steroidalanti-inflammatorydrugs(甾体抗炎药)•3.Disease-modifyinganti-rheumaticdrugs(DMARDs,改善病情的抗风湿药）mainlyimmunosuppressants•4.Otheradjuvantdrugs•Analgesicdrugs（镇痛药）•Bonemetabolism-regulatingdrugs（骨代谢调节药）•Antibacterialdrugs（抗菌药）•Goutsuppressants（痛风治疗药）DMARDs•1.Glucocorticoids(糖皮质激素类)：•prednisolone(泼尼松龙),methylprednisolone(甲泼尼松龙)•2.Calcineurininhibitors(钙调磷酸酶抑制剂)：•cyclosporine(CsA,环孢素),tacrolimus(FK506,他克莫司)•3.Antiproliferativeandantimetabolicdrugs(抗增殖/抗代谢类)：•rapamycin(雷帕霉素,sirolimus西罗莫司),mycophenolatemofetil(MMF,霉酚酸酯),azathioprine(Aza,硫唑嘌呤),cyclophosphamide(CTX,环磷酰胺)•methotrexate(氨甲喋呤,MTX),chloroquine(氯喹),hydroxychloroquine(羟氯喹）sulfasalazine(柳氮磺吡啶),leflunomide(来氟米特)•4.Antibodiesandotherbiologicalagents(抗体及其他生物制剂)：•ActiveTCMcomponents(中药有效成分,尚未进入国际药物分类)：•tripterygiumglycosides(雷公藤总苷)Analgesicdrugs•Opioidanalgesics(centrallyacting)•opiates•syntheticagents•Antipyretic,analgesic,andanti-inflammatorydrugs(peripherallyacting)•aspirin,indomethacin•Otherdrugs(forspecialtypesofpain)•carbamazepine,atropine,nitroglycerin,etc.Bonemetabolism-regulatingdrugs•Hormones（激素类）•estrogens（雌激素类）：diethylstilbestrol（己烯雌酚）•androgens（雄激素类）：Testosterone（睾酮）•parathyroidhormone（甲状旁腺激素，PTH）andteriparatide（特立帕肽）,calcitonin（降钙素）•Diphosphonates（双膦酸盐类药物）•alendronatesodium（阿仑膦酸钠）•CalciumandVitaminD3（钙及维生素D3）•Others•Glucosamine（氨基葡萄糖）,chondroitinsulfate（硫酸软骨素）,fluorides（氟化物）Calciumandphosphatemetabolisminthebodyandtheregulationparathyroidhormone(PTH),Calcitonin(CT)，1,25(OH)2D3(D),fibroblastgrowthfactor23(FGF23)Antibacterialdrugs•Agentsagainststreptococcal（链球菌）infections•Penicillins（青霉素类）：penicillinG(benzylpenicillin,苄青霉素)•Cepharosporins（头孢菌素类）•Macrolides（大环内酯类）：erythromycin(红霉素)•Lincomycins（林可霉素类）•Quinolones(喹诺酮类)•Sulfonamides(磺胺类)Goutsuppressants•Colchicine(秋水仙碱):•relievingthepainandinflammationofgoutyarthritis•Indomethacin(吲哚美辛)andotherNSAIDs(exceptaspirin,salicylatesandtolmetin):•inhibitinguratecrystalphagocytosis(尿酸结晶体吞噬)•Probenecid(丙磺舒)andsulfinpyrazone(磺吡酮):•decreasingreabsorptionofuricacidintheproximaltubule,therebyacceleratinguricacidexcretion(uricosuricdrugs,尿酸促排剂)•Allopurinol(别嘌醇)andfebuxostat:•Inhibitingxanthineoxidase,therebyreducinguricacidsynthesis3.Drugtreatmentofrheumaticdiseases•(1)Rheumatoidarthritis(RA,类风湿关节炎)•(2)Systemiclupuserythematosus(SLE,系统红斑狼疮)•(3)Osteoarthritis(OS,骨关节炎)•(4)Rheumaticfever(RF,风湿热)3.Drugtreatmentofrheumaticdiseases•(1)Rheumatoidarthritis(RA)Keypathologicalchangesinthesynoviuminrheumatoidarthritis•Treatmentofsymptoms•Analgesicsreducepain•Non-steroidalantiinflammatorydrugs(NSAIDs)lessenpainandstiffness•NSAIDshavelosttheirhistoricalroleasfirst-linetreatmentbecauseofconcernsabouttheirlimitedeffectiveness,inabilitytomodifythelong-termcourseofdisease,andgastrointestinalandcardiactoxiceffects.Theseagentsshouldbegivenwithproton-pumpinhibitorsforgastroprotection,withshort-actingdrugsadministeredforshortperiodstominimiserisks.•(1)Rheumatoidarthritis(RA)•(1)Rheumatoidarthritis(RA)•Disease-modifyingantirheumaticdrugs(DMARDs)•Aheterogeneouscollectionofagentsgroupedtogetherbyuseandconvention.•Theyarethemainstayoftreatmentforrheumatoidarthritis.Theirdiversemechanismsofactionareincompletelyunderstood.•Theyreducejointswellingandpain,decreaseacute-phasemarkers,limitprogressivejointdamage,andimprovefunction.•Methotrexate(MTX)isthedominantDMARD.•Sulfasalazine(柳氮磺吡啶)andleflunomide(来氟米特)arealsowidelyused.Theirefficacyhasbeenestablishedinplacebo-controlledtrials.•Hydroxychloroquine(羟氯喹)andchloroquine(氯喹)haveDMARD-likeproperties.•Gold(sodiumaurothiomalate)andcyclosporinareadditionalDMARDs•Theiruseislimitedbytoxiceffects.•(1)Rheumatoidarthritis(RA)EvolutionofRAdrugtreatment•(1)Rheumatoidarthritis(RA)•Biologicalagents•TNFinhibitors[etanercept(依那西普),infliximab(英夫利西单抗),adalimumab(阿达木单抗)]werethefirstlicensedbiologicalagents,followedbyabatacept(阿巴西普,CTLA-Ig),rituximab(利妥昔单抗),andtocilizumab:theyarehighlyeffective.•Effectsofbiologicalagentscanbeespeciallystrikinginthesubsetofinadequatelytreatedornon-responsivepatientsselectedfortrials.•(1)Rheumatoidarthritis(RA)•(1)Rheumatoidarthritis(RA)ACR50responsesintrialsofDMARDsandbiologicalagentsACR50=50%improvementsinfiveofthesevenmeasuresofAmericanCollegeofRheumatologycriteria.Errorbars=95%CIs.trialsofindividualdrugsmeta-analysis