2SystemiclupuserythematosusSLE系统红斑狼疮.pptx

Drugs Treating Rheumatism1.Definitions 风湿病（风湿病（风湿病（风湿病（rheumatism,rheumatic diseasesrheumatism,rheumatic diseases）是一组侵）是一组侵）是一组侵）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犯关节、骨骼、肌肉、血管及有关软组织或结缔组织为主犯关节、骨骼、肌肉、血管及有关软组织或结缔组织为主犯关节、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。发病多较隐蔽而缓的疾病，其中多数为自身免疫性疾病。发病多较隐蔽而缓的疾病，其中多数为自身免疫性疾病。发病多较隐蔽而缓的疾病，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：慢，病程较长，且大多具有遗传倾向。包括：慢，病程较长，且大多具有遗传倾向。包括：慢，病程较长，且大多具有遗传倾向。包括：1.1.弥漫性结缔组织病弥漫性结缔组织病弥漫性结缔组织病弥漫性结缔组织病:类风湿关节炎类风湿关节炎类风湿关节炎类风湿关节炎(rheumatoid arthritis,RA)(rheumatoid arthritis,RA)、系统红斑狼疮、系统红斑狼疮、系统红斑狼疮、系统红斑狼疮(systemic lupus erythematosus,SLE)(systemic lupus erythematosus,SLE)、硬皮病、硬皮病、硬皮病、硬皮病、多肌炎、重叠综合征、血管炎多肌炎、重叠综合征、血管炎多肌炎、重叠综合征、血管炎多肌炎、重叠综合征、血管炎 2.2.脊柱关节病脊柱关节病脊柱关节病脊柱关节病:强制性脊柱炎、强制性脊柱炎、强制性脊柱炎、强制性脊柱炎、ReiterReiter综合征、银屑病关节炎、未综合征、银屑病关节炎、未综合征、银屑病关节炎、未综合征、银屑病关节炎、未分化脊柱关节病等分化脊柱关节病等分化脊柱关节病等分化脊柱关节病等 3.3.退行性变退行性变退行性变退行性变:骨关节炎骨关节炎骨关节炎骨关节炎（osteoarthritis,OS）4.4.与代谢和内分泌相关的风湿病与代谢和内分泌相关的风湿病与代谢和内分泌相关的风湿病与代谢和内分泌相关的风湿病:痛风、假性痛风、马方综合痛风、假性痛风、马方综合痛风、假性痛风、马方综合痛风、假性痛风、马方综合征、免疫缺陷病等征、免疫缺陷病等征、免疫缺陷病等征、免疫缺陷病等 5.5.和感染相关的风湿病和感染相关的风湿病和感染相关的风湿病和感染相关的风湿病:反应性关节炎、反应性关节炎、反应性关节炎、反应性关节炎、风湿热（风湿热（风湿热（风湿热（rheumatic rheumatic fever,RFfever,RF）等等等等 6.6.肿瘤相关性风湿病肿瘤相关性风湿病肿瘤相关性风湿病肿瘤相关性风湿病:原发性原发性原发性原发性(滑膜瘤、滑膜肉瘤等滑膜瘤、滑膜肉瘤等滑膜瘤、滑膜肉瘤等滑膜瘤、滑膜肉瘤等)；继发性；继发性；继发性；继发性(多多多多发性骨髓瘤、转移瘤等发性骨髓瘤、转移瘤等发性骨髓瘤、转移瘤等发性骨髓瘤、转移瘤等)7.7.神经血管疾病神经血管疾病神经血管疾病神经血管疾病:神经性关节病、压迫性神经病变神经性关节病、压迫性神经病变神经性关节病、压迫性神经病变神经性关节病、压迫性神经病变(周围神经受压、周围神经受压、周围神经受压、周围神经受压、神经根受压等神经根受压等神经根受压等神经根受压等)、雷诺病等、雷诺病等、雷诺病等、雷诺病等 8.8.骨与软骨病变骨与软骨病变骨与软骨病变骨与软骨病变:骨质疏松、骨软化、肥大性骨关节病、弥漫性骨质疏松、骨软化、肥大性骨关节病、弥漫性骨质疏松、骨软化、肥大性骨关节病、弥漫性骨质疏松、骨软化、肥大性骨关节病、弥漫性原发性骨肥厚、骨炎等原发性骨肥厚、骨炎等原发性骨肥厚、骨炎等原发性骨肥厚、骨炎等 9.9.非关节性风湿病非关节性风湿病非关节性风湿病非关节性风湿病:关节周围病变、椎间盘病变、特发性腰痛、关节周围病变、椎间盘病变、特发性腰痛、关节周围病变、椎间盘病变、特发性腰痛、关节周围病变、椎间盘病变、特发性腰痛、其他痛综合征其他痛综合征其他痛综合征其他痛综合征(如精神性风湿病如精神性风湿病如精神性风湿病如精神性风湿病)等等等等 10.10.其他有关节症状的疾病其他有关节症状的疾病其他有关节症状的疾病其他有关节症状的疾病:周期性风湿热、间歇性关节积液、周期性风湿热、间歇性关节积液、周期性风湿热、间歇性关节积液、周期性风湿热、间歇性关节积液、药物相关的风湿综合征、慢性活动性肝炎等药物相关的风湿综合征、慢性活动性肝炎等药物相关的风湿综合征、慢性活动性肝炎等药物相关的风湿综合征、慢性活动性肝炎等2.Drugs treating rheumatism1.Non-steroidal anti-inflammatory drugs1.Non-steroidal anti-inflammatory drugs (NSAIDs,(NSAIDs,非甾体抗炎药非甾体抗炎药非甾体抗炎药非甾体抗炎药）antipyretic,analgesic and anti-antipyretic,analgesic and anti-inflammatory drugsinflammatory drugs (解热镇痛抗炎药解热镇痛抗炎药解热镇痛抗炎药解热镇痛抗炎药)2.Glucocorticosteroids2.Glucocorticosteroids (糖皮质激素糖皮质激素糖皮质激素糖皮质激素)steroidal anti-steroidal anti-inflammatory drugs inflammatory drugs(甾体抗炎药甾体抗炎药甾体抗炎药甾体抗炎药)3.3.Disease-modifying anti-rheumatic drugsDisease-modifying anti-rheumatic drugs(DMARDs,(DMARDs,改善病情的抗风湿药改善病情的抗风湿药改善病情的抗风湿药改善病情的抗风湿药）mainly immunosuppressantsmainly immunosuppressants4.Other adjuvant drugs4.Other adjuvant drugs Analgesic drugs Analgesic drugs（镇痛药镇痛药镇痛药镇痛药）Bone metabolism-regulating drugsBone metabolism-regulating drugs（骨代谢调节药骨代谢调节药骨代谢调节药骨代谢调节药）Antibacterial drugsAntibacterial drugs（抗菌药抗菌药抗菌药抗菌药）Gout suppressants Gout suppressants（痛风治疗药痛风治疗药痛风治疗药痛风治疗药）DMARDs 1.1.GlucocorticoidsGlucocorticoids (糖皮质激素类糖皮质激素类糖皮质激素类糖皮质激素类)：prednisolone prednisolone(泼尼松龙泼尼松龙泼尼松龙泼尼松龙),methylprednisolone methylprednisolone(甲泼尼松龙甲泼尼松龙甲泼尼松龙甲泼尼松龙)2.Calcineurin inhibitors 2.Calcineurin inhibitors(钙调磷酸酶抑制剂钙调磷酸酶抑制剂钙调磷酸酶抑制剂钙调磷酸酶抑制剂)：cyclosporine cyclosporine(CsA,(CsA,环孢素环孢素环孢素环孢素),),tacrolimustacrolimus (FK506,(FK506,他克莫司他克莫司他克莫司他克莫司)3.Antiproliferative and antimetabolic drugs 3.Antiproliferative and antimetabolic drugs(抗增殖抗增殖抗增殖抗增殖/抗代谢类抗代谢类抗代谢类抗代谢类)：rapamycin rapamycin(雷帕霉素雷帕霉素雷帕霉素雷帕霉素,sirolimus,sirolimus 西罗莫司西罗莫司西罗莫司西罗莫司),),mycophenolate mofetil mycophenolate mofetil(MMF,(MMF,霉酚酸酯霉酚酸酯霉酚酸酯霉酚酸酯),),azathioprine azathioprine(Aza,(Aza,硫唑嘌呤硫唑嘌呤硫唑嘌呤硫唑嘌呤),),cyclophosphamide cyclophosphamide(CTX,(CTX,环磷酰胺环磷酰胺环磷酰胺环磷酰胺)methotrexatemethotrexate(氨甲喋呤氨甲喋呤氨甲喋呤氨甲喋呤,MTXMTX),),),),chloroquine chloroquine(氯喹氯喹氯喹氯喹),),),),h hydroxychloroquineydroxychloroquine(羟氯喹）羟氯喹）羟氯喹）羟氯喹）sulfasalazine(sulfasalazine(柳氮磺吡啶柳氮磺吡啶柳氮磺吡啶柳氮磺吡啶),),leflunomide leflunomide(来氟米特来氟米特来氟米特来氟米特)4.Antibodies and other biological agents 4.Antibodies and other biological agents(抗体及其他生物制剂抗体及其他生物制剂抗体及其他生物制剂抗体及其他生物制剂)：Active TCM components Active TCM components(中药有效成分中药有效成分中药有效成分中药有效成分,尚未进入国际药物分类尚未进入国际药物分类尚未进入国际药物分类尚未进入国际药物分类)：tripterygium tripterygium glycosides(雷公藤总苷雷公藤总苷雷公藤总苷雷公藤总苷)Analgesic drugsOpioid analgesics Opioid analgesics(centrally acting)(centrally acting)opiatesopiates synthetic agentssynthetic agentsAntipyretic,analgesic,and anti-inflammatory Antipyretic,analgesic,and anti-inflammatory drugs drugs(peripherally acting)(peripherally acting)aspirin,indomethacinaspirin,indomethacinOther drugs Other drugs(for special types of pain)(for special types of pain)carbamazepine,carbamazepine,atropine,atropine,nitroglycerin,nitroglycerin,etc.etc.Bone metabolism-regulating drugs HormonesHormones（激素类）（激素类）（激素类）（激素类）e estrogensstrogens（雌激素类）（雌激素类）（雌激素类）（雌激素类）：diethylstilbestroldiethylstilbestrol（己烯雌酚）（己烯雌酚）（己烯雌酚）（己烯雌酚）androgensandrogens（雄激素类）（雄激素类）（雄激素类）（雄激素类）：TestosteroneTestosterone（睾酮）（睾酮）（睾酮）（睾酮）parathyroid hormoneparathyroid hormone（甲状旁腺激素，（甲状旁腺激素，（甲状旁腺激素，（甲状旁腺激素，PTHPTH）and teriparatideand teriparatide（特特特特立帕肽立帕肽立帕肽立帕肽）,calcitonin,calcitonin（降钙素）（降钙素）（降钙素）（降钙素）DiphosphonatesDiphosphonates（双膦酸盐类药物（双膦酸盐类药物（双膦酸盐类药物（双膦酸盐类药物 ）alendronate sodiumalendronate sodium（阿仑膦酸钠（阿仑膦酸钠（阿仑膦酸钠（阿仑膦酸钠 ）Calcium and Vitamin DCalcium and Vitamin D3 3（钙及维生素（钙及维生素（钙及维生素（钙及维生素D D3 3）OthersOthers GlucosamineGlucosamine（氨氨氨氨基基基基葡葡葡葡萄萄萄萄糖糖糖糖）,chondroitin chondroitin sulfatesulfate（硫硫硫硫酸酸酸酸软软软软骨骨骨骨素素素素）,fluoridesfluorides（氟化物）（氟化物）（氟化物）（氟化物）Calcium and phosphate metabolism in the body and the regulationCalcium and phosphate metabolism in the body and the regulationparathyroid hormone(PTH),Calcitonin(CT)parathyroid hormone(PTH),Calcitonin(CT)，1,25(OH)1,25(OH)2 2 D D3 3(D),fibroblast growth (D),fibroblast growth factor 23(FGF23)factor 23(FGF23)Antibacterial drugs Agents against streptococcalAgents against streptococcal （链球菌）（链球菌）（链球菌）（链球菌）infectionsinfections Penicillins Penicillins（青霉素类）（青霉素类）（青霉素类）（青霉素类）：penicillin Gpenicillin G(benzylpenicillin,benzylpenicillin,苄青霉素苄青霉素苄青霉素苄青霉素)CepharosporinsCepharosporins（头孢菌素类）（头孢菌素类）（头孢菌素类）（头孢菌素类）MacrolidesMacrolides（大环内酯类）（大环内酯类）（大环内酯类）（大环内酯类）：erythromycin erythromycin(红霉素红霉素红霉素红霉素)LincomycinsLincomycins（林可霉素类）（林可霉素类）（林可霉素类）（林可霉素类）Quinolones Quinolones(喹诺酮类喹诺酮类喹诺酮类喹诺酮类)Sulfonamides Sulfonamides(磺胺类磺胺类磺胺类磺胺类)Gout suppressantsColchicineColchicine (秋水仙碱秋水仙碱秋水仙碱秋水仙碱):relievrelievinging the pain and inflammation of gouty arthritis the pain and inflammation of gouty arthritisIndomethacin Indomethacin(吲吲吲吲哚哚哚哚美美美美辛辛辛辛)and and other other NSAIDs NSAIDs(except(except aspirin,salicylates and tolmetin)aspirin,salicylates and tolmetin):inhibiting urate crystal phagocytosisinhibiting urate crystal phagocytosis (尿酸结晶体吞噬尿酸结晶体吞噬尿酸结晶体吞噬尿酸结晶体吞噬)Probenecid Probenecid(丙磺舒丙磺舒丙磺舒丙磺舒)and sulfinpyrazone and sulfinpyrazone(磺吡酮磺吡酮磺吡酮磺吡酮):decreasing decreasing reabsorption reabsorption of of uric uric acid acid in in the the proximal proximal tubule,tubule,thereby thereby accelerating accelerating uric uric acid acid excretionexcretion (uricosuric drugs,尿尿尿尿酸酸酸酸促促促促排排排排剂剂剂剂)Allopurinol Allopurinol(别嘌醇别嘌醇别嘌醇别嘌醇)and febuxostat:and febuxostat:Inhibiting xanthine oxidase,thereby reducing uric acid synthesisInhibiting xanthine oxidase,thereby reducing uric acid synthesis3.Drug treatment of rheumatic diseases(1)Rheumatoid arthritis(RA,类风湿关节炎类风湿关节炎类风湿关节炎类风湿关节炎)(2)Systemic lupus erythematosus(SLE,系系系系统红斑狼疮统红斑狼疮统红斑狼疮统红斑狼疮)(3)Osteoarthritis(OS,骨关节炎骨关节炎骨关节炎骨关节炎)(4)Rheumatic fever(RF,风湿热风湿热风湿热风湿热)3.Drug treatment of rheumatic diseases(1)Rheumatoid arthritis(RA)Key pathological changes in the synovium in rheumatoid arthritisKey pathological changes in the synovium in rheumatoid arthritisTreatment of symptomsAnalgesics reduce painNon-steroidal antiinflammatory drugs Non-steroidal antiinflammatory drugs(NSAIDs)lessen pain and stiffness(NSAIDs)lessen pain and stiffness NSAIDs have lost their historical role as first-line treatment NSAIDs have lost their historical role as first-line treatment because of concerns about their limited effectiveness,inability because of concerns about their limited effectiveness,inability to modify the long-term course of disease,and gastrointestinal to modify the long-term course of disease,and gastrointestinal and cardiac toxic effects.These agents should be given with and cardiac toxic effects.These agents should be given with proton-pump inhibitors for gastroprotection,with short-acting proton-pump inhibitors for gastroprotection,with short-acting drugs administered for short periods to minimise risks.drugs administered for short periods to minimise risks.(1)Rheumatoid arthritis(RA)(1)Rheumatoid arthritis(RA)Disease-modifying antirheumatic drugs(DMARDs)A heterogeneous collection of agents grouped together by use and convention.They are the mainstay of treatment for rheumatoid arthritis.Their diverse mechanisms of action are incompletely understood.They reduce joint swelling and pain,decrease acute-phase markers,limit progressive joint damage,and improve function.Methotrexate(MTX)Methotrexate(MTX)is the dominant DMARDis the dominant DMARD.Sulfasalazine(Sulfasalazine(柳氮磺吡啶柳氮磺吡啶柳氮磺吡啶柳氮磺吡啶)and leflunomide()and leflunomide(来氟米来氟米来氟米来氟米特特特特)are also widely used.Their efficacy has been are also widely used.Their efficacy has been established in placebo-controlled trials.established in placebo-controlled trials.Hydroxychloroquine(Hydroxychloroquine(羟氯喹羟氯喹羟氯喹羟氯喹)and chloroquine)and chloroquine(氯喹氯喹氯喹氯喹)have DMARD-like propertieshave DMARD-like properties.Gold(sodium aurothiomalate)and Gold(sodium aurothiomalate)and cyclosporin cyclosporin are additional DMARDsare additional DMARDsTheir use is limited by toxic effects.Their use is limited by toxic effects.(1)Rheumatoid arthritis(RA)Evolution of RA drug treatmentEvolution of RA drug treatment(1)Rheumatoid arthritis(RA)Biological agents TNF TNF inhibitorsinhibitors etanerceptetanercept (依那西普依那西普依那西普依那西普),),infliximabinfliximab (英夫利英夫利英夫利英夫利西单抗西单抗西单抗西单抗),),adalimumabadalimumab (阿达木单抗阿达木单抗阿达木单抗阿达木单抗)were the first licensed were the first licensed biological agents,followed bybiological agents,followed by abataceptabatacept (阿巴西普阿巴西普阿巴西普阿巴西普,CTLA-Ig),CTLA-Ig),rituximabrituximab (利妥昔单抗利妥昔单抗利妥昔单抗利妥昔单抗),),and and tocilizumabtocilizumab:they are they are highly effective.highly effective.Effects of biological agents can be especially striking in Effects of biological agents can be especially striking in the subset of inadequately treated or non-responsive the subset of inadequately treated or non-responsive patients selected for trials.patients selected for trials.(1)Rheumatoid arthritis(RA)(1)Rheumatoid arthritis(RA)ACR50 responses in trials of DMARDs and biological agentsACR50=50%improvements in five of the seven measures of American College of Rheumatology criteria.Error bars=95%CIs.trials of individual drugstrials of individual drugsmeta-analysismeta-analysisGlucocorticoids(GCs)Short-term GCs reduce synovitisLong term GCs decrease joint damage GCS can be especially useful in two settings:GCS can be especially useful in two settings:Short-term useShort-term use during flare-ups in disease can lead to during flare-ups in disease can lead to rapid improvement and allow other treatmentssuch as rapid improvement and allow other treatmentssuch as DMARDs,which have a slower onset of actionto be DMARDs,which have a slower onset of actionto be adjusted.Use of GCs in this way is low risk.adjusted.Use of GCs in this way is low risk.Intra-articular GCsIntra-articular GCs are a highly effective local treatment are a highly effective local treatment for individual active jointsfor individual active joints.(1)Rheumatoid arthritis(RA)Dosage of GCs in the treatment of RADosage of GCs in the treatment of RA(2)Systemic lupus erythematosus(SLE)(2)Systemic lupus erythematosus(SLE)Pharmacological management The main advances in the past decade in the conventional management The main advances in the past decade in the conventional management of SLE have included studies showing efficacy for of SLE have included studies showing efficacy for mycophenolate mycophenolate as an as an induction agent for lupus nephritis and the equivalent efficacy of low-induction agent for lupus nephritis and the equivalent efficacy of low-dose dose cyclophosphamidecyclophosphamide given every 2 weeks in comparison with the given every 2 weeks in comparison with the preceding National Institutes of Health protocol.preceding National Institutes of Health protocol.Many other immunosuppressives,such as Many other immunosuppressives,such as methotrexate,cyclosporin,methotrexate,cyclosporin,andand leflunomide,leflunomide,are used as steroid-sparing agents to treat SLE and are used as steroid-sparing agents to treat SLE and the other autoimmune rheumatic diseases.the other autoimmune rheumatic diseases.Glucocorticoids Glucocorticoids Changes gene expression,decreases pro-inflammatory Changes gene expression,decreases pro-inflammatory cytokines and adhesion molecules,and induces anti-infl cytokines and adhesion molecules,and induces anti-infl ammatory cytokinesammatory cytokines Rapid onset of action,dose dependent on degree of organ Rapid onset of action,dose dependent on degree of organ involvement(typically 560 mg daily)involvement(typically 560 mg daily)Substantial long-term side-effects including osteoporosis,Substantial long-term side-effects including osteoporosis,diabetes,and hypertension;major predictor of damage accrual diabetes,and hypertension;major predictor of damage accrual in systemic lupus erythematosus at 15 year follow-up.in systemic lupus erythematosus at 15 year follow-up.(2)Systemic lupus erythematosus(SLE)HydroxychloroquineHydroxychloroquine Changes lysosomal pH and has immunomodulative action Changes lysosomal pH and has immunomodulative action through changing activation of toll-like receptor.through changing activation of toll-like receptor.Effective for control of articular,cutaneous,and constitutional Effective for control of articular,cutaneous,and constitutional symptoms(eg,fatigue),usual dose 200400 mg per daysymptoms(eg,fatigue),usual dose 200400 mg per day Findings from a recent systematic review showed improved Findings from a recent systematic review showed improved disease activity,reduced mortality,and a modest effect on disease activity,reduced mortality,and a modest effect on thrombotic risk and damage accrual,potential beneficial effect thrombotic risk and damage accrual,potential beneficial effect on lipid profile and cardiovascular disease,safe for use in on lipid profile and cardiovascular disease,safe for use in pregnancypregnancy(2)Systemic lupus erythematosus(SLE)Azathioprine Purine analogue,inhibits synthesis of xanthylic and adenylic Purine analogue,inhibits synthesis of xanthylic and adenylic acids acids Used for active systemic disease including maintenance Used for active systemic disease including maintenance treatment of lupus nephritis,selective use as induction treatment of lupus nephritis,selective use as induction treatment for lupus nephritis,usual dose 13 mg/kg per day.treatment f