课件：内分泌系统药理.ppt

Drugs affecting endocrine system,Shi-Hong Zhang 张世红 ,1,Thyroid hormones and antithyroid drugs（甲状腺激素及抗甲状腺药，1课时） Insulin and oral hypoglycemic drugs（胰岛素和口服降糖药，1.5课时） Adrenocorticoids （肾上腺皮质激素类药物，1.5 课时）,Contents,2,甲状腺激素及抗甲状腺药Thyroid hormones and antithyroid drugs,Shi-Hong Zhang (张世红) ,Front view,Thyroid gland,甲状腺素的生物合成,摄取碘 碘经氧化而活化（I+），碘化甲状腺球蛋白（TG）中的酪氨酸残基，生成MIT和DIT (peroxidase mediated) MIT、DIT偶联生成T4和 T3 (peroxidase mediated) 甲状腺球蛋白水解，释放T3、T4 (proteolytic enzymes) 5. 受促甲状腺激素 (TSH)、 T4、 T3的调节,三碘甲状腺原氨酸,四碘甲状腺原氨酸,甲状腺激素分泌的调节,甲状腺素的生理作用,1维持正常生长发育 2促进代谢和产热 3提高交感神经系统的反应性,甲状腺功能低下Hypothyroidism,Cretinism (呆小症),瘿,simple goiter (单纯性甲状 腺肿),Hypothyroidism After treatment,甲状腺功能亢进Hyperthyroidism,颤抖,腱反射亢进,心慌，心脏肥大,甲状腺肿大，突眼，情绪激动,多食、腹泻、消瘦,甲状腺危象Throid crisis（storm）,恶心、呕吐 高热 无力、头昏、昏迷 低血钾 心律失常、心衰、休克,碘及碘化物 (small doses)：补碘 甲状腺激素,甲状腺功能低下的药物治疗,甲状腺激素的临床应用 1. 补充疗法：呆小病；甲状腺功能低下（黏液性水肿，不典型及亚临床型甲状腺功能减退）；甲状腺癌切除术后；单纯性甲状腺肿；甲亢内科治疗期间。 2. T3抑制试验：服用T3后摄碘率下降50%者为单纯性甲状腺肿， 50%者为甲亢,抗甲状腺药（antithyroid drugs） Thiourea derivatives 硫脲类 Iodine and iodides 碘和碘化物 （大剂量） receptor antagonists Radioiodines 放射性碘: 131I,甲状腺功能亢进的药物治疗,丙硫氧嘧啶 PTU,卡比马唑，甲亢平,甲巯咪唑，他巴唑 MMI,Thiourea derivatives,抗甲状腺药,硫脲类,1. 药理作用和机制 (1) 抑制甲状腺过氧化物酶：竞争性被氧化，进而抑制酪氨酸碘化和偶联过程 症状改善：2-3 weeks 基础代谢率恢复正常： 1-2 months (2) 抑制外周组织的 T4 T3 (propylthiouracil 丙硫氧嘧啶) 减轻重症甲亢和甲状腺危象 (3) 减弱受体介导的糖代谢：减少心肌、骨骼肌的受体数目 (4) 免疫抑制作用：减少甲状腺刺激性免疫球蛋白TSI生成（slight）,硫脲类,2. 临床应用 (1) 甲亢的内科治疗: 疗程1-2y (2) 甲亢手术前准备: PTU，结合大剂量碘剂 (3) 甲状腺危象的治疗: PTU，结合大剂量碘剂 3. 不良反应 过敏反应 ：最常见 粒细胞缺乏症 (0.2% or more)：最严重 GI 反应 甲状腺肿(goiter): TSH，组织增生充血 甲状腺功能减退 哺乳和妊娠妇女禁用（PTU除外）。结节性甲状腺肿及甲状腺癌禁用,硫脲类,1. 药理作用 (1) 小剂量: 单纯性甲状腺肿 (2) 短期大量使用: 抑制甲状腺激素的合成和释放（抑制TSH，抑制GSH还原酶使甲状腺球蛋白对水解酶不敏感，抑制过氧化物酶，减少酪氨酸的碘化和偶联），长期使用作用消失。 腺体缩小变韧，血管减少,碘及碘化物,复方碘溶液（卢戈液），碘酸钾，碘化钾（钠）,2. 临床应用 (1) 单纯性甲状腺肿（小剂量） (2) 甲亢的手术前准备: 结合硫脲类药物(PTU) (3) 甲状腺危象: 结合硫脲类药物(PTU) 3. 不良反应 粘膜刺激症状 ，水肿 过敏反应 甲状腺功能紊乱,碘及碘化物,1. 药理作用 (1) Heart: 1 block (2) CNS: 镇静作用 (3) Presynaptic 2 receptor: NE release (4) Decrease T3: 抑制T4脱碘 2. 临床应用 甲亢的辅助治疗和术前准备；甲状腺危象的紧急处理, receptor antagonists,21,131I, 125I, 123I 破坏甲状腺组织: ray，射程短 适用于不宜手术或手术后复发及硫脲类无效或过敏的甲亢患者。 甲状腺摄碘功能的检测（射线）,放射性碘（Radioiodines）,Case report,A 47-year-old woman consulted her physician because of heart palpitations, tremulousness, weight loss and heat tolerance. Examination: heart rate 110, BP 150/70, diffusely enlarged thyroid glands, wide-eyed stare, lid lag, FT4 40 pmol/L (normal: 10-31), FT3 10.6 pmol/L(normal: 4-10), TSH undetectable (2-10 mU/L), TSI. The diagnosis was Gravess disease.,Case report,Continued She was started on treatment with propranolol, 40 mg tid, propylthiouracil (丙硫氧嘧啶) 200 mg bid. She became euthyroid (甲状腺功能正常) in 6 weeks, and the propranolol dose was gradually reduced and finally discontinued. She continued receiving a maintenance dose of propylthiouracil (50 mg bid) for 1 year, after which the drug was discontinued.,Case report,Continued The symptoms of hyperthyroidism recurred 3 years later, and treatment with propranolol and propylthiouracil was reinitiated. However, she developed severe rash over her whole body. Therefore, the treatment was changed with oral Na131I for definitive control of her hyperthyroidism.,Case report,Continued Three months later, the patient complained of lethargy, tiredness, a feeling of coldness at room temperature, puffiness (肿胀) around the eyes, and constipation. Laboratory testes showed lowered level of T4 and T3, but elevated level of TSH, confirming the diagnosis of hypothyroidism. She was started on levothyroxine 0.1 mg daily, and 6 weeks later, her complaints disappeared. She has remained well on this therapy.,胰岛素及其他降血糖药 Insulin & antidiabetic drugs,Shi-Hong Zhang 张世红 ,胰高血糖素 胰岛素 生长抑素,胰岛素与糖代谢,Amended from Dinneen SF. Diabetes Med. 1997;14(suppl 3):S19-24.,Insulin secretion,Glucose disposal ,Persistent hepatic glucose output ,Glucose absorption,Lipogenesis,Lipolysis,Glycogenesis ,糖尿病的分型,“Beta-cell failure”,prediabetic metabolic syndrome,糖尿病的症状,糖尿病的并发症,急性并发症 Diabetic ketoacidosis (酮症酸中毒) Hyperosmotic nonketotic coma (高渗性非酮症性昏迷） 慢性并发症,药物治疗,胰岛素（insulin） 口服降糖药 双胍类（biguanides ） 促进胰岛素分泌的药物 磺酰脲类（sulfonylureas，SUs） 格列奈类（meglitinides，Non-SUs） GLP-1 (胰高血糖素样肽-1) agonists and DPP-4 inhibitors 胰岛素增敏药：噻唑烷二酮类（thiazolidinediones, TZDs) -葡萄糖苷酶抑制剂 -glucosidase inhibitors Amylin analogue 胰淀粉样多肽类似物,Insulin胰岛素,Frederick Sanger (1918- 2013),Insulin,1. 药理作用 (1) 糖代谢: 糖原分解 ，糖原合成, 糖异生 , 转运和氧化，降低血糖水平 (2) 脂肪代谢：脂肪合成，分解，游离脂肪酸，酮体 (3) 蛋白质代谢：氨基酸转运和蛋白质合成，蛋白分解 (4) 加快心率，加强心肌收缩力，减少肾血流 (5) 促进钾离子进入细胞,Mechanism of insulin actions: Interact with insulin receptors,2. 临床应用 (1) 1型糖尿病 (2) 2型糖尿病：血糖极高的初始治疗者、经其他治疗血糖未能控制者 (3) 严重或急性糖尿病并发症: 酮症酸中毒，高渗性非酮症性昏迷 (4) 糖尿病合并其他严重情况：高热，严重感染，妊娠，创伤，手术等 (5) 细胞内缺钾：严重心肌缺血、强心苷中毒等,Insulin,3. 胰岛素制剂 （1）速效胰岛素 Regular insulin 正规胰岛素（RI） Monocomponent insulin 单组分胰岛素（McI） Lispro insulin 赖脯胰岛素（颠倒B28、29脯赖顺序） 溶解度高 可静脉注射（or 雾化吸入，Afrezza） 起效快，作用时间短（0.5-1h after injection, peak at 24h, last 8h） 可用于餐后血糖高者，重症糖尿病初治及严重并发症者,Insulin,3. 胰岛素制剂 （2）中效胰岛素 Neutral protamine Hagedorn (NPH, isophane insulin ) 中性精蛋白锌胰岛素 Globin zinc insulin （GZI）珠蛋白锌胰岛素 Start working 1-1.5h after injection, peak at 8-12h, and last 1824h.,Insulin,3. 胰岛素制剂 （3）长效胰岛素 Protamine zinc insulin (PZI) 精蛋白锌胰岛素 Insulin glargine甘精胰岛素 （B链C端加两个精氨酸，A21甘氨酸替代门冬酰胺） Insulin determir地特胰岛素（去除B30苏氨酸，B29赖氨酸加脂肪酸侧链） Start working 4-8h after s.c. injection, peak at 14-20h, and last 24-36h.,Insulin,胰岛素笔,4. 不良反应 (1) 低血糖：交感兴奋症状（sweating, hunger, weakness, tachycardia, blurred vision, headache, etc.), 严重者用iv 50% glucose治疗 (2) 过敏反应：治疗用H1 受体拮抗剂，糖皮质激素，并用人或高纯度胰岛素替代 (3) 胰岛素抵抗：acute, chronic (受体前、受体及受体后异常) (4) 脂肪萎缩：注射部位，用纯化制剂减少 (5) 其他：体重增加，屈光不正，水肿等,Insulin,Oral hypoglycemic drugs 口服降血糖药,Biguanides 双胍类,1. 药理作用 增加胰岛素敏感性，改善胰岛素抵抗，增加血糖转运和分解 抑制胰高血糖素的作用，减少肝糖原分解和糖异生 减少肠吸收葡萄糖,Metformin 二甲双胍 Phenformin苯乙双胍,2. 临床应用 2型糖尿病的一线用药，特别是肥胖及单用饮食控制无效者 对正常人血糖无影响，降低体重 降低心血管意外 价格实惠 3. 不良反应 胃肠道反应，乳酸酸中毒（苯乙双胍），肾功能不全、肝功能不全、严重感染、缺氧或接受手术者停用,Metformin,Tolbutamide (D860) 甲苯磺丁脲 Chlorpropamide 氯磺丙脲 Gliburide 格列本脲 （优降糖） Glipizide 格列吡嗪（美吡达） Gliclazide 格列齐特 （达美康） Glimepiride 格列美脲（亚莫利）,Oral hypoglycemic drugs 口服降血糖药,促胰岛素分泌剂,磺酰脲类（Sulfonylureas, SUs）,1. 药理作用 (1) 促进胰岛素分泌：阻断细胞ATP-sensitive K+ channel，增加Ca2+ 内流,Sulfonylureas,1. 药理作用 2) 增加胰岛素与其受体的结合能力 (long-term use) 3) 促进葡萄糖的利用以及合成糖原和脂肪 4) 抗利尿作用(氯磺丙脲/格列本脲) ：ADH 5) 抗血小板作用(格列齐特),Sulfonylureas,2. 临床应用 (1) 2型糖尿病：alone or combined with metformin or insulin (2) 尿崩症：氯磺丙脲,Sulfonylureas,3. 不良反应 (1) GI reactions (2) CNS reactions：嗜睡、眩晕 (3) 低血糖: 老年人，肝肾功能不全，黄疸，药物影响 (4) 其他: 白细胞减少，胆汁郁积性黄疸，肝脏损害，体重增加,与胰岛细胞上的SUR1结合促进胰岛素分泌 有Repaglinide (瑞格列奈) 和Nateglinide (那格列奈) 两种 疗效与SUs相似，但起效迅速（1h）t1/21h，适合餐时给药用于控制餐后血糖 与二甲双胍合用有协同作用 低血糖的不良反应弱于SUs 经胆汁排泄，适用于肾功能不全患者,格列奈类（Non-SU）,Oral hypoglycemic drugs 口服降血糖药,促胰岛素分泌剂,GLP-1: glucogons-like peptide 1， 依可那肽（Exenatide）：GLP-1 agonist，刺激胰岛素分泌（injection only） Sitagliptin (西他列汀), vildagliptin (维格列汀)：DPP-4（二肽基肽酶）抑制剂,GLP-1 agonists and DPP-4 inhibitors,促胰岛素分泌剂,Oral hypoglycemic drugs 口服降血糖药,1. 药理作用 PPAR (过氧化物酶增殖体激活受体)激活物 (1) 改善胰岛素抵抗，促进葡萄糖转运至肌肉和脂肪组织，降低血糖 (2) 改善脂肪代谢紊乱：TG, free fatty acid (3) 对血管并发症的防治作用: anti-platelet, renal protection, anti-atherosclerosis (4) 改善胰岛细胞功能,Thiazolidinediones噻唑烷二酮类,胰岛素增敏剂,Oral hypoglycemic drugs 口服降血糖药,2. 临床应用特点 用于治疗胰岛素抵抗和2型糖尿病 起效慢 （peak at 8-12 weeks ） 单用一般不引起低血糖 不依赖于肾脏排泄,Thiazolidinediones,3. 不良反应 水肿：见于高剂量、与胰岛素合用、老年人、病情复杂者等，与肾集合管的PPAR gama的激活导致重吸收减少有关 可能增加心血管事件（罗格列酮）和膀胱癌风险（吡格列酮） 嗜睡、头痛、肌痛 胃肠道反应 心衰及严重肝病者禁用。,Thiazolidinediones,Acarbose 阿卡波糖 Miglitol 米格列醇 Voglibose 伏格列波糖,Alpha-Glucosidase inhibitors -葡萄糖苷酶抑制剂,Alpha-Glucosidase inhibitors,阿卡波糖是一种低聚糖，很少被吸收；米格列醇类似于葡萄糖，吸收少 抑制小肠上段-glucosidase（葡萄糖苷酶），抑制寡糖分解为单糖，减少淀粉、糊精和双糖的吸收 阿卡波糖也抑制胰淀粉酶 进餐时服用，控制餐后高血糖。 单用不引起低血糖 不良反应包括胀气、腹泻,Amylin analogues 淀粉样多肽类似物,Pramlintide (Symlin普兰林肽) 作用机制 抑制胰高血糖素分泌 减慢胃排空，延缓葡萄糖吸收 增加饱腹感 用于T1DM和T2DM辅助治疗，不能代替胰岛素 增加发生严重低血糖风险 可引起关节痛、咳嗽、头痛、头晕,中国 2 型糖尿病防治指南（2013 年版）,Case report,A 45-year-old man first consulted his physician because of nocturia (夜尿), mild thirst, and some fatigue. At the time, he was somewhat overweight and sedentary (久坐) in his habits. Laboratory tests showed an elevated fasting blood glucose level of 15 mmol/L, glucose but no ketones in the urine. Diabetes was diagnosed and he was placed on diabetic diet low in free sugar and fat. Two months later, he was found to have higher fasting blood glucose, 2-hr postlunch glucose, glycosylated hemoglobin (HbA1C). Therefore, He was started on glyburide 5mg before breakfast and 5 mg before dinner, but the blood glucose remained elevated. The dosage was therefore raised to 10 mg twice daily, and this achieved a good result.,Case report,After 3 years, he developed unstable angina pectoris, and the blood glucose and HbA1C levels were again found to be elevated. Addition of metformin to his treatment produced some improvement, but his cardiac symptoms gradually worsened over the next 3 years. He showed intermittent glycosuria and proteinuria. His weight had fallen to a normal level. His physician therefore decided to transfer him to insulin therapy, started on a regimen of 22 units of Lente insulin and 12 units of regular insulin every morning before breakfast. The dosage was gradually raised to 35 units according to the glucose level in the blood and urine. During the next year he had three mild hypoglycemic reactions. He was found to have stable background retinopathy, mild nephropathy and mild numbness and tingling in both feet, but the blood pressure remained normal.,Adrenocorticoids 糖皮质激素类药物,65,肾上腺皮质的结构和功能,Zona Reticularis,Adrenaline,Zona Faseciculata,Androgens,66,ACTH,糖皮质激素的调节,促皮质激素释放激素,促肾上腺皮质激素,HPA axis,1. 基本结构,A,B,C,D,甾体结构,Glucocorticoid drugs,1,2,3,4,5,6,7,8,9,10,12,13,14,15,16,18,19,68,酮基,双键,羰基,1. 基本结构,(1) 1位和2位碳之间改成不饱和的双键 (抗炎作用增加，对糖代谢的影响增加，对电解质代谢下降): cortisone (可的松) prednisone (泼尼松，强的松); hydrocortisone (氢化可的松) prednisolone (泼尼松龙). (2) 16引入羟基 (抗炎作用增强): triamcinolone (曲安西龙). (3) 6引入甲基 (抗炎作用增强，作用时间延长): 6-methylprednisone (6甲基泼尼松). (4) 9引入氟原子 (抗炎和水钠潴留作用增强): fludrocortosone (氟氢可的松).,1,2,3,4,5,6,7,8,10,9,12,13,14,15,16,18,19,A,B,C,D,基本结构,Glucocorticoid drugs,69,Cortisone (可的松),Prednisone (泼尼松),(地塞米松),Hydrocortisone (氢化可的松, Cortisol),Fluocinolone (氟轻松),70,抗炎作用增强，持续时间延长,抗炎作用、水钠潴留增强,Prednisolone (泼尼松龙),Methylrednisolone (甲泼尼龙),抗炎作用增强,2. ADME 肝脏代谢 可的松在肝内代谢为氢化可的松；泼尼松代谢为有活性的泼尼松龙 肝药酶诱导剂增加代谢 (phenobarbital, phenytoin, rifampine, etc.),Glucocorticoid drugs,71,常用糖皮质激素类药物 Short-acting: hydrocortisone (cortisol) 氢化可的松 cortisone 可的松 Intermediate-acting: prednisone 泼尼松, 强的松 prednisolone 泼尼松龙, 强的松龙 methylprednisolone 甲泼尼龙 Long-acting: dexamethasone 地塞米松 Topical: fluocinolone 氟轻松,Glucocorticoid drugs,72,T1/2=812h,T1/2=1236h,T1/236h,73,胞浆糖皮质激素受体(GR) 转位到核内 与GRE or nGRE结合 调节基因转录 生物学效应( slow),Glucocorticoid drugs,糖皮质激素的作用机制,nGRE: negative GC response element,膜GR/细胞膜/受体外成分 胞内信号通路 生物学效应(fast),糖皮质激素的作用模式,CBG: corticosteroid binding globulin S: glucocorticoid steroids GR: glucocorticoid receptor HSP: heat shock protein IP: immunophilin GRE: glucocorticoid-response element,75,GR的核转位,地塞米松,76,糖皮质激素抑制促炎因子的基因转录（e.g，AP-1 and NFB),77,1. 药理作用 (1)对代谢的影响（糖、脂肪、蛋白质、水盐） (2)抗炎作用 (3)抑制免疫和过敏反应 (4)抗休克作用 (5)其他,Glucocorticoid drugs,78,(1) 对代谢的影响 1) 糖代谢: 糖异生，葡萄糖氧化利用 血糖. 2) 蛋白代谢: 合成, 分解 3) 脂肪代谢: 血浆胆固醇，脂肪重新分布 (向心性肥胖central obesity: 满月脸moon face, 水牛背buffalo hump, etc.). 4) 水盐代谢: Na+ 排泄, K+ 排泄, Ca2+ 排泄 重吸收,Glucocorticoid drugs,79,糖皮质激素 (cortisol氢化可的松) 对盐皮质激素受体的作用,80,(2) 抗炎作用 1) 急性炎症 a) 减少炎症介质产生 诱导脂皮素，抑制PLA2，减少PGs和LTs的产生，抑制COX-2和iNOS b) 抑制细胞因子和粘附分子的产生和功能: TNF, IL-1, IL-2, IL-5, IL-6, IL-8, etc. c) 诱导炎症细胞凋亡,A. Glucocorticoid drugs,81,(2) 抗炎作用 2) 慢性炎症: 抑制成纤维细胞增殖 抑制胶原蛋白合成 抑制瘢痕形成,Glucocorticoid drugs,82,(3) 抑制免疫和过敏反应 a) induce apoptosis of T and B lymphocytes b) induce DNA degradation of T and B lymphocytes c) Inhibit DNA and protein synthesis of T and B lymphocytes (inhibition of proliferation) d) inhibit transcription factor activity (eg. AP-1, NF-B) e) Inhibit mast cells (anti-allergic),Glucocorticoid drugs,83,(4) anti-shock effect 1) improve cardiovascular functions 2) inhibit the production of inflammatory factors 3) stabilize lysosome membrane: decrease the release of myocardial depressant factor (MDF) 4) increase the tolerance to endotoxin from bacteria (4) Permissive action: potentiate the effects of catecholamines and glucagon,Glucocorticoid drugs,84,(5) 其他作用 1）允许作用（permissive action）：增强其他激素的作用 2）解热作用 3）血液和造血器官 刺激骨髓造血功能，红细胞/血红蛋白、血小板、中性粒细胞（功能），淋巴细胞 4）骨骼: osteoporosis骨质疏松 5）CNS: 增加兴奋性（情绪高涨，欣快，失眠，精神失常，癫痫等）,Glucocorticoid drugs,85,3. Clinical uses (1) Immune diseases 1) autoimmune disorders: rheumatic fever, rheumatic carditis, rheumatic arthritis, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, polyarthritis nodosa, nephritic syndrome, etc. 2) rejection of organ transplantation 3) allergic diseases: urticaria (风疹), serum sickness, contact dermatitis, drug allergic reactions, chronic severe asthma, status asthmaticus, angioneurotic edema, etc.,Glucocorticoid drugs,86,3. 临床应用 (2) Severe infection and inflammation 1) acute severe infections: merely suppress inflammatory manifestations but at times lifesaving Caution: combination with effective antibiotic drugs; Large doses; short term administration ! Usually not used for viral and fungal infections except for those with cerebral edema or severe systemic symptoms 2) prevention of sequelae (后遗症) of some types of inflammation, such as in brain, heart, eye, joint, etc.,A. Glucocorticoid drugs,87,3. Clinical uses (3) Septic shock: Caution: larger dose, short-term, and combined with effective antibiotic drugs. (4) Hematological diseases: acute lymphocytic leukemia, lymphomas, aplastic anemia (再生障碍性贫血), hemolytic anemia, granulocytopenia, thrombocytopenia, etc. (5) Topical applications: skin, eye, respiratory tract, joint (local injection) (6) Replacement therapy,A. Glucocorticoid drugs,88,4. 不良反应 (1) 长期大剂量应用引起的不良反应 1) 医源性肾上腺皮质功能亢进（Hypercorticism-like syndrome）：向心性肥胖（满月脸，水牛背），皮肤变薄，多毛，水肿，高血压，糖尿病，低血钾等 2) 诱发和加重感染（esp. in pats. with low immune function） Caution: specific antibiotic drugs should be administered with GCs. Live virus vaccination! 3) 消化系统: 消化性溃疡、出血、穿孔.,Glucocorticoid drugs,89,4. 不良反应 4) 心血管系统：高血压、高脂血症、动脉粥样硬化 5) 骨质疏松、肌肉萎缩、伤口愈合延缓：影响儿童生长发育，骨质疏松导致脊柱压缩性骨折和自发性骨折（esp. in 老人、儿童和绝经后妇女），股骨头坏死 6) 糖尿病 7) CNS: 行为异常，诱发癫痫和精神病,Glucocorticoid drugs,90,91,4. 不良反应 (2) 撤药反应 1) HPA轴抑制（功能恢复可长达2年） 医源性肾上腺皮质功能减退，肾上腺皮质功能危象。 防治：缓慢停药，ACTH一周，必要时及时给予足量糖皮质激素 2) 反跳现象：原有疾病复发或恶化 (3) 禁忌症 精神疾病，癫痫，活动性消化性溃疡，骨折，肾上腺皮质功能亢进，高血压，糖尿病，病毒或真菌感染，etc.,A. Glucocorticoid drugs,92,Consider benefit/risk before the use of GCs !,93,5. 用法 (1)大剂量冲击疗法： i.v. gtt 氢化可的松，地塞米松 (2)小剂量替代疗法：口服氢化可的松 (3) 一般剂量长期疗法：口服泼尼松或泼尼松龙等 每日晨给药法 隔晨给药法 Notes: 保护HPA轴 (4) 局部用药：曲安奈德，倍氯米松等,Glucocorticoid drugs,94,Plasma glucocorticoids,95,Some indications for the use of glucocorticoids,荨麻疹,96,97,Case report,The patient was a 39-year-old male physician based at the intensive-care unit of a small hospital in Guangzhou, China, had no concurrent medical illness. Many patients with SARS were admitted to the hospital where he worked during the eight weeks before April 4, 2003, when he presented with a sore throat and a low-grade fever (37.3C). Five days later, he had a high fever (38.5C) and a low leukocyte count (3.4 109 per liter; 63.6% neutrophils and 26.2% lymphocytes), and he was admitted to the hospital with suspected SARS. /doi/pdf/10.1056/NEJM200307313490519,98,Case report,The patient was treated with twice-daily methylprednisolone (甲基强的松龙, 80 mg in the morning and 40 mg in the evening) for two days; the dose was decreased to 20 mg twice daily as the fever subsided on April 12. The fever recurred on April 14, and chest radiography showed an infiltrate in the left lower lobe; the leukocyte count was 13.5 109 per liter (94.0% neutrophils and 6.0% lymphocytes). Methylprednisolone was given again (20 mg in the morning and 80 mg in the evening), and the patient was transferred to a larger hospital on April 15.,99,Case report,Intravenous methylprednisolone therapy (80 mg twice daily) was then administered. The patients clinical condition improved; he had no fever and could walk without dyspnea. The infiltrate in the left lung diminished in density, and the dose of methylprednisolone was reduced to 40 mg twice daily on April 19. On April 29, the patient was again dyspneic, and radiographs showed a left basilar infiltrate. On May 4, the patient was transferred to a university teaching hospital. Methylprednisolone (240 mg twice daily) was given, but the next day the oxygen saturation fell to 60 percent, and endotracheal intubation was performed to allow mechanical ventilation.,100,Case report,The patient showed signs that were consistent with the presence of tentorial herniation (小脑幕疝); his pupils were fixed and dilated. Computed tomographic examination of the cranium showed diffuse cerebral edema with localized hemorrhage. Enzyme-linked immunosorbent assay and indirect immunofluorescence established the presence of specific antibodies against a SARS-associated virus in the serum. Despite massive supportive care, the patient died on May