1. Thyroid hormones and antithyroid drugs Dept of Pharmacology Shi-Hong Zhang ( 张世红 ) shzhang713@zju.edu.cn

2. Front view Thyroid gland

3. Thyroid hormones 1. Uptake of iodide 2. Oxidation of iodide (peroxidase) and iodination and coupling of tyrosine 3. Formation of thyroxine (T 4 ) and triiodothyronine (T 3 ) from iodotyrosine 4. Secretion of thyroid hormones (proteolytic enzymes) 5. Regulation by thyroid stimulating hormone (TSH), T 4, T 3

6. 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

7. Hypothyroidism cretinism ( 呆小症 ) 瘿 simple goiter ( 单纯性甲状腺肿 )

10. Hyperthyroidism: – antithyroid drugs: thiourea derivatives 硫脲类 iodine and iodides 碘和碘化物  receptor antagonists Radioiodines 放射性碘 : 131 I Hypothyroidism: – thyroid hormones – iodine and iodides Therapeutic drugs on thyroid dysfunction

12. 丙硫氧嘧啶 卡比马唑 甲巯咪唑 Thiourea derivatives Antithyroid drugs

13. Thiourea derivatives 1. Pharmacological effects (1) Inhibiting the formation of thyroid hormones by interfering with iodination: inhibiting peroxidation, then the iodination and coupling Symptom relieving: 2-3 weeks Basic metabolic rate returning: 1-2 months (2) Inhibiting peripheral deiodination of T 4 : T 4  T 3  (propylthiouracil 丙硫氧嘧啶 ) Antithyroid drugs

14. Thiourea derivatives 1. Pharmacological effects (3) Inhibiting glucose metabolism by down- regulating βreceptor (4) Immunosuppression: TSI↓ Antithyroid drugs

15. Mechanism of inhibition of thyroid hormone synthesis by thioureas: Thioureas are oxidized by oxidized thyroid peroxidase (TPO)

16. 2. Clinical uses (1) Non-operative therapy of hyperthyroidism: latent period (2) Preoperative therapy of hyperthyroidism: combined with iodide (3) Thyrotoxic crisis: combined with larger dose of iodide, propylthiouracil 3. Adverse effects (1) Agranulocytosis (0.2%) (2) Hypersensitivity (3) GI reactions (5) Goitrogenic action (goiter): TSH↑ Thiourea derivatives

17. Iodine and iodides 1. Pharmacological effects (1) Small doses: simple goiter (2) Larger doses: inhibiting the release of thyroid hormones (proteolysis  ) and synthesis After iodide use, the thyroid vascularity is reduced, and the gland becomes much firmer, the cells become smaller. Antithyroid drugs

18. Mechanism of iodides

19. 2. Clinical uses (1) Simple goiter (2) Preoperative therapy of hyperthyroidism: combined with thiourea derivatives (2) Thyrotoxic crisis: combined with thiourea derivatives (propylthiouracil) Lugol’s solution 卢戈氏液 : 5% iodine and 10% potassium iodide Antithyroid drugs

20. 3. Adverse effects (1) Acute effects: hypersensitivity, angioedema, swelling of the larynx (2) Chronic intoxication (iodism) (3) Thyroid dysfunction: exacerbation of hyperthyroidism, goiter Antithyroid drugs

21. Radioiodines 131 I, 125 I, 123 I Destroying thyroid tissue: βray Careful use for hyperthyroidism and differentiated thyroid carcinoma Radioactive iodine uptake test Antithyroid drugs

22.  receptor antagonists 1. Pharmacological effects (1) Heart:  1 block (2) CNS: relieving anxiety (3) Presynaptic  2 receptor: NE release  2. Clinical uses Adjuvant therapeutic drug Antithyroid drugs

23. Pancreatic hormones & antidiabetic drugs

24. 胰高血糖素 胰岛素 生长抑素

25. Overview of Glucose Regulation by insulin 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

26. Different forms of diabetes mellitus

27. “Beta-cell failure” prediabetic metabolic syndrome

29. Complications of diabetes mellitus Acute complications –Diabetic ketoacidosis ( 酮症酸中毒 ) –Hyperosmotic nonketotic coma ( 高渗性非酮症性昏迷） Chronic complications –Cardiovascular diseases –Renal damage –Retinal damage –Nerve degeneration –Infection –Myopathy –etc.

31. Pharmacological therapy  Insulin  Oral hypoglycemic drugs  Insulin secretagogues ( 促胰岛素分泌药 ):  Sulfonylureas 磺酰脲类  Meglitinides (Non-SU) 格列奈类  GLP-1 agonists and DPP-4 inhibitors  Insulin sensitizers 胰岛素增敏剂 :  Thiazolidinediones (TDs ，噻唑烷二酮类 )  Biguanides 双胍类  α-glucosidase inhibitors α- 葡萄糖苷酶抑制剂  Amylin analogue 胰淀粉样多肽类似物  Aldose reductase inhibitor 醛糖还原酶

32. A. Insulin

33. Frederick Sanger (1918- )

34. A. Insulin 1. Pharmacological effects (1) Carbohydrate metabolism: reducing blood glucose levels by glycogenolysis , glycogen synthesis , gluconeogenesis  (ketone bodies  ), glucose transport . (2) lipid metabolism: fat synthesis , lipolysis , plasma free fatty acids  (3) Protein metabolism: active transport of amino acids , incorporation of amino acids into protein , protein catabolism  (4) Mechanism of insulin actions Interacting with insulin receptor

36. 2. Clinical uses (1) Insulin-dependent patients with diabetes mellitus (type 1 diabetes mellitus) (2) Insulin-independent patients: failure to other drugs (3) Diabetic complications: diabetic ketoacidosis ( 酮症 酸中毒 ), hyperosmotic nonketotic coma （高渗性非酮症性昏迷） (4) Critical situations of diabetic patients: fever, severe infection, pregnancy, trauma, operation (5) Others: promotion of K + uptake into the cells A. Insulin

37. 3. Preparations Fast-acting insulin Regular insulin 正规胰岛素 Monocomponent insulin 单组分胰岛素 Start working 0.5-1h after injection, reach peak 2-4h, and last 5-7h. A. Insulin

38. 3. Preparations Intermediate-acting insulin Neurtral protamine hagedorn (NPH) 中性精蛋白锌胰岛素 Isophane insulin 低精蛋白锌胰岛素 Globin zinc insulin 珠蛋白锌胰岛素 Start working 1-1.5h after injection, reach peak 8-12h, and last 24h. A. Insulin

39. 3. Preparations Long-acting insulin Protamine zinc insulin(PZI) 鱼精蛋白锌胰岛素 Start working 4-8h after injection, reach peak 14-20h, and last 24-36h. A. Insulin

40. 3. Preparations Mixed insulin Human insulin isophane 低精蛋白锌胰岛素 + Human insulin 人胰岛素 Start working 0.5h after injection, reach peak 2-12h, and last 16-24h. A. Insulin

41. 3. Preparations Fast-acting insulin analogs Insulin aspart 门冬胰岛素 Insulin lispro 赖脯胰岛素 Start working 5-15 minutes after injection, reach peak at 1h, and last ~4 hours. A. Insulin

42. 3. Preparations Super-long acting insulin analogs Insulin glargine 甘精胰岛素 Onsets 1-2 h after injection and continues to work for as long as 24 hours. Used to treat type 1 or type 2 diabetes mellitus. Less soluble than native human insulin at physiological pH, and precipitates in skin following subcutaneous injection, resulting in delayed absorption. A. Insulin

44. For patients who eat meals out, may consider use of an insulin pen. Most insulins now available as pen

45. Insulin Pump and Glucose Monitoring Insulin Pump – “Open Loop” Patient sets basal infusion rate and superimposed boluses Continuous Glucose Monitor “Closed Loop” insulin pump system is ultimate goal: infusion rate adjusted based on input from continuous glucose monitor.

46. 4. Adverse effects (1) Hypersensitivity: treated with H 1 receptor antagonist, glucocorticoids (2) Hypoglycemia: adrenaline secretion (sweating, hunger, weakness, tachycardia, blurred vision, headache, etc.), treated with 50% glucose (3) Insulin resistance: acute, chronic (4) Lipoatrophy and lipohypertrophy (5) Weight gain (6) Refractive errors (7) Edema A. Insulin

47. B. Oral hypoglycemic drugs  Insulin secretagogues （促胰岛素分泌药） :  Sulfonylureas 磺酰脲类  Meglitinides (Non-SU) 格列奈类 ( 苯丙胺酸衍生物 )  GLP-1 agonists and DPP-4 inhibitors  Insulin sensitizers 胰岛素增敏剂 :  Thiazolidinediones (TDs ，噻唑烷二酮类 )  Biguanides 双胍类  α-glucosidase inhibitors α- 葡萄糖苷酶抑制剂  Amylin analogue 胰淀粉样多肽类似物  Aldose reductase inhibitor 醛糖还原酶

48. Sulfonylureas （磺酰脲类） Tolbutamide (D860) 甲苯磺丁脲 Chlorpropamide 氯磺丙脲 Glibenclamide 格列本脲 ( 优降糖 ) Glipizide 格列吡嗪（美吡达） Gliclazide 格列齐特 ( 达美康 ) B. Oral hypoglycemic drugs

49. 1. Pharmacological effects 1) Increase insulin release: blocking ATP sensitive K + channel, Ca 2+ inflow  Sulfonylureas

50. 1. Pharmacological effects 2) Increase receptor affinity to insulin (long- term use) 3) Promote glucose uses 4) Increase sensitivity of  cells to glucose 5) Anti-uretic effect (Chlorpropamide 氯磺丙脲 ) 6) Anti-platelet effect (Gliclazide 格列齐特 ) Sulfonylureas

51. 2. Clinical uses (1) Insulin-independent diabetic patients (type 2): alone or combined with insulin (2) Diabetes insipidus ( 尿崩症 ): Chlorpropamide ( 氯磺丙脲 ): anti-uretic hormone (ADH)  Sulfonylureas

52. 3. Adverse effects (1) GI reactions (2) CNS reactions (3) Hypoglycemia: especially in elderly, hepatic or renal insufficiencies (4) Others: leukopenia ( 白细胞减少 ), cholestatic jaundice ( 胆汁郁积性黄疸 ), hepatic damage Sulfonylureas

53. 4. Drug interactions (1) Potentiation of hypoglycemic effects replacement in plasma protein binding: salicylic acid, sulfates, indomethacin, penicillin, warfarin, etc. inhibition of hepatic microsomal enzymes: chloramphenicol, warfarin (2) Attenuation of hypoglycemic effects induction of hepatic microsomal enzymes: phenytoin, phenobarbital, etc. interactions in pharmacodynamics: glucagon, thiazides, etc. Sulfonylureas

54. Act by binding to SUR1 on beta cells to promote insulin secretion. Repaglinide ( 瑞格列奈 ) and Nateglinide ( 那格列奈 ) are current agents in class. Major advantage is rapid onset and offset –Can dose just prior to meals with better post-prandial control –Fewer overnight lows –Ability to skip the dose if skip the meal. Efficacy for repaglinide appears to be similar to SU’s Non-SU Insulin Secretagogues

55. Hepatic metabolism permits use in patients with impaired renal function. Major side effect is hypoglycemia. Many drug interactions. Most concerning is gemfibrozil ( 吉非罗齐 ) which increases repaglinide ( 瑞 格列奈 ) concentration and may result in prolonged effect. Cost may be an issue (1 or 2 mg tabs: $122.09/month at drugstore.com) Non-SU Insulin Secretagogues

56. Exenatide ( 依可那肽 ): only available as injection Sitagliptin ( 西他列汀 ) GLP-1 agonists and DPP-4 inhibitors

57. Insulin sensitizers Thiazolidinediones (TZDs) 噻唑烷酮类化合物 Rosiglitazone 罗格列酮 Pioglitazone 吡格列酮 Biguanides （双胍类） Metformin 二甲双胍 B. Oral hypoglycemic drugs

58. 1. Pharmacological effects Selective agonists for nuclear peroxisome proliferator activated receptor-  (PPAR , 过氧化物酶 增殖体激活受体  ), increasing glucose transport into muscle and adipose tissue. (1) Lowering insulin resistance (2) Lipid metabolism regulation: TG, free fatty acid  (3) Preventive effects on diabetic complications (4) Improve  cell function Thiazolidinediones

60. 2. Clinical uses Used for treatment of insulin-resistant diabetic patients or type 2 patients; Delayed onset of action – takes 8-12 weeks to achieve maximal effect; Absence of hypoglycemia when used as monotherapy; No reliance on renal excretion Thiazolidinediones

61. 3. Adverse effects Edema: at higher doses and used with insulin, in older patients, patients with multiple medical problems, patients with underlying CAD or CHF Headache Myalgia ( 肌痛 ) GI reactions Hepatic damage (troglitazone). Contraindicated with Class III or IV heart failure or significant liver disease. Thiazolidinediones

62. 1. Pharmacological effects Increasing glucose uptake in fat tissues and anaerobic glycolysis in skeletal muscles Decreasing glucose absorption in gut and glucagon release 2. Clinical uses Mild insulin-independent patients with obesity Major advantages: Lack of weight gain; Absence of hypoglycemia; Low cost with generic prep. 3. Adverse effects Severe lactic acidosis, malabsorption of vitamin B 12 and folic acid Biguanides

63. Alpha-Glucosidase inhibitors Acarbose-Precose 阿卡波糖 Miglitol-Glyset 米格列醇 Voglibose 伏格列波糖 B. Oral hypoglycemic drugs

64. Alpha-Glucosidase inhibitors Acarbose is an oligosaccharide, whereas miglitol resembles a monosaccharide. Miglitol is fairly well-absorbed by the body, as opposed to acarbose. Reducing intestinal absorption of starch ( 淀粉 ), dextrin ( 糊精 ), and disaccharides ( 二糖 ) by inhibiting the action of intestinal brush border  -glucosidase. Acarbose also blocks pancreatic alpha-amylase ( 淀粉酶 ). Used for diabetes mellitus type 2, particularly with regard to postprandial hyperglycemia.

65. Must be taken at the start of main meals to have maximal effect. Efficacy will depend on the amount of complex carbohydrates in the meal. Absence of hypoglycemia when used as monotherapy. Side effects: gastrointestinal side effects such as flatulence and diarrhea; voglibose, in contrast to acarbose, has less of GI side effects and more economical. Alpha-Glucosidase inhibitors

66. Amylin analogues Mechanism of action: –Inhibits postprandial glucagon secretion, thereby reducing hepatic glucose production –Slows gastric emptying –Promotes satiety  reduces caloric intake Pramlintide (Symlin 普兰林肽 ) is the only amylin analog on the market As adjunct therapy for patients with type 1 or 2 diabetes to control postprandial glucose Increases the risk of severe hypoglycemia Main side effect is nausea. Riddle and Drucker. Diabetes Care 2006; 29:435-49. B. Oral hypoglycemic drugs

67. Alsose reductase –Aldose reductase activity increases in those tissues that are not insulin sensitive, including lenses, peripheral nerves and glomerulus. –Epalrestat ( 依帕司他 ) inhibits aldose reductase. –Delay the progression of diabetic neuropathy and ameliorate the associated symptoms of the disease. B. Oral hypoglycemic drugs

68. Mechanism of ActionClass of AgentIndications for Use Stimulators of insulin secretionSulfonylureas Glinides Primary Insulin sensitizersThiazolidinediones (PPAR agonists) Primary or Secondary Suppressors of hepatic glucose production BiguanidesPrimary or Secondary Reduces postprandial glucose excursion Alpha-glucosidase Inhibitors Glinides Secondary Enhance incretin/GLP1 actionGLP1 analogs DPPIV inhibitors Secondary B. Oral hypoglycemic drugs

69. Type II Diabetic Medications MedicationSite of Action/Mechanism Side-Effects Sulfonylurea (eg. glyburide) Augments insulin secretion, binds SUR Hypoglycemia, caution renal insufficiency, elderly Thiazolidinediones (eg. rosiglitazone) PPARg receptor/increased insulin sensitivity Liver, LE edema, congestive heart failure, MI Biguanide (metformin)Reduced hepatic gluconeogenesis GI upset, Lactic acidosis (very rare), only use if creatinine<1.5 mg/dl Glinides (repaglinide)Bind SUR, short actionHypoglycemia, caution in renal insufficiency Alpha-glucosidase inhibitors (acarbose) Inhibits brush border enzyme/Reduce glucose absorption Flatulence, diarrhea Incretins/GLP-1 (exenatide)Stimulates insulin, delays gastric emptying, satiety Nausea, vomiting (given by injection) DPP4 Inhibitors (vildagliptin) Inhibits GLP1 breakdownGI side effects

70. Adrenocorticoids & adrenocortical antagonists

71. Adrenocortical hormones –Glucocorticoids (Glucocorticosteroids) –Mineralocorticoids –Sex hormones

72. Structure and function of adrenal cortex Zona Reticularis Adrenaline Zona Faseciculata Androgens

73. ACTH Regulation of glucocorticoids ‒

75. Basic structure of glucocorticoid drugs AB CD 甾体结构 H A. Glucocorticoid drugs 1 2 3 4 5 6 7 8 9 10 12 13 14 15 16 18 19

76. Structure (1) 1 位和 2 位碳之间改成不饱和的双键 : cortisone  prednisone; hydrocortisone  prednisolone. (2) 16  引入羟基 : triamcinolone( 曲安西龙 ). (3) 6  引入甲基 : 6  -methylprednisone (6  甲基泼尼松 ). (4) 9  引入氟原子 : fludrocortosone ( 氟氢可的松 ). 1 2 3 4 5 6 7 810 9 12 13 14 15 16 18 19 A B C D 基本结构 H A. Glucocorticoid drugs

77. H Cortisone ( 可的松 ) Prednisone ( 泼尼松 ) ( 地塞米松 ) Hydrocortisone ( 氢化可的松, Cortisol) Prednisolone ( 泼尼松龙 ) Fluocinolone ( 氟轻松 )

78. 2. ADME and properties of commonly used drugs Cortisone and prednisone are reduced and transformed to hydrocortisone and prednisolone (active forms) in the liver Metabolism will be increased by hepatic enzyme inductors (phenobarbital, phenytoin, rifampine, etc.) A. Glucocorticoid drugs

79. Commonly used drugs 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 Long-acting: dexamethasone 地塞米松 Topical: fluocinolone 氟轻松 A. Glucocorticoid drugs

82. binding to glucocorticoid receptor (GR) nuclear translocation binding to GRE or nGRE regulating related gene transcription biological effects (usually slow) A. Glucocorticoid drugs Mechanisms of glucocorticoid actions

83. Genetic action mode of glucocorticoid drugs CBG: corticosteroid binding globulin S: glucocorticoid steroids GR: glucocorticoid receptor HSP: heat shock protein IP: immunophilin GRE: glucocorticoid-response element

84. Nuclear translocation of glucocorticoid receptors (GR) Dexamethasone

85. Examples of glucocorticoid actions: Inhibition of proinflammatory gene transcription (AP-1 and NF  B)

86. 1. Pharmacological effects (1) Effects on metabolism (2) Permissive action (3) Anti-inflammatory effects (4) Effects on immune and allergy (5) Anti-shock (6) Other effects antipyretic effects effects on blood and blood-forming organs skeletal system CNS effects A. Glucocorticoid drugs

87. (1) Effects on metabolism ① Glucose metabolism: gluconeogenesis , glucose oxidation and utilization   blood glucose . ② Protein metabolism: synthesis , degradation . ③ Lipid metabolism: plasma cholesterol , fat redistribution (central obesity: moon face, buffalo hump, etc.). ④ Water and electrolytic metabolism: Na+ excretion , K+ excretion , Ca2+ excretion  and absorption . A. Glucocorticoid drugs

88. Weaker action of glucocorticoid drugs (cortisol 氢化可的松 ) on mineralocorticoid receptor

89. (2) Anti-inflammatory effects 1) Acute a) Increasing anti-inflammatory proteins and enzymes inducing lipocortin ( 脂皮素 ), inhibiting phospholipase A 2 activity, decreasing mediators: PGs, LTs, PAF inducing vasocortin ( 血管内皮素 ), decreasing microvascular permeability inhibiting the expression of COX-2, inducible NOS, etc. b) Inhibiting cytokines: decreasing the transcription and activities of TNFα, IL-1, IL-2, IL-5, IL-6, IL-8, etc. c) Inhibiting adhesion molecules d) Inducing apoptosis of inflammatory cells A. Glucocorticoid drugs

90. (2) Anti-inflammatory effects Chronic: inhibiting fibroblast proliferation deposition of collagen cicatrization ( 瘢痕形成 ) A. Glucocorticoid drugs

91. Inhibition of proinflammatory gene transcription (AP-1 and NF  B)

92. (3) Suppressive effects on immune and allergy a) inducing apoptosis of T and B lymphocytes b) inducing DNA degradation of T and B lymphocytes c) Inhibiting DNA and protein synthesis of T and B lymphocytes d) inhibiting transcription factor activity (eg. AP-1, NF-  B e) Inhibiting mast cells (anti-allergic) (4) Permissive action Potentiating the effects of catecholamines and glucagon A. Glucocorticoid drugs

93. (5) anti-shock a) improving cardiovascular functions b) inhibiting the production of inflammatory factors c) stabilizing lysosome membrane: decreasing the release of myocardial depressant factor (MDF) d) increasing the tolerance to endotoxin from bacteria A. Glucocorticoid drugs

94. (6) Other effects a) antipyretic effects b) effects on blood and blood-forming organs red cell  ; lymphocytes  ; neutrophils  (function  ); eosinophils  ; platelets  c) skeletal system: osteoporosis d) CNS: increasing excitability (elevated mood, euphoria, insomnia, restlessness, increased motor activity) A. Glucocorticoid drugs

95. 3. Clinical uses (1) Immune diseases a) autoimmune disorders: rheumatic fever, rheumatic carditis, rheumatic arthritis, rheumatoid arthritis, osteoarthritis, systemic lupus erythematosus, polyarthritis nodosa, nephritic syndrome, etc. b) rejection of organ transplantation c) allergic diseases: urticaria ( 风疹 ), serum sickness, contact dermatitis, drug allergic reactions, chronic severe asthma, status asthmaticus, angioneurotic edema, etc. A. Glucocorticoid drugs

96. 3. Clinical uses (2) Severe infection and inflammation a) acute severe infections: merely suppressing inflammatory manifestations but at times lifesaving Caution: ① combination with effective anti-microbial drugs; ② Large dose; ③ short term administration ! Usually be not used in viral and fungal infections except for those with cerebral edema or severe systemic symptoms b) prevention of sequelae ( 后遗症 ) of some types of inflammation, such as in brain, heart, eye, joint, etc. A. Glucocorticoid drugs

97. 3. Clinical uses (3) Septic shock: Caution: larger dose, short-term, and combined with antimicrobial drugs. (4) Hemological diseases: acute lymphocytic leukemia, lymphomas, aplastic anemia ( 再生障碍性贫血 ), hemolytic anemia, leukocytopenia, thrombocytopenia, etc. (5) Topical applications: skin, eye, respiratory tract, joint (local injection) (6) Some types of tumors: breast and prostatic cancers, acute lymphocytic leukemia, etc. A. Glucocorticoid drugs

98. 4. Adverse effects (1) Effects resulting from continued used of large doses a) Hypercorticism-like syndrome: central obesity (moon face, buffalo hump, etc.); hypertension; glycosuria, hypokalemia; etc. b) Increasing susceptibility to infections: Caution: specific antimicrobial drugs should be administered with GCs c) Ingestive system: peptic ulcers, etc. A. Glucocorticoid drugs

99. 4. Adverse effects d) Cardiovascular system: hypertension, arteriosclerosis e) Myopathy and osteoporosis: vertebral compression fractures, spontaneous fractures, especially in postmenopausal women f) CNS: behavioral disturbances, induction of epileptic seizures g) Inhibition or arrest of growth in children A. Glucocorticoid drugs

101. Suppression of hypothalamic- pituitary-adrenal axis and glucocorticoid drugs ‒ ACTH

102. 4. Adverse effects (2) Withdrawal syndrome a) Suppression of hypothalamic-pituitary-adrenal axis b) Exacerbation of the underlying diseases (rebound) (3) Contraindications psychiatric disorders; epilepsy; active peptic ulcers; fractures; hypercorticism; severe hypertension; diabetes mellitus; viral or fungal infections, etc. A. Glucocorticoid drugs

103. Balance the ratio of benefit/risk before the use of GCs !

104. 5. Applications (1) Replacement therapy: usually using hydrocortisone (2) Prompt intensive treatment: i.v. gtt hydrocortisone, dexamethasone (3) Long-term therapy: oral prednisone or prednisolone morning single dose alternate-day therapy Notes: for less severe and less sustained patients; less suppression on hypothalamic-pituitary- adrenal (HPA) axis (4) Typical applications: skin; eye; respiratory tract A. Glucocorticoid drugs

105. Some indications for the use of glucocorticoids

107. Aldosterone 醛固酮 Roles: Na + excretion , K + excretion  edema hypertension hypokalemia, etc. Used for adrenocortical dysfunction with imbalance of water and electrolytes B. Mineralocorticoid drugs

108. Action of aldosterone on mineralocorticoid receptor

109. Mineralocorticoid receptor signal transduction. MR: mineralocorticoid receptor; HRE: hormone responsive element. AIP: Aldosterone induced protein AIP

110. Adrenocorticotropic hormone (ACTH) 1.Used for diagnosis of adrenocortical function 2.inhibition of secretion of adrenocortical hormones after long-term glucocorticoid drug use 3.Easily inducing allergy to ACTH C. Adrenocorticotropic hormone and corticosteroid synthetase inhibitors

112. 2. Corticosteroid synthetase inhibitors Mitotane 米托坦 Metyrapone 美替拉酮 Aminoglutethimide 氨鲁米特 Used for adrenocortical tumors or hypercorticism C. Adrenocorticotropic hormone and corticosteroid synthetase inhibitors