Adrenocorticosteroids [ə,dri:nəu,kɔ:tikəu'stiərɔid] Chapter 30 Adrenocorticosteroids [ə,dri:nəu,kɔ:tikəu'stiərɔid] 肾上腺皮质激素类药 Shutcm-MBL 1

下丘脑 垂体 肾上腺 Control of secretion of glucocorticoids Kidney with adrenal gland Mineralocorticoid [,minərələu'kɔ:tikɔid] 盐皮质激素 Glucocorticoid 肾上腺 [,ɡlu:kəu'kɔ:tikɔid] 糖皮质激素 Control of secretion of glucocorticoids Shutcm-MBL

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Physiological actions of glucocorticoids Actions of glucocorticoids at doses corresponding to normal daily production levels 1 Metabolic effects on carbohydrate (increase serum glucose levels), protein (decrease protein synthesis and increase protein breakdown) , and lipid metabolism (redistribution of body fat); 2 Maintenance of fluid and electrolyte balance; 3 Preservation of normal function of the cardiovascular system, the immune system, the kidney, skeletal muscle, the endocrine system, and the nervous system. Shutcm-MBL

Pharmacological actions of glucocorticoids Effects seen only at doses exceeding the normal daily production of glucocorticoids 1. Anti- inflammatory actions Characteristics ① inhibit all kinds of inflammatory responses (radiant, mechanical, chemical, infectious, and immunological inflammation); ② suppress either acute or chronic inflammations; inhibit the formation of cicatrice ['sikətris]伤痕；[皮肤]瘢痕; ③ induce or aggravate infection and affect healing of wound. Shutcm-MBL

Pathophysiological process of inflammation Infection Inflammatory cell chemotaxis [,kemə‘tæksis] 趋化 Release of inflammatory mediators like IL, NO, PGs, TNF-α vasodilatation Injury and repair acute inflammation chronic inflammation

• Inhibition of phospholipase A2 [fɔsfəu'laipeis]磷脂酶; Mechanisms: • Inhibition of phospholipase A2 [fɔsfəu'laipeis]磷脂酶; • Stabilize the membranes of lysosome[‘laisəsəum]溶酶体; • Reduce the production and release of inflammatory mediators; • Reduce the number and activity of circulating immunocytes； • reduce capillary permeability • Decrease activity of fibroblasts Shutcm-MBL

Animal cell Cell membrane Lysosome Golgi apparatus Nucleolus Microtubule Nucleus Mitochondria Smooth endoplasmic reticulum Centrosome Ribosome Rough endoplasmic reticulum Vacuole Cytoplasm

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2. Immunosuppression and anti-anaphylaxis [ænəfi'læksis] Mechanisms: • Suppress immune responses Reduce the production and functions of lymphocytes Inhibit complement system • Stabilize the membranes of cells • Reduce the production and release of anaphylactic mediators 过敏性反应 Shutcm-MBL

• Enhance myocardial contraction, increase cardiac output; 4. Anti-shock • Enhance myocardial contraction, increase cardiac output; • Improve microvascular circulation; decrease capillary permeability; • Stabilize lysosomal membranes, reduce the production of myocardia-depressant factor (MDF). Shutcm-MBL

5. Effects on the bone marrow • increase the number of red blood cells, hemoglobin, platelets; • decrease the number of lymphocytes (T and B cells) 6. Others • central excitation; • increase the section of gastric acid and pepsin, promote digestion Shutcm-MBL

Clinical uses 1. Substitution therapy: adrenal cortical insufficiency; 2. Severe bacterial infections or inflammation: combined with adequate antibiotics; 3. Autoimmune disorders and allergic disorders; 4. Shocks: such as infective intoxicated shock, anaphylactic shock, cardiogenic shock; 5. Hematologic diseases 6. Local application: skin diseases [,ænəfi‘læktik] 过敏性的 [,hemə‘tɔlədʒikəl] 血液的 Shutcm-MBL

Adverse reactions 1. Induced by using GC with large doses or for long time a. Cushing’s syndrome: Shutcm-MBL

b. Induce or exacerbate peptic ulcers; c. Glaucoma, cataracts; d. Growth retardation in children; e. Sodium and fluid retention with edema; f . Osteoporosis 2. Induced by withdrawal of therapy rapidly or abruptly: rebound syndromes or drugs stop syndromes Shutcm-MBL

Contraindications peptic ulcer Glucocorticoids must be used with great caution in patients with peptic ulcer heart disease or hypertension with heart failure certain infectious illnesses such as varicella tuberculosis [tju:,bə:kju‘ləusis]结核病 psychoses [saɪ‘kəusiz]精神病 diabetes, osteoporosis [,ɔstiəupə'rəusis]骨质疏松症 glaucoma [‘peptik] 消化的/消化器官的 [,væri'selə]水痘 Shutcm-MBL

Therapeutic course and doses Pulse therapy with higher glucocorticoid doses: could stop abruptly; To diminish HPA axis suppression: 1) the steroid preparations should be given in the morning as a single dose. 2) alternate-day therapy shutcm

大纲要求 掌握糖皮质激素类药物的作用、用途、不良反应。 了解用药方法与禁忌症。 shutcm

思考题 从以下病症中分别选出糖皮质激素的适应症和禁忌证，并说明相应的理由 结核性脑膜炎 肾病综合征 癫痫 活动性十二指肠溃疡 血小板减少症 结核性脑膜炎 肾病综合征 癫痫 活动性十二指肠溃疡 血小板减少症 严重高血压 中毒性菌痢 骨质疏松 shutcm