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

Supplementary reading Glucocorticoids (GCs) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor (GR), that is present in almost every vertebrate animal cell. The name glucocorticoid (glucose + cortex + steroid) is composed from its role in regulation of glucose metabolism, synthesis in the adrenal cortex, and its steroidal structure (see structure to the right). A less common synonym /‘sinənim/ 同义词 is glucocorticosteroid. GCs affect cells by binding to the glucocorticoid receptor (GR). The activated GR complex, in turn, up-regulates the expression of anti-inflammatory proteins in the nucleus (a process known as transactivation) and represses the expression of proinflammatory proteins in the cytosol by preventing the translocation of other transcription factors from the cytosol into the nucleus (transrepression). Shutcm-MBL

大纲要求 Objective and requirements Master the effects, indications, and adverse reactions of glucocorticoid; Understand the mode of application and contraindications of glucocorticoid. Teaching contents (1) Classification of adrenal corticosteroids; (2) Effects (anti-inflammation, immunosuppression, antitoxic action, anti-shock, hematologic effects, effects on blood cells, the central nervous, system, and the digestive system), indications (adrenal cortical insufficiency, severe acute infection, shocks, prevention of inflammation of vital organs, immune disease; allergic diseases, hemopathy, and skin diseases), adverse reactions (hypercorticoidism, induce or aggravate infection, peptic ulcer, osteoporosis, delay the healing of wound, delay of growth, adrenal atrophy and cortical insufficiency, psychosis, and rebound phenomenon), contraindications, mode of application of glucocorticoids. shutcm

Essential vocabulary Adrenocorticosteroids Glucocorticoid Anti- inflammatory actions Inflammatory responses Inflammation inflammatory mediators Immunosuppression and anti-anaphylaxis Anti-shock Alternate-day therapy shutcm