Glucocorticoid is a kind of steroid hormone secreted by fascicular zone of adrenal cortex, mainly cortisol, which has the functions of regulating the biosynthesis and metabolism of sugar, fat and protein, and also has the functions of inhibiting immune response, anti-inflammation, anti-toxicity and anti-shock. It is called "glucocorticoid" because its activity of regulating carbohydrate metabolism was first recognized by people. The secretion of this hormone is regulated by ATCH. The basic structural features of glucocorticoids include C3 carbonyl, δ 4 and 17β ketol side chains of adrenocortical hormones, and 17α-OH and1β-oh peculiar to glucocorticoids. At present, the concept of glucocorticoid includes not only endogenous substances with the above characteristics and activities, but also many synthetic drugs with similar structures and activities after structural optimization. At present, glucocorticoid drugs are divided into short-term, medium-term and long-term drugs according to their plasma half-life. The plasma half-life refers to the time when the plasma concentration of drugs drops by half, which has nothing to do with the plasma concentration in most cases, reflecting the speed of drug excretion, biotransformation and storage in the body. Biological half-life refers to the time when a drug drops by half. Generally speaking, plasma half-life and biological half-life are positively correlated. Short-acting hormones include hydrocortisone and cortisone. The intermediate hormones include prednisone, prednisolone, methylprednisolone and triamcinolone acetonide. The long-acting hormones include dexamethasone, betamethasone and other drugs. The main function of glucose metabolism is to promote liver glycogen heterogenesis, increase glycogen storage, and inhibit the utilization of sugar by peripheral tissues, thus raising blood sugar. Protein metabolism mainly promotes protein decomposition. Excessive secretion often leads to growth stagnation, and protein in muscles, skin, bones and other tissues decreases. For fat metabolism, it mainly promotes the decomposition of fat in limbs and produces the centripetal distribution of fat. GCS has different effects at different doses and concentrations. There are not only quantitative differences, but also qualitative differences. At low dose or physiological level, it mainly produces physiological effects, while at high dose or high concentration, it produces pharmacological effects. Physiological function 1, glucose metabolism: promote glycogen heterogenesis and glycogen synthesis, inhibit aerobic oxidation and anaerobic glycolysis of sugar, thereby increasing blood sugar pathways, reducing pathways and raising blood sugar. 2. protein metabolism: promote protein decomposition, inhibit its synthesis, and form a negative nitrogen balance. GCS can improve the activity of proteolytic enzymes and promote the decomposition of protein in various tissues (lymph, muscle, skin, bone, connective tissue, etc.). ), and the amino acids retained in the liver are converted into sugars and glycogen, thereby reducing the synthesis of protein. 3. Promote lipolysis and inhibit its synthesis. It can activate subcutaneous lipase of limbs, decompose fat and redistribute it on face, neck and trunk. 4. Water-salt metabolism: it has a weak MCS-like effect, which preserves sodium and discharges potassium. Causing hypocalcemia can also increase glomerular filtration rate and antagonize the diuretic effect of ADH. Pharmacological effects A large dose or high concentration will have the following pharmacological effects. 1. Anti-inflammatory effect: GCS has a rapid, powerful and non-specific anti-inflammatory effect. It is effective for various inflammations. In the early stage of inflammation, GCS inhibits capillary dilation, reduces exudation and edema, and inhibits infiltration and phagocytosis of white blood cells, thus alleviating inflammatory symptoms. In the late stage of inflammation, it inhibits the proliferation of capillaries and fibroblasts and delays the formation of granulation tissue. And adhesion. However, it should be noted that sufficient and effective antibacterial drugs must be used at the same time to prevent the spread of inflammation and the deterioration of the original condition. Anti-inflammatory mechanism: GCS diffuses into cytoplasm and binds to GR-HSP. At the same time, Hsp was isolated The complex of GCS and GR enters the nucleus, combines with GRE of target gene promoter sequence, increases transcription of anti-inflammatory cytokine gene, and combines with nGRE. Inhibit the gene transcription of proinflammatory factors and produce anti-inflammatory effects. 1) induces the synthesis of anti-inflammatory factors. (1) induces the synthesis of lipodermin, inhibits the activity of PA2, and reduces the production of PGs and LTs. (2) Induction of ACE synthesis, promotion of bradykinin degradation and increase of angiotensin II production. (3) Inducing the synthesis of inflammatory proteins. At the same time, it inhibits the production of inflammatory protease in white blood cells. (4) Inducing the synthesis of IL- 10, but inhibiting the secretion of IL- 1, IL-2, IL-8, TNF and other factors by Mφ. 2) Inhibit the synthesis of inflammatory factors. (1) inhibits the synthesis and secretion of IL (IL- 1, IL-3, IL-2, IL-5, IL-6, IL-8) and TNFα. GM-CSF。 (2) inhibiting the activity of NOS in mφ and reducing the synthesis of inflammatory factor NO; (3) inhibiting the expression of adhesion molecules such as ELAM- 1 and ICAM- 1 at the level of gene transcription. 3) Inducing apoptosis of inflammatory cells. 4) Contraction of blood vessels and inhibition of proteolytic enzyme release. 5) Inhibit the recruitment and phagocytosis of monocytes, neutrophils and mφ to inflammatory departments. 2. Immunosuppression: GCS inhibits M φ' s phagocytosis and treatment of antigen; Promote the destruction and disintegration of lymphocytes, promote them to move out of blood vessels, and reduce the number of lymphocytes in circulation; At low dose, it mainly inhibits cellular immunity; At high dose, plasma cells and antibody production were inhibited, and humoral immune function was inhibited. 3. Anti-shock effect: 1) GCS can directly dilate spastic blood vessels and reduce their sensitivity to CA, thus improving microcirculation and improving or correcting shock. 2) Stabilize lysosomal membrane, reduce MDF production and enhance myocardial contractility. 3) Anti-toxic effect, GCS itself is a stress hormone, which can greatly improve the body's tolerance to bacterial endotoxin, protect the body from danger and win the rescue time. But it has no effect on bacterial exotoxin. 4) Antipyretic effect: GCS can directly inhibit the thermoregulatory center, reduce its sensitivity to pyrogen, stabilize lysosomal membrane, reduce the release of endogenous pyrogen, and have good antipyretic and symptom improvement effects on serious infections, such as septicemia and meningitis. 4. Other effects 1) and hematopoietic system: GCS stimulates hematopoietic function of bone marrow. Increasing red blood cells, Hb and platelets can increase the number of neutrophils, but inhibit their function. Reduce mononuclear, eosinophilic and basophilic cells. For patients with adrenal cortex hyperfunction. Will shrink the lymphoid tissue. Reduce the number of lymphocytes. But for patients with hypoadrenocortical function. It promotes the proliferation of lymphoid tissue and increases the number of lymphocytes. 2) Central nervous system: GCS excites the central nervous system. Excitement, excitement, insomnia, euphoria, etc. May induce psychosis and epilepsy. 3) Digestive system: GCS promotes gastric acid and pepsin secretion, inhibits mucus secretion, and can induce or aggravate ulcer disease. 【 In vivo process 】 GCS is easily absorbed by oral injection. The drug BPCR reached 90%, and the drug was metabolized during swelling, mainly because C4-5 double bonds were reduced to single bonds and C3 keto groups were reduced to hydroxyl groups. Then it is combined with glucuronic acid or sulfuric acid and excreted with urine. It is worth noting that cortisone and prednisone can only take effect after the liver is hydrogenated into hydrocortisone and prednisolone. Therefore, hydrocortisone and prednisone should be used directly when liver function is low. In addition, liver drug enzyme inducer can accelerate the metabolism of GCS and weaken its effect. Clinical application: 1, replacement therapy: used as supplementary replacement therapy after acute and chronic adrenal insufficiency, anterior pituitary dysfunction and subtotal adrenalectomy. 2. Severe acute infection or inflammation. 1) Severe acute infection. For severe acute bacterial infection, adequate and effective antibacterial drugs should be used. Compatible with GCS, it has anti-inflammatory and anti-toxic effects, can relieve symptoms and help patients get through the critical period. For virus infection, GCS is generally not used, and patients with chickenpox and herpes zoster can aggravate their condition after using it. But it can relieve symptoms for patients with severe hepatitis, mumps, measles and Japanese encephalitis. 2) Prevention of inflammatory sequelae, meningitis, pericarditis, arthritis and burns. After using GCS, scars and adhesions can be alleviated, and inflammatory sequelae can be alleviated. For iriditis, keratitis and retinitis, in addition to the above effects, it can also produce anti-inflammatory and analgesic effects. 3. Autoimmune and allergic diseases 1) Autoimmune diseases: GCS can relieve the symptoms of autoimmune diseases such as rheumatic fever, rheumatoid arthritis and systemic lupus erythematosus. After organ transplantation, rejection can be inhibited. 2) Allergic diseases: GCS can relieve the symptoms of allergic diseases such as urticaria, hay fever and allergic rhinitis. But there is no cure. 4. Treatment of shock: It has the best effect on toxic shock caused by infection. Followed by anaphylactic shock, cardiogenic shock and hypovolemic shock are also effective. 5. Hematological diseases: effective for acute lymphoblastic leukemia. It can also relieve aplastic anemia, granulocytopenia, thrombocytopenia and allergic purpura. However, it requires long-term high-dose medication. 6, skin diseases: psoriasis, eczema, contact dermatitis, can be used locally, but for serious skin diseases such as pemphigus, exfoliative dermatitis, you need systemic medication. 7. Malignant tumor: malignant lymphoma, advanced breast cancer and prostate cancer are all effective. Adverse reactions 1, a large number of long-term adverse reactions should be caused. 1) Cortisolism. Full moon face, buffalo back, hypertension, hirsutism, diabetes, thinning skin, etc. It is caused by metabolic disorder caused by GCS. 2) Induce or aggravate infection. 3) Induce or aggravate ulcer disease. 4) Induced hypertension and arteriosclerosis. 5) Osteoporosis, muscular atrophy and delayed wound healing. 6) Induced psychosis and epilepsy. 2. Drug withdrawal reaction 1) Adrenal cortex atrophy or dysfunction. Long-term use of GCS will cause cortical atrophy. After stopping the drug suddenly, if you encounter stress, you may have an adrenal crisis due to the lack of GCS in your body. 2) rebound phenomenon.