The history of glucocorticoid development

Introduction to Glucocorticoids

Glucocorticoid (GCS) is a class of steroid hormones secreted by the gluteal band of the adrenal cortex, mainly cortisol, which regulates the biosynthesis and metabolism of sugars, fats, and proteins. Inhibition of immune response, anti-inflammatory, anti-virus, anti-shock effect. Called “glucocorticoid” because of its regulation of the activity of carbohydrate metabolism is the earliest known in the clinical work of hormones because of a strong anti-inflammatory anti-allergic effect and is widely used in bronchial asthma treatment, in recent years The incidence of asthma in the world is on the rise in the routine treatment of bronchial asthma when the application of antibiotics, bronchodilator use, cough and phlegm and other symptomatic treatment can not achieve satisfactory results, in the absence of absolute contraindications should be the early application of hormone shock treatment.

The history of glucocorticoid development

Since 1855 people have been studying the physiological role of glucocorticoids and clinical application, 1927 Rogoff and stewart with adrenal gland homogenate extract for the removal of the adrenal gland dog intravenous to survive, proved the presence of glucocorticoids, some people According to this experiment, the biological activity of the extract was caused by a single substance, but later it was isolated from the extract of 47 compounds, including endogenous glucocorticoid hydrocortisone and cortisone.

Early glucocorticoid drugs are derived from animal organs homogenate extract, the production cost is very high, and later with the development of steroid chemistry and organic synthesis, the synthesis of steroid hormones can be achieved by the most simple organic compounds Synthetic dietary hormone, but taking into account the actual cost of production, people generally use diosgenin glycosides as a synthetic starting material, diosgenin from Dioscoreaceae (Dioscoreaceae) Dioscorea (Dioscorea) plants such as yam, piercing dragon, etc. Of the roots of the extraction of terpene compounds glycosides, the price is lower, the use of diosgenin greatly reduces the cost of production.

In the synthesis of hydrocortisone on the basis of people continue to study the structural optimization of glucocorticoids, people from a kidney cancer patients to extract a steroid with a 16α-hydroxy compound triamcinolone, found it has a good Of glucocorticoids, while not as hydrocortisone can cause sodium retention.

Through the study of the metabolic process of hydrocortisone in 1958, it was found that dexamethasone with better stability and better anti-inflammatory activity and lower sodium retention.

In the dexamethasone on the basis of people through the introduction of methyl thiophene like a steroid ring, halogen and other structures, have developed a betamethasone, beclomethasone, fluoride and other drugs.

Pharmacological effects of glucocorticoid

High dose or high concentration of the following pharmacological effects.

1, anti-inflammatory effect: GCS has a fast, strong but not specific anti-inflammatory effect. For all kinds of inflammation are effective. In the early stages of inflammation, GCS inhibited telangiectasia, reduce oozing and edema, and inhibit the infiltration and phagocytosis of white blood cells, and reduce the symptoms of inflammation. In the late inflammation, inhibition of capillaries and fibroblasts proliferation, delay granulation tissue formation. And reduce the scar and adhesions and other inflammatory sequelae. However, it should be noted that glucocorticoids in the inhibition of inflammation, reduce symptoms, but also reduce the body’s defense function, must also apply a sufficient amount of effective antibiotics to prevent the spread of inflammation and the original condition deteriorated.

2, immunosuppressive effect: glucocorticoid inhibition of MΦ on the antigen phagocytosis and treatment; to promote the destruction and disintegration of lymphocytes, to promote its removal of blood vessels and reduce the number of circulating lymphocytes; small dose of the main inhibition of cell immunity; high dose inhibition of plasma cells And antibody production and inhibit humoral immune function.

3, anti-shock effect:

1) inhibit the production of certain inflammatory factors, reduce systemic inflammatory response and tissue damage

2) stable lysosomal membrane, reduced myocardial inhibitory factor (MDF) generation, strengthen myocardial contractility.

3) anti-drug effect, glucocorticoid itself as a stress hormone, can greatly improve the body’s tolerance to bacterial endotoxin, and protect the body through the dangerous period and win the rescue time. But not effective against bacterial exotoxin.

4) antipyretic effect: glucocorticoid can directly inhibit the body temperature regulation center, reduce its sensitivity to pyrogen, but also to stabilize the lysosomal membrane and reduce the release of heat within the heat, and severe infections, such as sepsis, meningitis Good fever and improve symptoms.

5) to reduce the sensitivity of blood vessels to some vasoconstrictor substances, microcirculation hemodynamics returned to normal, improve shock.

4, other effects: and hematopoietic system: glucocorticoid stimulation of bone marrow hematopoietic function. So that red blood cells, Hb, platelets increased, can increase the number of neutrophils, but inhibit its function. So that mononuclear, eosinophilic and basophilic cells are reduced. Of adrenal cortical hyperfunction. Can cause lymphoid tissue atrophy. Reduce the number of lymphocytes. But on the adrenal cortex dysfunction. It will promote lymphoid tissue proliferation and increase the number of lymphocytes.

5, anti-drug effects: glucocorticoid can improve the body’s tolerance to bacterial endotoxin, that is, a good antipyretic effect, there are obvious relief of the role of toxemia. But can not neutralize endotoxin, can not destroy endotoxin, exotoxin also no effect.

The role of glucocorticoid in asthma

Glucocorticoid drugs have a wide range of pharmacological effects, the anti-inflammatory mechanism may be: inhibition of arachidonic acid metabolism, to prevent inflammatory cells chemotaxis and activation of stable leukocyte lysosomal membrane, inhibition of leukotrienes and prostaglandins Generation, reduce oozing, improve the role of adenylate cyclase and other aspects of the role is the strongest antihypertensive drugs. glucocorticoid Commonly used prednisone, dexamethasone, beclomethasone, etc., but the incidence of oral or injection of adverse reactions is high, and serious, in order to reduce this harm, in recent years to promote the local aerosol inhalation way medication. Such as beclomethasone aerosol, local anti-inflammatory effect than dexamethasone hundreds of times, basically does not show the absorption effect, can significantly reduce the body’s adverse reactions, and a good anti-asthma effect. The latest release of budesonide aerosol, is currently the strongest local role, the shortest side effects of asthma drugs.

At present, moderate and severe asthma should be the first time, the initiative to use such corticosteroid anti-inflammatory agents, inhalation of adrenal cortex hormones have been selected international guidelines for asthma treatment, as a first-line drugs to control bronchial asthma. Need to be reminded that: adrenal cortex hormones, although a strong anti-inflammatory effect, can lift the bronchial spasm, but slow onset. For acute asthma, glucocorticoid drugs can be combined with timely control of symptoms.