Adrenal cortex hormones and their synthetic analogues
The mammalian and human adrenal cortex produces a large amount of steroid hormones called corticosteroids.
They are derivatives of pregnane and can be divided by chemical structure into 11-deoxysteroids, 11-oxysteroids and 11, 17-oxysteroids. The first group includes deoxycorticosterone, which does not have an oxygen atom in position 11 of the steroid nucleus. Group 11, 17-oxysteroids include cortisol (hydrocortisone) and cortisone. These substances are isolated from the adrenal cortex in crystalline form.
For use as medicines, corticosteroids are currently synthetically prepared. A number of synthetic drugs are widely used in medical practice.
Endogenous hormones of the adrenal cortex are essential for human and animal life. Animals die a few days after removal of the adrenal glands (adrenectomy). Acute adrenal insufficiency is accompanied by blood clotting, lowering blood pressure, gastrointestinal upsets, asthenia, lowering body temperature and basic metabolism; sodium loss and potassium retention, hypoglycemia, and nitrogen retention in the blood are also observed. The administration of corticosteroids to adrenectated animals (especially with the simultaneous administration of sodium chloride and water) leads to the disappearance of pathological phenomena and the preservation of life.
According to the effect on metabolism, the main corticosteroids are divided into two groups: mineralocorticosteroids and glucocorticosteroids, or mineralocorticoids and glucocorticoids.
The main representatives of the first group are aldosterone and deoxycorticosterone. These hormones actively affect the exchange of electrolytes and water and relatively little - on carbohydrate and protein metabolism. Of the drugs belonging to the group of mineral-corticosteroids, the most widely used in medical practice has deoxycorticosterone acetate (DOXA).
The main endogenous (natural) glucocorticosteroids are cortisol (hydrocortisone) and cortisone. They actively affect carbohydrate and protein metabolism, but are less active in relation to water and salt metabolism. They contribute to the accumulation of glycogen in the liver, increase blood glucose, and cause an increase in urinary nitrogen excretion.
Under the influence of glucocorticosteroids, the picture of red and white blood changes, eosinopenia, lymphopenia and neutrophilia develop.
Glucocorticosteroids have anti-inflammatory, desensitizing and anti-allergic effects. They also have anti-shock and anti-toxic properties.
Characteristic for glucocorticosteroids is the presence of immunosuppressive activity in them. Unlike cytostatics, the immunosuppressive properties of glucocorticosteroids are not associated with a mitostatic effect.
Their immunosuppressive effect is the total result of the suppression of different stages of immunogenesis: stem cell (bone marrow) migration, B-cell migration and the interaction of T and B lymphocytes.
According to modern data, corticosteroids inhibit the release of cytokinins (interleukins 1 and 2 and interferon) from lymphocytes and macrophages, inhibit the release of inflammatory mediators by eosinophils, and reduce the metabolism of arachidonic acid (see Prostaglandins). By stimulating steroid receptors, they induce the formation of a special class of lipocortin proteins with decongestant activity.
In relatively large doses, glucocorticosteroids inhibit the development of lymphoid and connective tissue, including reticuloendothelium; reduce the number of mast cells, which are the site of formation of hyaluronic acid; inhibit the activity of hyaluronidase and contribute to a decrease in the permeability of capillaries. Under the influence of glucocorticosteroids, synthesis is delayed and the breakdown of proteins is accelerated.
The production of adrenal hormones is controlled by the central nervous system and is closely related to the function of the pituitary gland. Adrenocorticotropic pituitary hormone (ACTH; corticotropin - see) is a physiological stimulant of the adrenal cortex; without it, the normal function of the adrenal cortex is impossible. With various adverse effects causing a state of tension (stress) in the body, there is an increase in the functions of the pituitary gland, accompanied by the release of an increased amount of corticotropin and stimulation of the function of the adrenal cortex. Corticotropin primarily enhances the formation and release of glucocorticosteroids. The latter in turn affect the pituitary gland, inhibiting the production of corticotropin and thus reducing further adrenal gland excitation. Prolonged administration of glucocorticosteroids (cortisone and its analogues) into the body can lead to inhibition and atrophy of the adrenal cortex, as well as to inhibition of the formation of gonadotropic and thyroid-stimulating pituitary hormones.
Of the natural glucocorticosteroids, cortisone, hydrocortisone and deoxycorticosterone obtained synthetically have been found to be of practical use as medicines. A number of synthetic analogues of cortisone and hydrocortisone (prednisone, prednisolone, dexamethasone, etc.) have been obtained, which have found wide application. These compounds are more active than natural glucocorticosteroids, act in smaller doses, have a weaker effect on mineral metabolism; some of them (mainly fluorinated derivatives) are more convenient for local use, as they are less absorbed. Synthetic analogues have now almost completely replaced cortisone.
The main indications for the use of glucocorticosteroids are collagenoses, rheumatism, rheumatoid arthritis (infectious non-specific polyarthritis), bronchial asthma, acute lymphoblastic and myeloid leukemia, infectious mononucleosis, neurodermatitis, eczema and other skin diseases, various allergic diseases. Glucocorticosteroids are also used in case of Addison’s disease, acute hormonal insufficiency of the adrenal cortex, hemolytic anemia, glomerulonephritis, acute pancreatitis, viral hepatitis and other diseases. In connection with the anti-shock effect, glucocorticosteroids are prescribed for the prevention and treatment of shock (post-traumatic, surgical, toxic, anaphylactic, burn, cardiogenic, etc.).
The immunosuppressive effect of glucocorticosteroids allows their use in organ and tissue transplantation to suppress the rejection reaction, as well as in various so-called autoimmune diseases.
Glucocorticosteroids are in many cases very valuable therapeutic agents. However, it must be borne in mind that they can cause a number of side effects, including Itsenko Cushing's symptom complex (sodium and water retention in the body with the possible occurrence of edema, increased excretion of potassium, increased blood pressure); hyperglycemia up to diabetes mellitus (steroid diabetes); increased calcium excretion and osteoporosis; slowing down the regeneration processes; exacerbation of peptic ulcer of the stomach and duodenum, ulceration of the digestive tract, perforation of an unrecognized ulcer, hemorrhagic pancreatitis, decrease in resistance to infections; increased blood coagulation with the possibility of thrombosis; the appearance of acne, a moon-shaped face, obesity, menstrual irregularities, etc.
Nervous and mental disorders are also possible: insomnia, agitation (with the development of psychosis in some cases), epileptiform convulsions, euphoria.
Some side effects (especially those associated with sodium and water retention in the body) are less pronounced with the use of synthetic glucocorticosteroids (triamcinolone, dexamethasone, etc.) due to their lower mineralocorticoid effect.
With prolonged use of glucocorticosteroids, the possibility of inhibition of adrenal cortex function with suppression of hormone biosynthesis should be considered; adrenal atrophy is not ruled out. Administration of corticotropin simultaneously with glucocorticosteroids prevents adrenal atrophy.
Sudden cessation of glucocorticosteroid administration can exacerbate the process. The end of treatment should be done by gradually reducing the dose. Within 3 to 4 days after discontinuation of the drug, small doses of corticotropin (10 to 20 units per day) are prescribed to stimulate the function of the adrenal cortex.
The frequency and strength of side effects caused by glucocorticosteroids can be expressed to varying degrees. With the right dose selection, observing the necessary precautions, careful monitoring of the course of treatment, side effects may be absent.
In connection with a possible side effect, the use of glucocorticosteroids should be carried out only if there are clear indications and under close medical supervision.
To reduce side effects during treatment with glucocorticosteroids, a sufficient amount of complete protein should be introduced into the body, reduce the introduction of chlorides and increase the proportion of potassium (1, 5 - 2 g per day). It is necessary to constantly monitor the level of blood pressure, glucose in the blood, blood coagulation, diuresis and body weight of the patient.
Contraindications to the use of glucocorticosteroids coincide mainly with contraindications to the use of corticotropin (see).
Drugs containing glucocorticosteroids (ointments, drops) should not be used for viral diseases of the eyes and skin (including drugs with the addition of antibacterial agents), since in connection with the inhibition of regeneration processes, the formation of common ulcers up to the perforation of the cornea is possible.
Ointments containing corticosteroids should not be used for fungal and parasitic skin lesions unless special antifungal or antiparasitic agents have been added to these ointments (see Mycosolonum).
All glucocorticosteroid preparations are maintained with caution (List B), in a dark place.
Subgroup Hormones, their analogues and antihormonal drugs include drugs:
- Alclometasone (Alclometasone)
- Arfazetin (Arfasetinum)
- Beclomethasone dipropionate (Beclometasoni dipropionas)
- Betamethasone (Betamethasonum)
- Budesonidum (Budesonidum)
- Halometasone (Halometasone)
- Hydrocortisone (Hydrocortisonum)
- Hydrocortisone Acetate (Hydrocortisoni acetas)
- Hydrocortisone hemisuccinate (Hydrocortisoni hemisuccinas)
- Desoxycorticosterone Acetate (Desoxycorticosteroni acetas)
- Desoxycorticosterone trimethylacetate (Desoxycorticosteroni trimethylacetas)
- Dexamethasone (Dexamethasonum)
- Clobetasol (Clobetasol)
- Methylprednisolonum (Methylprednisolonum)
- Methylprednisolone aceponate (Methylprednisolone aceponate)
- Prednisolonum (Prednisolonum)
- Prednisolone hemisuccinate (Prednisolon hemisuccinas)
- Sinaflanum (Synaflanum)
- Triamcinolone (Triamcinolonum)
- Triamcinolone acetonide (Triamcinoloni acetonidum)
- Fludrocortisone (Fludrocortisone)
- Flumethasone Pivalate (Flumethasoni pivalas)
- Fluticasone (Flunicasone)