SCS - what is it in medicine? Effects and effects of glucocorticosteroid preparations

Surely you have ever heard of steroid hormones. Our body continuously develops them to regulate the processes of life. In this article we will consider glucocorticoids - steroid hormones, which are formed in the adrenal cortex. Although most of all we are interested in their synthetic analogues - GCS. What is this in medicine? What are they used for and what harm do they do? Let's see.

General information on GCS. What is this in medicine?

Our body synthesizes such steroid hormones as glucocorticoids. They are produced by the adrenal cortex, and their use is mainly associated with the treatment of adrenal insufficiency. Nowadays, not only natural glucocorticoids are used, but also their synthetic analogues - GCS. What is this in medicine? For mankind, these analogues have a lot to do, since they exert anti-inflammatory, immunosuppressive, anti-shock, anti-allergic action on the body.

Glucocorticoids began to be used as medicines (further in the article - drugs) in the 40s of the XX century. By the end of the 30s of the 20th century, scientists discovered steroid hormonal compounds in the adrenal cortex of a person, and already in 1937 a mineralocorticoid deoxycorticosterone was isolated. In the early 40-ies, glucocorticoids hydrocortisone and cortisone were also excreted. The pharmacological effects of cortisone and hydrocortisone were so diverse that it was decided to use them as a drug. After a while, scientists made their synthesis.

The most active glucocorticoid in the human body is cortisol (analog - hydrocortisone, the price of which is 100-150 rubles), it is considered the main one. It is also possible to identify less active: corticosterone, cortisone, 11-deoxycortisol, 11-dehydrocorticosterone.

Of all the natural glucocorticoids, only hydrocortisone and cortisone were used as a drug. However, the latter causes side effects more often than any other hormone, because of which currently its use in medicine is limited. To date, glucocorticoids only use hydrocortisone or its esters (hydrocortisone hemisuccinate and hydrocortisone acetate).

As for glucocorticosteroids (synthetic glucocorticoids), a number of such agents have been synthesized, including fluorinated (flumethasone, triamcinolone, betamethasone, dexamethasone, etc.) and non-fluorinated (methylprednisolone, prednisolone, prednisone) glucocorticoids.

Such funds are more active than their natural counterparts, and smaller doses are required for treatment.

Mechanism of action of GCS

The effect of glucocorticosteroids at the molecular level has not been clarified to the end. Scientists believe that these drugs act on cells at the level of regulation of gene transcription.

Glucocorticosteroids interact with glucocorticoid intracellular receptors, which are present in virtually every cell of the human body. In the absence of this hormone, the receptors (they are cytosolic proteins) are simply inactive. In the inactive state, they are part of heterocomplexes, which also include immunophilin, heat shock proteins, and so on.

When glucocorticosteroids penetrate the cell (through the membrane), they bind to the receptors and activate the glucocorticoid + receptor complex, after which it penetrates into the nucleus of the cell and interacts with DNA sites that are located in the promoter fragment of the steroid-responsive gene (they are also called the glucocorticoid -responsive elements). The complex "glucocorticoid + receptor" is able to regulate (suppress or, conversely, activate) the process of transcription of some genes. This is what leads to suppression or stimulation of mRNA formation, as well as to a change in the synthesis of various regulatory enzymes and proteins that mediate cellular effects.

Various studies show that the glucocorticoid + receptor complex interacts with different transcription factors, for example, such as Kappa B nuclear factor (NF-kB) or activator transcription protein (AP-1), which regulate genes that participate in the immune response and Inflammation (adhesion molecules, cytokine genes, proteinases, etc.).

Main effects of GCS

Effects of glucocorticosteroids on the human body are numerous. These hormones have antitoxic, anti-shock, immunodepressive, anti-allergic, desensitizing and anti-inflammatory actions. Let's take a closer look at how the GCS works.

• Anti-inflammatory effect of GCS. Due to the suppression of the activity of phospholipase A _2. In the inhibition of this enzyme in the human body, suppression of the release of arachidonic acid and the inhibition of the formation of certain inflammatory mediators (such as prostaglandins, leukotrienes, troboxane, etc.) occur. Moreover, the intake of glucocorticosteroids leads to a decrease in fluid exudation, vasoconstriction (narrowing) of the capillaries, and improvement of microcirculation in the inflammatory focus.
• Antiallergic effect of GCS. It occurs as a result of a decrease in the secretion and synthesis of mediators of allergy, a decrease in circulating basophils, inhibition of the release of histamine from basophils and sensitized mast cells, a decrease in the number of B and T lymphocytes, a decrease in the sensitivity of cells to mediators of allergy, changes in the immune response of the organism, and inhibition of antibody formation.
• Immunosuppressive activity of SCS. What is this in medicine? This means that drugs inhibit immunogenesis, suppress the production of antibodies. Glucocorticosteroids inhibit the migration of bone marrow stem cells, inhibit the activity of B- and T-lymphocytes, inhibit the release of cytokines from macrophages and leukocytes.
• Antitoxic and anti-shock effects of SCS. This effect of hormones is due to increased blood pressure in humans, as well as activation of liver enzymes, which are involved in the metabolism of xeno- and endobiotics.
• Mineralocorticoid activity. Glucocorticosteroids have the ability to retard sodium and water in the human body, stimulate the excretion of potassium. In this synthetic substitutes are not as good as natural hormones, but they still have such an effect on the body.

Pharmacokinetics

By the duration of action, systemic glucocorticosteroids can be divided into:

1. Glucocorticosteroids with a short action (for example, hydrocortisone, the price of which varies from 100 to 150 rubles).
2. Glucocorticosteroids with an average duration of action (prednisolone (reviews of which are not very good), methylprednisolone).
3. Glucocorticosteroids with prolonged action (triamcinolone acetonide, dexamethasone, betamethasone).

But not only the duration of the action can determine glucocorticosteroids. Their classification can also be according to the mode of administration:

• Oral;
• Intranasal;
• Inhaled glucocorticosteroids.

This classification, however, applies only to systemic glucocorticosteroids.

Also there are some preparations in the form of ointments and creams (local SCS). For example, "Afloderm". Reviews about such drugs are good.

Let's look at the types of system GCSs separately.

Oral glucocorticosteroids are perfectly absorbed into the digestive tract without causing problems. Actively bind to proteins in the plasma (transcortin, albumin). The maximum concentration of oral glucocorticosteroids in the blood is reached after 1.5 hours after administration. They undergo biotransformation in the liver, kidneys (partially) and in other tissues by conjugation with sulfate or glucuronide.

Approximately 70% of conjugated GCS is excreted in the urine, another 20% will be excreted later with feces, and the remainder - with other biological fluids (for example, afterwards). Half-life is from 2 to 4 hours.

It is possible to compile a small table with the pharmacokinetic parameters of oral GCS.

Glucocorticosteroids. Preparations (names)	Half-life of tissues	The half-life of plasma
Hydrocortisone	8-12 hours	0,5-1,5 hours
Cortisone	8-12 hours	0.7-2 hours
Prednisolone (reviews are not exactly good)	18-36 hours	2-4 hours
Methylprednisolone	18-36 hours	2-4 hours
Fludrocortisone	18-36 hours	3,5 hours
Dexamethasone	36-54 hours	5 o'clock

Inhaled glucocorticosteroids in current clinical practice are represented by triamcinolone acetonide, fluticasone propionate, mometasone furoate, budesonide and beclomethasone dipropionate.

Their pharmacokinetic parameters can also be represented in the form of a table:

Glucocorticosteroids. Preparations (names)	Local anti-inflammatory activity	Volume of distribution	The half-life of plasma	Efficacy of passage through the liver
Beclomethasone dipropionate	0.64 units.	-	0.5 hour	70%
Budesonide	1 unit	4,3 l / kg	1.7-3.4 hours	90%
Triamcinolone acetonide	0.27 units.	1.2 l / kg	1.4-2 hours	80-90%
Fluticasone propionate	1 unit	3.7 l / kg	3.1 hours	99%
Flunisolide	0.34 units.	1.8 l / kg	1.6 hours	-

Intranasal glucocorticosteroids in modern medicine are represented by fluticasone propionate, flunisolide, triamcinolone acetonide, mometasone furoate, budesonide and beclomethasone dipropionate. Some of them are called the same as inhaled glucocorticosteroids.

After applying intranasal GCS, a portion of the dose is absorbed in the intestine, and a part of it comes from the mucous membrane of the respiratory tract directly into the blood.

Glucocorticosteroids, trapped in the digestive tract, are absorbed by about 1-8 percent, and when first passed through the liver, they are almost completely biotransformed to inactive metabolites.

Glucocorticosteroids that get into the blood are hydrolyzed to inactive substances. Here is the table with their pharmacokinetic parameters:

Glucocorticosteroids. Preparations	Bioavailability when entering the blood, in percent	Bioavailability when absorbed from the gastrointestinal tract, in percent
Budesonide	34	eleven
Beclomethasone dipropionate	44	20-25
Mometasone furoate	<0.1	<1
Triamcinolone acetonide	No data	10.6-23
Fluticasone propionate	0.5-2
Flunisolide	40-50	21

Such drugs as "Afloderm" (reviews about which are increasingly appearing on the net), there is no point in describing separately. In each of them there is a main active substance, which, most likely, has already been mentioned above. These drugs are local glucocorticosteroids, and they are often presented in the form of ointments or creams.

Place GCS in therapy (indications for use)

For each type of glucocorticosteroids, their indications for use. So, oral glucocorticosteroids are used to treat:

• Crohn's disease;
• Nonspecific ulcerative colitis;
• Interstitial lung diseases;
• Acute respiratory distress syndrome;
• Severe pneumonia;
• Chronic obstructive pulmonary disease in the phase of exacerbation;
• Bronchial asthma;
• Subacute thyroiditis;
• Congenital dysfunction of the adrenal cortex (in this case a person does not produce corticoids himself and is forced to take their synthetic analogues);
• Acute adrenal insufficiency.

Also, glucocorticosteroids are used in the replacement therapy of primary and secondary renal failure.

Intranasal glucocorticosteroids are used for:

• Idiopathic rhinitis (vasomotor);
• Non-allergic rhinitis with eosinophilia;
• Pililosis of the nose;
• Year-round allergic rhinitis (persistent);
• Seasonal allergic rhinitis (intermittent).

Inhaled glucocorticosteroids are used in the treatment of chronic obstructive pulmonary disease, bronchial asthma.

Contraindications

With caution, it is worthwhile to treat SCS in such clinical cases:

• Lactation period;
• glaucoma;
• Some corneal diseases that are combined with epithelial pathologies;
• Fungal or viral diseases of the eyes;
• Purulent infections;
• The period of vaccination;
• syphilis;
• Active form of tuberculosis;
• Herpetic infection;
• Systemic fungal infections;
• Some mental illness with productive symptoms;
• Severe degree of renal failure;
• arterial hypertension;
• Thromboembolism;
• Peptic ulcer of the duodenum or stomach;
• diabetes;
• Itenko-Cushing's disease.

Strictly contraindicated intranasal administration of GCS in such cases:

• Frequent nasal bleeding in the anamnesis;
• Hemorrhagic diathesis;
• Hypersensitivity.

Glucocorticosteroids: side effects

Side effects of GCS can be divided into local and systemic.

Local side effects

They are subdivided into effects from inhaled and intranasal GCS.

1. Local side effects of inhaled glucocorticosteroids:

• cough;
• dysphonia;
• Candidiasis of the pharynx and oral cavity.

2. Local side effects from intranasal GCS:

• Perforation of the nasal septum;
• Nasal bleeding;
• Burning and dryness of the mucous membrane of the pharynx and nose;
• Sneezing;
• Itching in the nose.

Systemic side effects

They are subdivided depending on the part of the organism to which they act.

1. From the central nervous system:

• Psychoses;
• depression;
• euphoria;
• Insomnia;
• Increased nervous excitability.

2. From the side of the cardiovascular system:

• Thromboembolism;
• Deep vein thrombosis;
• Increased blood pressure;
• Myocardial dystrophy.

3. On the part of the reproductive system:

• Hirsutism;
• Delay in sexual development;
• Violation of sexual functions;
• An unstable menstrual cycle.

4. From the digestive system:

• Fatty degeneration of the liver;
• Pancreatitis;
• Bleeding from the gastrointestinal tract;
• Steroid ulcers of the intestine and stomach.

5. From the endocrine system:

• diabetes;
• Cushing's syndrome;
• obesity;
• Atrophy of the adrenal cortex due to oppression of its functions.

6. On the part of the organs of vision:

• glaucoma;
• Posterior subcapsular cataract.

7. From the musculoskeletal system:

• Muscle hypotrophy;
• Myopathy;
• Growth retardation in children;
• Aseptic necrosis and fractures of bones;
• osteoporosis.

8. From the side of the skin:

• alopecia;
• Stria;
• Thinning of the skin.

9. Other side effects:

• Exacerbation of infectious and inflammatory processes of chronic form;
• Edema;
• Water and sodium retention in the body.

Precautionary measures

In some cases, glucocorticosteroids should be used with caution.

For example, in patients with cirrhosis of the liver, hypothyroidism, hypoalbuminemia, as well as in senile or elderly patients, the effect of GCS may be enhanced.

When using GCS during pregnancy, it is necessary to take into account the expected effect of treatment for the mother and the risk of a negative effect of the drug on the fetus, since SCS can lead to impaired development of fetal growth and even such defects as the wolf mouth and so on.

If during the application of SCS the patient suffers an infectious disease (chickenpox, measles, etc.), it can be very difficult.

In the treatment of SCS patients with autoimmune or inflammatory diseases (rheumatoid arthritis, intestinal diseases, systemic lupus erythematosus, etc.), there may be cases of occurrence of steroid resistance.

Patients receiving oral glucocorticosteroids for a long time should periodically take a fecal occult blood test and undergo fibro-esophagogastroduodenoscopy, since steroid ulcers may not disturb during SCS treatment.

In 30-50% of patients treated with glucocorticosteroids for a long time, osteoporosis develops. As a rule, it affects the feet, brushes, pelvic bones, ribs, spine.

Interaction with other drugs

All glucocorticosteroids (the classification here does not matter) on contact with other drugs give a certain effect, and not always this effect is positive for our body. Here's what you need to know before using glucocorticosteroids in conjunction with other drugs:

1. GCS and antacids - absorption of glucocorticosteroids decreases.
2. GCS and barbiturates, diphenine, hexamidine, dimedrol, carbamazepine, rifampicin - biotransformation of glucocorticosteroids in the liver increases.
3. GCS and isoniazid, erythromycin-biotransformation of glucocorticosteroids in the liver decreases.
4. GCS and salicylates, butadione, barbiturates, digitoxin, penicillin, chloramphenicol - all these drugs increase elimination.
5. GCS and isoniazid - violations of the human psyche.
6. SCS and reserpine - the appearance of a depressive state.
7. GCS and tricyclic antidepressants - increased intraocular pressure.
8. GCS and adrenomimetics - the effect of these drugs is increasing.
9. SCS and theophylline - the anti-inflammatory effect of glucocorticosteroids is enhanced, cardiotoxic effects develop.
10. GCS and diuretics, amphotericin, mineralocorticoids - increases the risk of hypokalemia.
11. SCS and indirect anticoagulants, fibrinolytics, butadine, ibuprofen, ethacrynic acid - hemorrhagic complications may follow.
12. GCS and indomethacin, salicylates - this combination can lead to ulcerative damage to the digestive tract.
13. GCS and paracetamol - the toxicity of this drug is increased.
14. SCS and azathioprine - increased risk of cataracts, myopathies.
15. GCS and mercaptopurine - a combination can lead to an increase in the concentration of uric acid in the blood.
16. GCS and hingamin - the undesirable effects of this drug are increased (corneal opacity, myopathy, dermatitis).
17. GCS and methandrostenolone - the unwanted effects of glucocorticosteroids are exacerbated.
18. GCS and iron preparations, androgens - an increase in the synthesis of erythropoietin, and against this background and the increase in erythropoiesis.
19. SCS and sugar reducing drugs - almost complete reduction in their effectiveness.

Conclusion

Glucocorticosteroids are drugs, without which modern medicine is unlikely to manage. They are used both for the treatment of very severe disease stages, and simply to enhance the effect of any drug. However, like all medicines, glucocorticosteroids have side effects and contraindications too. Do not forget this. Above we have listed all cases when it is not necessary to use glucocorticosteroids, and also provided a list of interactions of GCS with other drugs. Also, the mechanism of the GCS action and all their effects was described in detail here. Now all you need to know about GCS is in one place - this article. However, in no case do not start treatment only after reading the general information on GCS. These drugs, of course, can be purchased without a doctor's prescription, but why do you need it? Before using any medicines, you must first contact a specialist. Be healthy and do not self-medicate!