GCS - what is it in medicine? The action and effects of glucocorticosteroid preparations

Surely you've heard of steroid hormones at least once. Our body continuously produces them to regulate the processes of life. In this article, we will consider glucocorticoids - steroid hormones that form in the adrenal cortex. Although most of all we are interested in their synthetic counterparts - GCS. What is this in medicine? What are they used for and what harm do they cause? Let's see.

General information about the 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 humanity, these analogues are very important, as they have anti-inflammatory, immunosuppressive, anti-shock, anti-allergic effects on the body.

Glucocorticoids began to be used as medicines (hereinafter referred to as drugs) back in the 40s of the twentieth century. By the end of the 30s of the XX century, scientists discovered steroid hormonal compounds in the human adrenal cortex, and already in 1937 the mineralocorticoid deoxycorticosterone was isolated. At the beginning of the 40s, glucocorticoids hydrocortisone and cortisone were also bred. The pharmacological effects of cortisone and hydrocortisone were so diverse that it was decided to use them as drugs. After some time, scientists carried out their synthesis.

The most active glucocorticoid in human organism is cortisol (the analogue is hydrocortisone, the price of which is 100-150 rubles), and it is considered the main one. Less active ones can also be distinguished: corticosterone, cortisone, 11-deoxycortisol, 11-dehydrocorticosterone.

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

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

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

GCS mechanism of action

The effect of glucocorticosteroids at the molecular level is not fully understood. 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 almost every cell in the human body. In the absence of this hormone, the receptors (they are cytosolic proteins) are simply inactive. In an inactive state, they are part of heterocomplexes, which also include immunophilin, heat shock proteins , etc.

When glucocorticosteroids penetrate into the cell (through the membrane), they bind to the receptors and activate the glucocorticoid + receptor complex, after which it penetrates the cell nucleus and interacts with the DNA that are located in the promoter fragment of the steroid-responsive gene (they are also called glucocorticoid -responding elements). The glucocorticoid + receptor complex is able to regulate (suppress or, conversely, activate) the transcription process of certain genes. This is precisely what leads to suppression or stimulation of mRNA formation, as well as 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, such as nuclear factor kappa B (NF-kB) or activator transcription protein (AP-1), which regulate the genes involved in the immune response and inflammation (adhesion molecules, cytokine genes, proteinases, etc.).

The main effects of corticosteroids

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

• Anti-inflammatory effect of corticosteroids. Due to the suppression of the activity of phospholipase A _2. When this enzyme is suppressed in the human body, the liberalization (release) of arachidonic acid and the inhibition of the formation of certain inflammatory mediators (such as prostaglandins, leukotrienes, troboxan, etc.) are suppressed. Moreover, taking glucocorticosteroids leads to a decrease in fluid exudation, vasoconstriction (narrowing) of the capillaries, and an improvement in microcirculation in the focus of inflammation.
• Antiallergic action of corticosteroids. It occurs as a result of a decrease in the secretion and synthesis of allergy mediators, 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 allergy mediators, a change in the body's immune response, and inhibition of antibody formation.
• Immunosuppressive activity of corticosteroids. What is this in medicine? This means that drugs inhibit immunogenesis, inhibit the production of antibodies. Glucocorticosteroids inhibit bone marrow stem cell migration, inhibit the activity of B and T lymphocytes, and inhibit the release of cytokines from macrophages and leukocytes.
• Antitoxic and antishock action of corticosteroids. This effect of hormones is due to an increase in blood pressure in humans, as well as the activation of liver enzymes, which are involved in the metabolism of xeno- and endobiotics.
• Mineralocorticoid activity. Glucocorticosteroids have the ability to retain sodium and water in the human body, stimulate the excretion of potassium. In this synthetic substitutes are not as good as natural hormones, but still they have such an effect on the body.

Pharmacokinetics

According to 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 (prednisone (which reviews are not very good), methylprednisolone).
3. Long-acting glucocorticosteroids (triamcinolone acetonide, dexamethasone, betamethasone).

But not only the duration of action can determine glucocorticosteroids. Their classification can also be by the method of administration:

• oral
• intranasal;
• inhaled glucocorticosteroids.

This classification, however, applies only to systemic glucocorticosteroids.

There are also some drugs in the form of ointments and creams (local corticosteroids). For example, Afloderm. Reviews about these drugs are good.

Let's look at the types of systemic corticosteroids separately.

Oral glucocorticosteroids are perfectly absorbed in the digestive tract, without causing problems. Actively bind to plasma proteins (transcortin, albumin). The maximum concentration of oral corticosteroids in the blood is reached 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% is excreted later with feces, and the remainder with other biological fluids (for example, then). The elimination half-life is from 2 to 4 hours.

You can make a small table with the pharmacokinetic parameters of oral corticosteroids.

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

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

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

After the use of intranasal GCS, part of the dose is absorbed in the intestine, and another part enters directly from the mucous membrane of the respiratory tract.

Glucocorticosteroids that enter the gastrointestinal tract are absorbed by about 1-8 percent and, when they first pass through the liver, they are almost completely biotransformed to inactive metabolites.

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

Such drugs as Afloderm (reviews of which are increasingly appearing on the network), it makes no sense to describe separately. In each of them there is the main active substance, which, most likely, has already been mentioned above. These drugs are local glucocorticosteroids, and they are most often presented in the form of ointments or creams.

The place of corticosteroids in therapy (indications for use)

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

• Crohn's disease;
• ulcerative colitis;
• interstitial lung disease ;
• acute respiratory distress syndrome;
• severe pneumonia;
• chronic obstructive pulmonary disease in the acute phase;
• bronchial asthma;
• subacute thyroiditis;
• congenital dysfunction of the adrenal cortex (in this case, the person does not produce corticoids himself and is forced to take their synthetic analogues);
• acute adrenal insufficiency.

Glucocorticosteroids are also used in replacement therapy for primary and secondary adrenal insufficiency.

Intranasal glucocorticosteroids are used for:

• idiopathic rhinitis (vasomotor);
• non-allergic rhinitis with eosinophilia;
• nasal pyliposis;
• year-round allergic rhinitis (persistent);
• seasonal allergic rhinitis (intermittent).

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

Contraindications

With caution, it is worth treating corticosteroids in such clinical cases:

• lactation period;
• glaucoma;
• some diseases of the cornea that are combined with pathologies of the epithelium;
• fungal or viral diseases of the eyes;
• purulent infections;
• vaccination period;
• syphilis;
• active form of tuberculosis;
• herpetic infection;
• systemic mycoses;
• some mental illnesses with productive symptoms;
• severe renal failure;
• arterial hypertension;
• thromboembolism;
• peptic ulcer of the duodenum or stomach;
• diabetes;
• Itsenko-Cushing's disease.

Intranasal administration of GCS is strictly contraindicated in such cases:

• history of frequent nosebleeds;
• hemorrhagic diathesis;
• hypersensitivity.

Glucocorticosteroids: side effects

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

Local side effects

They are divided into effects from inhaled and intranasal corticosteroids.

1. Local side effects of inhaled glucocorticosteroids:

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

2. Local side effects from intranasal corticosteroids:

• perforation of the nasal septum;
• nosebleeds;
• burning and dryness of the mucous membrane of the pharynx and nose;
• sneezing
• itchy nose.

Systemic side effects

They are divided depending on the part of the body on which they act.

1. From the side of the central nervous system:

• psychoses
• depression;
• euphoria;
• insomnia
• increased nervous irritability.

2. From the cardiovascular system:

• thromboembolism;
• deep vein thrombosis;
• increase in blood pressure;
• myocardial dystrophy.

3. From the reproductive system:

• hirsutism;
• delayed sexual development;
• violation of sexual functions;
• unstable menstrual cycle.

4. From the digestive system:

• fatty liver disease;
• pancreatitis
• gastrointestinal bleeding;
• steroid ulcers of the intestines and stomach.

5. From the endocrine system:

• diabetes;
• Cushing's syndrome;
• obesity;
• atrophy of the adrenal cortex due to inhibition 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 bone fractures;
• osteoporosis.

8. From the skin:

• alopecia;
• striae;
• thinning of the skin.

9. Other side effects:

• exacerbation of infectious and inflammatory processes of a chronic form;
• swelling
• 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 patients of old or old age, 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 GCS can lead to impaired development of fetal growth and even such defects as a cleft palate and so on.

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

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

Patients receiving oral glucocorticosteroids for a long time should periodically take a stool test for occult blood and undergo fibroesophagogastroduodenoscopy, since steroid ulcers may not bother during the treatment of corticosteroids.

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

Interaction with other drugs

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

1. GCS and antacids - the absorption of glucocorticosteroids is reduced.
2. GCS and barbiturates, diphenin, hexamidine, diphenhydramine, carbamazepine, rifampicin - the biotransformation of glucocorticosteroids in the liver increases.
3. GCS and isoniazid, erythromycin - the biotransformation of glucocorticosteroids in the liver decreases.
4. GCS and salicylates, butadione, barbiturates, digitoxin, penicillin, chloramphenicol - all of these drugs are enhanced elimination.
5. GCS and isoniazid - a violation of the human psyche.
6. GCS 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 enhanced.
9. GCS and theophylline - the anti-inflammatory effect of glucocorticosteroids is enhanced, cardiotoxic effects develop.
10. GCS and diuretics, amphotericin, mineralocorticoids - the risk of hypokalemia increases.
11. GCS and indirect anticoagulants, fibrinolytics, butadine, ibuprofen, ethacrylic acid - hemorrhagic complications can follow.
12. GCS and indomethacin, salicylates - this combination can lead to ulcerative lesions of the digestive tract.
13. GCS and paracetamol - the toxicity of this drug is increased.
14. GCS and azathioprine - the risk of cataracts, myopathies increases.
15. GCS and mercaptopurine - a combination can lead to an increase in the concentration of uric acid in the blood.
16. GCS and hingamine - the unwanted effects of this drug (clouding of the cornea, myopathy, dermatitis) are amplified.
17. GCS and methandrostenolone - the undesirable effects of glucocorticosteroids are enhanced.
18. GCS and iron preparations, androgens - increased synthesis of erythropoietin, and against this background, increased erythropoiesis.
19. GCS and sugar-lowering drugs - an almost complete decrease in their effectiveness.

Conclusion

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