Systemic glucocorticoids. Pharmacological group - Glucocorticosteroids What is the danger with oral administration of corticosteroids

PhD L.I. DYATCHINA

By now, a huge amount has been accumulated; experience with the use of glucocorticosteroids (GCS). A striking clinical effect, a powerful anti-inflammatory effect, a pronounced immunomodulatory activity of corticosteroids allows them to be used in many diseases. The impact of glucocorticosteroids; on organs and systems is necessary for the normal functioning of the whole organism as a whole.

REGULATION OF GLUCOCORTICOSTEROID RELEASE

The main endogenous GCS is cortisol, which is synthesized and secreted by the adrenal cortex in response to the stimulating effect of adrenocorticotropic hormone (ACTH). Normally, about 15-30 mg of cortisol is secreted daily. The release of the hormone occurs in pulses - 8-10 pulses / day. The level of cortisol secretion does not remain constant during the day (the maximum concentration in the blood is reached by 7-8 am, the minimum - by midnight). Under stress (infection, surgery, hypoglycemia), the synthesis and secretion of corticosteroids increases approximately 10 times (up to 250 mg / day).

The regulation of GCS release is controlled by the hypothalamic-pituitary mechanism. With a decrease in the concentration of free cortisol, the hypothalamus secretes cortnotropin, a releasing factor that stimulates the release of adrenocorticotropic hormone (corticotropin) in the anterior pituitary gland. Adrenocorticotropic hormone (ACTH), in turn, causes the release of corticosteroids from the adrenal cortex.

MECHANISM OF ACTION OF GLUCOCORTICOSTEROIDS

The action of glucocorticosteroid hormones on the cell is manifested by their effect on the genetic apparatus of the cell. The primary link in the action of glucocorticosteroids on the cell is their interaction with specific receptors of target organs.
GCS are substances of a lipid nature (derivatives of cholesterol) and can dissolve in cell membranes. The penetration of the hormone into the cell is possible not only in a bound form (with the help of a carrier protein), but also passively. Steroid receptors are found in the cytoplasm of cells. However, their density in different cells is not the same: from 10 to 100 steroid-sensitive receptors, which may cause different sensitivity of tissues to GCS. In addition, GCS can have different tropism for GCR. Thus, the endogenous glucocorticosteroid cortisol preferentially binds to the HCR of the cytoplasmic membrane, while the synthetic GCS, dexamethasone, binds to the cytosolic HCR to a greater extent. The number of glucocorticosteroid receptors (GCR) can vary significantly and change during GCS therapy.
The next step is to move the hormone receptor complex (HRC) to the cell nucleus. Penetration of HRKs into the nucleus is possible after the restructuring of their structure (activation), which leads to the appearance of their ability to bind to the components of the nucleus.
Activated GRK binds in the nucleus to a specific DNA region. The GRK-DNA complex promotes an increase in RNA synthesis. Recent studies have shown that the effect of glucocorticosteroid hormones on the biosynthesis of messenger RNA (mRNA) is the main step in the implementation of the biological effects of GCS in the cells of target organs.

GCS can have both a specific stimulating effect and an inhibitory effect on the synthesis of various RNAs. Multidirectional effects can manifest themselves in the same organ and, possibly, the final response of the cell to the hormonal signal depends on their ratio. GCS also affect the activity of RNA polymerase. The possibility of interaction of steroids with non-histone chromatin proteins, which leads to a change in their structure, is described. The anti-inflammatory effect of steroids is mediated through specific HCRs, changes in HRC activity, and RNA and protein synthesis (nuclear pathway).

PHARMACODYNAMIC EFFECTS OF GLUCOCORTICOSTEROIDS

1. The anti-inflammatory effect of GCS is manifested in the form of antiexudative and antiproliferative effects.
2. Immunosuppressive action
3. Antiallergic action
4. Influence on metabolic processes

The anti-exudative effect of GCS o6 is conditional (table No. 1):

• Membrane stabilizing effect and, as a result, a decrease in the permeability of cellular and subcellular membranes (mitochondria and lysosomes);
• A decrease in the permeability of the vascular wall, in particular, capillaries and vasoconstriction in the focus of inflammation. Vasoconstriction is a specific effect of corticosteroids on the vascular bed in the focus of inflammation. At the same time, their impact on other vessels can cause, on the contrary, vasodilation. The mechanism of this action of GCS has not been fully elucidated, it is associated with the suppression of the release of lipid mediators and activators of the kinin system, a decrease in the activity of hyaluronidase;
• Suppression of the synthesis of certain cytokines involved in inflammatory reactions, as well as blockade of the synthesis of cytokine receptor proteins;
• Decreased production of interleukins (IL): IL-1, IL-3, IL-4, IL-5, IL-b and IL-8, tumor necrosis factor-alpha (TNF-α), granulocyte-macrophage-colony-stimulating factor (GM-CSF) ), through suppression, transcription, or shortening of the messenger RNA half-life;
• Inhibition of migration of mast cells and eosinophils to the focus of inflammation. It is known that glucocorticosteroids reduce the number of eosinophils by suppressing the production of GM-CSF and IL-5;
• Suppression of degranulation of mast cells and release of biologically active amines (histamine, serotonin, kinins and prostaglandins) from mast cells;
• Decreased intensity of energy generation processes in the focus of inflammation;
• Inhibition of the migration of neutrophils to the focus of inflammation, a violation of their functional activity (chemotactic and phagocytic). Corticosteroids cause peripheral leukocytosis both after a single appointment (for 4-6 hours) and during long-term treatment (on the 14th day) with a subsequent decrease in the level of leukocytes;
• Suppression of monocyte migration by slowing down the release of mature monocytes from the bone marrow and a decrease in their functional activity.

ANTI-INFLAMMATORY EFFECT OF GLUCOCORTICOSTEROIDS

Anti-exudative effect	stabilization of cellular and subcellular membranes (mitochondria and lysosomes); decrease in the permeability of the vascular wall, in particular capillaries; vasoconstriction in the focus of inflammation; decrease in the release of biologically active amines (histamine, serotonin, kinins and prostaglandins) from mast cells; decrease in the intensity of energy formation processes in the focus of inflammation; inhibition of migration of neutrophils and macrophages to the focus of inflammation, violation of their functional activity (chemotactic and phagocytic), peripheral leukocytosis; suppression of monocyte migration, slowing down the release of mature monocytes from the bone marrow and a decrease in their functional activity; inducing the synthesis of lipomodulin, which blocks phospholipase A of cell membranes, disrupts the release of phospholipid-bound arachidonic acid and the formation of pro-inflammatory prostaglandins, leukotrienes and thromboxane A2; inhibition of the formation of leukotrienes (leukotriene B4 reduces leukocyte chemotaxis, and leukotrienes C4 and D4 (slowly reacting substance) reduce the contractile ability of smooth muscles, vascular permeability and secretion of mucus in the airways); suppression of the synthesis of certain pro-inflammatory cytokines and blockade of the synthesis of cytokine receptor proteins in tissues.
Antiproliferative effect	suppression of nucleic acid synthesis; violation of the differentiation of fibrocytes from fibroblasts; decrease in the functional activity of fibrocytes

Currently, there is a hypothesis that in the mechanism of the anti-inflammatory action of corticosteroids, their ability to induce the synthesis of some (lipomodulin) and suppress the synthesis of others (collagen) proteins in cells is important. The mediator of the anti-inflammatory action of GCS, most likely, is lipomodulin (macrocortin, lipocortin), the synthesis of which occurs under the influence of small concentrations of these hormones in various cell types. Lipomodulin blocks the phospholipase A2 of cell membranes and thereby disrupts the release of phospholipid-bound arachidonic acid, which is then converted to prostaglandins, leukotrienes and thromboxane. The latter are actively involved in the processes of inflammation. Inhibition of leukotriene B4 reduces leukocyte chemotaxis, and leukotriene C4 and D4 (slowly reacting substance) reduces the contractile ability of smooth muscles, vascular permeability and secretion of mucus in the airways.

The decrease in the production of cytokines, in particular IL-1, caused by GCS also inhibits the activity of phospholipase A2 and, to a large extent, cyclooxygenase-2 (COX-2).
Currently, nitric oxide (NO) is also considered as the most important initiator of the inflammatory reaction. Glucocorticosteroids reduce the production of nitric oxide by inhibiting the activity of the NO-synthetase (NOS) enzyme, as shown in an experiment on monocytes.
An increase in the expression of neutral endopeptidase is important in the implementation of the anti-inflammatory effect of glucocorticosteroids in neurogenic inflammation. Neutral endopeptidase plays a role in the breakdown of tachykinin, the latter being released from sensory nerve endings. Endopeptidases have also been shown to be responsible for the degradation of bronchoconstrictor peptides such as bradykinin, tachykinin, and endothelin-1.
The antiproliferative effect of GCS is associated with:

• with their suppression of the synthesis of nucleic acids;
• violation of the differentiation of fibrocytes from fibroblasts;
• a decrease in their functional activity, which also leads to the inhibition of sclerosis processes in the focus of inflammation.

EFFECT OF GLUCOCORTICOSTEROIDS ON THE IMMUNE RESPONSE

The effect of glucocorticosteroids on the immune system is mediated by the presence of specific glucocorticoid receptors on lymphoid cells. Under the influence of steroids, there is a decrease in the number of lymphocytes in the peripheral blood. This is largely due to the redistribution of lymphocytes from the blood to tissues, primarily to the bone marrow and spleen. At the same time, corticosteroids cause apoptosis of immature or activated T- and B-lymphocytes. There is a point of view that the immunosuppressive effect of glucocorticosteroids is realized by controlling the absolute number of lymphoid cells and their subpopulations.
Cytokines play an important role in immune responses. The key cytokine is IL-2, which is involved in the induction of immune responses that occur after the interaction of a T-cell with an antigen-presenting cell. GCS significantly reduce the production of IL-2, resulting in a decrease in IL-2-dependent phosphorylation of various proteins. This leads to suppression of T cell proliferation. In addition, glucocorticosteroids suppress T-cell activation by inhibiting the production of IL-3, IL-4, IL-6 and other cytokines. Since glucocorticosteroids suppress cytokines secreted by other cells, there is a decrease in the function of T-helpers, T-suppressors, cytotoxic T-lymphocytes and, in general, immunological reactions. At the same time, T-helpers are more sensitive to glucocorticosteroids than T-suppressors.
The inhibitory effect of GCS on B-cells is weakly expressed. Moderate and low doses of corticosteroids do not cause any significant changes in the level of immunoglobulins in the blood. A decrease in the content of immunoglobulins is achieved by prescribing high and very high doses of glucocorticosteroids (pulse therapy). Steroids inhibit the activity of the complement system and the formation of fixed immune complexes.
GCS have a pronounced effect on the activity of macrophages and monocytes. Given that monocytes and macrophages play a significant role in the development of the inflammatory process and the involvement of other types of cells in it, it is obvious that the effect of GCS on their migration, secretion, and functional activity can also be decisive in the inflammatory response itself.
Other effects of corticosteroids are associated with the inhibition of phagocytosis, the release of pyrogenic substances, a decrease in the bactericidal activity of cells, inhibition of the secretion of collagenase, elastase and plasminogen activators, and impaired release of macrophage factors that cause mucus formation.
The main immunosuppressive effects of GCS are shown in Table 2.

IMMUNODEPRESSIVE EFFECT OF GLUCOCORTICOSTEROIDS

Mechanisms underlying this effect

Immunosuppressive effect

a decrease in the number of lymphocytes in the peripheral blood (lymphopenia), due to the transition of circulating lymphocytes (mainly T cells) into the lymphoid tissue, and possibly their accumulation in the bone marrow; increased apoptosis of immature or activated T- and B-lymphocytes; suppression of T cell proliferation; decreased function of T-helpers, T-suppressors, cytotoxic T-lymphocytes; inhibition of the activity of the complement system; inhibition of the formation of fixed immune complexes; decrease in the level of immunoglobulins (high doses of glucocorticoids); inhibition of delayed-type hypersensitivity reactions (type IV allergic reactions), in particular tuberculin test; violation of cooperation between T - and B - lymphocytes; violation of the synthesis of immunoglobulins and antibodies, including autoantibodies; a decrease in the number of monocytes in the vascular bed.

In the immune inflammatory process, as well as in the development of a stress response, the hypothalamus-pituitary-adrenal cortex system plays a significant role. Many cytokines stimulate the functional hypothalamus-pituitary-adrenal system.

EFFECT OF GLUCOCORTICOSTEROIDS ON TISSUE METABOLISM

The effect of GCS on carbohydrate metabolism is to stimulate the processes of gluconeogenesis, i.e. synthesis of glycogen from the products of protein and nitrogen metabolism. At the same time, the rate of glucose utilization by tissues is disturbed due to a decrease in its penetration into the cell. As a result, some patients may experience transient hyperglycemia and glucosuria. Prolonged hyperglycemia leads to depletion of the insular apparatus of the pancreas and the development of "steroidal" diabetes mellitus.
The effect of GCS on protein metabolism is manifested by increased protein breakdown in most organs and tissues, and, above all, in muscle tissue. The consequence of this is an increase in the content of free amino acids and products of nitrogen metabolism in blood plasma. In the future, the products of protein and nitrogen metabolism are used in the processes of gluconeogenesis.
The breakdown of muscle tissue proteins causes emaciation, muscle atrophy, muscle weakness, impaired growth of cartilage and bone tissue. Suppression of protein synthesis in the bone matrix of the vertebrae leads to a delay in the formation of the skeleton in children. Dystrophic processes occurring in other tissues are accompanied by the development of "steroid" ulcers, myocardial dystrophies, skin atrophy (striae).
An increase in the processes of protein catabolism is observed with the use of medium therapeutic doses of corticosteroids. The use of small doses of corticosteroids, on the contrary, stimulates the synthesis of albumin in the liver from free amino acids in the blood plasma. This is especially important in patients with impaired protein-synthetic function of the liver.
The influence of GCS on fat metabolism is manifested in the form of their lipolytic and at the same time lipogenetic action. The lipolytic effect is observed in the subcutaneous fat of the arms and legs, the lipogenetic effect is manifested by the predominant deposition of fat in the anterior abdominal wall, interscapular region, face and neck. This process is most pronounced with long-term use of GCS, leads to a change in the appearance of patients and is described in the literature as Cushingoid (moon-shaped face, pituitary-type obesity, impaired glucose tolerance, etc.). The action of GCS is manifested by an increase in the content of cholesterol and lipoproteins in the blood serum. GCS accelerate the process of converting carbohydrates into fats, which also contributes to the development of obesity.
The effect of GCS on water-mineral metabolism is associated, on the one hand, with the suppression of the secretion of antidiuretic hormone, which is accompanied by an increase in the glomerular filtration rate, the release of sodium and water from the body. At the same time, in patients with severe heart failure, corticosteroids can stimulate the synthesis of aldosterone, which leads to sodium and fluid retention and an increase in edematous syndrome. Protein breakdown in tissues is accompanied by an increase in potassium and calcium in the blood plasma. Gradually developing hypocaligistia contributes to an increase in dystrophic processes in tissues and, first of all, in the heart muscle, which can cause cardiac arrhythmias, cardialgia and lead to an increase in the severity of heart failure. GCS inhibit the absorption of calcium in the intestine, increase its excretion in the urine. As a result, the release of calcium from the bone tissue increases, which contributes to the formation of "steroid" osteoporosis. Hypercalciuria and, at the same time, an increase in the content of urea and uric acid in the urine leads in a number of patients who take GCS for a long time to the development of uric acid diathesis, exacerbation of gout. Calcium deficiency in the bones can contribute to the occurrence of pathological bone fractures in children and the elderly.
The effect of GCS on tissue metabolism processes is presented in table #3.

INFLUENCE OF GLUCOCORTICOSTEROIDS ON THE PROCESSES OF TISSUE METABOLISM

Types of exchange
for carbohydrate metabolism	stimulation of gluconeogenesis processes; violation of the rate of glucose utilization by tissues; transient hyperglycemia and glycosuria depletion of the insular apparatus of the pancreas.
for protein metabolism	increased protein breakdown; an increase in the content of free amino acids and products of nitrogen metabolism in blood plasma; stimulation of gluconeogenesis processes; stimulation of the synthesis of albumin in the liver and free plasma amino acids.
for fat metabolism	lipolytic effect in the subcutaneous fat of the hands; lipogenetic action with predominant deposition of fat in the anterior abdominal wall, interscapular region, face and neck; increased levels of cholesterol and lipoproteins in blood plasma; acceleration of the process of converting carbohydrates into fats.
for water and mineral exchange	suppression of the secretion of antidiuretic hormone, an increase in the glomerular filtration rate and stimulation of the release of sodium and water from the body (with short courses); stimulation of aldosterone synthesis and sodium and fluid retention, an increase in edematous syndrome (with prolonged use); an increase in the content of potassium calcium in the blood plasma, hypocaligistia; an increase in the content of calcium in the blood plasma, hypercalciuria; increases the content of urea, uric acid in the blood, uric acid diathesis.

It should be said about the effect of GCS on the functions of other organs and systems that are not responsible for the formation of the main pharmacological response.

• The appointment of GCS leads to an increase in the production of hydrochloric acid and pepsin in the stomach.
• The effect of GCS on the endocrine organs is manifested in the inhibition of the secretion of ACTH and gonadotropin in the anterior pituitary gland, a decrease in the function of the gonads with the development of secondary amenorrhea and infertility, and the suppression of the secretion of thyroid hormones.
• GCS in the CNS can increase the excitability of the cortical structures of the brain and reduce the seizure threshold. They have a euphoric effect in a number of patients, and under certain conditions cause the development of depression.
• GCS have an effect on peripheral blood (table No. 4).

EFFECT OF GLUCOCORTICOSTEROIDS ON PERIPHERAL BLOOD

PHARMACOKINETICS OF GLUCOCORTICOSTEROIDS

When taken orally, corticosteroids are absorbed mainly in the small intestine. Absorption occurs in the proximal (75%) and distal (25%) small intestine.
The adrenal cortex of a healthy adult, under the influence of corticotropin, produces daily 15-60 mg of cortisol and 1-4 mg of corticosterone. More than 95% of plasma cortisol forms complexes with plasma proteins, mainly with corticosteroid-binding alpha-globulin (transcortin). The affinity of the hormone for transcortin is very high, however, the binding ability of transcortin is low and with an increase in plasma cortisol concentration above 20 μg / 100 ml it is completely exhausted. In this case, the transfer of the drug is carried out by plasma albumins (from 40 to 90% of GCS in the blood plasma are in a state associated with albumins). At the same time, only the unbound (free) fraction of GCS is physiologically active, which exerts its pharmacological effect on target cells. Side effects in patients receiving corticosteroids are determined by the amount of free corticosteroid fraction. However, there is no correlation between the half-life and the duration of the physiological action of a particular GCS preparation.
Corticosteroids are classified into short, intermediate and long-acting drugs, depending on the duration of ACTH suppression after a single dose. At the same time, the half-life of GCS is much shorter: from 30 minutes for cortisone and 60 minutes for prednisolone to 300 minutes for dexamethasone.
Interestingly, the maximum pharmacological activity of corticosteroids falls on the period of time when their peak concentrations in the blood are already behind. So, according to pharmacokinetic studies, the peak concentration of prednisolone in plasma is reached after 1-3 hours, the half-life is 2-3.5 hours, and the maximum biological effect develops in about 6 hours. This suggests that the effects of corticosteroids are more dependent on their induction of enzymatic activity inside the cell than on direct action. The period of anti-inflammatory activity of GCS is approximately equal to the duration of their suppression of the hypothalamic-pituitary-adrenal axis - HPA (from 4 to 8 days).
Normally, cortisol levels begin to rise at 2 AM with a peak at 8 AM and return to basal levels by 12 PM. Symptoms of RA (stiffness, inflammatory activity) usually subside a few hours after waking up at the peak of cortisol synthesis. Until recently, it was believed that taking corticosteroids in the morning inhibits the synthesis of ACTH and cortisol to a lesser extent than at night and in the evening. Recently, data have appeared that a circadian increase in the level of IL-6 can also be associated with an increase in RA activity in the morning. Daily fluctuations in IL-6 are observed in the norm and in patients with RA. Normally, the peak concentration of IL-6 occurs a little earlier than ACTH and cortisol between 1 - 4 o'clock in the morning. However, in RA, the peak of IL-6 is delayed and occurs between 2-7 am and the concentration of IL-6 is significantly higher than normal. Therefore, the appointment of GCS (5-7.5 mg) at night (at about 2 am) is more preferable in terms of suppressing IL-6 secretion and is associated with a significantly more pronounced decrease in the duration of morning stiffness, joint pain, Lansbury index, Ritchie index.
In untreated patients with active RA, there is also a decrease in basal and corticotropin-stimulated cortisol synthesis. Moreover, about 10% of patients with RA show signs of adrenal insufficiency. Obviously, in these patients, we can expect a higher efficacy of low doses of corticosteroids than in patients without a defect in the HPA axis.
The different activity of GCS is also determined by the different degree of binding to plasma proteins. Thus, most of the natural cortisol is in a bound state, while only 3% of methylprednisolone and less than 0.1% of dexamethasone binds to corticosteroid-binding globulin.
Microsomal liver enzymes metabolize GCS to inactive compounds, which are then excreted by the kidneys. Metabolites are excreted in the urine as glucuronides, sulfates, and unconjugated compounds. Conjugation reactions occur mainly in the liver and, to a lesser extent, in the kidneys. Metabolism in the liver increases with hyperthyroidism and is induced by phenobarbital and ephedrine. Hypothyroidism, cirrhosis, concomitant treatment with erythromycin leads to a decrease in hepatic clearance of GCS. In patients with hepatocellular insufficiency and low serum albumin levels in plasma, the concentration of the free fraction of prednisolone increases, which contributes to the more rapid development of side effects. During pregnancy, on the contrary, the proportion of its free fraction decreases.

CLASSIFICATION OF GLUCOCORTICOSTEROIDS

Depending on the duration of ACTH inhibition after a single dose of corticosteroids, they are divided into: a) short-acting corticosteroids - inhibit ACTH activity up to 24-36 hours, b) medium-duration corticosteroids - up to 48 hours and c) long-acting corticosteroids - over 48 hours.
I. NATURAL- Cortisol, Cortisone (Hydrocortisone), Cortisone acetate - inhibit ACTH activity up to 24-36 hours.
II. SEMI-SYNTHETIC

1. Short-acting drugs - Prednisolone, Prednisone, Methylprednisolone (Urbazon, Metipred) - inhibit the activity of AGTH up to 24-36 hours.
2. Intermediate-acting drugs - Triamcinolone (Polcortolon) - inhibits ACTH for up to 48 hours.
3. Long-acting drugs - Betamethasone, dexamethasone - inhibit ACTH for more than 48 hours.

USE OF GLUCOCORTICOSTEROIDS

The classical scope of therapeutic application of corticosteroids are such general pathological processes as inflammation, allergy, sclerosis and degeneration of connective tissue derivatives.
GCS are used as anti-inflammatory, anti-allergic and immunosuppressive agents, as well as replacement therapy for adrenal insufficiency.
There are the following options for GC-therapy:

1. Systemic:
   • average therapeutic doses
   • alternative therapy
   • pulse therapy
   • "mini-pulse" therapy
   • combined (primarily with cytotoxic drugs)
2. Local (intra-articular, inhalation, rectal administration, etc.);
3. Local (ointments, drops, aerosol).

Systemic corticosteroid therapy is one of the most effective treatments for a number of diseases. The use of steroids can significantly improve the prognosis and increase the life expectancy of patients.
In the treatment of GCS, the following phases are conditionally distinguished:

• Induction: use short-acting corticosteroids (prednisolone or methylprednisolone) at a dose approximately corresponding to 1 mg/kg of body weight per day with an 8-hour interval.
• Consolidation: involves the transition to a single dose of the entire dose of GCS in the morning.
• Reduction: the rate of reduction of GCS depends on the dose. Switching to alternative therapy is possible.
• Maintenance treatment: the use of the minimum effective dose of drugs.
• Prevention of complications of corticosteroid therapy: begins with the induction phase.

When conducting systemic therapy with corticosteroids, it is necessary to take into account several general principles of pharmacotherapy, compliance with which can increase the effectiveness and safety of treatment, as well as reduce the incidence of unwanted side effects.
GC therapy should be started only if there are strong indications and as early as possible, without trying to apply more "soft" methods of treatment at first. In this case, hormonal therapy should be used together with conventional therapy, and not be prescribed instead. Rational therapy involves the use of short-acting corticosteroids in the optimal dose and, if possible, for a period that is necessary to control the activity of the process.
GCS should be prescribed only under medical supervision of their use in order to detect side effects early and correct them. When prescribing hormone therapy, not only the doctor, but also the patient should be informed in detail about the possibilities and complications of this method of treatment.

• Prednisolone is considered the standard among GCS, and the effectiveness of other drugs in this group is evaluated in relation to it. The average therapeutic doses of corticosteroids in terms of prednisolone are 0.5-1 mg per kg of body weight.
• When prescribing GCS, the principle of equivalent doses should be observed in order to obtain the same anti-inflammatory effect. Equivalent doses - prednisolone - 5 mg: triamcinolone - 4 mg; methylprednisolone - 4 mg; dexamethasone - 0.5 mg; betamethasone - 0.75 mg; hydrocortisone - 25 mg. In this case, the calculation always goes to prednisolone. When transferring patients from parenteral administration of GCS to oral administration, it is necessary to reduce the daily dose by 5-6 times.
• In cases where prolonged use of GCS is expected, patients should be transferred as soon as possible to a single dose of the entire dose in the morning, and then to an alternating regimen of GCS therapy. At the beginning of treatment, the daily dose of the drug is usually divided into 3 doses (induction phase), then they switch to a single dose of the drug in the morning (consolidation phase).
• The choice of the initial dose of corticosteroids, the determination of the duration of therapy and the rate of dose reduction should be carried out not empirically, but taking into account standardized clinical and laboratory indicators of the activity of the process and the nature of the disease. When prescribing GCS therapy, attention should be paid to the following:
  • the required daily dose should be selected individually, starting with the minimum average therapeutic doses usually recommended for this disease;
  • in chronically occurring diseases, corticosteroids should not be prescribed in large doses and for a long course, and when remission occurs, corticosteroids should be discontinued;
  • in life-threatening conditions, large doses of corticosteroids should be prescribed immediately.
• In the process of hormone therapy in the peripheral blood, there is a decrease in the number of eosinophils, lymphocytes, erythrocytes, a decrease in the level of hemoglobin with a simultaneous increase in the content of leukocytes due to neutrophils (up to 12,000). Such a hemogram can be erroneously interpreted as a continuation of the exacerbation of the process. At the same time, these changes should be considered favorable and indicate a sufficient dosage of GCS.
• The rate of reduction in the dose of corticosteroids. After achieving a clinical effect, the dose of GCS should be reduced to a maintenance dose. To do this, the initial dose of GCS is gradually reduced to the minimum level at which the positive effect obtained is maintained. If the daily dose of the ongoing course of treatment is in the range of 15-40 mg / day in terms of prednisolone, then the abolition should be carried out at 2.5-5 mg every 5-7 days until the physiological dose is reached. When prescribing GCS in doses of 40 mg or more, the dose reduction can be faster (5 mg and even in some cases 10 mg per week) to the level of 40 mg, and then as mentioned above. In these cases, the rate of reduction in the dose of corticosteroids is determined by the duration of their use. The shorter the duration of the ongoing course of treatment, the faster the cancellation of GCS is possible. However, the lower the dose of corticosteroids, the longer should be the periods between successive dose reductions. This tactic allows you to create conditions for the restoration of the functionality of the hypothalamic-pituitary-adrenal system already during drug withdrawal.
• In case of recurrence of the disease, hormone therapy is resumed. The dose of GCS is increased to the one at which the patient showed stabilization of the process. In the future, the cancellation should be carried out more carefully and gradually. The determination of the duration of therapy and the rate of dose reduction should not be carried out empirically, but taking into account standardized clinical and laboratory indicators of the activity of the process and the nature of the disease. There are several laboratory criteria for determining the effectiveness of corticosteroid therapy: stabilization of ESR for 7 days, decrease in the level of C-reactive protein, fibrinogen, etc.
• Cancellation of glucocorticosteroids. Problems associated with the abolition of glucocorticosteroids arise after a long course of therapy. In this case, a more abrupt withdrawal of drugs threatens the development of complications of two types. Firstly, these are manifestations of adrenal insufficiency associated with suppression of the hypothalamic-pituitary-adrenal system. Secondly, it is a recurrence of the inflammatory process underlying the disease itself.
  • Suppression of adrenal function depends on the dose of hormones taken and, to an even greater extent, on the duration of glucocorticoid therapy, as well as on the properties of the drug used and the underlying disease.
  • The dose of prednisolone in the range of 10-15 mg gives a complete replacement effect and is considered physiological. In this regard, the abolition of the drug to a physiological dose can be carried out quickly enough. Further reduction in the dose of corticosteroids should take place at a much slower pace.
  • During treatment, it must be remembered that the inhibition of the hypothalamic-pituitary-adrenal axis persists in patients who received even small doses of corticosteroids (over 10 mg / day for three or more weeks) for a long time (up to 1 year) after discontinuation of the drug.
  • Rapid withdrawal of the drug (within 1-2 days) is carried out extremely rarely only in the case of acute steroid psychosis, or with generalization of herpes virus infection.
  • In cases where it is not possible to completely avoid glucocorticosteroid therapy, patients should be transferred to maintenance doses of hormones, individual for each patient and corresponding, as a rule, to replacement doses at the rate of 5-15 mg of prednisolone per day. Hormone intake should be carried out in the morning (from 6 to 9 am), taking into account the natural biorhythm of their release.
  • There is evidence of no significant inhibition of the hypothalamic-pituitary-adrenal axis if the dose of prednisolone does not exceed 10 mg per day. Against the background of GCS treatment, the occurrence of adverse reactions is significantly more common in patients who received more than 10 mg of prednisolone per day. The risk of developing side effects is less with a decrease in the total dose of prednisolone and taking the drug at a certain time. At the same time, treatment with low doses of corticosteroids can reduce the potential risk of osteoporosis due to inhibition of IL-6 synthesis.
  • In order to reduce the dose of corticosteroids, it is recommended to combine them with NSAIDs, basic therapy. However, this increases the likelihood of developing ulcerative lesions of the gastrointestinal tract. To stimulate the production of one's own hormones, in some cases it is possible to prescribe ACTH (corticotropin) against the background of the gradual withdrawal of GCS.
  • When using GCS as a replacement therapy for primary insufficiency of the adrenal cortex (Addison's disease), the appointment of both a glucocorticosteroid and a mineralocorticosteroid is indicated. Cortisone acetate or hydrocortisone in combination with deoxycorticosterone acetate or fludrocortisone are recommended as corticosteroids.

With secondary insufficiency of the adrenal cortex, due to the preserved basic secretion of aldosterone, in most cases it is possible to use one GCS. With adrenogenital syndrome, patients throughout their lives should receive maintenance doses of corticosteroids. Hormone-dependent patients with the development of severe intercurrent diseases or the need for surgical interventions must necessarily receive corticosteroid replacement therapy at doses 5-10 mg higher than those that patients take constantly.

MAIN INDICATIONS FOR GLUCOCORTICOSTEROIDS

1. Rheumatic diseases:
   • rheumatism 2-3 tbsp. process activity in the presence of rheumatic heart disease, especially in combination with polyarthritis and polyserositis - average therapeutic doses of corticosteroids;
   • systemic lupus erythematosus during an exacerbation (pulse therapy), in chronic forms - average therapeutic doses of corticosteroids or as maintenance therapy;
   • systemic dermatomyositis during an exacerbation - GCS pulse therapy or as maintenance therapy;
   • periarteritis nodosa during an exacerbation - pulse therapy with corticosteroids or as maintenance therapy;
   • rheumatoid arthritis in combination with visceritis (fever syndrome, carditis, nephritis, serositis); with rapidly progressive articular forms of rheumatoid arthritis and a high titer of rheumatoid factor - pulse therapy, then, often, supportive therapy; ineffectiveness of previous therapy with NSAIDs and basic therapy - medium therapeutic doses of corticosteroids, with monoarthritis - intraarticular administration of corticosteroids;
   • juvenile rheumatoid arthritis.

The main indications for the appointment of GCS in rheumatic diseases are shown in table No. 5.

The use of corticosteroids in rheumatic diseases
Diseases	Indications	A drug
RA Rheumatoid Vasculitis	Ineffectiveness of NSAIDs or contraindications for the appointment of NSAIDs (+basic therapy)	Previous 10 mg/day	– 2 mg/kg/day
	Arthritis, low disease activity. Kidney and CNS damage	Previous 15 mg/day	Previous 1 mg/kg/day + CF
PM/DM Sjögren's syndrome Polyarteritis nodosa Cherg-Strauss syndrome Wegener's granulomatosis	Vasculitis moderate activity high activity	Previous 1 mg/kg/day Previous 1 mg/kg/day Previous 1 mg/kg/day + CF 1 mg/kg/day	2 mg/kg/day -2 mg/kg/day -2 mg/kg/day
SD Eosinophilia-myalgia syndrome	Myositis, pleurisy, vasculitis, pericarditis, arthritis	Previous 15-60 mg/day Previous 1 mg/kg/day
Recurrent polychondritis		Previous 0.5 - 1.0 mg / kg / day
Side effects of basic therapy	Gold salts, penicillamine, sulfasalazine, etc.	Previous 15 - 60 mg / day
Note: Previous - prednisolone.

1. Systemic vasculitis - systemic therapy with corticosteroids.
2. Carditis (infectious-allergic myocarditis, Abramov-Fiedler myocarditis, subacute septic endocarditis - immunological phase) - systemic therapy with corticosteroids.
3. Diseases of the musculoskeletal system:
   • post-traumatic osteoarthritis - for short-term use in the acute period or for intra-articular administration of GCS;
   • ankylosing spondylitis (Bekhterev's disease);
   • subacute gouty arthritis - for short-term use in the acute period or for intra-articular administration of GCS;
   • acute and subacute bursitis;
   • acute nonspecific tendosynovitis;
   • psoriatic arthritis.
4. Kidney diseases (chronic nephritis with nephrotic syndrome - the most indicated is the appointment of corticosteroids in membranous and membranous-proliferative variants; with lupus nephritis) - systemic therapy with corticosteroids.
5. Diseases of the gastrointestinal tract (ulcerative colitis, Crohn's disease, SPRU) - systemic therapy with corticosteroids.
6. Liver diseases (autoimmune hepatitis) - systemic therapy with corticosteroids.
7. Diseases of the bronchopulmonary system (obstructive bronchitis, allergic bronchial asthma, sarcoidosis - systemic therapy and inhaled corticosteroids).
8. Hematological diseases: acquired (autoimmune) hemolytic anemia, thrombocytopenic purpura - systemic therapy with corticosteroids.
9. allergic conditions. Control of allergic conditions when conventional means are ineffective: seasonal or chronic allergic rhinitis, nasal polyps, bronchial asthma (including asthmatic condition), contact dermatitis, atopic dermatitis (neurodermatitis), hypersensitivity to drugs and serum sickness (anaphylactic shock, Quincke's edema, syndrome Lyell, Steven-Johnson, drug or food agranulocytosis, thrombocytopenia, giant urticaria).
10. Ocular diseases: severe acute and chronic allergic reactions and inflammatory processes in the eyes and adjacent structures, such as allergic conjunctivitis, keratitis, allergic marginal corneal ulcer, corneal herpes, iritis and iridocyclitis, chorioretinitis, anterior segment inflammation, diffuse posterior uveitis and choroiditis, retrobulbar neuritis, sympathetic ophthalmia.
11. Skin diseases: eczema (chronic dermatitis), in the treatment of keloids and localized hypertrophic infiltrating inflammations (introduction of GCS into the lesions), lichen planus, psoriasis, granuloma annulare, lichen simplex chronicus (neurodermatitis), discoid lupus erythematosus, lipoid necrobiosis of diabetics, nested alopecia, psoriasis, erythema nodosum and others - local therapy with corticosteroids.
12. Tumor diseases: palliative treatment of leukemias and lymphomas in adults, acute childhood leukemia.
13. Endocrine disorders: primary or secondary adrenal insufficiency, acute adrenal insufficiency, bilateral adrenectomy, congenital adrenal hyperplasia, acute thyroiditis and thyrotoxic crisis, hypercalcemia associated with cancer.
14. Shock conditions: hemodynamic, traumatic, endotoxic, cardiogenic (heart attack).
15. Cerebral edema (increased intracranial pressure) - GCS are needed as an adjunct to reduce the intensity or prevent cerebral edema associated with surgical or other brain injury, strokes, primary or metastatic malignant brain tumors. The use of glucocorticosteroids should not be considered as a substitute for neurosurgical treatment.
16. Prevention of renal allograft rejection. The drug is used in combination with commonly used immunosuppressants.

Often a person finds the optimal solution to any problems in himself. Where, for example, does the body get the strength to fight diseases?

As scientific studies carried out in the middle of the 20th century showed, an important role in this matter belongs to the hormones glucocorticoids.

They are produced by the adrenal glands for almost all cells of the human body, and it is these hormones that help fight various inflammatory processes.

Synthesized analogues of the hormone are now successfully used in medicine.

Glucocorticosteroids (GCS) - what is it in medicine

Glucocorticoids and glucocorticosteroids are the same, synonymous words for hormones produced by the adrenal cortex, both natural and synthetic, sometimes use the abbreviation GCS for short.

Together with mineralocorticoids, corticosteroids make up an extensive group of corticosteroids, but it is corticosteroids that are especially in demand as medicines. You can read about what these drugs are - corticosteroids.

They provide the doctor with great opportunities for the treatment of serious diseases, "extinguish" foci of inflammation, can enhance the effect of other medications, relieve swelling, dull the feeling of pain.

By artificially increasing the amount of corticosteroids in the patient's body, doctors solve problems that previously seemed impossible.

Medical science has also achieved GCS today can be used "addressed"- act exclusively on the problem area, without disturbing others, healthy ones.

As a result of such topical application, the risk of side effects is reduced.

The scope of glucocorticoid drugs is quite wide. These funds are used:

In addition, corticosteroids are used in the treatment of injuries ( they have an effective anti-shock effect), and also to restore body functions after complex operations, radiation and chemotherapy.

The regimen for taking GCS takes into account the possible syndrome of glucocorticoid withdrawal, that is, the risk of a deterioration in the patient's well-being after stopping these drugs.

The patient may even develop a so-called glucocorticoid deficiency.

To prevent this from happening treatment with glucocorticoids is usually completed smoothly, carefully reducing the dose of the drug at the end of the treatment course.

All the most important, systemic processes take place under the influence of GCS at the cellular, including the genetic level.

It means that only specialists can work with medicinal preparations of this kind, self-medication is strictly prohibited, since it can cause all sorts of complications.

The mechanism of action of glucocorticoids on the body is not yet fully understood. GCS, as scientists managed to find out, are formed according to the “command” of the pituitary gland: it releases a substance called “corticotropin” into the blood, which already sends its own signal - about how much GCS the adrenal glands should give out.

One of their main products is an active glucocorticoid called cortisol, also called the “stress hormone”.

Such hormones are produced for various reasons, their analysis helps physicians to identify disorders in the endocrine system, serious pathologies and select such drugs (including corticosteroids) and treatment methods that will be most effective in each specific situation.

Glucocorticoids affect the body in several ways at once. One of the most important is their anti-inflammatory effect.

GCS can reduce the activity of enzymes that destroy body tissues, isolating the affected areas from healthy ones.

GCS affect the cell membranes, making them coarser, and therefore complicate the metabolism, as a result, the infection does not give a chance to spread throughout the body, put it in a "hard frame".

Among other ways of the influence of GCS on the human body:

• immunoregulatory effect- under different circumstances, immunity increases slightly or, on the contrary, immunity suppression occurs (this property of GCS is used by doctors during tissue transplantation from donors);
• antiallergic;
• anti-shock - effective, for example, in anaphylactic shock, when the drug should provide a lightning-fast result to save the patient.

GCS can affect the production of insulin (this helps patients with hypoglycemia), accelerate the production of a substance such as erythropoietin in the body (with its participation in the blood, the hemoglobin content increases), can raise blood pressure, affect protein metabolism.

When prescribing drugs, doctors have to take into account many nuances, including the so-called resorptive effect, when the drug, after absorption, enters the general bloodstream, and from there into the tissues. Many types of corticosteroids allow the use of drugs more locally.

Unfortunately, not all "activities" of glucocorticoids are 100% beneficial to a person.

An excess of corticosteroids as a result of long-term use of the drug leads, for example, to the fact that internal biochemistry changes - calcium is washed out, bones become brittle, osteoporosis develops.

Glucocorticoids are distinguished by how long they work inside the body.

Short acting drugs remain in the patient's blood from two hours to half a day (examples - Hydrocortisone, Cyclesonide, Mometasone). You can read the instructions for using Hydrocortisone.

GCS medium action- up to one and a half days (Prednisolone, Methylprednisolone), long-term action - 36-52 hours (Dexamethasone, Beclomethasone).

There is a classification according to the method of administration of the drug:

Fluorinated glucocorticoids have a particularly powerful effect on the patient's body. These funds also have their own classification.

Depending on the amount of fluorine contained in them, they are monofluorinated, di- and trifluorinated.

A variety of drugs using GCS gives physicians the opportunity to choose the right form of drug (tablets, cream, gel, ointment, inhaler, patch, nasal drops) and the appropriate “content” in order to get exactly those pharmacological effects that are needed, and in no case not aggravate the patient's condition by causing any side effects in the body.

Pharmacology is the lot of specialists, only a doctor understands in all the subtleties what effect this or that drug can have on the body, when and according to what scheme it is used.

As an example, we give the names of glucocorticoid drugs:

Treatment Methods

Various types of treatment methods using GCS have been developed:

• replacement - is used if the adrenal glands cannot independently produce the amount of hormones the body needs;
• suppressive - for children with congenital abnormalities in the functioning of the adrenal cortex;
• pharmacodynamic(it includes intensive, limiting and long-term treatment) - in anti-allergic and anti-inflammatory therapy.

In each case, certain doses of the drug taken and the frequency of their use are provided.

So, alternating therapy involves taking glucocorticoids once every two days, pulse therapy means the prompt administration of at least 1 g of the drug for urgent assistance to the patient.

Why are glucocorticoids dangerous for the body? They change its hormonal balance and sometimes cause the most unexpected reactions., especially if for some reason an overdose of the drug has occurred.

The diseases provoked by corticosteroids include, for example, hyperfunction of the adrenal cortex.

The fact is that the use of a drug that helps the adrenal glands perform their functions, gives them the opportunity to “relax”. If the drug is abruptly stopped, the adrenal glands can no longer engage in full-fledged work.

What other troubles can await after taking GCS? This:

If the danger is noticed in time, almost all the problems that have arisen can be safely resolved. The main thing is not to aggravate them with self-medication, but act only in accordance with the recommendations of the doctor.

Contraindications

The standards of treatment with glucocorticoids suggest only one absolute contraindication for the use of corticosteroids once - this is an individual intolerance to the drug by the patient.

If treatment is required for a long time, then the list of contraindications becomes wider.

These are diseases and conditions such as:

• pregnancy;
• diabetes;
• diseases of the gastrointestinal tract, kidneys, liver;
• tuberculosis;
• syphilis;
• mental disorders.

Pediatric glucocorticoid therapy provided only in very rare cases.

Systemic glucocorticoids

Systemic glucocorticoids are divided into several groups:
■ Origin:
- natural (hydrocortisone);
- synthetic: (prednisolone, methylprednisolone, triamcinolone, dexamethasone, betamethasone).
■ By duration of action:
- preparations of short (hydrocortisone), medium duration (prednisolone, methylprednisolone) and long-term (triamcinolone, dexamethasone, betamethasone) action.

Pharmacokinetics

When taken orally, glucocorticoids are well absorbed from the gastrointestinal tract. The maximum concentration in the blood is created after 1.5 hours.

Glucocorticoids bind to plasma proteins:
a) with α1-globulin (transcortin), forming complexes with it that do not penetrate into tissues, but create a depot of these hormones;
b) with albumins, forming complexes with them that penetrate into tissues. Only free glucocorticoids are biologically active.
They are quickly excreted from the plasma, easily penetrate the histohematogenous barriers, including the blood-brain, placental and breast milk, accumulating in the tissues, where they remain active much longer. 25-35% free glucocorticoids are deposited by erythrocytes and leukocytes. If hydrocortisone binds to transcortin by 80-85%, to albumin - by 10%, then synthetic glucocorticoids bind to proteins by 60-70%, i.e. their free fraction, which penetrates well into tissues, is much larger. The amount of glucocorticoids penetrating cells is also affected by their ability to bind to specific intracellular receptors.

Glucocorticoids undergo biotransformation in the liver, partly in the kidneys and other tissues, mainly by conjugation with glucuronide or sulfate. They are excreted in the bile and urine by glomerular filtration and are reabsorbed by 80-90% of the tubules. 20% of the dose is excreted by the kidneys unchanged. A small part (on average 0.025%) of the dose of intravenously administered prednisolone is excreted in breast milk. At the same time, the decrease in the concentration of glucocorticoid in breast milk occurs faster than in blood serum. The plasma half-life (T1 / 2) of hydrocortisone is 60-90 minutes, prednisone, prednisolone and methylprednisolone - 180-200 minutes, triamcinolone and fluorocortolone - 210 minutes, dexamethasone, betamethasone and paramethasone - 190-300 minutes. That is, the elimination of synthetic glucocorticoids, especially fluorinated ones, is slower, and they have a greater inhibitory effect on the adrenal cortex. The half-life of hydrocortisone from tissues is 8-12 hours, prednisone, prednisolone and methylprednisolone - 12-36 hours, triamcinolone and fluorocortolone - 24-48 hours, dexamethasone and betamethasone - 36-54 hours (up to 72 hours).

In the treatment of a number of diseases of the musculoskeletal system, especially of an inflammatory nature, drugs such as glucocorticosteroids have been widely used. Before understanding the main therapeutic effects, indications and contraindications, it is necessary to know what glucocorticosteroids (GCS) are.

Glucocorticosteroids are drugs that belong to the group of steroid hormones and have anti-inflammatory, anti-allergic, anti-shock, immunosuppressive and other properties.

Classification

To date, there are several classifications of glucocorticosteroids according to various parameters. The most clinically significant is the classification that divides drugs according to the duration of their action. According to it, the following drug groups are distinguished:

• Short-acting drugs (Hydrocortisone, Cortef).
• Drugs with an average duration of action (Prednisolone, Medopred).
• Long-acting drugs (Dexamethasone, Triamcinolone,).

GCS is the abbreviation for glucocorticosteroid drugs, which is quite often used in medicine.

When is it applied?

In the treatment of diseases of the joints and spine, the main indication for the use of glucocorticosteroids is a severe inflammatory process, which is particularly intense and cannot be treated with non-steroidal anti-inflammatory drugs. What articular pathologies can be used:

1. Arthritis (rheumatoid, post-traumatic, gouty, psoriatic, etc.).
2. Polyarthritis.
3. Osteoarthritis (if there are signs of an inflammatory process).
4. Bechterew's disease.
5. Periarthritis.
6. Inflammation of the synovial or articular bag.

When prescribing GCS, the doctor tries to achieve the maximum therapeutic effect using the minimum dosage of the drug. The regimen of glucocorticosteroid treatment depends more on the severity of the disease, the condition of the patient and his response to therapy than on age and weight.

Clinical Efficiency

Several recent scientific studies have shown the high effectiveness of the use of glucocorticosteroids in the treatment of severe forms of joint inflammation. It is also possible to achieve a rapid clinical effect with the simultaneous use of corticosteroids in low doses and non-steroidal anti-inflammatory drugs. It has been established that the majority of patients with disability due to polyarthritis become much easier in functional terms after a few days of GCS therapy. What does the doctor expect when prescribing glucocorticosteroids:

• Significantly reduce the severity of pain in the affected joints.
• Improve the functional state of the joints.
• Slow down destructive processes.
• Deal with inflammation.
• Significantly reduce the need for non-steroidal anti-inflammatory drugs.
• To increase the effectiveness of the use of basic anti-inflammatory drugs.

Clinical experience has shown that many patients with rheumatoid arthritis often become functionally dependent on glucocorticosteroid therapy and are forced to switch to long-term courses of their intake, which undoubtedly leads to the development of side effects.

How is it applied?

Several routes of administration of GCS preparations are possible. As a rule, in the treatment of inflammatory pathology of the musculoskeletal system, glucocorticosteroids are injected into the joint. By directly acting on the focus of inflammation, the maximum therapeutic effect is achieved.

It should be noted that quite often fluid (exudate) can accumulate in the cavity of large joints. In such cases, it is first necessary to remove this fluid, and only then to carry out intra-articular administration of the drug. Sometimes, in order to achieve a better effect, they combine the introduction of GCS into the joint with glucocorticosteroid therapy in tablets. This type of treatment is used in severe forms of the inflammatory process with a pronounced tendency to progression.

Intra-articular injections of drugs are performed only by a specialist doctor under sterile conditions (clean dressing room).

GCS preparations are also quite often prescribed orally in the form of tablets or administered parenterally (into a vein or muscle).

the duration of the course and the dosage of the drug depend on the severity and nature of the disease. For some patients, the therapeutic course is several months or even years. With a high activity of the pathological process in the joints, the so-called pulse therapy is used. In this case, the drug is administered intravenously (through a dropper) for 3 days in a row. In most cases, pulse therapy with glucocorticosteroids allows you to quickly suppress the activity of the inflammatory process.

Contraindications

GCS preparations, like many other drugs, may not be prescribed to all patients. Depending on the route of administration of the drug, certain contraindications must be taken into account. For example, intravenous, intramuscular or oral glucocorticosteroids should not be used in the following diseases or pathological conditions:

• Bacterial, viral or fungal infection.
• immunodeficiency states.
• 8 weeks before vaccination.
• Up to 2 weeks after vaccination.
• Erosive and ulcerative lesions of the gastrointestinal tract.
• Severe pathology of the cardiovascular system (myocardial infarction, arterial hypertension, etc.).
• Serious pathology of the endocrine system (diabetes mellitus, thyrotoxicosis, Itsenko-Cushing's disease, etc.).
• Severe disorders of the kidneys and liver.
• progressive osteoporosis.
• Severe forms of obesity.

In addition, corticosteroids are not injected into the affected joint with increased bleeding, severe osteoporosis, and ineffectiveness from previous injections. Also, this route of administration for glucocorticosteroids is contraindicated in intra-articular fractures, periarthritis of an infectious nature and before joint surgery (arthroplasty).

GCS preparations are never used for prophylactic purposes and for the treatment of joint inflammation, the cause of which has not been established.

Adverse reactions

According to clinical observation, despite the fact that most of the side effects from long-term use of corticosteroids in inflammatory diseases of the joints and spine are considered quite severe, some of them appear an order of magnitude less frequently than with other anti-inflammatory drugs. Many experts conditionally divide side effects with prolonged systemic use of glucocorticosteroids into two groups:

• Potentially controlled (diabetes mellitus, persistent increase in blood pressure, sleep disturbance, glaucoma, heart failure, gastrointestinal ulcers, osteoporosis).
• Uncontrolled (weight gain, cataracts, mental disorders, skin rashes, various infections, osteonecrosis, atherosclerosis).

At the same time, it was found that the use of non-steroidal anti-inflammatory drugs more often provokes the development of severe erosive and ulcerative pathology of the gastrointestinal tract than the use of drugs from the GCS group. Treatment with glucocorticoids is justifiably associated with an increased risk of infectious complications, but this is typical mainly for patients who receive high doses of drugs. Criteria for inadequate glucocorticosteroid therapy should be mentioned:

• Too high a dose or, conversely, too low.
• Unreasonably long course of treatment.
• Lack of basic anti-inflammatory drugs.

With intra-articular administration of corticosteroids, one of the most dangerous, but rather rare complications is infection in the joint cavity during the injection process. In addition, the immunosuppressive property of glucocorticoids contributes to the development of a purulent inflammatory process. In rare cases, “post-injection synovitis” can be observed, when after an injection there is an increase in the inflammatory process in the synovial membrane of the joint, which can last from several hours to 2-3 days.

It is highly undesirable to introduce the drug into muscle tissue, since atrophic or necrotic processes may develop.

Glucocorticosteroid osteoporosis

One of the most unfavorable complications of prolonged glucocorticosteroid treatment is. However, according to some experts, the high inflammatory activity of rheumatoid arthritis and reduced physical activity are considered no less important factors in the onset of osteoporosis than long-term treatment with corticosteroids.

To reduce the risk of developing this complication, many doctors recommend significantly adjusting their lifestyle, especially for those patients who receive glucocorticosteroids for a long time. What exactly needs to be done:

1. Give up smoking and alcohol.
2. Exercise regularly.
3. Eat foods rich in calcium and vitamin D.
4. Be in the sun more often.
5. If necessary, take medications prescribed by a doctor (, calcitonin, etc.).

Pregnancy and lactation

Targeted clinical studies on the safety of the use of glucocorticosteroids during pregnancy have not been conducted. However, doctors may prescribe this drug to a pregnant woman, but only if the expected benefit of the treatment far outweighs the perceived risk to the baby. In addition, nursing mothers are strongly advised to suspend breastfeeding for the duration of glucocorticosteroid therapy.

Overdose

In the event of an overdose of GCS drugs, a significant increase in blood pressure, the occurrence of edema of the lower extremities, and an increase in the side effects of the drug itself can be observed. If an acute overdose is recorded, then it is necessary to wash the stomach as soon as possible or provoke vomiting. If the condition worsens, you should immediately contact a specialized medical facility. A specific antidote has not yet been developed.

Interaction

Multiple scientific studies have proven that glucocorticosteroids interact with many drugs, provoking the development of various adverse reactions. To avoid unwanted effects, it is recommended to consult with your doctor before combining the use of corticosteroids with any other medicine.

Price

To purchase any drug from the group of glucocorticosteroids, you must have a prescription. It will not be superfluous to recall once again that all GCS have very specific features of use and a very wide range of adverse reactions, therefore it is strongly not recommended to self-medicate. For information purposes only, here are the prices for some medicines:

• A package of Prednisolone tablets costs about 100-110 rubles. One ampoule containing 30 mg of the drug will cost 25 rubles.
• The price of Hydrocortisone in suspension for injection is about 180 rubles.
• The cost of one ampoule of Diprospan ranges from 175–210 rubles.
• A pack of tablets is available for 40 rubles. In ampoules, this drug will cost 210 rubles.

If your health condition worsens or any symptoms develop during or after glucocorticosteroid therapy, contact your doctor immediately.

6890 0

Index of drug descriptions

Betamethasone
Hydrocortisone
Methylprednisolone
Prednisolone
Triamcinolone
flumethasone
INN is missing

• Lorinden A
• Lorinden S
• Triderm

Steroid anti-inflammatory drugs based on natural corticosteroids are the most active anti-inflammatory drugs and are used in dentistry, as a rule, locally, less often systemically.

Mechanism of action and pharmacological effects

The mechanism of action of corticosteroids is associated with their ability to interact with specific receptors in the cell cytoplasm: the steroid-receptor complex penetrates the cell nucleus, binds to DNA, affecting the transcription of a wide range of genes, which leads to a change in the synthesis of proteins, enzymes, nucleic acids. GCS affect all types of metabolism, have a pronounced anti-inflammatory, anti-allergic, anti-shock and immunosuppressive effect.

The mechanism of the anti-inflammatory action of GCS is to suppress all phases of inflammation. Stabilizing the membranes of cellular and subcellular structures, incl. lysis, steroidal anti-inflammatory drugs prevent the release of proteolytic enzymes from the cell, inhibit the formation of free oxygen radicals and lipid peroxides in membranes. In the focus of inflammation, GCS constrict small vessels and reduce the activity of hyaluronidase, which contributes to the inhibition of the exudation stage, prevents the adhesion of neutrophils and monocytes to the vascular endothelium, limits their penetration into tissues, and reduces the activity of macrophages and fibroblasts.

In the realization of the anti-inflammatory effect, the ability of GCS to inhibit the synthesis and release of inflammatory mediators (PG, histamine, serotonin, bradykinin, etc.) plays a significant role. They induce the synthesis of lipocortins - inhibitors of the biosynthesis of phospholipase A2 and reduce the formation of COX-2 in the focus of inflammation. This leads to a limitation of the release of arachidonic acid from cell membrane phospholipids and to a decrease in the formation of its metabolites (PG, leukotrienes and platelet activating factor).

GCS are able to inhibit the proliferation phase, tk. they limit the penetration of monocytes into the inflamed tissue, preventing their participation in this phase of inflammation, inhibit the synthesis of mucopolysaccharides, proteins and inhibit the processes of lymphopoiesis. In case of inflammation of an infectious genesis, GCS, given their immunosuppressive effect, should be combined with antimicrobial therapy.

The immunosuppressive effect of GCS is due to a decrease in the number and activity of T-lymphocytes circulating in the blood, a decrease in the production of immunoglobulins and the influence of T-helpers on B-lymphocytes, a decrease in the complement content in the blood, the formation of fixed immune complexes and a number of interleukins, inhibition of the formation of a factor that inhibits the migration of macrophages .

The antiallergic effect of GCS is due to a decrease in the number of circulating basophils, a violation of the interaction of Fc receptors located on the surface of mast cells, with the Fc site of IgE and the C3 component of complement, which prevents the signal from entering the cell and is accompanied by a decrease in the release of histamine, heparin, and serotonin from sensitized cells and other immediate-type allergy mediators and prevents their effect on effector cells.

The anti-shock effect is due to the participation of GCS in the regulation of vascular tone; against their background, the sensitivity of blood vessels to catecholamines increases, which leads to an increase in blood pressure, changes in water-salt metabolism, sodium and water are retained, plasma volume increases and hypovolemia decreases.

Pharmacokinetics

Most corticosteroids (except for synthetic drugs for topical use) are well absorbed from the gastrointestinal tract, regardless of food intake. Drugs penetrate well through the mucous membranes and histohematic barriers, incl. through the BBB and placenta. In the blood, they mostly bind to proteins (60-90%) - transcortin (this complex does not penetrate tissues, being a kind of hormone depot) and albumin (this complex penetrates tissues). GCS are metabolized mainly in the liver by hydroxylation and conjugation, as well as in the kidneys and other tissues. Excreted mainly by the kidneys as inactive metabolites.

Place in therapy

In dental practice, injectable corticosteroids are used for emergency care in shock conditions; locally (less often systemically) - for the treatment of pulpitis and periodontitis, diseases of the oral mucosa and salivary glands of an inflammatory and allergic nature, for arthritis and arthrosis of the temporomandibular joint, as well as for osteomyelitis, periostitis, pemphigus and lichen planus.

Tolerability and side effects

This group of drugs quite often causes side effects: it is possible to suppress the reactivity of the body, exacerbate chronic infectious diseases and gastrointestinal diseases. With prolonged use, an increase in blood pressure, the development of steroid diabetes, edema, muscle weakness, myocardial dystrophy, Itsenko-Cushing's syndrome, and adrenal atrophy are possible.

Sometimes when taking drugs, agitation, insomnia, increased intracranial pressure, psychosis are observed. With prolonged systemic use of corticosteroids, a violation of bone tissue synthesis and calcium-phosphorus metabolism is possible, which ultimately leads to osteoporosis and spontaneous fractures.

Contraindications

• Hypersensitivity.
• severe infections.
• Viral and fungal diseases.
• Severe form of tuberculosis.
• AIDS.
• Peptic ulcer of the stomach, stomach bleeding.
• Severe forms of hypertension.
• Syndrome Itsenko-Cushing.
• Nephritis.
• Syphilis.
• Diabetes.
• Osteoporosis.
• Pregnancy.
• Breast-feeding.
• Acute psychoses.
• Younger children's age.

When applied topically:

• Infectious (bacterial, viral, fungal) lesions of the skin and mucous membranes.
• Skin tumors.
• Violation of the integrity of the skin and mucous membranes.
• Younger children's age.

Interaction

GCS enhance the bronchodilatory effect of β-agonists and theophylline, reduce the hypoglycemic effect of insulin and oral antidiabetic agents, and the anticoagulant activity of coumarins (indirect anticoagulants).

Difenin, ephedrine, phenobarbital, rifampicin and other drugs that cause the induction of microsomal liver enzymes shorten T1 / 2 GCS. Somatotropin and antacids reduce the absorption of GCS. When combined with cardiac glycosides and diuretics, the risk of arrhythmias and hypokalemia increases; when combined with NSAIDs, the risk of gastrointestinal damage and gastrointestinal bleeding increases.