Glucocorticoid use. Glucocorticosteroids: indications, contraindications and side effects

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 secretes 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 GCS 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, nose 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 a particular 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 care 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.

Thank you

The site provides reference information for informational purposes only. Diagnosis and treatment of diseases should be carried out under the supervision of a specialist. All drugs have contraindications. Expert advice is required!

Introduction (characteristics of preparations)

Natural corticosteroids

Corticosteroids- common name hormones adrenal cortex, which includes glucocorticoids and mineralocorticoids. The main glucocorticoids produced in the human adrenal cortex are cortisone and hydrocortisone, and the mineralocorticoid is aldosterone.

Corticosteroids perform many very important functions in the body.

Glucocorticoids refer to steroids, which has an anti-inflammatory effect, they are involved in the regulation of the metabolism of carbohydrates, fats and proteins, control puberty, kidney function, the body's response to stress, and contribute to the normal course of pregnancy. Corticosteroids are inactivated in the liver and excreted in the urine.

Aldosterone regulates sodium and potassium metabolism. Thus, under the influence mineralocorticoid Na + is retained in the body and the excretion of K + ions from the body increases.

Synthetic corticosteroids

Practical application in medical practice has found synthetic corticosteroids, which have the same properties as natural ones. They are able to suppress the inflammatory process for a while, but they do not have an effect on the infectious onset, on the causative agents of the disease. Once the corticosteroid drug wears off, the infection reappears.

Corticosteroids cause tension and stress in the body, and this leads to a decrease in immunity, since immunity is provided at a sufficient level only in a relaxed state. Given the above, we can say that the use of corticosteroids contributes to the protracted course of the disease, blocks the regeneration process.

In addition, synthetic corticosteroids suppress the function of natural corticosteroid hormones, which entails a violation of the function of the adrenal glands in general. Corticosteroids affect the work of other endocrine glands, the hormonal balance of the body is disturbed.

Corticosteroid drugs, eliminating inflammation, also have an analgesic effect. Synthetic corticosteroid drugs include Dexamethasone, Prednisolone, Sinalar, Triamcinolone and others. These drugs have a higher activity and cause fewer side effects than natural ones.

Forms of release of corticosteroids

Corticosteroids are produced in the form of tablets, capsules, solutions in ampoules, ointments, liniments, creams. (Prednisolone, Dexamethasone, Budenofalm, Cortisone, Cortinef, Medrol).

Preparations for internal use (tablets and capsules)

• Prednisolone;
• Celeston;
• Triamcinolone;
• Kenacort;
• Cortineff;
• Polcortolon;
• Kenalog;
• Metipred;
• Berlikort;
• Florinef;
• Medrol;
• Lemod;
• Decadron;
• Urbazon and others.

Preparations for injection

• Prednisolone;
• Hydrocortisone;
• Diprospan (betamethasone);
• Kenalog;
• Flosteron;
• Medrol etc.

Preparations for local use (topical)

• Prednisolone (ointment);
• Hydrocortisone (ointment);
• Locoid (ointment);
• Corteid (ointment);
• Afloderm (cream);
• Laticort (cream);
• Dermovate (cream);
• Fluorocort (ointment);
• Lorinden (ointment, lotion);
• Sinaflan (ointment);
• Flucinar (ointment, gel);
• Clobetasol (ointment), etc.

Topical corticosteroids are divided into more and less active.
Weakly active agents: Prednisolone, Hydrocortisone, Cortade, Locoid;
moderately active: Afloderm, Laticort, Dermovate, Fluorocort, Lorinden;
Highly active: Akriderm, Advantan, Kuterid, Apulein, Cutiveit, Sinaflan, Sinalar, Synoderm, Flucinar.
Very highly active Clobetasol.

Corticosteroids for inhalation

• Beclamethasone in the form of metered-dose aerosols (Becotid, Aldecim, Beclomet, Beclocort); in the form of back disks (powder in a single dose, inhaled with a diskhaler); in the form of a metered-dose aerosol for inhalation through the nose (Beclomethasone-nasal, Beconase, Aldecim);
• Flunisolide in the form of metered-dose aerosols with a spacer (Ingacort), for nasal use (Sintaris);
• Budesonide - metered aerosol (Pulmicort), for nasal use - Rinocort;
• Fluticasone in the form of aerosols Flixotide and Flixonase;
• Triamcinolone is a metered-dose aerosol with a spacer (Azmacort), for nasal use - Nazacort.

Indications for use

Corticosteroids are used to suppress the inflammatory process in many branches of medicine, with many diseases.

Indications for the use of glucocorticoids

• Rheumatism;
• rheumatoid and other types of arthritis;
• collagenosis, autoimmune diseases (scleroderma, systemic lupus erythematosus, periarteritis nodosa, dermatomyositis);
• blood diseases (myeloid and lymphoblastic leukemias);
• some types of malignant neoplasms;
• skin diseases (neurodermatitis, psoriasis, eczema, seborrheic dermatitis, discoid lupus erythematosus, atopic dermatitis, erythroderma, lichen planus);
• bronchial asthma;
• allergic diseases;
• pneumonia and bronchitis, fibrosing alveolitis;
• ulcerative colitis and Crohn's disease;
• acute pancreatitis;
• hemolytic anemia;
• viral diseases (infectious mononucleosis, viral hepatitis and others);
• otitis externa (acute and chronic);
• treatment and prevention of shock;
• in ophthalmology (for non-infectious diseases: iritis, keratitis, iridocyclitis, scleritis, uveitis);
• neurological diseases (multiple sclerosis, acute spinal cord injury, optic neuritis;
• in organ transplantation (to suppress rejection).

Indications for the use of mineralocorticoids

• Addison's disease (chronic insufficiency of hormones of the adrenal cortex);
• myasthenia gravis (an autoimmune disease manifested by muscle weakness);
• violations of mineral metabolism;
• adynamia and muscle weakness.

Contraindications

Contraindications for the appointment of glucocorticoids:

• hypersensitivity to the drug;
• severe infections (except tuberculous meningitis and septic shock);
• immunization with a live vaccine.

Carefully glucocorticosteroids should be used for diabetes mellitus, hypothyroidism, gastric ulcer and duodenal ulcer, ulcerative colitis, high blood pressure, cirrhosis of the liver, cardiovascular insufficiency in the stage of decompensation, increased thrombosis, tuberculosis, cataracts and glaucoma, mental illness.

Contraindications for prescribing mineralocorticoids:

• high blood pressure;
• diabetes;
• low levels of potassium in the blood;
• renal and hepatic insufficiency.

Adverse reactions and precautions

Corticosteroids can cause a wide variety of side effects. When using weakly active or moderately active agents, adverse reactions are less pronounced and rarely occur. High doses of drugs and the use of highly active corticosteroids, their long-term use can cause such side effects:

• the appearance of edema due to the retention of sodium and water in the body;
• increased blood pressure;
• increased blood sugar levels (perhaps even the development of steroid diabetes mellitus);
• osteoporosis due to increased calcium excretion;
• aseptic necrosis of bone tissue;
• exacerbation or occurrence of gastric ulcer; gastrointestinal bleeding;
• increased thrombus formation;
• weight gain;
• the occurrence of bacterial and fungal infections due to a decrease in immunity (secondary immunodeficiency);
• violation of the menstrual cycle;
• neurological disorders;
• development of glaucoma and cataracts;
• skin atrophy;
• increased sweating;
• the appearance of acne;
• suppression of the tissue regeneration process (slow wound healing);
• excess hair growth on the face;
• suppression of adrenal function;
• mood instability, depression.

Long-term courses of corticosteroids can lead to a change in the patient's appearance (Itsenko-Cushing's syndrome):

• excessive deposition of fat in certain parts of the body: on the face (the so-called "moon-shaped face"), on the neck ("bull neck"), chest, stomach;
• limb muscles are atrophied;
• bruising on the skin and striae (stretch marks) on the abdomen.

With this syndrome, growth retardation, violations of the formation of sex hormones (menstrual disorders and male type of hair growth in women, and signs of feminization in men) are also noted.

To reduce the risk of adverse reactions, it is important to respond in a timely manner to their occurrence, adjust doses (using small doses if possible), control body weight and calorie content of foods consumed, and limit salt and fluid intake.

How to use corticosteroids?

Glucocorticosteroids can be used systemically (in the form of tablets and injections), locally (intra-articular, rectal administration), topically (ointments, drops, aerosols, creams).

The dosage regimen is prescribed by the doctor. The tablet preparation should be taken from 6 o'clock in the morning (first dose) and no later than 14 o'clock subsequent. Such intake conditions are necessary to approach the physiological intake of glucocorticoids into the blood when they are produced by the adrenal cortex.

In some cases, at high doses and depending on the nature of the disease, the dose is distributed by the doctor for a uniform intake during the day for 3-4 doses.

Tablets should be taken with meals or immediately after meals with a small amount of water.

Treatment with corticosteroids

The following types of corticosteroid therapy are distinguished:

• intensive;
• limiting;
• alternating;
• intermittent;
• pulse therapy.

At intensive care(in the case of an acute, life-threatening pathology), the drugs are administered intravenously and, upon reaching the effect, are canceled at once.

limiting therapy used for long-term, chronic processes - as a rule, tablet forms are used for several months or even years.

To reduce the inhibitory effect on the function of the endocrine glands, intermittent drug regimens are used:

• alternative therapy - use glucocorticoids with a short and medium duration of action (Prednisolone, Methylprednisolone) once from 6 to 8 am every 48 hours;
• intermittent therapy - short, 3-4-day courses of taking the drug with 4-day breaks between them;
• pulse therapy- rapid intravenous administration of a large dose (at least 1 g) of the drug for emergency care. The drug of choice for such treatment is methylprednisolone (it is more accessible for injection into the affected areas and has fewer side effects).

Daily doses of drugs(in terms of Prednisolone):

• Low - less than 7.5 mg;
• Medium - 7.5 -30 mg;
• High - 30-100 mg;
• Very high - above 100 mg;
• Pulse therapy - above 250 mg.

Treatment with corticosteroids should be accompanied by the appointment of calcium supplements, vitamin D for the prevention of osteoporosis. The patient's diet should be rich in proteins, calcium and include a limited amount of carbohydrates and table salt (up to 5 g per day), fluids (up to 1.5 liters per day).

For prevention undesirable effects of corticosteroids on the gastrointestinal tract, before taking the tablets, it is possible to recommend the use of Almagel, jelly. It is recommended to exclude smoking, alcohol abuse; moderate exercise.

Corticosteroids for children

Systemic glucocorticoids are prescribed to children only on absolute indications. In the case of broncho-obstruction syndrome that threatens the child's life, intravenous administration of prednisolone is used at a dose of 2-4 mg per 1 kg of the child's body weight (depending on the severity of the course of the disease), and the dose, if there is no effect, is increased by 20-50% every 2-4 hours until getting the effect. After that, the drug is canceled immediately, without a gradual decrease in dosage.

Children with hormonal dependence (with bronchial asthma, for example) after intravenous administration of the drug are gradually transferred to a maintenance dose of prednisolone. With frequent relapses of asthma, beclamethasone dipropionate is used in the form of inhalations - the dose is selected individually. After obtaining the effect, the dose is reduced gradually to a maintenance dose (selected individually).

Topical glucocorticoids(creams, ointments, lotions) are used in pediatric practice, but children have a higher predisposition to the systemic effects of drugs than adult patients (development and growth retardation, Itsenko-Cushing's syndrome, inhibition of the function of the endocrine glands). This is due to the fact that in children the ratio of body surface area to body weight is greater than in adults.

For this reason, the use of topical glucocorticoids in children is necessary only in limited areas and in a short course. This is especially true for newborns. For children of the first year of life, only ointments containing no more than 1% hydrocortisone or a fourth-generation drug - Prednikarbat (Dermatol), and at the age of 5 years - Hydrocortisone 17-butyrate or ointments with medium-strength drugs can be used.

For the treatment of children older than 2 years, mometasone (ointment, has a prolonged action, is applied 1 r. per day) as directed by a doctor.

There are other drugs for the treatment of atopic dermatitis in children, with a less pronounced systemic effect, for example, Advantan. It can be used for up to 4 weeks, but its use is limited due to the possibility of local adverse reactions (dryness and thinning of the skin). In any case, the choice of drug for the treatment of the child remains with the doctor.

Corticosteroids during pregnancy and lactation

The use of glucocorticoids, even short-term, can "program" for decades to come the work of many organs and systems in an unborn child (blood pressure control, metabolic processes, behavior formation). The synthetic hormone imitates the mother's stress signal to the fetus and thereby causes the fetus to force the use of reserves.

This negative effect of glucocorticoids is enhanced by the fact that modern long-acting drugs (Metipred, Dexamethasone) are not deactivated by placental enzymes and have a long-term effect on the fetus. Glucocorticoids, by suppressing the immune system, help reduce the resistance of a pregnant woman to bacterial and viral infections, which can also adversely affect the fetus.

Glucocorticoid drugs can be prescribed to a pregnant woman only if the result of their use exceeds to a large extent the risk of possible negative consequences for the fetus.

Such indications may be:
1. The threat of premature birth (a short course of hormones improves the readiness of a premature fetus for birth); the use of a surfactant for the child after birth has minimized the use of hormones in this indication.
2. Rheumatism and autoimmune diseases in the active phase.
3. Hereditary (intrauterine) hyperplasia of the adrenal cortex in the fetus is a difficult-to-diagnose disease.

Previously, there was a practice of prescribing glucocorticoids to maintain pregnancy. But convincing data on the effectiveness of such a technique has not been obtained, therefore, it is not currently used.

In obstetric practice Metipred, Prednisolone and Dexamethasone are more commonly used. They penetrate the placenta in different ways: Prednisolone is destroyed by enzymes in the placenta to a greater extent, while Dexamethasone and Metipred are only 50%. Therefore, if hormonal drugs are used to treat a pregnant woman, it is preferable to prescribe Prednisolone, and if for the treatment of a fetus, Dexamethasone or Metipred. In this regard, Prednisolone causes less adverse reactions in the fetus.

Glucocorticoids in severe allergies are prescribed both systemic (injections or tablets) and local (ointments, gels, drops, inhalations). They have a powerful antiallergic effect. The following drugs are mainly used: Hydrocortisone, Prednisolone, Dexamethasone, Betamethasone, Beclomethasone.

Of the topical glucocorticoids (for local treatment), in most cases, intranasal aerosols are used: for hay fever, allergic rhinitis, nasal congestion (sneezing). They usually have a good effect. Fluticasone, Dipropionate, Propionate and others have found wide application.

In allergic conjunctivitis, due to a higher risk of side effects, glucocorticoids are rarely used. In any case, with allergic manifestations, it is impossible to use hormonal drugs on their own in order to avoid undesirable consequences.

Corticosteroids for psoriasis

Glucocorticoids in psoriasis should be used mainly in the form of ointments and creams. Systemic (injections or tablets) hormonal preparations can contribute to the development of a more severe form of psoriasis (pustular or pustular), so their use is not recommended.

Glucocorticoids for topical use (ointments, creams) are usually used 2 r. per day: creams during the day without dressings, and at night with coal tar or anthralin using an occlusive dressing. With extensive lesions, about 30 g of the drug is used to treat the whole body.

The choice of a glucocorticoid preparation according to the degree of activity for topical application depends on the severity of the course of psoriasis and its prevalence. As psoriasis foci decrease during treatment, the drug should be changed to a less active one (or less often used) to minimize the occurrence of side effects. When the effect is obtained after about 3 weeks, it is better to replace the hormonal drug with an emollient for 1-2 weeks.

The use of glucocorticoids over large areas for a long period can aggravate the process. Relapse of psoriasis after discontinuation of the drug occurs earlier than in treatment without the use of glucocorticoids.
, Coaxil, Imipramine and others) in combination with glucocorticoids can cause an increase in intraocular pressure.

Glucocorticoids (when taken for a long time) increase the effectiveness of adrenomimetics (Adrenaline, Dopamine, Norepinephrine).

Theophylline in combination with glucocorticoids contributes to the appearance of a cardiotoxic effect; enhances the anti-inflammatory effect of glucocorticoids.

Amphotericin and diuretics in combination with corticosteroids increase the risk of hypokalemia (decrease in blood potassium levels) and increased diuretic action (and sometimes sodium retention).

The combined use of mineralocorticoids and glucocorticoids increases hypokalemia and hypernatremia. With hypokalemia, side effects of cardiac glycosides may occur. Laxatives may exacerbate hypokalemia.

Indirect anticoagulants, Butadione, Ethacrynic acid, Ibuprofen in combination with glucocorticoids can cause hemorrhagic manifestations (bleeding), and salicylates and Indomethacin can cause ulcers in the digestive organs.

Glucocorticoids enhance the toxic effect on the liver of paracetamol.

Retinol preparations reduce the anti-inflammatory effect of glucocorticoids and improve wound healing.

The use of hormones together with Azathioprine, Methandrostenolone and Hingamine increases the risk of developing cataracts and other adverse reactions.

Glucocorticoids reduce the effect of Cyclophosphamide, the antiviral effect of Idoxuridin, and the effectiveness of hypoglycemic drugs.

Estrogens enhance the action of glucocorticoids, which may allow their dosage to be reduced.

Androgens (male sex hormones) and iron preparations increase erythropoiesis (erythrocyte formation) when combined with glucocorticoids; reduce the process of excretion of hormones, contribute to the appearance of side effects (increased blood clotting, sodium retention, menstrual irregularities).

The initial stage of anesthesia with the use of glucocorticoids is lengthened and the duration of anesthesia is reduced; doses of fentanyl are reduced.

Corticosteroid Withdrawal Rules

With prolonged use of glucocorticoids, drug withdrawal should be gradual. Glucocorticoids suppress the function of the adrenal cortex, therefore, with rapid or sudden withdrawal of the drug, adrenal insufficiency may develop. There is no unified regimen for the abolition of corticosteroids. The mode of withdrawal and dose reduction depends on the duration of the previous course of treatment.

If the duration of the glucocorticoid course is up to several months, then the dose of Prednisolone can be reduced by 2.5 mg (0.5 tablets) every 3-5 days. With a longer duration of the course, the dose decreases more slowly - by 2.5 mg every 1-3 weeks. With great care, the dose is reduced below 10 mg - 0.25 tablets every 3-5-7 days.

If the initial dose of Prednisolone was high, then at first the decrease is made more intensively: by 5-10 mg every 3 days. Upon reaching a daily dose equal to 1/3 of the original dose, reduce by 1.25 mg (1/4 tablet) every 2-3 weeks. As a result of this reduction, the patient receives maintenance doses for a year or more.

The doctor prescribes a drug reduction regimen, and violation of this regimen can lead to an exacerbation of the disease - treatment will have to be started again with a higher dose.

Prices for corticosteroids

Because there are so many different forms of corticosteroids on the market, here are the prices for just a few:

• Hydrocortisone - suspension - 1 bottle 88 rubles; eye ointment 3 g - 108 rubles;
• Prednisolone - 100 tablets of 5 mg - 96 rubles;
• Metipred - 30 tablets of 4 mg - 194 rubles;
• Metipred - 250 mg 1 bottle - 397 rubles;
• Triderm - ointment 15 g - 613 rubles;
• Triderm - cream 15 g - 520 rubles;
• Dexamed - 100 ampoules of 2 ml (8 mg) - 1377 rubles;
• Dexamethasone - 50 tablets of 0.5 mg - 29 rubles;
• Dexamethasone - 10 ampoules of 1 ml (4 mg) - 63 rubles;
• Oftan Dexamethasone - eye drops 5 ml - 107 rubles;
• Medrol - 50 tablets of 16 mg - 1083 rubles;
• Flixotide - aerosol 60 doses - 603 rubles;
• Pulmicort - aerosol 100 doses - 942 rubles;
• Benacort - aerosol 200 doses - 393 rubles;
• Symbicort - an aerosol with a dispenser of 60 doses - 1313 rubles;
• Beclazone - aerosol 200 doses - 475 rubles.

Before use, you should consult with a specialist.

Catad_tema Clinical pharmacology - articles

Comparative analysis of the efficacy and safety of fluorinated and chlorinated topical glucocorticosteroids

Published in a magazine:
"Modern problems of dermatovenereology, immunology and medical cosmetology", 3, 2010 Svirshchevskaya E.V. 1 , Matushevskaya E. V. 2
1 FMBA Advanced Training Institute, Moscow
b Institute of Bioorganic Chemistry RAS
Svirshchevskaya Elena Viktorovna 117997, Moscow, st. Miklukho-Maclay, 16/10

Topical glucocorticosteroids and their mechanism of action

Topical glucocorticosteroids (GCS) are the main and practically uncontested drugs in the external treatment of many dermatoses. Recently, dermatologists have identified a number of skin diseases, the basis of treatment for which are corticosteroids. This group is called steroid-sensitive dermatoses. It includes diseases that differ in pathogenesis and clinical manifestations, but they are united by the need for a suppressive effect on the cells of the immune system associated with the skin. These are atopic dermatitis (AD), allergic dermatitis, eczema, seborrheic skin inflammation, psoriasis and many others. In accordance with the European classification of the activity of local corticosteroids, 4 classes of topical drugs are distinguished, divided by the degree of vasoconstrictor effect ( tab. 1).

When using topical corticosteroids, there is a local increase in the concentration of corticosteroids in the area of ​​the inflammatory process, due to which corticosteroids do not have a suppressive effect on both the central immune system and other body systems, which avoids severe side effects. Topical corticosteroids have pronounced anti-inflammatory, antiallergic, antiexudative and antipruritic actions. They inhibit the accumulation of leukocytes, the release of lysosomal enzymes and pro-inflammatory mediators in the focus of inflammation, inhibit phagocytosis, reduce vascular tissue permeability, and prevent the formation of inflammatory edema. Thus, it becomes clear that the use of topical corticosteroids is appropriate due to their local action on activated cells in the skin. Modern synthetic corticosteroids have a greater affinity for the glucocorticosteroid receptor (GCR), and therefore the action develops much faster and lasts longer.

Topical glucocorticosteroid analogues

Currently, a number of highly effective GCS preparations have been synthesized, used in the form of ointments, creams, lotions, aerosols, and, less often, in the form of solutions and suspensions. The structure of the main derivatives is shown in the figure. The most effective at the moment are fluorinated and chlorinated derivatives of cortisol ( tab. 2). Among fluorinated drugs, betamethasone dipropionate (BDP), containing one fluorine atom, and fluticasone propionate (FP), containing three fluorine atoms, have the highest activity. Among the chlorinated derivatives, mometasone furoate (MF), containing 2 chlorine atoms, and beclomethasone dipropionate (BCDP), containing one chlorine atom, are considered the most effective.

Comparison of fluorinated and chlorinated derivatives of cortisol was carried out in many respects. The most important parameters of action, such as the binding of steroids to HCC, the suppression of protein transcription, the decrease in the synthesis of various cytokines and vasoactive factors, etc., as a result of this, are shown in Table. 3 for the most studied chlorinated derivative of MF and fluorinated EP preparation compared to dexamethasone (DM). In in vitro tests, the activity of MF and FP practically does not differ and significantly exceeds DM.

Rice. 1. Structure of cortisol and synthetic GCS derivatives. Ring D is the basis of all GCS derivatives (based on the article by S. P. Umland)

Fluorinated corticosteroids are highly effective inhibitors of cell activation not only in vitro, but also when used in vivo. However, with prolonged use, they can cause skin atrophy in patients and an increase in the level of cortisone in the blood, and aggravate the course of osteoporosis. The data currently available indicate that the use of chlorinated derivatives is safer in long-term therapy, for example, seasonal rhinitis and atopic dermatitis. Thus, the use of MF in 68 patients with AD for 6 months led to the maintenance of remission in 61 patients; while minor complications were observed in only one patient. Efficacy and safety of MF (cream Uniderm) have also been confirmed in domestic studies of children and adults with atopic dermatitis and psoriasis.

Table 1. Classification of topical corticosteroids

Table 2. Classification of chlorinated and fluorinated GCS

Table 3 Comparative activity of fluorinated and chlorinated GCS derivatives in various tests, % of the activity of mometasone fuorate (according to Umland, 2002)

Action	MF	FP	DM
Binding to the GCS receptor	100	65-79	5-10
Suppression of transcriptional activation	100	25	5
Suppression of the synthesis of IL-4 and IL-5	100	90-100	20
Suppression of constitutive expression of adhesion molecules	100	90-100	15
Suppression of expression of VCAM-1 and ICAM-1 adhesion molecules induced by TNF-α	0	0	0
Suppression of expression of adhesion molecules VCAM-1 and ICAM-1 induced by rhinovirus	100	100	18
Suppression of eosinophil function	100	90-100	20
Suppression of leukotriene production	100	90-100	15
Inhibition of migration of leukocytes into tissue	100	100

Notes:
MF - mometasone furoate
FP - fluticasone propionate
DM - dexamethasone
IL - interleukin
TNF-α - tumor necrosis factor alpha

A comparative study of BDP and MF showed that once-daily use of mometasone furoate in AD patients resulted in faster resolution of disease symptoms with fewer side effects than twice-daily use of BDP. However, with short-term use (from 2 to 4 weeks) of fluorinated drugs, side effects were practically not observed.

An analysis of drug costs in England showed that MF is about 2.5 to 3 times more expensive than BDP. At the same time, the use of MF once a day can reduce the cost of treatment. If it is necessary to use topical steroids for a long time, especially on large surfaces of the skin, when they are applied to the face, neck, folds, it makes sense to use MF, and if a short course is necessary, the use of cheaper and equally effective fluorinated drugs is quite adequate (Table 4).

Table 4 Comparative characteristics of the effectiveness of action and features of the use of fluorinated and chlorinated topical corticosteroids of class III

Betamethasone dipropionate	mometasone furoate
Contains 1 fluorine atom	Contains 2 chlorine atoms
The speed of the onset of the therapeutic effect (in the first 4 - 5 days)	The speed of the onset of the therapeutic effect (in the first 2 - 3 days)
Apply to the face, neck, folds for no more than 5 days	Apply to face, neck, folds no more than 14 days
Mainly on small surfaces	Mainly on large surfaces
Dosage form - ointment, cream	Dosage form - cream
High local security	High local security
Apply 2 times a day	Apply 1 time per day
"Line" with combinations of active ingredients ( Akriderm)	Monopreparation( Uniderm)
OTC drug	prescription drug
Approved for use in children from 1 year	Approved for use in children from 6 months

Given the long-term nature of the course of many skin diseases, an intermittent scheme for the use of topical corticosteroids is becoming increasingly relevant - two days a week or every other day for several months. The effectiveness and safety of this scheme has been proven by foreign and Russian studies.

One possible option for topical corticosteroid therapy is combination with antimycotic or antibacterial drugs. So, in the presence of concomitant infections, the use of drugs such as Akriderm SK, Akriderm GK and Akriderm Genta, which include betamethasone dipropionate as an active corticosteroid, as well as salicylic acid (SA), the antibiotic gentamicin (Genta) or gentamicin and an antifungal agent, is effective. clotrimazole (GC), respectively. However, it should be noted that randomized studies have shown that the use of steroids alone for the treatment of bacterial and mycotic infections was as effective as the use of combined topical preparations.

Currently, "strong" topical corticosteroids (betamethasone dipropionate and mometasone furoate) are recommended by leading experts in Russia and abroad as the drugs of choice in the treatment of many dermatoses.

List of used literature

1. Weston W.L. The use and abuse of topical steroids // Contemp. Pediatr. - 1988. - Vol. 5. - P. 57 - 66.
2. Medansky R. S., Brody N. I., Kanof N. B. Clinical investigations of momethasone furoate - a novel, non-fluorinated, topical corticosteroid // Semin. Dermatol. - 1987. - Vol. 6. - P. 94 - 100.
3. Viglioglia P., Jones M. L., Peers E. A. Once daily 0.1% momethasone furoate cream versus twice daily 0.1% betamethasone valerate cream in the treatment of a variety of dermatoses // J. Int. Med. Res. - 1990. - Vol. 18. - P. 460 - 467.
4. Rouumestan C., Henriquet C., Bousquet J. et al. Fluticasone propionate and mometasone furoate have equivalent transcriptional potencies // Clin. Exp. Allergy. - 2003. - Vol. 33. - P. 895 - 901.
5. Umland S.P., Schleimer R.P., Johnston S.L. Review of the molecular and cellular mechanisms of action of glucocorticoids for use in asthma // Pulmonary Pharmacol. & Therapeutics. - 2002. - Vol. 15. - P. 35 - 50.
6. Stoppoloni G., Prisco F., Santinelli R. Potential hazards of topical steroid therapy // Am. J. Dis. child. - 1983. - Vol. 137. - P. 1130 - 1331.
7. Faergemann J., Christensen O., Sjovall P. et al. An open study of efficacy and safety of long-term treatment with mometasone furoate fatty cream in the treatment of adult patients with atopic dermatitis // J. Eur. Acad. Dermatol. Venereol. -2000. - Vol. 14, No. 5. - P. 393 - 396.
8. Potekaev N. N., Zhukova O. V., Lekasheva N. N. and others. Non-invasive diagnostic methods in evaluating the effectiveness of external therapy for chronic inflammatory dermatoses. Klin. dermatol. and venerol. - 2010. - No. 2. - P. 32 - 37.
9. Korotkiy N. G., Gamayunov B. N., Tikhomirov A. A.. The practice of using new external agents in the treatment of atopic dermatitis in children. Klin. dermatol. and venerol. - 2010. - No. 1. - P. 2 - 6.
10. Green C., Colquitt J. L., Kirby J. et al. Clinical and cost-effectiveness of once-daily versus more frequent use of the same potency topical corticosteroids for atopic eczema: a systematic review and economic evaluation // Health Technol. assessment. - 2004. - Vol. 8. - P. 47.
11. Tayab Z. R., Fardon T. C., Lee D. K. C. et al. Pharmacokinetic/pharmacodynamic evaluation of urinary cortisol suppression after inhalation of fluticasone propionate and mometasone furoate // Br. J.Clin. Pharmacol. - 2007. - Vol. 64, No. 5. - P. 698 - 705
12. Bruni F. M., De Luca G., Venturoli V. et al. Intranasal corticosteroids and adrenal suppression // Neuroimmunomodulation. - 2009. - Vol. 16, No. 5. - P. 353 - 362.
13. Lebrun-Vignes B., Legrain V., AmoricJ. et al. Comparative study of efficacy and effect on plasma cortisol levels of micronised desonide cream 0.1 p. 100 versus betamethasone dipropionate cream 0.05 p. 100 In the treatment of childhood atopic dermatitis // Ann. Dermatol. Venereol. - 2000. - Vol. 127, No. 6 - 7. - P. 590 - 595.
14. Delescluse J., van der EndtJ. D.A comparison of the safety, tolerability, and efficacy of fluticasone propionate ointment, 0.005%, and betamethasone-17,21-dipropionate ointment, 0.05%, in the treatment of eczema // Cutis. - 1996. - Vol. 57, No. 2, Suppl. - P. 32 - 38.
15. Hanifin J., Gupta A. K., Rajagopalan R. Intermittent dosing of fluticasone propionate cream for reducing the risk of relapse in atopic dermatitis patients // J. Dermatol. - 2002. - Vol. 147, No. 3. - P. 528 - 537.
16. Veien N. K., Olholm Larsen P., Thestrup-Pedersen K. et al. Long-term, intermittent treatment of chronic hand eczema with mometasone furoate // Br. J. Dermatol. - 1999. - Vol. 140, No. 5. - P. 882 - 886.
17. Sokolovsky E. V., Monakhov K. N., Kholodilova N. A. and others. Intermittent therapy with betamethasone for atopic dermatitis and hand eczema // Ros. magazine skin. and venus. diseases. - 2009. - No. 3. - S. 16 - 21.
18. Larsen F. S., Simonsen L., Melgaard A. et al. An efficient new formulation of fusidic acid and betamethasone 17-valerate (fucicort lipid cream) for treatment of clinically infected atopic dermatitis // Acta Derm. Venereol. - 2007. - Vol. 87, No. 1. - P. 62 - 68.
19. Khobragade K.J. Efficacy and safety of combination ointment "fluticasone propionate 0.005% plus mupirocin 2.0%" for the treatment of atopic dermatitis with clinical suspicion of secondary bacterial infection: an open label uncontrolled study // Indian J. Dermatol. Venereol. Leprol. - 2005. - Vol.71, No. 2. - P. 91 - 95.
20. Hjorth N., Schmidt H., Thomsen K. Fusidic acid plus betamethasone in infected or potentially infected eczema // Pharmatherapeutica. - 1985. - Vol. 4, No. 2. - P. 126 - 131.
21. Matushevskaya E. V., Shakurov I. G., Khismatulina Z. R.. Efficacy and tolerability of drugs "line" Akriderm® in the practice of a dermatovenereologist // Klin. dermatol. and venerol. - 2008. - No. 2. - S. 2 - 4.
22. Mosges R., Domrose C. M., Loffler J. Topical treatment of acute otitis externa: clinical comparison of an antibiotics ointment alone or in combination with hydrocortisone acetate // Eur. Arch. Otorhinolaryngol. - 2007. - Vol. 264, No. 9. - P. 1087 - 1094.
23. Gong J. Q., Lin L., Lin T. et al. Skin colonization by Staphylococcus aureus in patients with eczema and atopic dermatitis and relevant combined topical therapy: a double-blind multicentre randomized controlled trial // Br. J. Dermatol. - 2006. - Vol. 155, No. 4. - P. 680 - 687.
24. Birnie A.J., Bath-Hextall F.J., Ravenscroft J.C. et al. Interventions to reduce Staphylococcus aureus in the management of atopic eczema // Cochrane Database Syst. Rev. - 2008. - Vol. 16, No. 3. - CD003871.