PREPARATIONS OF HORMONES AND THEIR ANALOGUES. Part 2

PREPARATIONS OF ADRENAL CORTAL HORMONES (CORTICOSTEROIDS, GLUCOCORTICOIDS, GLUCOCORTICOSTEROIDS)

This is very important group drugs, which are widely used in clinical practice.

There are two main groups of hormones:

1. Mineralocorticoid hormones (corticosteroids that cause a predominantly sodium-retaining effect): a) aldosterone; b) 11-deoxycorticosterone.

2. Glucocorticoid hormones (corticosteroids that affect the deposition of glycogen in the liver): a) cortisol (hydrocortisone); b) cortisone; c) 11-deoxycortisol; d) 11-dehydrocorticosterone.

In addition to these groups, a group of sex hormones is distinguished:

Androsterone;

Androstenediol;

Estrone and progesterone.

The hormones listed are natural. Currently synthesized pharmacological preparations - complete analogues these hormones.

PREPARATIONS OF NATURAL HORMONES - GLUCOCORTICOIDS

It should be said that synthetic drugs - analogues of natural glucocorticoid hormones also have weak mineralocorticoid activity (retention of sodium and water ions, loss of potassium and calcium ions). IN recent years A whole series of synthetic hormonal drugs was created, mainly having only glucocorticoid activity:

1) prednisone, prednisolone, methylprednisolone, mazipredone;

3) triamcinolone;

4) beclomethasone (Becotide), flunisolide (Ingacort);

5) betamethasone;

6) flumethasone, flucortolone, fluocinolone.

7) budesonide, etc.

New drugs are almost completely devoid of mineralocorticoid activity. The pharmacological effects of synthetic drugs coincide with the physiological ones. At the same time pharmacological action All glucocorticoids are almost identical in direction. They are released in response to stress, adapting the body, mobilizing and increasing its resistance. Therefore, glucocorticoids have a diverse effect on all types of metabolism: protein, carbohydrate, fat.

I. The effect of glucocorticoids on carbohydrate metabolism:

In peripheral tissues, for example in muscles, protein synthesis from amino acids is inhibited (anti-metabolic effect), the level of amino acids in the blood increases significantly;

In the liver, the synthesis of glucose from amino acids is stimulated (gluconeogenesis), protein synthesis in the liver and kidneys is reduced;

The absorption, assimilation and utilization of glucose by tissues decreases, which leads to an increase in blood glucose levels (hyperglycemia), and the resorption of carbohydrates in the gastrointestinal tract decreases.

II. The effect of glucocorticoids on protein metabolism:

Glucocorticoids enhance the mobilization of amino acids from tissues, in particular from skeletal muscles, and inhibit protein synthesis, particularly in the bones (osteoporosis).

III. The effect of glucocorticoids on fat metabolism:

Glucocorticoids play a “permissive” role in the mobilization of fats from the depot (which also occurs under the influence of adrenaline and growth hormone). At long-term use hormones, fat redistribution occurs. In some tissues, there is an increase in lipolysis processes (extremities), while the amount of free fatty acids in the blood plasma increases, while in other tissues there is an increase in lipogenesis processes ( upper part torso, face - “moon-shaped face”, neck - “buffalo hump”). Hypercholesterolemia occurs in the blood.

IV. The effect of glucocorticoids on water and electrolyte metabolism:

Natural and early synthetic glucocorticoids have a weak sodium-retaining, as well as calcium- and potassium-removing effect. Therefore, when a patient is prescribed large doses (more than 300 mg/day), sufficient sodium retention is observed.

New synthetic analogues of natural glucocorticoids do not have this activity and, on the contrary, can even cause a significant loss of sodium ions in the urine.

INFLUENCE OF GLUCOCORTICOIDS ON INFLAMMATION

Glucocorticoid hormones inhibit all main phases of inflammation: alteration, exudation and proliferation. There are many hypotheses in this regard.

The most acceptable are the following:

1. Glucocorticoids stabilize the membranes of cells and lysosomes (membrane stabilizing effect), thereby limiting the release of enzymes from them and, as a result, tissue damage (during inflammation, hypoxia, shock, burns). Glucocorticoids help maintain the integrity of the cell membrane even in the presence of toxins, which reduces cell swelling.

2. Glucocorticoids enhance the synthesis of lipomodulin, an endogenous inhibitor of phospholipase A-2, thereby inhibiting its activity. Phospholipase A-2 promotes the mobilization of arachidonic acid from phospholipids of cell membranes and the formation of metabolites of this acid (prostaglandins and leukotrienes), which play a key role in the process of inflammation.

In addition, glucocorticoids stimulate the synthesis of intercellular substance - hyaluronic acid, reducing permeability vascular wall. A decrease in exudation is also associated with a decrease in histamine secretion, as well as a change in the sensitivity of adrenergic receptors to catecholamines (adrenaline). Vascular tone increases and permeability decreases.

Inhibition of proliferation by glucocorticoids is associated with a decrease in protein synthesis and a decrease in the flow of leukocytes into tissues. There is a restriction of chemotaxis and spontaneous migration.

Thus, corticosteroids do not affect the cause of inflammation, therefore their anti-inflammatory activity is nonspecific and is observed both with systemic and local use.

ANTI-ALLERGIC AND IMMUNOSUPPRESSIVE EFFECTS OF GLUCOCORTICOIDS

Glucocorticoids cause both absolute and relative T-lymphocytopenia, that is, they inhibit cellular immunity.

Glucocorticoids inhibit the graft rejection reaction, as they suppress the delayed-type hypersensitivity reaction.

At the same time, hormones of this group do not change the production of antibodies by B lymphocytes, as well as the formation of immune complexes.

Glucocorticoids inhibit phagocytosis and digestive function of microphages and macrophages.

In addition, glucocorticoids increase the sensitivity of adrenoceptors

tors to catecholamines (permissive effect).

INFLUENCE OF GLUCOCORTICOIDS ON THE BLOOD SYSTEM

Glucocorticoid hormones cause rapid lysis lymphoid tissue and lymphopenia against the background of general leukocytosis. There is a decrease in the number of eosinophils.

However, at the same time, glucocorticoids help increase platelet and red blood cell levels.

It should be remembered that in addition to all the listed effects, glucocorticoids have one more purely pharmacological effect- they reproduce the effects of natural hormones when they are deficient in the body.

Indications for the use of glucocorticoid hormones:

1. As a means replacement therapy with adrenal insufficiency (with Addison's disease) in combination with mineralocorticoids).

2. As a means of anti-inflammatory therapy:

For collagenosis (diffuse connective tissue diseases, for example, rheumatism, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus); Typically, for this indication, glucocorticoids are prescribed in combination with other drugs in the most severe cases:

At severe forms glomerulonephritis;

In severe forms of hepatitis;

For eye diseases inflammatory etiology(interstitial keratitis, conjunctivitis, iritis, iridocyclitis, sympathetic ophthalmia, etc.);

For skin diseases (inflammatory dermatoses, eczema, psoriasis, etc.).

3. As a means of antiallergic therapy:

At bronchial asthma;

For autoimmune hemolytic anemia, thrombocytopenia.

4. In order to reduce the permeability of the vascular wall and membranes in general:

At acute edema brain and lungs;

For toxic and toxicoseptic forms of pneumonia (especially in children);

Toxic, toxicoseptic lesions of the gastrointestinal tract of staphylococcal and viral etiology;

For complex therapy of shock (any).

5. In order to influence the blood system:

For anemia, thrombocytopenia;

For lymphoid leukemia, lymphoma;

To suppress graft rejection during organ and tissue transplantation.

For all indications, it should be remembered that glucocorticoids do not act on the main triggers for the development of the listed pathologies, but only suppress symptoms. In this regard, glucocorticoids are a means of palliative (maintenance) therapy.

TACTICS OF THERAPY WITH GLUCOCORTICOID DRUGS

Glucocorticosteroid therapy varies depending on clinical tasks, methods of drug administration, doses used, duration and treatment regimens. Optimal dosage regimens and choice of route of administration are aimed at increasing the effectiveness of therapy and reducing the risk of developing undesirable effects.

Among the methods of drug administration, the most common is oral. In urgent therapy, intravenous administration of drugs is used. Special forms of long-acting drugs are used intramuscularly; however, it is necessary to take into account the undesirable effects that often occur with this type of drug administration:

1) muscle tissue atrophy;

2) atrophy of adipose tissue at the injection site.

Besides, this type administration does not allow modulating the body's circadian rhythms, which increases the risk of suppression of the hypothalamic-pituitary system.

Used in the treatment of patients with bronchial asthma inhalation type introduction aerosol preparations(becotide, ingacort). In this case, the drugs have a powerful local effect with minor systemic influence. The lack of systemic action is due to the fact that practically no absorption occurs. This makes it possible to avoid many side effects characteristic of systemic corticosteroid therapy.

Thus, the use of hormonal drugs in case of urgent need allows them to be considered as conventional drugs. Usage dosage forms glucocorticoids for local application(ointments, creams, aerosols) are also practically not dangerous. Long-term use of glucocorticoids is justified only in cases of severe pathology. When prescribing tablet dosage forms, it is necessary to take into account chronobiological features and patterns. It is necessary to strive to prescribe drugs every other day, which reduces the risk of suppression of the adrenal cortex and nonspecific resistance body to infection. If this method of administration is unsuitable, it is best to administer the daily dose once in the morning.

Based on the timing of treatment, there are two types of glucocorticoid therapy:

1. Short-term (intensive) glucocorticosteroid therapy. The drugs are administered once or over several days.

This type of therapy is used for health reasons (shock of any etiology, systemic allergic reactions, intoxication). In this case, maximum dosages are required. There is no withdrawal syndrome in this case.

2. Long-term (maintenance) glucocorticosteroid therapy.

This type of therapy is used in the treatment of patients with subacute or chronic course diseases, with exacerbation of chronic pathology.

FEATURES OF DOSAGE REDUCTION AND CANCELLATION OF GLUCOCORTICOIDS

The use of prednisolone in a dose of more than 10 mg already after one week causes functional insufficiency of the adrenal cortex, lasting 1-2 days, and multi-month therapy in doses of more than 5 mg leads to structural atrophy of the adrenal cortex in half of the patients.

When decreasing daily dose glucocorticoids, it is necessary to take into account that doses of drugs (for example, prednisolone) exceeding 10 mg have a complete replacement effect of endogenous hormones. Therefore, reducing the dose of prednisolone to 10-15 mg/day from a higher dose can be done quickly. However, in the future everything must be done slowly, usually no faster than 2.5-5 mg over 5-7 days.

Within six months from the date of discontinuation of long-term glucocorticosteroid therapy in cases of stress, accession infectious diseases hormonal drugs should be re-prescribed.

Before surgery (even during tooth extraction, endoscopic studies) the patient should be given 25-30 mg of prednisolone, repeated an hour before surgery and then every six hours during the day.

COMPLICATIONS, SIDE EFFECTS OF GLUCOCORTICOSTEROID THERAPY

The number of complications and side effects is very high, about 20-100%, including:

1. The phenomena of hyperglycemia (“steroid diabetes”).

In this regard, a diet with limited carbohydrates is necessary, and insulin is used if necessary.

2. Decrease in protein synthesis, which is realized in the form

Muscle pain, increased muscle fatigue;

Osteoporosis;

Delayed wound healing;

Teratogenic effect;

Developmental and growth retardation in children (when using glucocorticoids for six months or more);

Reduced absorption (the gastric mucosa suffers) of calcium and phosphorus ions, which in children leads to rickets;

Exacerbation or even the appearance of new ulcerations

intestinal mucosa (inhibition of proliferation processes);

Opacification of the lens and development of cataracts. Especially with long-term use of glucocorticoids in children;

Increased irritability in children;

Increased blood pressure, salt and fluid retention, especially in adolescents;

Redistribution of fat (“moon face”, “buffalo hump”);

Decreased immunity, immunosuppressive effect, which is realized by an increase in colds.

3. The development of withdrawal syndrome is possible, especially with abrupt withdrawal of drugs (adrenal insufficiency). Therefore, after long-term use of glucocorticoids, dosages should be reduced extremely slowly. It is possible to stimulate the adrenal cortex by administering ACTH or its synthetic analogue, corticotropin.

Contraindications to the use of glucocorticoids:

1. Diabetes mellitus.

2. Osteoporosis.

3. Pregnancy.

4. Peptic ulcer.

5. Presence of a wound process.

6. Hypertension.

7. Epilepsy.

All listed contraindications are relative.

Currently, in order to prevent complications associated with the resorptive effect of glucocorticoids, it has been created large number their dosage forms for topical use. For example, ointments produced by Gedeon Richter (Hungary): apulein (budesonide), aurobin, dermosolone, deperzolon (mazipredone), hydrocortisone, prednisolone, fluorocort (triamcinolone), mycosolone; eye drops: prednisolone; eye ointment: hydrocortisone, etc.

Are becoming widespread combination ointments containing not only glucocorticoids, but also substances that have an antiseptic effect (for example, "Aurobin"); antifungal and antimicrobial effect(“Mikozolon” ​​and “Dermozolon”), etc.

THYROID HORMONE AND ANTITHYROID MEDICINES

Under the influence thyroid-stimulating hormone adenohypophysis follicular cells thyroid gland Two main iodine-containing hormones are produced and released into the blood:

1) thyroxine (T4);

2) triiodothyronine (T3).

The interstitial cells of the thyroid gland produce the hormone thyrocalcitonin (calcitonin). The thyroxine molecule contains four iodine atoms, and the triiodothyronine molecule contains three. T4 and T3 are found in plasma, partly bound to proteins and partly in free states. The content of T4 in the blood plasma is reflected by the amount of iodine bound to plasma proteins. Free hormones are physiologically active, while the bound fraction serves as a reserve. Despite the fact that in thyroid gland thyroxine is synthesized in more than triiodothyronine, the latter has greater (five times) activity against most body tissues. In peripheral tissues, about 30% of T4 is converted to T3.

There are three main stages in the life of these hormones, which are controlled by TSH of the adenohypophysis:

1. Capture of iodides by the gland.

2. The combination of iodine with the amino acid tyrosine, which is contained in the thyroglobulin molecule, to successively form mono- and diiodotyrosine.

3. When two molecules of diiodotyrosine combine, thyroxine (T4) is formed, and when monoiodotyrosine and diiodotyrosine combine, triiodothyronine (T3) is formed.

At the last stage, hormones are released into the blood.

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PHYSIOLOGICAL EFFECTS OF HORMONES AND PHARMACOLOGICAL EFFECTS OF THEIR DRUGS

1. Effect on thermoregulation:

Increased oxygen consumption and heat production by all tissues, with the exception of the brain, genitals and lymphoid tissue.

2. Effect on tissue growth and differentiation.

3. Effect on metabolic processes:

In addition to promoting growth, these hormones also promote protein synthesis ( anabolic effect);

In high doses, catabolic effect;

The rate of cholesterol catabolism increases;

Affects water-electrolyte metabolism

(for example, with hypofunction of the thyroid gland - water and electrolyte retention).

4. Impact on cardiovascular system:

The speed and force of myocardial contractions are stimulated and cardiac output is increased.

5. Effect on the central nervous system:

Myelination of nerve fibers increases.

6. Effect on blood:

With hypofunction of the thyroid gland, anemia develops.

Conditions of hypo- and hyperfunction of the thyroid gland may occur in the clinic. With hypofunction of the thyroid gland (hypothyroidism), three forms of pathology are observed:

1) myxedema (in adults);

2) cretinism (in children);

3) endemic simple goiter (primary hypothyroidism).

To treat all three forms of hypothyroidism, use the following drugs:

I. THYREOIDIN (Thyreoidinum; available in powders and tablets of 0.05 and in film-coated tablets of 0.1 and 0.2).

The drug is available and cheap. The powder is obtained from the dried, defatted thyroid glands of slaughter cattle. The effect of this drug is associated with the presence of two hormones: thyroxine and triiodothyronine. Thyroidin is most effective for myxedema, when, thanks to the use of this drug, it is possible to achieve a good clinical effect for years.

Indications for use:

1. Cretinism (it is advisable that treatment be started as early as possible, since brain development generally ends by the third year of a person’s life).

2. When treating patients with thyroid cancer before tumor removal.

3. The drug is used with great caution in patients with atherosclerosis.

Side effects:

Allergic reactions;

Symptoms of thyrotoxicosis (in case of overdose): tachycardia, sweating, weakness, worsening of the course coronary disease heart disease, worsening of diabetes, etc.

II. TRIDOTHYRONINE HYDROCHLORIDE (available in tablets of 0.02 and 0.05).

This drug is a synthetic drug that corresponds in structure and action to the natural thyroid hormone. The drug is absorbed faster and has more quick effect and acts generally quickly, but briefly. The onset of action is after 4-8 hours, the maximum effect develops after 24 hours. The effect of the drug gradually decreases over the course of a week (half-life is two days).

The drug is used for the same indications as thyroidin, but mainly for subacute conditions.

Indications for use:

1. Primary hypothyroidism and myxedema, cretinism (it is more appropriate to use the drug in the first stage of treatment).

2. With partial adenectomy of the thyroid gland due to its hyperfunction.

3. With resistance to thyroidin.

4. For myxedema coma and psychosis (most effective).

The side effects are the same as for thyroidin.

III. LEVOTHYROXINE (L-thyroxine) is a synthetic analogue of thyroxine. Available in tablets of 25, 50, 75, 100, 125, 150, 200 mcg.

It differs from previous drugs in that it is slowly absorbed and excreted slowly. therapeutic effect observed after 7-12 days. The drug is prescribed once a day.

The indications and side effects are the same.

IV. Synthetic combination drugs:

THYROCOMB (contains T3, T4 and potassium iodide);

THYROTOM (contains T3 and T4).

In addition, for thyrotoxicosis, beta-blockers (anaprilin, metaprolol) are used to reduce tachycardia, etc.

DRUGS FOR HYPERTHYROIDISM

In this condition, it develops clinical picture diffuse toxic goiter to varying degrees gravity. Thyrotoxicosis is manifested by exophthalmos, tachycardia, sweating, increased metabolism, etc.

In general, there are two groups of antithyroid drugs

I. A group of drugs used for hyperfunction of the thyroid gland - hormone synthesis inhibitors (thiamazole, synonym: mercazolil).

TIAMAZOL (Thiamazole; issued in tablets of 0.005) is a synthetic, easily soluble in alcohol and water. The drug causes a decrease in the synthesis of thyroxine in the gland by inhibiting the enzyme oxidase. The basal metabolism decreases. The drug accumulates in the gland for a long time, and therefore has a long latent period, and the clinical effect develops within 1-2 weeks, and the maximum effect within 4-8 weeks. Therefore, the drug is usually prescribed for long period- on average for one year or more, since the drug simply cannot be prescribed for a shorter period.

Side effects:

1. Inhibition of hematopoiesis (leukopenia, anemia, agranulocytosis).

2. Skin rash(the drug affects nucleic acid metabolism).

3. Lymphadenopathy.

3. The drug crosses the placenta, causing inhibition of fetal development.

4. Penetrates easily breast milk mother.

5. Goitrogenic effect (hyperplasia of the thyroid gland in response to the active synthesis of TSH by the adenohypophysis - implementation of the feedback effect: Mercazolil causes a decrease in the synthesis of gland hormones, as a result of which the synthesis of releasing hormones increases, which entails an increase in the release of TSH and, as a consequence, proliferation thyroid gland.

II. The second group of antithyroid drugs used in the treatment of patients with hyperfunction of the thyroid gland is IODINE PREPARATIONS (iodides).

This is the oldest group of drugs used to treat patients with thyroid dysfunction. First of all, it should be said about preparations containing elemental iodine. These are Lugol's solution (5% iodine solution in 10% potassium iodide solution) and inorganic iodides (potassium and sodium iodides). The idea behind prescribing these drugs is that their iodine content significantly exceeds physiological needs body. However, tissue receptors do not respond to hormone molecules, but to the iodine that is part of them. With large dosages of iodine, the receptors are deceived, which leads to a decrease in the production of releasing hormones. This, in turn, leads to a decrease in TSH production, the iron decreases, its atrophy occurs, and its vascularization sharply decreases.

The drugs act quickly, and the effect appears 24 hours after the start of treatment. The maximum clinical effect is observed after 10-14 days. However, after a certain period of time healing effect decreases significantly. With long-term treatment with these drugs, the patient's condition may even return to its original state or worsen even further. Thus, these drugs are not suitable for long-term treatment and are used only for one indication - in preparing patients for surgery on the thyroid gland, in order to reduce vascularization.

Side effects

Iodism (runny nose, cough, conjunctivitis);

Irritation of the gastric mucosa.

PITUITARY HORMONE PREPARATIONS

The pituitary gland consists of three lobes - anterior, intermediate and posterior, each of which is essentially an endocrine gland. The anterior lobe, purely glandular in structure, is called the adenohypophysis. The adenohypophysis consists of three types of cells:

Chief (chromophobe) cells;

Acidophilic cells producing growth hormone and prolactin;

Basophil cells producing adrenocorticotropic, thyroid-stimulating and gonadotropic (follicle-stimulating and luteinizing) hormones.

The hormone produced by the intermediate lobe of the pituitary gland is intermedin or melanocyte-stimulating hormone.

Preparations of the anterior and intermediate lobes of the pituitary gland are usually obtained from the pituitary glands of the large cattle and is usually used for the purpose of replacement therapy for appropriate indications.

Of great importance are preparations of the posterior lobe of the pituitary gland, which is called the neurohypophysis. Two hormones are released from the posterior pituitary gland:

1) antidiuretic hormone (vasopressin);

2) oxytocin.

The mechanism of action of antidiuretic hormone is associated both with increased reabsorption of water by the walls of the collecting ducts of the kidneys and with contraction of vascular smooth muscle, which leads to an increase in blood pressure (meaning large doses).

The second hormone of the neurohypophysis, oxytocin, stimulates the contraction of the smooth muscles of the uterus, especially at the end of pregnancy, and also affects the secretion of milk.

Due to the fact that oxytocin is currently used mainly in obstetrics, it seems necessary knowledge agents affecting the tone of the uterus.

DRUGS AFFECTING THE TONE OF THE UTERUS (UTERINE DRUGS)

Classification of mother products

I. Myometrial stimulating agents

A: Drugs that stimulate rhythmic contractions of the uterus

1. Drugs of the oxytocin group:

Oxytocin (syn.: syntocinon);

Methyloxytocin;

Sandopart (demoxytocin);

Pituitrin;

Mammophysin.

2. Prostaglandin preparations:

Dinoprost (enzaprost F, prostin F2-alpha);

Dinoprostone (Prostin E2).

B: Drugs that stimulate tonic contractions of the uterus

1. Ergot preparations:

Methylergometrine (syn.: methergine, methylergobrevin);

Ergometrine (syn.: panergal);

Ergotamine (syn.: gynofort, cornutamine);

Ergotal.

II. Myometrial relaxants (tocolytics)

1. Beta-2 adrenergic agonists:

Partusisten (syn.: fenoterol);

Salbupart (salbutamol);

Ginipral (hexoprenaline);

Bricanil (terbutaline);

Pre-steam (ritodrine).

2. Drugs of different groups:

Anesthetic agents (ether for anesthesia, etc.)

Antispasmodics of myotropic action (magnesium sulfate, no-spa, etc.).

Drugs that stimulate the myometrium and enhance its rhythmic contractions include drugs of the oxytocin group.

OXYTOCIN (Oxytocinum; 1 ml (5 units) per amp., Gedeon Richter, Hungary) is a hormone of the neurohypophysis. Currently, its synthetic analogue has been obtained. The sensitivity of the uterus at the beginning of pregnancy to this hormone and its synthetic analogues is very low, however, towards the end of pregnancy this sensitivity increases sharply. In this regard, the hormone is a regulator labor activity.

When used, the main pharmacological effect is increased contraction of the uterine muscles, while contraction of the myometrium is associated with:

1) with an increase in the amplitude of muscle contraction;

2) with an increase in the frequency of uterine contractions.

Thus, contractions of the uterus continue to remain rhythmic, that is, after contraction of the myometrium, its complete relaxation occurs. The latter makes it possible to restore placental blood circulation, which preserves the physiology of the contractile activity of the myometrium.

Oxytocin also increases milk secretion by increasing the production of lactogenic hormone by the anterior pituitary gland.

The drug oxytocin is released as an official drug in ampoules of 1 ml (5 units per 1 ml). The drug is administered intravenously, previously diluted in 500 ml of isotonic solution, dropwise at a certain speed.

Indications for use:

1) induction of labor (2-5 units diluted in 500 ml of 5% glucose solution, administered by drip);

2) stimulation of labor during prolonged labor, its arrest or inertia of the uterus (the drug is most effective for premature rupture of water);

3) to stop hypotonic uterine postpartum hemorrhage, since in large doses the drug increases the tone of the uterus. In this case, the drug is administered intramuscularly (or subcutaneously), since in this case it has a less drastic effect;

4) in case of complicated pregnancy (II-III trimester) for the purpose of artificially inducing labor (20-30 units injected into a vein, intramuscularly or subcutaneously).

To this day, PITUITRIN is an old drug that is an aqueous extract from the posterior lobes of the pituitary glands of cattle. It's not very good drug, it has uterine, vasopressor and antidiuretic activity (contains oxytocin and vasopressin).

Pituitrin is used for the same indications as oxytocin, as well as to normalize uterine involution in the postpartum and post-abortion periods.

PAKHIKARPIN is a ganglion blocker that increases tone and enhances contraction of the uterine muscles. This is an old drug but is still used to enhance labor.

Of the newer drugs in this group, it is necessary to say about prostaglandin preparations (local, tissue hormones). These are short-lived compounds. The two drugs that are most widely used are:

PROSTAGLANDIN F2-alpha under international name DINOPROST (Dinoprost; prostin F2-alpha; in Hungary it is sold under the name enzaprost F); issue in amp. 4 ml and 8 ml (5 mg prostaglandin F2-alpha per 1 ml)). The drug has a pronounced stimulating effect on the smooth muscles of the uterus.

Depending on the dosage, dinoprost is used for the following indications:

1) excitation and stimulation of the contractile activity

of the uterus in different terms pregnancy;

2) inducing abortion.

The second drug is DINOPROSTONE (Dinoproston (syn.: Prostin E2; sold in tablets of 0.00005 and in amps of 0.75 ml). Prostaglandin preparations are administered intravenously, intraamnially, intravaginally, and also orally.

The fundamental difference between prostaglandin preparations is that the uterus is sensitive to them at any stage of pregnancy. The effectiveness of these drugs (expel the fertilized egg) is very high (about 90%).

Complications when taking prostaglandin drugs (nausea, vomiting, etc.) occur in 90% of cases.

1) uterine atony and related uterine bleeding(hemostatic effect is associated with compression of the walls of blood vessels during contraction of the myometrium);

2) acceleration of the reverse development (involution) of the uterus in the postpartum period;

3) with menstrual bleeding.

The most commonly used ergot preparations are:

1) ERGOTAMINE (Ergotaminum; issued in tablets of 0.001, in amps of 1 ml of 0.05% solution, in bottles of 10 ml of 0.1% solution);

2) ERGOMETRINE (Ergometrinum; issued in tablets of 0.0002, in amps of 0.5 ml and 1 ml of 0.02% solution).

Ergometrine is one of the main alkaloids of ergot. It acts stronger and faster on the muscles of the uterus, increasing its tone and increasing the frequency of contractions.

These drugs, unlike oxytocin, primarily increase myometrial tone. Thus, ergot preparations do not cause rhythmic contractions of the myometrium and compress the vessels of the uterine body.

These drugs are contraindicated for inducing labor. When using large doses, poisoning is possible (peripheral vascular spasms, nausea, vomiting, tachycardia, mental disorders etc.).

A group of drugs that relax the muscles of the uterus - TOCOLYTICS. They have an inhibitory effect on the myometrium various means. Until recently, there were practically no means to relax the myometrium during overly violent labor. There were extreme measures:

1) general anesthesia;

2) use of ethyl alcohol.

Currently, various drugs are used for this indication, which is associated with the detection of tissue alpha and beta adrenergic receptors in the uterus.

Excitation of alpha-adrenergic receptors leads to uterine contraction (adrenaline, norepinephrine). This explains the occurrence of contractions (labor) in women in labor during excitement.

Beta-2 adrenergic receptors are inhibitory, they are found both in the uterus and in the bronchi. Stimulation of beta-adrenergic receptors leads to a decrease in myometrial tone. For this purpose, you can use isadrin, however, it is a non-selective beta-adrenergic agonist, so it is better to use selective agents: salbutamol, berotec, fenoterol. Berotec used for this indication is known as Partusisten. This drug effective in cases of threatened premature birth and does not have a negative effect on the fetus. The drug is prescribed either intravenously or orally.

Close in structure and action to Berotek is the drug RITODRIN. Side effects: tachycardia, hand tremors, muscle weakness, drop in blood pressure, sweating, nausea, vomiting.

SEXUAL HORMONE PREPARATIONS (their derivatives, synthetic substitutes and antagonists)

PREPARATIONS OF FEMALE GENITAL GLANDS HORMONES

In the ovaries, hormones are produced by follicles (estrogens) and cells corpus luteum(gestagens).

The main follicular hormone is estradiol, produced during the development of egg cells. Estrone and estriol are formed from estradiol in the body (they can be found in the blood and urine).

Estrogens ensure the development of genital organs and secondary sexual characteristics. In addition, under their influence, endometrial proliferation occurs in the first half menstrual cycle. As a result of ovulation, the corpus luteum is formed, the main hormone of which is progesterone. Gestagens promote further growth of the uterine mucosa in the second half of the menstrual cycle, and during fertilization of the egg - the formation of the decidua and placenta. This is a pregnancy hormone.

The production of gonadal hormones is regulated by gonadotropic hormones of the anterior pituitary gland.

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ESTROGEN DRUGS AND THEIR ANTAGONISTS I. Estrogen drugs:

1. Steroids (natural hormones and their derivatives):

a) ESTRON (syn.: folliculin; Sol. Oestroni oleosae; dispensed in amp. 1 ml of 0.05% solution (5000 IU)).

b) ESTRADIOL DIPROPIONATE (more active than estrone and has a longer action; dispensed in amp. 1 ml 0.1% oil solution).

2. Semi-synthetic drugs:

a) ETHINILESTRADIOL (Ethynilestrаdiolum; edition in the table: 0.00001 and 0.00005). The company "Gedeon Richter" (Hungary) produces this drug under the name "Microfollin".

This is the most active estrogen. Effective when taken orally. The drug is prescribed one tablet 1-2 times a day.

3. Synthetic drugs (non-steroids):

a) SINESTROL (available in tablets of 0.001 and in amps of 1 ml of 0.1% oil solution, as well as 1 ml of 2% solution) is equal in activity to estrone. It is prescribed orally and intramuscularly.

b) DIETHYLSTILBESTROL (released in amp. 1 ml of 3% oil solution) has great activity and is toxic.

Indications for the use of estrogens:

1. Insufficient functional activity of the ovaries (amenorrhea, dysmenorrhea, hypogonadism in girls).

2. For menopausal and post-castration disorders.

3. To suppress unwanted lactation during the postpartum period.

4. Complex therapy patients with prostate cancer, that is, some hormone-dependent tumors in men.

5. Breast cancer in women over 60 years of age.

II. Antiestrogenic drugs:

a) CLOMIFHENE CITRATE (clostilbegit; issue in the table.

This drug, depending on the dose and content of estrogenic hormones in the blood, gives an estrogenic or antiestrogenic effect. So, in a large dose, the drug reduces the secretion of gonadotropic hormone from the pituitary gland. When the content of estrogen hormones in the body is low, the drug stimulates the receptors, causing an estrogenic effect; in the opposite situation, clomiphene citrate blocks the receptors.

Used to treat infertility in women and men,

as well as for the treatment of patients with breast cancer.

b) TAMOXIFEN (issued in tablets of 0, 01, 0, 02, 0, 03,

This drug is used in oncology, as it blocks receptors for autogenous estrogens and, thus, reduces the progress of tumor growth, which is stimulated by estrogens.

Tamoxifen is used for breast cancer in women over 60 years of age, as well as for kidney cancer, melanoma and post-castration disorders in men.

GESTAGENS

As medicines use PROGESTERONE (released in amp. 1 ml of 1% and 2.5% oil solution) and its synthetic derivatives:

OXYPROGESTERONE CAPRONATE (released in amp. 1 ml

12.5% ​​and 25% oil solution; acts more slowly

PREGNIN (issued in tablets of 0.01; less active, tab.

tapholes are prescribed under the tongue).

Progesterone affects the myometrium, preparing it for egg implantation (the proliferative stage turns into the secretory stage), suppresses the excitability of the myometrium, prevents ovulation, promotes proliferation glandular tissue mammary glands.

It is used for insufficient functional activity of the corpus luteum for:

1) prevention of miscarriage (in the first half of pregnancy);

2) treatment of dysmenorrhea.

TURINAL (active substance - allylestrenol) is also a gestagen drug. The drug is produced in tablets of 0.005 by Gedeon Richter (Vegria). Turinal has a pronounced progestogenic effect, helps maintain pregnancy, and normalizes the function of the placenta. Indications for use are threatened miscarriage, habitual miscarriage, threatened premature birth.

Side effects: dyspepsia, headache, dizziness.

The drug NORCOLUT (Gedeon Richter, Hungary) also has gestagenic activity. active substance which is norethisterone. The drug has gestagenic activity, as well as weak estrogenic and androgenic effects. Under the influence of the drug, the uterine mucosa transforms from the proliferation phase to secretory phase, and after fertilization contributes to its transition to a state favorable for the development of a fertilized egg. The drug reduces the excitability and contractility of the myometrium.

Indications for use:

Dysfunctional uterine bleeding;

Menopausal syndrome;

Premenstrual syndrome;

Endometriosis;

Mastopathy;

Pregnancy prevention;

Termination and prevention of lactation;

When menstruation is delayed.

Side effects: dyspepsia, increased fatigue, paresthesia, allergic reactions, changes in body weight. IN medical practice finds application in lately the drug Mifepristone, which is an antagonist of gestagens (antigestagenic agent). Mifepristone (RU 486), actively binding to gestagen receptors of the uterus, prevents the action of gestagens (progesterone). In this regard, it is used as a means that can cause abortion. The drug is most effective in early dates pregnancy. To terminate pregnancy, it is prescribed in combination with prostaglandins (dinoprost, dinoprostone).

The antigestagen mifepristone is also used to normalize the menstrual cycle.

CONTRACEPTIVE (CONTRACEPTIVE) DRUGS

Most effective method protection against unplanned pregnancy is hormonal contraception giving almost 100% effect. About 65 million women use this method of contraception.

Research by Gregory and Pincus (1960) showed that the combination of various steroid hormones (estrogens and gestagens) results in an anovulatory effect. Currently, there is a tendency to reduce the content of estrogens, as well as progestin components in combination drugs. Modern contraceptives containing up to 0.03 mg of estrogens and up to 0.15 mg of gestagens, have the least number of side effects.

ETHINYLESTRADIOL (highest activity) is increasingly used as an estrogenic component, and LEVONORGESTREL is used as a progestogen component, which does not undergo preliminary metabolic transformations and has a pronounced action on the endometrium.

These drugs are used to regulate birth control and prevent unwanted pregnancy, as well as for the purpose of regulating the timing of pregnancy.

For these indications use:

I. Combined estrogen-progestogen drugs:

1. Single-phase:

NON-OVLON;

RIGEVIDON ("Gedeon Richter", Hungary);

OVIDON ("Gedeon Richter", Hungary);

MARVELON et al.;

2. Biphasic (characterized by a constant dose of estrogen and a changing dose of gestagens taken in different phases menstrual cycle): -

3. Three-phase (characterized by the fact that the content of estrogen and gestagen in the drug corresponds to those of the normal cycle).

TRIQUILAR;

TRI-REGOL ("Gedeon Richter", Hungary);

TRIZISTON.

II. Preparations with microdoses of gestagens:

FEMULEN;

CONTINUINE;

MINI-PILI;

MICRONOR.

III. Postcoital drugs, for example, POSTINOR (Gedeon Richter, Hungary) and progesterone antagonists

(MIFEPRISTONE).

IV. Prolonged hormonal contraceptives(DEPOT

PROVERA, NORPLANT).

The ratio of estrogens and gestagens in combined estrogen-gestagen drugs ranges from 1: 50 to 1: 10. The mechanism of action of contraceptives of this group is to suppress ovulation (as the production of follicle-stimulating and luteinizing hormones of the pituitary gland is suppressed; regression of the proliferative phase of the endometrium occurs, which ultimately creates an obstacle to egg implantation). These drugs provide an almost 100% guarantee of suppressing ovulation. With a 28-day cycle, they are prescribed from the 5th or 1st day of the menstrual cycle and taken for 21 days.

After stopping medication reproductive function is being restored.

Side effects: headache, dizziness, breast engorgement, changes in libido, weight gain, thrombophlebitis, intermenstrual spotting, increased blood pressure, dyslipoproteinemia.

Estrogen-progestin drugs are used not only as contraception, but also with therapeutic purpose. They are prescribed for dysmenorrhea, polyposis, endometriosis and other gynecological diseases.

Modern low-dose combined hormonal contraceptives rarely cause side effects.

PREPARATIONS OF HORMONES OF THE MALE GENITAL GLANDS (ANDROGENS)

Leydig cells produce the hormone testosterone (steroidal nature). It promotes the development of the genital organs and secondary sexual characteristics, and also controls spermatogenesis.

TESTOSTERONE and its preparations (TESTOSTERONE PROPIONATE, TESTOSTERONE ENANTATE) have a pronounced effect on protein metabolism, promoting protein synthesis (anabolic effect), increases the reabsorption of water, sodium, calcium and chlorine ions in the renal tubules. In the liver, testosterone is converted to androsterone.

The synthetic androgen - METHYLTESTOSTERONE - is inferior in activity to testosterone, however, it is more active when prescribed sublingually.

Androgenic drugs are used for the following indications:

1. Insufficiency of the functional activity of the male gonads: - hypogonadism in boys; - some types of impotence; - menopausal disorders in men.

2. For hormone-dependent types of tumors in women (breast and ovarian cancer in women under 60 years of age).

3. For dysmenorrhea and menopausal disorders in women.

Side effects:

1. In women - a masculinizing effect (virilism): deepening of the voice, male-type hair growth.

2. Sodium and water retention, increased blood pressure, cholestatic hepatitis, polycythemia.

Antiandrogenic drugs - CIPROTERONE, FLUTAMIDE, etc. These drugs are used for severe hirsutism in women, for sexual deviations in men, for inoperable prostate cancer. Side effects: weight gain, increased blood pressure, decreased libido.

ANABOLIC STEROID

Androgens increase protein synthesis, that is, they have anabolic activity. This manifests itself in an increase in mass skeletal muscles, a number of parenchymal organs, bone tissue. As a result, body weight increases and the release of nitrogen, phosphorus and calcium from the body is delayed.

Usage anabolic action androgenic drugs are limited by their high androgenic activity. That's why they were created synthetic products, at whom

of which anabolic properties predominate, and androgenic activity is low, these are the so-called ANABOLIC STEROIDS.

The most widely used drugs are:

1. NEROBIL. Duration of action is 7-15 days.

2. RETABOLIL (Gedeon Richter, Hungary). Duration of action is three weeks.

Their effect develops gradually, after 1-3 days. These drugs are prescribed in the form intramuscular injections oil solutions.

3. METHANDROSTENOLONE (Methandrostenolonum; issued in tablets of 0.001 and 0.005).

This drug has a short-term effect and is prescribed daily 1-2 times a day. Anabolic steroids promote protein synthesis, improve appetite, and increase body weight. In patients with osteoporosis, bone calcification accelerates. Have a beneficial effect anabolic steroid on regeneration processes.

This group of drugs is used for:

1. Cachexia.

2. Asthenia.

3. In case long-term use glucocorticoid hormones.

4. Radiation therapy.

5. Osteoporosis.

6. To stimulate regenerative processes (bone fractures).

Side effects (due to androgenic activity)

1. Masculinizing effect in women (insignificant).

2. Nausea.

4. Excessive calcium deposition in bone tissue.

Contraindications for use:

1. Pregnancy.

2. Lactation period.

3. Prostate cancer.

4. Liver diseases.