Dexamethasone ampoules 4mg 1ml №25

pharmachologic effect

Synthetic glucocorticoid (GCS), methylated fluoroprednisolone derivative. It has anti-inflammatory, anti-allergic, immunosuppressive effects, increases the sensitivity of beta-adrenergic receptors to endogenous catecholamines.

It interacts with specific cytoplasmic receptors (there are receptors for GCS in all tissues, especially in the liver) with the formation of a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells.)

Protein metabolism: reduces the amount of globulins in the plasma, increases the synthesis of albumin in the liver and kidneys (with an increase in the ratio of albumin / globulin), reduces the synthesis and enhances protein catabolism in muscle tissue.

Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation occurs mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.

Carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract; increases the activity of glucose-6-phosphatase (increased glucose uptake from the liver into the bloodstream); increases phosphoenolpyruvate carboxylase activity and aminotransferase synthesis (activation of gluconeogenesis); contributes to the development of hyperglycemia.

Water-electrolyte metabolism: delays Na⁺ and water in the body, stimulates the excretion of K⁺(mineralocorticoid activity), reduces the absorption of Ca⁺ from the gastrointestinal tract, reduces the mineralization of bone tissue.

The anti-inflammatory effect is associated with inhibition of release of inflammatory mediators by eosinophils and mast cells; inducing the formation of lipocortins and reducing the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes (especially lysosomal) and organelle membranes. Affects all stages of the inflammatory process: inhibits the synthesis of prostaglandins (Pg) at the level of arachidonic acid (lipocortin inhibits phospholipase A2,inhibits the arachidonic acid liberation and inhibits the biosynthesis of endoperacids, leukotrienes, promoting inflammation, allergies, etc.), the synthesis of "proinflammatory cytokines" (interleukin 1, tumor necrosis factor alpha, etc.); increases the resistance of the cell membrane to the action of various damaging factors.

The immunosuppressive effect is caused by the involution of lymphoid tissue, the suppression of lymphocyte proliferation (especially T-lymphocytes), the suppression of B-cell migration and the interaction of T- and B-lymphocytes, and the inhibition of the release of cytokines (interleukin-1, 2; gamma-interferon) from lymphocytes and macrophages and reduced antibody production.

Antiallergic effect develops as a result of reduced synthesis and secretion of allergy mediators, inhibition of release from sensitized mast cells and basophils of histamine and other biologically active substances, reduction in the number of circulating basophils, T and B lymphocytes, mast cells; suppressing the development of lymphoid and connective tissue, reducing the sensitivity of effector cells to mediators of allergy, suppressing antibody production, changes in the immune response of the body.

In obstructive respiratory tract diseases, the action is mainly due to the inhibition of inflammatory processes, prevention or reduction of mucosal edema, decreased eosinophilic infiltration of the submucous layer of the bronchial epithelium and deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of eroding and desquamation of the mucous membrane. Increases the sensitivity of beta-adrenoreceptors of the bronchi of small and medium caliber to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production.

Inhibits the synthesis and secretion of ACTH and secondary synthesis of endogenous corticosteroids.

It inhibits connective tissue reactions during the inflammatory process and reduces the possibility of scar tissue formation.

The peculiarity of the action is a significant inhibition of pituitary function and the almost complete absence of mineralocorticosteroid activity.

Doses of 1-1.5 mg / day inhibit the function of the adrenal cortex; biological half-life - 32-72 h (duration of inhibition of the hypothalamus-pituitary-adrenal cortex substance).

The strength of glucocorticoid activity of 0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisone (or prednisolone), 15 mg of Hydrocortisone or 17.5 mg of Cortisone.

Pharmacokinetics

It binds in the blood (60-70%) with a specific carrier protein - transcortin. Easily passes through histohematogenous barriers (including through the hemato-encephalic and placental).

Metabolized in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites.

Excreted by the kidneys (a small part - by lactating glands). T_1/2 plasma dexamethasone - 3-5 h.

Indications

Diseases requiring the introduction of high-speed corticosteroids, as well as cases where oral administration of the drug is not possible:

• endocrine diseases: acute insufficiency of the adrenal cortex, primary or secondary insufficiency of the adrenal cortex, congenital adrenal hyperplasia, subacute thyroiditis;
• shock (burn, traumatic, operational, toxic) - with the ineffectiveness of vasoconstrictor drugs, plasma substituting drugs and other symptomatic therapy;
• cerebral edema (with brain tumor, traumatic brain injury, neurosurgical intervention, cerebral hemorrhage, encephalitis, meningitis, radiation damage);
• asthmatic status; severe bronchospasm (exacerbation of bronchial asthma, chronic obstructive bronchitis);
• severe allergic reactions, anaphylactic shock;
• rheumatic diseases;
• systemic connective tissue diseases;
• acute severe dermatosis;
• malignant diseases: palliative treatment of leukemia and lymphoma in adult patients; acute leukemia in children; hypercalcemia in patients with malignant tumors, with the impossibility of oral treatment;
• blood diseases: acute hemolytic anemia, agranulocytosis, idiopathic thrombocytopenic purpura in adults;
• severe infectious diseases (in combination with antibiotics);
• in the ophthalmology corneas;
• local application (in the area of ​​pathological formation): keloids, discoid lupus erythematosus, annular granuloma.

Dosing regimen

The dosage regimen is individual and depends on the indications, the patient's condition and his reaction to therapy. The drug is administered in / in a slow stream or drip (in acute and emergency conditions); in / m; it is also possible local (in pathological education) introduction. In order to prepare a solution for intravenous drip infusion, isotonic sodium chloride solution or 5% dextrose solution should be used.

In the acute period, with various diseases and at the beginning of therapy, Dexamethasone is used in higher doses. During the day, you can enter from 4 to 20 mg of Dexamethasone 3-4 times.

Dosage forchildren (V / m):

The dose of the drug during replacement therapy (in case of insufficiency of the adrenal cortex) is 0.0233 mg / kg of body weight or 0.67 mg / m² body surface area, divided into 3 doses, every 3rd day or 0.00776 - 0.01165 mg / kg of body weight or 0.233 - 0.335 mg / m² body surface areas daily. For other indications, the recommended dose ranges from 0.02776 to 0.16665 mg / kg body weight, or 0.833 - 5 mg / m² body surface area every 12-24 h.

When the effect is achieved, the dose is reduced until maintenance or until cessation of treatment. The duration of parenteral administration is usually 3-4 days, then switch to maintenance therapy with dexamethasone tablets.

Prolonged use of high doses of the drug requires a gradual reduction in dose in order to prevent the development of acute insufficiency of the adrenal cortex.

Side effect

Dexamethasone is usually well tolerated. It has a low mineralocorticoid activity, i.e. its effect on water and electrolyte metabolism is small. As a rule, low and medium doses of Dexamethasone do not cause sodium and water retention in the body, increased excretion of potassium. The following side effects are described:

On the part of the endocrine system:reduced glucose tolerance, steroid diabetes or a manifestation of latent diabetes mellitus, adrenal suppression, Cushing's (moon face, obesity, pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, muscle weakness, striae) syndrome, delayed sexual development in children.

From the digestive system:nausea, vomiting, pancreatitis, steroid gastric and duodenal ulcer, erosive esophagitis, Gastrointestinal bleeding and perforation of the gastrointestinal wall, increased or decreased appetite, indigestion, flatulence, hiccups. In rare cases - increased activity of hepatic transaminases and alkaline phosphatase.

Since the cardiovascular system:arrhythmias, bradycardia (up to cardiac arrest); development (in susceptible patients) or increased severity of heart failure , changes in the electrocardiogram, characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction - the spread of necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle.

From the nervous system:delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, cerebellar pseudo-tumor, headache, convulsions.

From the senses:posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral infections of the eye, trophic changes of the cornea, exophthalmos, sudden loss of vision (with parenteral administration in the head, neck, nasal shell, scalp) the deposition of crystals of the drug in the vessels of the eye).

Metabolism:increased Calcium excretion, hypocalcemia, increased body weight, negative nitrogen balance (increased protein breakdown), increased sweating.

Conditioned by mineralocorticoid activity- fluid and sodium retention (peripheral edema), hypoplasia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

From the musculoskeletal system:growth retardation and ossification processes in children (premature closure of the epiphyseal growth zones), osteoporosis (very rarely - pathological bone fractures, aseptic necrosis of the head of the humerus and femur), muscle tendon rupture, steroid myopathy, muscle mass decrease (atrophy)

From the skin and mucous membranes:delayed wound healing, petechiae, ecchymosis, skin thinning, hyper or hypopigmentation, steroid acne, striae, tendency to the development of pyoderma and candidiasis.

Allergic reactions:skin rash, itching, anaphylactic shock, local allergic reactions.

Local with parenteral administration:burning, numbness, pain, tingling at the injection site, infection at the injection site, rarely - necrosis of surrounding tissues, scarring at the injection site; atrophy of the skin and subcutaneous tissue when i / m administration (especially the introduction into the deltoid muscle).

Other:the development or exacerbation of infections (the occurrence of this side effect is facilitated by jointly used immunosuppressants and vaccination), leukocyturia, "flushes" of blood to the face, "withdrawal" syndrome.

Contraindications

For short-term use for vital reasons, the only contraindication is hypersensitivity to dexamethasone or components of the drug.

In children during the growth period, GCS should be used only if absolutely indicated and under the most careful supervision of the attending physician.

WITHcaution the drug should be prescribed for the following diseases and conditions:

• Gastrointestinal tract diseases - peptic ulcer of the stomach and duodenum, esophagitis, gastritis, acute or latent peptic ulcer, a newly created intestinal anastomosis, ulcerative colitis with the threat of perforation or abscess formation, diverticulitis;
• parasitic and infectious diseases of a viral, fungal or bacterial nature (at present or recently transferred, including recent contact with a patient) - herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amebiasis, strongyloidosis; systemic mycosis; active and latent tuberculosis. Use in severe infectious diseases is permissible only against the background of specific therapy.
• pre- and post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination;
• immunodeficiency states (including AIDS or HIV infection);
• diseases of the cardiovascular system (including recent myocardial infarction - in patients with acute and subacute myocardial infarction, necrosis can spread, slowing the formation of scar tissue and, consequently, rupture of the heart muscle), severe chronic heart failure, arterial hypertension, hyperlipidemia);
• endocrine diseases - diabetes mellitus (incl.violation of tolerance to carbohydrates), thyrotoxicosis, hypothyroidism, Itsenko-Cushing disease, obesity (III-IV century).
• severe chronic renal and / or hepatic failure, nephroluritis;
• hypoalbuminemia and conditions predisposing to its occurrence;
• systemic osteoporosis, myasthenia gravis, acute psychosis, poliomyelitis (with the exception of the form of bulbar encephalitis), open-and closed-angle glaucoma;
• pregnancy.

Use during pregnancy and lactation

In pregnancy (especially in the first trimester), the drug can be used only when the expected therapeutic effect exceeds the potential risk to the fetus. With long-term therapy during pregnancy, the possibility of fetal growth disorder is not excluded. In the case of use at the end of pregnancy there is a risk of atrophy of the adrenal cortex in the fetus, which may require replacement therapy in the newborn.

If it is necessary to carry out drug treatment during breastfeeding, then breastfeeding should be stopped.

Application for violations of the liver

Contraindications: severe chronic liver failure.

Application for violations of kidney function

Contraindications: severe chronic renal failure, nephroluritiasis.

Use in children

In children during the growth period, GCS should be used only if absolutely indicated and under the most careful supervision of the attending physician.

special instructions

During treatment with Dexamethasone (especially long-term), it is necessary to observe an oculist, control blood pressure and the state of water and electrolyte balance, as well as pictures of peripheral blood and blood glucose levels.

In order to reduce side effects, you can assign antacids, and you should increase the flow of K⁺ in the body (diet, potassium drugs). Food should be rich in proteins, Vitamins , with a restriction of the content of fats, carbohydrates and salt.

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