DEXAMETHASONE AMPOULES 4MG 1ML

injection

International non-proprietary or grouping name: dexamethasone

Pharmacotherapeutic group: glucocorticosteroid

pharmachologic effect

Pharmacodynamics. Dexamethasone is a synthetic hormone of the adrenal cortex, a glucocorticosteroid (GCS), a methylated fluoroprednisolone derivative. It has anti-inflammatory, anti-allergic, desensitizing, anti-shock, anti-toxic and immunosuppressive effects.

It interacts with specific cytoplasmic receptors of glucocorticosteroids to form a complex that penetrates into the cell nucleus and stimulates the synthesis of matrix ribonucleic acid, the latter induces the formation of proteins, including lipocortin, mediating cellular effects. Lipocortin inhibits phospholipase A2, inhibits the release of arachidonic acid and inhibits the synthesis of endoperekisy, prostaglandins, leukotrienes, contributing to the processes of inflammation, allergies, etc.

Protein exchange: reduces the amount of protein in plasma (due to globulins) with an increase in the albumin / globulin ratio, increases the synthesis of albumin in the liver and kidneys; 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 (GIT); increases the activity of glucose-6-phosphatase, which leads to an increase in glucose from the liver into the blood; increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases, which leads to the activation of gluconeogenesis.

Water and electrolyte exchange: retains sodium (Na+) and water in the body, stimulates the excretion of potassium (K+) (mineralocorticoid activity), reduces Calcium absorption (Ca2+) from the digestive tract, "washes out" Ca2+ from the bones, increases Ca excretion2+ by the kidneys.

Anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils; induction of lipocortin formation and a decrease in the number of mast cells that produce hyaluronic acid; with a decrease in capillary permeability; stabilization of cell membranes and membranes of organelles (especially lysosomal).

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

In chronic obstructive pulmonary disease, the action is mainly based on the inhibition of inflammatory processes, inhibition of development or prevention of mucosal edema, inhibition of eosinophilic infiltration of the submucosal epithelium of the bronchi, deposition of circulating immune complexes in the mucous membrane of the bronchi, as well as inhibition of erosion and desquamation of the mucous membrane of the bronchi 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 due to inhibition or reduction of its products.

Anti-shock and anti-toxic effects associated with increased blood pressure (BP) (by increasing the concentration of circulating catecholamines and restoring sensitivity of adrenoreceptors to them, as well as vasoconstriction), reducing the permeability of the vascular wall, membrane-protective properties, activation of liver enzymes involved in the metabolism of endo-and xenobiotics.

The immunodepressive effect is due to the inhibition of the release of cytokines (interleukin-1 and interleukin-2, gamma-interferon) from lymphocytes and macrophages.

Therefore, it has 30 times more pronounced effect than endogenous cortisol.

Dexamethasone has 30 times more pronounced effect than endogenous cortisol.Therefore, it is a more potent inhibitor of the secretion of corticotropin-releasing hormone and ACTH. In pharmacological doses it inhibits the hypothalamic-pituitary-adrenal system, contributes to the development of secondary adrenal insufficiency. It suppresses the synthesis and release of pituitary adrenocorticotropic hormone (ACTH) and, secondarily, the synthesis of endogenous GCS. Inhibits the secretion of thyroid-stimulating hormone and follicle-stimulating hormone. Suppresses the release of beta-lipotropin, but does not reduce the content of circulating beta-endorphin.

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

Increases the excitability of the central nervous system, reduces the number of lymphocytes and eosinophils, increases - red blood cells (by stimulating the production of erythropoietin).

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

Pharmacokinetics

Absorption

The maximum concentration of dexamethasone in plasma is reached already 5 minutes after intravenous administration and 1 hour after intramuscular administration.

Distribution

Communication with plasma proteins (mainly with albumin) is 77%. It penetrates the hematoencephalic and placental barriers. The half-life (T1/2) from plasma is 190 min.

Metabolism

Metabolized in the liver. A small amount of dexamethasone is metabolized in the kidneys and other organs.

Removal

Up to 65% of the dose is excreted by the kidneys within 24 hours.

The time of development of the clinical effect

With intravenous administration, the action develops rapidly; with intramuscular use, the clinical effect develops after 8 hours. The effect is prolonged: from 17 to 28 days after intramuscular use and from 3 days to 3 weeks after topical administration. With local injection into the joints or soft tissues (in the lesions), absorption is slower than with intramuscular administration.

Indications for use

Replacement therapy for adrenal insufficiency (in combination with sodium chloride and / or mineralocorticoid): acute insufficiency of the adrenal cortex (Addison's disease, bilateral adrenalectomy); relative insufficiency of the adrenal cortex, which develops after discontinuation of treatment of GCS; primary or secondary adrenal insufficiency.

Symptomatic and pathogenetic therapy of other diseases requiring the introduction of a fast-acting glucocorticosteroid, as well as in cases where oral administration of the drug is impossible:

- endocrine diseases: congenital hyperplasia of the adrenal cortex, subacute thyroiditis;

- shock (burn, traumatic, operative, toxic) - with the ineffectiveness of vasoconstrictor drugs, plasma substituting drugs and other symptomatic therapy;

- cerebral edema (with brain tumor, traumatic brain injury, neurosurgical intervention, brain hemorrhage, encephalitis, meningitis,radiation injury);

- asthmatic status; severe bronchospasm (exacerbation of bronchial asthma);

- severe allergic reactions, anaphylactic shock;

- rheumatic diseases;

- Systemic diseases of the connective tissue;

- 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;

- in ophthalmologic practice (subconjunctival, retrobulbar or parabulbar introduction);

- local application (in the area of ​​pathological formation): keloids, discoid lupus erythematosus, annular granuloma;

- poisoning with cauterizing liquids (reduction of inflammatory phenomena and prevention of cicatricial stenosis).

Dosage and administration

The dosage regimen is individual and depends on the indications, the patient's condition and his reaction to therapy. The drug is administered intravenously (w / w) slowly in a jet or drip (for acute and emergency conditions); intramuscularly (intramuscularly); it is also possible local (inpathological formation) and subconjunctival, retrobulbar or parabulbar injection. In order to prepare a solution for intravenous infusion, isotonic sodium chloride solution or 5% dextrose solution should be used.

The drug is administered intravenously and intramuscularly at a dose of 0.5–24 mg / day in 2 doses (equivalent to 1 / 3–1 / 2 of the oral dose) as soon as possible in the minimum effective dose, the treatment is canceled gradually. Prolonged treatment should be carried out at a dose not exceeding 0.5 mg / day. V / m in the same place injected no more than 2 ml.

In case of emergency, they are used in higher doses: the initial dose is 4–20 mg, which is repeated until the desired effect is achieved, the total daily dose rarely exceeds 80 mg. After reaching a therapeutic effect, dexamethasone is administered in doses of 2-4 mg as necessary, followed by gradual withdrawal of the drug. To maintain a long-lasting effect, the drug is administered every 3-4 hours or as a long-term drip infusion. After the relief of acute conditions of the patient is transferred to the reception of dexamethasone inside.

Doses of the drug for children (IM):

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 body weight or 0.233-0.335 mg / m2 body surface areas daily. For other indications, the recommended dose is from 0.02776 to 0.16665 mg / kg body weight or 0.833-5 mg / m2 body surface area every 12-24 hours.