pharmachologic effect
Synthetic glucocorticosteroid (GCS) is a methylated derivative of fluoroprednisolone. It has anti-inflammatory, antiallergic, desensitizing, immunosuppressive, antishock and antitoxic effects, increases the sensitivity of beta-adrenergic receptors to endogenous catecholamines.
Interacts with cytoplasmic receptors of glucocorticosteroids (GCS) (receptors for GCS are found in all tissues, especially in the liver) to form a complex that induces the formation of proteins (including enzymes that regulate vital processes in cells.)
Protein metabolism: reduces the amount of globulins in plasma, increases the synthesis of albumins in the liver and kidneys (with an increase in the albumin/globulin ratio in the blood plasma); reduces synthesis and enhances protein catabolism in muscle tissue.
Lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (mobilization from the subcutaneous tissue of the extremities and accumulation of fat 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 (increasing the flow of glucose from the liver into the blood); increases the activity of phosphoenolpyruvate carboxylase and the synthesis of aminotransferases (activation of gluconeogenesis); promotes the development of hyperglycemia.
Water-electrolyte metabolism: retains sodium ions and water in the body, stimulates the excretion of potassium ions (mineralocorticoid activity), reduces the absorption of calcium ions from the gastrointestinal tract, causes “leaching” of calcium from the bones and increases its renal excretion, reduces bone mineralization.
The anti-inflammatory effect is associated with inhibition of the 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. Acts on all stages of the inflammatory process: inhibits the synthesis of prostaglandins (Pg) at the level of arachidonic acid (lipocortin inhibits phospholipase A2, suppresses the release of arachidonic acid and inhibits the biosynthesis of endoperoxides, leukotrienes, which contribute to 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, inhibition of the proliferation of lymphocytes (especially T-lymphocytes), suppression of the migration of B-lymphocytes and the interaction of T- and B-lymphocytes, inhibition of the release of cytokines (interleukin-1,2; interferon gamma) from lymphocytes and macrophages and decreased antibody formation.
The antiallergic effect develops as a result of a decrease in the synthesis and secretion of allergy mediators, inhibition of the release of histamine and other biologically active substances from sensitized mast cells and basophils, a decrease in the number of circulating basophils, suppression of the development of lymphoid and connective tissue, a decrease in the number of T- and B-lymphocytes, mast cells, reducing the sensitivity of effector cells to allergy mediators, inhibiting antibody formation, changing the body's immune response.
In obstructive diseases of the respiratory tract, the effect is due mainly to inhibition of inflammatory processes, prevention or reduction of the severity of swelling of the mucous membranes, reduction of eosinophilic infiltration of the submucosal layer of the bronchial epithelium and deposition of circulating immune complexes in the bronchial mucosa, as well as inhibition of erosion and desquamation of the mucous membrane. Increases the sensitivity of beta-adrenergic receptors of small and medium-sized bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of mucus by reducing its production.
Suppresses the synthesis and secretion of adrenocorticotropic hormone and, secondarily, the synthesis of endogenous corticosteroids.
The peculiarity of the action is 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 is 32-72 hours (duration of inhibition of the hypothalamus-pituitary-adrenal cortex system).
In terms of the strength of glucocorticoid activity, 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.
Indications for use
- Primary and secondary adrenal insufficiency (usually in combination with mineralocorticoids);
- congenital hyperplasia of the adrenal cortex;
- subacute thyroiditis;
- hypercalcemia in malignant neoplasms; bronchial asthma;
- systemic connective tissue diseases (rheumatoid arthritis in the acute phase, systemic lupus erythematosus, scleroderma, etc.);
- skin diseases (psoriasis, eczema, dermatitis, pemphigus, acute erythroderma, etc.);
- ulcerative colitis;
- diseases of the hematopoietic organs: agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lympho- and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia;
- cerebral edema (usually after prior parenteral use of a glucocorticosteroid);
- carrying out a test for the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.
Directions for use and doses
The dosage regimen of the drug is individual and depends on the indications, severity of the disease and the patient’s response to therapy.
Dexamethasone is prescribed orally during or after meals, once in the morning (small dose) or in 2-3 doses (large dose). The average daily dose for adults ranges from 2-3 mg to 6 mg. The maximum daily dose is 10-15 mg.
After achieving a therapeutic effect, the dose is gradually reduced (usually by 0.5 mg every 3 days) to a maintenance dose of 2-4.5 mg/day or more. The maximum effective dose is 0.5-1 mg/day.
Children are prescribed 0.0833-0.3333 mg/kg or 0.0025-0.0001 mg/m2 per day in 3-4 doses, depending on age.
The duration of use of Dexamethasone depends on the nature of the pathological process and the effectiveness of treatment and ranges from several days to several months or more. Treatment is stopped gradually.
Best before date
There are different dosage forms of dexamethasone:
- in tablets,
- eye drops,
- solution for injection.
At the same time, for a certain type of drug there are its own storage rules.
- For tablets (there can be 10, 20, 50 pieces in a package), the shelf life of dexamethasone is limited to 5 years. The period is valid provided that the storage standards specified in the instructions are observed.
- The shelf life eye drops (5 and 10 ml) does not exceed 3 years. Their further use is not permitted. It is a colorless, transparent liquid (sometimes with a yellowish tint).
- In the form of an injection , the drug has a concentration of 4 mg/ml and is supplied in cardboard boxes of 10 ampoules. Its shelf life is 2 years from the date of production.
special instructions
Before starting treatment, the patient should be examined to identify possible contraindications. Clinical examination should include examination of the cardiovascular system, x-ray examination of the lungs, examination of the stomach and duodenum, urinary system, and visual organs; control of blood formula, glucose and electrolytes in blood plasma.
During treatment with Dexamethasone (especially long-term), observation by an ophthalmologist, monitoring of blood pressure and water-electrolyte balance, as well as peripheral blood patterns and blood glucose levels are necessary.
In order to reduce side effects, antacids can be prescribed, as well as increasing the intake of K+ into the body (diet, potassium supplements). Food should be rich in proteins, vitamins, and limit the content of fats, carbohydrates and table salt.
The effect of the drug is enhanced in patients with hypothyroidism and liver cirrhosis.
The drug may worsen existing emotional instability or psychotic disorders. If a history of psychosis is indicated, Dexamethasone in high doses is prescribed under the strict supervision of a physician.
In stressful situations during maintenance treatment (for example, surgery, trauma or infectious diseases), the dose of the drug should be adjusted due to an increased need for glucocorticosteroids.
With daily use, atrophy of the adrenal cortex develops by 5 months of treatment. The patient should be carefully monitored for a year after the end of long-term therapy with Dexamethasone due to the possible development of relative insufficiency of the adrenal cortex. If stressful situations arise during this period, GCS is prescribed (according to indications), if necessary in combination with mineralocorticoids.
With sudden withdrawal, especially in the case of previous use of high doses, the development of withdrawal syndrome (anorexia, nausea, lethargy, generalized musculoskeletal pain, general weakness) is possible, as well as an exacerbation of the disease for which Dexamethasone was prescribed.
During treatment with Dexamethasone, vaccination should not be carried out due to a decrease in its effectiveness (immune response).
When prescribing Dexamethasone for intercurrent infections, septic conditions and tuberculosis, it is necessary to simultaneously treat with bactericidal antibiotics.
Dexamethasone may mask some symptoms of infections.
In children during long-term treatment with Dexamethasone, careful monitoring of the dynamics of growth and development is necessary. Children who during the treatment period were in contact with patients with measles or chickenpox are prescribed specific immunoglobulins prophylactically.
In patients with diabetes mellitus, blood glucose levels should be monitored and therapy adjusted if necessary.
X-ray monitoring of the osteoarticular system (images of the spine, hand) is indicated.
In patients with latent infectious diseases of the kidneys and urinary tract, Dexamethasone can cause leukocyturia, which may have diagnostic value.
Dexamethasone increases the content of 11- and 17-hydroxyketocorticosteroid metabolites.
It must be taken into account that the drug can cause a number of side effects from the nervous system (dizziness, etc.), which can slow down the reaction rate.
Is it possible to use an expired drug?
This medication maintains its quality for the entire time indicated on the package. If the storage rules are followed, it can be used without fear even 2 - 3 days before the expiration of the time specified by the manufacturer.
If medications have been stored incorrectly, are past their expiration date, or have been damaged in packaging, their continued use may be hazardous. Or, at a minimum, ineffective in cases where urgent help is required (for example, with pulmonary edema).
Do not use an injection solution in which a precipitate has formed, cloudiness or a change in odor has occurred.
If the storage of deximethasone tablets was incorrect or the protective shells were damaged, they cannot be used for treatment.
The doctor must make all appointments and calculate the dosage of the drug. Self-medication or uncontrolled use of medications can cause serious harm to health. Especially in the presence of concomitant chronic diseases.
