pharmachologic effect
Why is the drug prescribed? Dexamethasone is a glucocorticosteroid hormone that is used in ophthalmology as an antiallergic, anti-inflammatory, and antiexudative agent. The active component of the drug helps stabilize cell membranes and reduces the permeability of the vascular wall. The antiexudative (decongestant) effect is associated with the stabilization of the membrane membrane of lysosomes.
After instillation, dexamethasone can penetrate through the cornea into the fluid of the anterior chamber of the eyeball, even through intact epithelial cover. The drug has indications and contraindications
Description of the dosage form
Tablets are white, flat-cylindrical with a chamfer.
Pharmacokinetics
Absorption
After oral administration, it is quickly and completely absorbed, the maximum concentration of dexamethasone in the blood plasma is 1-2 hours.
Distribution
In the blood it binds (60–70%) to a specific carrier protein – transcortin. Easily passes through histohematic barriers (including the blood-brain and placental barriers).
Metabolism
Metabolized in the liver (mainly by conjugation with glucuronic and sulfuric acids) to inactive metabolites.
Removal
Excreted by the kidneys (a small amount of dexamethasone passes into breast milk). Half-life is 3-5 hours.
Pharmacodynamics
Dexamethasone is a synthetic glucocorticosteroid (GCS), a methylated derivative of fluoroprednisolone. It has anti-inflammatory, antiallergic, desensitizing, immunosuppressive, antishock and antitoxic effects.
Inhibits the secretion of thyroid-stimulating hormone and follicle-stimulating hormone.
Increases the excitability of the central nervous system, reduces the number of lymphocytes and eosinophils, increases the number of red blood cells (stimulates the production of erythropoietin). Interacts with specific cytoplasmic receptors and forms a complex that penetrates the cell nucleus, stimulates the synthesis of matrix ribonucleic acid (mRNA); the latter induces the formation of proteins, including lipocortin, that mediate cellular effects. Lipocortin inhibits phospholipase A2, suppresses the release of arachidonic acid and suppresses the synthesis of endoperoxides, prostaglandins, leukotrienes, which contribute to inflammation, allergies and others.
Effect on protein metabolism: reduces the amount of protein in plasma (due to globulins) with an increase in the albumin/globulin ratio, increases albumin synthesis in the liver and kidneys; enhances protein catabolism in muscle tissue.
Effect on lipid metabolism: increases the synthesis of higher fatty acids and triglycerides, redistributes fat (fat accumulation mainly in the shoulder girdle, face, abdomen), leads to the development of hypercholesterolemia.
Effect on carbohydrate metabolism: increases the absorption of carbohydrates from the gastrointestinal tract (GIT); increases the activity of glucose-6-phosphatase, leading to an increase in the flow of 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.
Effect on water-electrolyte metabolism: retains sodium ions and water in the body, stimulates the excretion of potassium ions (mineralocorticosteroid activity), reduces the absorption of calcium ions from the gastrointestinal tract, “washes out” calcium ions from the bones, increases the excretion of calcium ions by the kidneys.
The anti-inflammatory effect is associated with inhibition of the release of inflammatory mediators by eosinophils; 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 and organelle membranes (especially lysosomal ones).
The antiallergic effect develops as a result of suppression of 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, suppressing antibody formation, changing the body's immune response.
In chronic obstructive pulmonary disease, the effect is based mainly on inhibition of inflammatory processes, inhibition of development or prevention of swelling of the mucous membranes, inhibition of eosinophilic infiltration of the submucosal layer of the bronchial epithelium, 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-caliber bronchi to endogenous catecholamines and exogenous sympathomimetics, reduces the viscosity of bronchial secretions due to inhibition or reduction of its production.
Antishock and antitoxic effects are associated with an increase in blood pressure (due to an increase in the concentration of circulating catecholamines and restoration of the sensitivity of adrenergic receptors to them, as well as vasoconstriction), a decrease in the permeability of the vascular wall, membrane protective properties, and activation of liver enzymes involved in the metabolism of endo- and xenobiotics.
The immunosuppressive effect is due to inhibition of the release of cytokines (interleukin-1, interleukin-2; interferon gamma) from lymphocytes and macrophages. Suppresses the synthesis and secretion of adrenocorticotropic hormone (ACTH), and secondarily the synthesis of endogenous GCS.
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 adrenal cortex; biological half-life is 32-72 hours (duration of inhibition of the hypothalamic-pituitary-adrenal cortex system).
In terms of the strength of glucocorticoid activity, 0.5 mg of dexamethasone corresponds to approximately 3.5 mg of prednisolone, 15 mg of hydrocortisone or 17.5 mg of cortisone for oral dosage forms.
Mode of application
To find out how much to drip the hormonal drug, read the instructions for use.
Children over 12 years old and adults:
- for chronic inflammatory changes, Dexamethasone should be instilled twice a day for a month;
- for acute inflammation, use 1-2 drops of the medicine, instill it 4-5 times a day only in the first two days, and after that 3-4 times for several more days;
- in case of injury or after surgery, the drug is instilled 2-4 times a day in a dose of 1-2 drops, the duration, depending on the intensity and severity of inflammation, is 2-4 weeks.
For children aged 6-12 years, the drug is prescribed for allergies and inflammation, 1 drop 2-3 times a day for 7-10 days. If longer use is required, it is necessary to first perform a fluorescein test to ensure the integrity of the corneal integumentary epithelium.
Before instillation, the bottle should be shaken so that the substance is evenly distributed in the solution.
Indications for use of Dexamethasone
Systemic connective tissue diseases (systemic lupus erythematosus, scleroderma, periarteritis nodosa, dermatomyositis, rheumatoid arthritis).
Acute and chronic inflammatory diseases of the joints: gouty and psoriatic arthritis, osteoarthritis (including post-traumatic), polyarthritis, glenohumeral periarthritis, ankylosing spondylitis (ankylosing spondylitis), juvenile arthritis, syndrome
Stilla in adults, bursitis, nonspecific tenosynovitis, synovitis and epicondylitis.
Rheumatic fever, acute rheumatic carditis.
Acute and chronic allergic diseases: allergic reactions to drugs and foods, serum sickness, urticaria, allergic rhinitis, angioedema, drug exanthema, hay fever.
Skin diseases: pemphigus, psoriasis, eczema, atopic dermatitis, diffuse neurodermatitis, contact dermatitis (affecting a large surface of the skin), toxicerma, seborrheic dermatitis, exfoliative dermatitis, toxic epidermal necrolysis (Lyell's syndrome), bullous dermatitis herpetiformis, malignant exudative erythema (syndrome) Stevens-Johnson).
Brain edema (only after confirmation of symptoms of increased intracranial pressure by magnetic resonance or computed tomography) caused by a brain tumor and/or associated with surgery or radiation injury.
Allergic eye diseases: allergic corneal ulcers, allergic forms of conjunctivitis.
Inflammatory eye diseases: sympathetic ophthalmia, severe sluggish anterior and posterior uveitis, optic neuritis.
Primary or secondary adrenal insufficiency (including the condition after removal of the adrenal glands).
Congenital adrenal hyperplasia.
Kidney diseases of autoimmune origin (including acute glomerulonephritis); nephrotic syndrome.
Subacute thyroiditis.
Diseases of the hematopoietic organs - agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, acute lymphoid and myeloid leukemia, lymphogranulomatosis, thrombocytopenic purpura, secondary thrombocytopenia in adults, erythroblastopenia (erythrocytic anemia), congenital (erythroid) hypoplastic anemia.
Lung diseases: acute alveolitis, pulmonary fibrosis, stage II-III sarcoidosis. Bronchial asthma (for bronchial asthma, the drug is prescribed only in severe cases, ineffectiveness or inability to take inhaled corticosteroids).
Tuberculous meningitis, pulmonary tuberculosis, aspiration pneumonia (in combination with specific chemotherapy).
Berylliosis, Loeffler's syndrome (not amenable to other therapy).
Lung cancer (in combination with cytostatics).
Multiple sclerosis.
Gastrointestinal diseases: ulcerative colitis, Crohn's disease, local enteritis.
Hepatitis.
Prevention of transplant rejection as part of complex therapy.
Hypercalcemia due to cancer, nausea and vomiting during cytostatic therapy.
Multiple myeloma.
Conducting a test for the differential diagnosis of hyperplasia (hyperfunction) and tumors of the adrenal cortex.
Contraindications
Dexamethasone is contraindicated for:
- with keratitis caused by the Varicella zoster and Herpes simplex viruses, as well as with viral damage to the conjunctiva and cornea;
- eye infection with mycobacteria;
- fungal infections of the eyeball;
- acute purulent pathologies of the eye;
- disruption of the structure of the corneal epithelium;
- increased intraocular pressure;
- the presence of individual sensitivity to drops.
Dexamethasone drops can be prescribed to women during pregnancy and feeding only in special cases when the possible benefit outweighs the threat and harm that can be caused to the fetus or newborn.
Use of Dexamethasone during pregnancy and children
Dexamethasone crosses the placenta (can reach high concentrations in the fetus) and into breast milk. During pregnancy, especially in the first trimester, or in women planning pregnancy, the use of Dexamethasone is indicated only if the expected therapeutic effect outweighs the risk of negative effects on the mother or fetus. GCS should be prescribed during pregnancy only for absolute indications. With long-term therapy during pregnancy, the possibility of fetal damage cannot be excluded. If used in the third trimester 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 treatment with the drug during breastfeeding, breastfeeding should be stopped.
special instructions
Due to a decrease in local immunity with long-term use of Dexamethasone, the development of a secondary fungal, viral or bacterial infection of the eye is possible.
Since intraocular hypertension may develop with prolonged use of the drug, intraocular pressure should be measured in case of treatment for more than 14 days.
Before instilling the solution into the subconjunctival sac, contact lenses should be removed. You can install them in their original place after a quarter of an hour.
If a secondary infection occurs during treatment, then additional antibacterial drops may be prescribed. If you are allergic, you should immediately stop using Dexamethasone drops.
Due to the fact that lacrimation may increase after instillation of the medicine, you should not use drops immediately before working with complex mechanisms or before driving a car.
Once opened, the bottle should be used within a month.
Drug interactions
Dexamethasone increases the toxicity of cardiac glycosides (due to the resulting hypokalemia, the risk of developing arrhythmias increases).
Accelerates the elimination of acetylsalicylic acid, reduces its concentration in the blood (when dexamethasone is discontinued, the concentration of salicylates in the blood increases and the risk of side effects increases).
When used simultaneously with live antiviral vaccines and against the background of other types of immunizations, it increases the risk of viral activation and the development of infections.
Increases the metabolism of isoniazid, mexiletine (especially in “fast acetylators”), which leads to a decrease in their plasma concentrations.
Increases the risk of developing the hepatotoxic effect of paracetamol (induction of “liver” enzymes and the formation of a toxic metabolite of paracetamol).
Increases (with long-term therapy) the content of folic acid.
Hypokalemia caused by GCS can increase the severity and duration of muscle blockade due to muscle relaxants.
In high doses, it reduces the effect of somatropin.
Antacids reduce the absorption of corticosteroids.
Dexamethasone reduces the effect of hypoglycemic drugs; enhances the anticoagulant effect of coumarin derivatives.
Weakens the effect of vitamin D on the absorption of calcium ions in the intestinal lumen.
Ergocalciferol and parathyroid hormone prevent the development of osteopathy caused by GCS.
Reduces the concentration of praziquantel in the blood.
Cyclosporine (inhibits metabolism) and ketoconazole (reduces clearance) increase toxicity.
Thiazide diuretics, carbonic anhydrase inhibitors, other corticosteroids and amphotericin B increase the risk of hypokalemia, sodium-containing drugs - edema and increased blood pressure.
Non-steroidal anti-inflammatory drugs and ethanol increase the risk of developing ulceration of the gastrointestinal mucosa and bleeding; in combination with non-steroidal anti-inflammatory drugs for the treatment of arthritis, it is possible to reduce the dose of GCS due to the summation of the therapeutic effect.
Indomethacin, displacing dexamethasone from its association with albumin, increases the risk of developing its side effects.
Amphotericin B and carbonic anhydrase inhibitors increase the risk of osteoporosis.
The therapeutic effect of GCS is reduced under the influence of phenytoin, barbiturates, ephedrine, theophylline, rifampicin and other inducers of “liver” microsomal enzymes (increased metabolic rate).
Mitotane and other inhibitors of adrenal function may necessitate an increase in the dose of GCS.
The clearance of GCS increases against the background of thyroid hormones.
Immunosuppressants increase the risk of developing infections and lymphoma or other lymphoproliferative disorders associated with Epstein-Barr virus.
Estrogens (including oral estrogen-containing contraceptives) reduce the clearance of corticosteroids, prolong the half-life and their therapeutic and toxic effects.
The appearance of hirsutism and acne is facilitated by the simultaneous use of other steroid hormonal drugs - androgens, estrogens, anabolic steroids, oral contraceptives.
Tricyclic antidepressants may increase the severity of depression caused by taking dexamethasone (not indicated for the treatment of these side effects).
The risk of developing cataracts increases when used in conjunction with other corticosteroids, antipsychotic drugs (neuroleptics), carbutamide and azathioprine.
Simultaneous administration with m-anticholinergics (including antihistamines, tricyclic antidepressants), nitrates contributes to the development of increased intraocular pressure.
When used simultaneously with fluoroquinolones, the risk of tendonopathy (mainly Achilles tendon) increases in elderly patients and in patients with tendon diseases.
Antimalarials (chloroquine, hydroxychloroquine, mefloquine) in combination with dexamethasone may increase the risk of developing myopathy and cardiomyopathy.
Angiotensin-converting enzyme inhibitors, when administered concomitantly with dexamethasone, can change the composition of peripheral blood.
