Relevance
The benefit of using dexamethasone or betamethasone in pregnant women at risk of preterm birth has been shown in countries with high health care costs.
However, the cost-effectiveness of this intervention in countries with low health care costs is unknown. A new study assessed the effectiveness and safety of antenatal glucocorticoid use in women in countries with low health care costs.
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.
results
- The study included 2852 women and their 3070 fetuses. The women were observed in hospitals in Bangladesh, India, Kenya, Nigeria and Pakistan.
- The study was completed earlier than planned because the second interim analysis showed a clear benefit from steroid therapy.
- Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and in 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% CI, 0.72-0. 97; P=0.03).
- Stillbirth or neonatal death occurred in 393 of 1532 fetuses and infants (25.7%) in the dexamethasone group and in 444 of 1519 fetuses and infants (29.2%) in the placebo group (relative risk, 0.88; 95% CI, 0.78-0.99; P=0.04).
- The incidence of maternal bacterial infection was 4.8% with dexamethasone compared with 6.3% in the control group (relative risk, 0.76; 95% CI, 0.56-1.03).
- According to the safety analysis, there were no significant differences between the groups in the frequency of side effects.
special instructions
Check with your doctor before using Dexamethasone if:
- you have malignant neoplasms of the hematopoietic organs, as the risk of developing a very rare, potentially life-threatening condition caused by the sudden destruction of tumor cells increases,
- you have problems with your kidneys or liver,
- you have high blood pressure or heart disease,
- you have diabetes mellitus or a family history of it,
- for osteoporosis, especially in women during menopause,
- muscle weakness has been observed in the past with the use of this or other corticosteroids,
- you have increased intraocular pressure (glaucoma) or have a family history of glaucoma,
- you have a stomach ulcer (peptic ulcer),
- you have a mental disorder or have a mental illness that can be complicated by the use of corticosteroids, such as “steroid psychosis”,
- you have epilepsy,
- you have a migraine,
- you have an infestation caused by parasites,
- you have tuberculosis,
- you have growth retardation,
- Do you have Cushing's syndrome?
- you have had a head injury,
- You have suffered a stroke.
If you are in any doubt if any of the above applies to you, talk to your doctor or pharmacist before using Dexamethasone.
Important information when using this type of medicine
If you develop an infection while taking this drug, you should call your doctor. Please tell the doctor, dentist or specialist treating you that you are currently taking or have recently taken corticosteroids.
Do not use Dexamethasone to treat acute respiratory distress syndrome (ARDS, a serious lung disease) if you were diagnosed with this condition more than 2 weeks ago.
Dexamethasone and viral infections
While taking this drug, you should avoid contact with people who have chickenpox, shingles, or measles, especially if you have never had these diseases, because specialized treatment will be needed if you get it or if you think you are at risk of developing any of these diseases. of these diseases, you should consult a doctor immediately. You should also tell your doctor if you have ever had measles or chickenpox and if you have been vaccinated against these diseases in the past. Please consult a doctor or specialist who is treating you in a hospital if:
- Did you have an accident,
- You are sick
- you are planning a surgical intervention, including oral surgery,
- You require vaccination.
If any of the above applies to you, contact your doctor or healthcare professional, even if you have stopped taking the drug.
If the drug is used in childhood, it is important that the doctor regularly monitor the child's growth and development. Dexamethasone should not be given empirically to premature infants with respiratory disease.
Special instructions and precautions
Consult your doctor if you experience:
Symptoms of neoplasm lysis syndrome such as muscle spasms, muscle weakness, restlessness, loss or blurred vision, and shortness of breath if a hematopoietic neoplasm is present.
Other medicines and Dexamethasone
- Tell your doctor if you are taking, have recently taken, or should take any other medications.
- Some drugs may increase the effect of Dexamethasone and your doctor should monitor you if you take these drugs (including some drugs used to treat HIV: ritonavir, cobicistat).
Other drugs and Dexamethasone may interact with each other.
Especially:
- Medicines to treat heart and circulatory diseases, such as warfarin, blood pressure medications and diuretics.
- Antibiotics such as rifampicin and rifabutin.
- Drugs to treat epilepsy such as phenytoin, carbamazepine, phenobarbitone and primidone.
- Painkillers or anti-inflammatory drugs such as aspirin or phenylbutazone.
- Drugs for the treatment of diabetes mellitus.
- Drugs that cause a decrease in potassium levels in the blood.
- Drugs that are used to treat myasthenia gravis.
- Antineoplastic drugs such as aminoglutethimide.
- Ephedrine (used to relieve nasal congestion symptoms).
- Acetazolamide, used for glaucoma.
- Carbenoxolone is sometimes used to treat stomach ulcers.
Important information about the drug
- Dexamethasone is a corticosteroid drug that is used to treat a variety of conditions, including serious illnesses.
- It must be used regularly to obtain maximum effect.
- You should not stop taking the drug without consulting a doctor. It is necessary to reduce the dose gradually.
- Dexamethasone may cause side effects in some people; some problems such as mood changes (depression or euphoria) or stomach problems can develop quite quickly. If you feel unwell, do not stop taking the drug, but consult a doctor immediately.
- Some side effects only develop after several weeks or months of use. These include weakness in the arms and knees or a rounding of the face (moon face).
- You should avoid people who have chickenpox or shingles, especially if you have never had these diseases. This is a big risk for you. If you have been in contact with someone who has chickenpox or shingles, contact your doctor immediately.
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
Hot injections
Hot injections for bronchitis in adults are prescribed in the presence of allergic reactions, to relieve symptoms of acute respiratory infections, and to quickly eliminate inflammatory processes.
Calcium chloride (Calcii chloridum) is recommended in case of allergic complications associated with taking pharmacological agents. Intravenous administration of the composition reduces inflammatory and exudative processes.
The solution is administered intravenously very slowly. When the drug is administered intravenously, a sharp increase in temperature is possible. Rapid infusion of calcium chloride increases the decrease in heart rate and the chaotic rhythm of the heart muscle.
Contraindications to the use of Dexamethasone
- For short-term use for “life-saving” indications, the only contraindication is hypersensitivity; systemic mycosis;
- simultaneous use of live and attenuated vaccines with immunosuppressive doses of the drug;
- sucrose intolerance, isomaltase/sucrase deficiency, glucose-galactose malabsorption; breastfeeding period; children up to 3 years old.
Carefully:
Parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently suffered, including recent contact with a patient) –
- herpes simplex, herpes zoster (viremic phase), chicken pox, measles;
- amebiasis, strongyloidiasis (established or suspected);
- active and latent tuberculosis.
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.
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.