Dexamethasone

General characteristics. Structure:

Active ingredient: 0,0005 g (0,5 mg) of dexamethasone.

Excipients: sugar, potato starch, stearic acid.

Pharmacological properties:

Pharmacodynamics. A synthetic glucocorticosteroid (GKS) — metilirovanny derivative a ftorprednizolona. Renders the antiinflammatory, antiallergic, desensibilizing, immunodepressive, antishock and anti-toxic effect, increases sensitivity of beta adrenoceptors to endogenous catecholamines.

Interacts with specific cytoplasmatic receptors (receptors for GKS are in all fabrics, especially their is a lot of in a liver) with formation of the complex inducing formation of proteins (including the enzymes regulating the vital processes in cells).

Protein metabolism: reduces amount of globulins in plasma, increases synthesis of albumine in a liver and kidneys (with increase in coefficient albumine/globulin); reduces synthesis and strengthens a protein catabolism in muscular tissue.

Lipidic exchange: increases synthesis of higher fatty acids and triglycerides, redistributes fat (mobilization from hypodermic cellulose of extremities and accumulation of fat is preferential in the field of a shoulder girdle, the person, a stomach), leads to development of a hypercholesterolemia.

Carbohydrate metabolism: increases absorption of carbohydrates from digestive tract; increases activity of glyukozo-6-phosphatase (increase in intake of glucose from a liver in blood); increases activity of a fosfoenolpiruvatkarboksilaza and synthesis of aminotransferases (activation of a gluconeogenesis); promotes development of a hyperglycemia.

Water and electrolytic exchange: Na + and water in an organism detains, stimulates removal of K+ (mineralokortikoidny activity), reduces absorption of Sa2 + from digestive tract, causes "washing away" of calcium from bones and increase in its renal excretion, reduces a mineralization of a bone tissue.

The antiinflammatory effect is connected with release oppression by eosinophils and mast cells of mediators of an inflammation; induction of formation of lipokortin and reduction of quantity of the mast cells producing hyaluronic acid; with reduction of permeability of capillaries; stabilization of cellular membranes (especially lizosomalny) and membranes of organellas. Affects all stages of inflammatory process: inhibits synthesis of prostaglandins (Pg) at the level of arachidonic acid (липокортин oppresses A2 phospholipase, suppresses a liberation of arachidonic acid and inhibits biosynthesis of endoperoxides, the leukotrienes promoting processes of an inflammation, an allergy, etc.), synthesis of "pro-inflammatory cytokines" (Interlaken 1, a tumor necrosis factor an alpha, etc.); increases resistance of a cellular membrane to action of various disturbing factors.

The immunodepressive effect is caused by the caused involution of an adenoid tissue, oppression of proliferation of lymphocytes (especially T lymphocytes), suppression of migration of V-cells and interactions of T - and V-lymphocytes, braking of release of cytokines (interleykina-1, 2; gamma interferon) from lymphocytes and markofag and decrease in antibody formation.
The antiallergic effect develops as a result of decrease in synthesis and secretion of mediators of an allergy, braking of release from sensitized mast cells and basophiles of a histamine, etc. biologically active agents, reduction of number of the circulating basophiles, suppression of development of adenoid and connecting tissue, reduction of number of T - and V-lymphocytes, mast cells, decrease in sensitivity of effector cells to mediators of an allergy, oppression of antibodyformation, change of an immune response of an organism.

At obstructive respiratory diseases action is caused, mainly, by braking of inflammatory processes, the prevention or reduction of expressiveness of hypostasis of mucous membranes, decrease in eosinophilic infiltration of a submucosal layer of an epithelium of bronchial tubes and adjournment in mucous bronchial tubes of the circulating cell-bound immune complexes, and also braking of an erozirovaniye and desquamation mucous. Increases sensitivity of beta adrenoceptors of bronchial tubes of small and average caliber to endogenous catecholamines and exogenous sympathomimetics, reduces viscosity of slime due to reduction of its products.

Slows down connective tissue reactions during inflammatory process and reduces a possibility of formation of cicatricial fabric.

Suppresses synthesis and secretion of AKTG and for the second time — synthesis of endogenous GKS.

Feature of action — considerable inhibition of function of a hypophysis and almost total absence of mineralokortikosteroidny activity.

Doses of 1-1,5 mg/days oppress function of bark of adrenal glands; a biological elimination half-life — 32-72 h (duration of oppression of system hypothalamus-hypophysis-cortical substance of adrenal glands).

On force of glucocorticoid activity of 0,5 mg of dexamethasone there correspond about 3,5 mg of Prednisonum (or Prednisolonum), 15 mg of a hydrocortisone or 17,5 mg of a cortisone.

Pharmacokinetics. After intake it is quickly and completely soaked up. The maximum concentration in blood is reached in 1-2 h. In blood contacts (60-70%) specific protein carrier — transcortinum. Easily passes through gistogematichesky barriers (including through hematoencephalic and placental). It is metabolized in a liver (generally by conjugation with glucuronic and sulfuric acids) to inactive metabolites. It is removed with urine (a small part — the lactating glands). The elimination half-life makes 3-5 hours.

Indications to use:

• primary and secondary adrenal insufficiency (usually — in combination with mineralokortikoida);
• inborn hyperplasia of bark of adrenal glands;
• subacute thyroiditis;
• hypercalcemia at malignant new growths;
• bronchial asthma;
• pseudorheumatism in an aggravation phase;
• general diseases of connecting fabric (system lupus erythematosus, scleroderma, etc.);
• skin diseases (psoriasis, eczema, dermatitis, pemphigus, acute erythrosis, etc.);
• nonspecific ulcer colitis;
• diseases of bodies of a hemopoiesis: an agranulocytosis, a panmyelopathia, autoimmune hemolitic anemia, acute lympho-and myeloid leukoses, лимфогрануломатоз, a Werlhof's disease, secondary thrombocytopenia at adults, an eritroblastopeniya (erythrocyte anemia), inborn (erythroidal) hypoplastic anemia;
• brain hypostasis (usually after preliminary parenteral use of a glucocorticosteroid);
• conducting test at differential diagnosis of a hyperplasia (hyperfunction) and tumors of bark of adrenal glands.

Route of administration and doses:

The mode of a drug dosing is individual and depends on indications, disease severity, and reaction of the patient to therapy.

Dexamethasone is appointed inside in time or after food, once in the morning (a small dose) or in 2-3 receptions (high dose). The average daily dose for adults makes from 2-3 mg to 6 mg. The maximum daily dose — 10-15 mg. After achievement of therapeutic effect the dose is gradually reduced (usually by 0,5 mg in 3 days) to supporting — 2-4,5 and more than a mg/days. Minimum effective dose — 0,5-1 mg/days.

To children appoint 0,0833-0,3333 mg/kg or 0,0025-0,0001 mg/sq.m a day in 3-4 receptions depending on age.

Duration of use of Dexamethasone depends on the nature of pathological process and efficiency of treatment and makes from several days to several months and more. Treatment is stopped gradually.

Features of use:

Before an initiation of treatment of the patient it has to be inspected regarding identification of possible contraindications. Clinical inspection has to include a research of cardiovascular system, X-ray inspection of lungs, a research of a stomach and duodenum, system of urination, organs of sight; control of a blood count, content of glucose and electrolytes in a blood plasma.

During treatment by dexamethasone (especially long) observation of the oculist, control of arterial pressure and a condition of water and electrolytic balance, and also a picture of peripheral blood and level of glucose of blood is necessary.

For the purpose of reduction of by-effects it is possible to appoint antacids, and also to increase receipt of K+ in an organism (a diet, potassium drugs). Food has to be protein-rich, vitamins, with restriction of content of fats, carbohydrates and table salt.

Effect of drug amplifies at patients with a hypothyroidism, and cirrhosis. Drug can increase the existing emotional instability or psychotic disturbances. At the instruction to psychoses in the anamnesis Dexamethasone in high doses is appointed under strict control of the doctor.

In stressful situations during the supporting treatment (for example, surgeries, an injury or infectious diseases) it is necessary to carry out dose adjustment of drug in connection with increase in need for glucocorticosteroids.

At daily use by 5 months of treatment the atrophy of bark of adrenal glands develops. It is necessary to watch carefully the patient within a year after the end of long therapy with Dexamethasone in connection with possible development of relative insufficiency of bark of adrenal glands. If during this period there are stressful situations, appoint (according to indications) for the period of GKS, in need of a combination to mineralokortikoida.

At sudden cancellation, especially in case of the previous use of high doses, development of a syndrome of "cancellation" (anorexia, nausea, block, generalized musculoskeletal pains, the general weakness), and also an exacerbation of a disease concerning which Dexamethasone was appointed is possible.

During treatment it is not necessary to carry out by Dexamethasone vaccination in connection with decrease in its efficiency (immune response).

Appointing Dexamethasone at intercurrent infections, septic states and tuberculosis, it is necessary to carry out treatment by antibiotics of bactericidal action at the same time.

Dexamethasone can mask some symptoms of infections. At children during prolonged treatment by dexamethasone careful observation of dynamics of growth and development is necessary. To children who during treatment were in contact with patients with measles or chicken pox preventively appoint specific immunoglobulins. At patients with a diabetes mellitus it is necessary to control the content of glucose of blood and if necessary to korrigirovat therapy.

Radiological control of bone and joint system (pictures of a backbone, brush) is shown. With latent infectious diseases of kidneys and urinary tract Dexamethasone is capable to cause a leukocyturia in patients that can have diagnostic value.

Dexamethasone increases the maintenance of metabolites of 11-and 17 oxyketocorticosteroids.

Use during pregnancy and breastfeeding. During pregnancy (especially in the I trimester) drug can be used only according to vital indications. At long therapy during pregnancy the possibility of a growth disorder of a fruit is not excluded. In case of use in the III trimester of pregnancy there is a danger of emergence of an atrophy of bark of adrenal glands at a fruit that can demand performing replacement therapy from the newborn.

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

Side effects:

Usually Dexamethasone is well transferred. It has low mineralokortikoidny activity, i.e. its influence on water and electrolytic exchange is small. As a rule, low and average doses of Dexamethasone do not cause a delay of sodium and water in an organism, the raised potassium excretion.

The following side effects are described:

- from endocrine system: decrease in tolerance to glucose, a steroid diabetes mellitus or manifestation of a latent diabetes mellitus, oppression of function of adrenal glands, an Icenco-Cushing syndrome (a crescent-shaped face, obesity of pituitary type, a hirsutism, increase in arterial pressure, a dysmenorrhea, an amenorrhea, muscular weakness, striya), a delay of sexual development at children.

- from the alimentary system: nausea, vomiting, pancreatitis, steroid stomach ulcer and duodenum, erosive esophagitis, bleedings and perforation of a GIT, increase or loss of appetite, digestion disturbance, meteorism, hiccups. In rare instances — increase in activity of "hepatic" transaminases and an alkaline phosphatase.

- from cardiovascular system: arrhythmias, bradycardia (up to a cardiac standstill); development (at predisposed patients) or strengthening of expressiveness of heart failure, ECG change characteristic of a hypopotassemia, increase in arterial pressure, hypercoagulation, fibrinferments. Patients with an acute and subacute myocardial infarction have a distribution of the center of a necrosis, delay of formation of cicatricial fabric that can lead to a rupture of a cardiac muscle.

- from a nervous system: delirium, disorientation, euphoria, hallucinations, maniac-depressive psychosis, depression, paranoia, increase in intracranial pressure, nervousness or concern, sleeplessness, dizziness, вертиго, cerebellum pseudoneoplasm, headache, spasms.

- from sense bodys: a back subkapsulyarny cataract, increase in intraocular pressure with possible injury of an optic nerve, tendency to development of consecutive bacterial, fungal or viral infections of eyes, trophic changes of a cornea, an exophthalmos.

- from a metabolism: the increased calcium removal, a hypocalcemia, increase in body weight, negative nitrogenous balance (the increased disintegration of proteins), the increased perspiration.

Caused by mineralokortikoidny activity: delay of liquid and sodium (peripheral hypostases), hypernatremia, gipoka-liyemichesky syndrome (hypopotassemia, arrhythmia, mialgiya or spasm of muscles, unusual weakness and fatigue).

- from a musculoskeletal system: delay of growth and processes of ossification at children (premature closing of epiphyseal regions of growth), osteoporosis (it is very rare — pathological fractures of bones, an aseptic necrosis of a head humeral and a femur), a rupture of sinews of muscles, a steroid myopathy, decrease in muscle bulk (atrophy).

- from integuments and mucous membranes: the slowed-down healing of wounds, petechias, ecchymomas, thinning of skin, hyper - or hypopigmentation, eels, striya, tendency to development of a pyoderma and candidiases.

Allergic reactions: skin rash, itch, acute anaphylaxis.

Others: development or an exacerbation of infections (emergence of this side effect is promoted jointly by the applied immunodepressants and vaccination), a leukocyturia, a syndrome of "cancellation".

Interaction with other medicines:

Co-administration of Dexamethasone with:
- inductors of "hepatic" microsomal enzymes (phenobarbital, rifampicin, Phenytoinum, theophylline, ephedrine) leads to decrease in its concentration;
- diuretics (especially "thiazide" and inhibitors of a karboangidraza) and Amphotericinum In can lead to strengthening of removal from K+ organism; with natriysoderzhashchy drugs — to development of hypostases and increase in arterial pressure;
- Amphotericinum In — the risk of development of heart failure increases;
- cardiac glycosides their portability worsens and the probability of development of ventricular premature ventricular contraction increases (because of the caused hypopotassemia);
- indirect anticoagulants weakens (strengthens) their action less often (it is required to dose adjustment);
- anticoagulants and trombolitika the risk of development of bleedings from ulcers in digestive tract increases;
- ethanol and non-steroidal anti-inflammatory drugs (NPVP) the risk of emergence of erosive cankers in digestive tract and development of bleedings (in a combination with NPVP at treatment of arthritises the dose decline of glucocorticosteroids because of summation of therapeutic effect is possible) amplifies;
- paracetamol the risk of development of a hepatotoxic (induction of liver enzymes and formation of a toxic metabolite of paracetamol) increases;
- acetylsalicylic acid accelerates its removal and reduces concentration in blood (at dexamethasone cancellation the level of salicylates in blood increases and the risk of development of by-effects increases);
- insulin and peroral hypoglycemic drugs, antihypertensives their efficiency decreases;
- vitamin D its influence on absorption of Sa2 + in intestines decreases;
- somatotropic hormone reduces efficiency of the last, and with prazikvantely — its concentration;
- M-holinoblokatorami (including antihistaminic drugs and tricyclic antidepressants) and nitrates promotes increase in intraocular pressure;
- an isoniazid and mekselitiny increases their metabolism (especially at "slow" atsetilator) that leads to decrease in their plasma concentration.

Inhibitors of a karboangidraza and "loopback" diuretics can increase risk of development of osteoporosis.

Indometacin, forcing out Dexamethasone from communication with albumine, increases risk of development of its side effects.

AKTG strengthens effect of Dexamethasone. Ergocalciferol and parathormone interfere with development of the osteopathy caused by Dexamethasone.

Cyclosporine and кетоконазол, slowing down metabolism of Dexamethasone can increase its toxicity in some cases.

Co-administration of androgens and steroid anabolic drugs with Dexamethasone promotes development of peripheral hypostases and a hirsutism, appearance of eels.

Are oestrogenic and oral estrogensoderzhashchy contraceptives reduce clearance of Dexamethasone that can be followed by strengthening of expressiveness of its action.

Mitotanum and other inhibitors of function of bark of adrenal glands can cause need of increase in a dose of Dexamethasone.

At simultaneous use with live antiviral vaccines and against the background of other types of immunizations increases risk of activation of viruses and development of infections.

Antipsychotic means (neuroleptics) and Azathioprinum increase risk of development of a cataract at purpose of Dexamethasone.

Co-administration of antacids reduces Dexamethasone absorption.

At simultaneous use with anti-thyroid drugs decreases, and with thyroid hormones — the clearance of Dexamethasone increases.

Contraindications:

The only contraindication for short-term use according to vital indications is hypersensitivity to dexamethasone or components of drug.

At children in a growth period of GKS have to be applied only according to absolute indications and under especially careful observation of the attending physician.

With care it is necessary to appoint drug at the following diseases and states:
- digestive tract diseases — a peptic ulcer of a stomach and duodenum, an esophagitis, gastritis, an acute or latent round ulcer, recently created intestines anastomosis, nonspecific ulcer colitis with threat of perforation or abscessing, a diverticulitis;
- parasitic and infectious diseases of the virus, fungal or bacterial nature (now or recently postponed, including recent contact with the patient) — the herpes simplex surrounding herpes (a viremichesky phase), chicken pox, measles; amebiasis, strongyloidosis; system mycosis; active and latent tuberculosis.
Use at serious infectious diseases is admissible only against the background of specific therapy.
- pre-and the postvaccinal period (8 weeks to and 2 weeks after vaccination), lymphadenitis after BTsZh inoculation. Immunodeficiency (including AIDS or HIV infection).
- diseases of cardiovascular system, including recently postponed myocardial infarction (at patients with an acute and subacute myocardial infarction distribution of the center of a necrosis, delay of formation of cicatricial fabric and, thereof — a rupture of a cardiac muscle is possible), heavy chronic heart failure, arterial hypertension, a lipidemia.
- endocrine diseases — a diabetes mellitus (including disturbance of tolerance to carbohydrates), a thyrotoxicosis, a hypothyroidism, Itsenko-Cushing's disease, obesity (the III-IV St).
- heavy chronic renal and/or liver failure, нефроуролитиаз. The hypoalbuminemia and states contributing to its emergence (cirrhosis, a nephrotic syndrome).
- system osteoporosis, gravis myasthenia, acute psychosis, poliomyelitis (except for a form of bulbar encephalitis), open and closed-angle glaucoma, pregnancy.

Overdose:

Strengthening of the by-effects described above is possible. It is necessary to reduce the Dexamethasone dose.

Symptomatic treatment.

Storage conditions:

Not to apply after the period of validity specified on packaging. List B. In dry, protected from light and the place, unavailable to children, at a temperature not above 25 °C. A period of validity - 4 years.

Issue conditions:

According to the recipe

Packaging:

Tablets on 0,0005 g (0,5 mg). On 50, 100 tablets in banks from glass melt of dark glass or banks from polymeric material. On 10 or 20 tablets in a blister strip packaging. Each can or on 1, 2, 5 or 10 blister strip packagings on 10 tablets, or on 1, 2, 3 or 5 blister strip packagings on 20 tablets together with the application instruction is placed in a pack from a cardboard.