Dexamethasone - instructions for use, dose, side effects, contraindications

Interaction with intracellular glucocorticoid receptors - the formation of dimers of the glucocorticoid-glucocorticoid receptor complex. Penetration of the activated receptor into the nucleus, binding to glucocorticoid-sensitive regulatory elements of DNA - a specific effect on gene expression (activation and inhibition).

The anti-inflammatory effect of dexamethasone is due to several factors.

1. The drug induces the synthesis of lipocortin, inhibiting the activity of phospholipase A₂. Inhibition of phospholipase A mediated₂ hydrolysis of membrane phospholipids of damaged tissues prevents the formation of arachidonic acid. The disruption of the formation of arachidonic acid actually means inhibition of the synthesis of prostaglandins,since arachidonic acid is a substrate for further metabolism along the cyclooxygenase pathway, and also along the lipoxygenase pathway, with appropriate inhibition of leukotriene synthesis.

2. The anti-inflammatory effect of glucocorticoids is potentiated by their ability to inhibit the expression of COX-2 genes, which also leads to a decrease in the synthesis of prostaglandins in the inflammatory focus, including pro-inflammatory prostaglandins E₂ and I₂.

3. Dexamethasone inhibits the expression of molecules of intercellular adhesion in the endothelium of blood vessels, violating the penetration of neutrophils and monocytes into the focus of inflammation. After the introduction of glucocorticoids, an increase in the concentration of neutrophils in the blood (due to their entry from the bone marrow and the restriction of migration from the blood vessels) is noted. This causes a decrease in the number of neutrophils in the site of inflammation.

Glucocorticoids inhibit the transcription of cytokine genes that stimulate the inflammatory and immune response (IL-1, IL-2, IL-6, IL-8), as well as tumor necrosis factor (and some others). Also, a decrease in the transcription rate and an increase in the degradation of the receptor genes for IL-1 and IL-2, inhibition of the transcription of the metalloproteinase (collagenase, elastase, etc.) genes,involved in increasing the permeability of the vascular wall, in the processes of scarring and destruction of cartilaginous tissue in diseases of the joints.

Immunosuppressive effect is due to inhibition of transcription of DNA encoding the main histocompatibility complex, pro-inflammatory cytokines and inhibition of proliferation of T-lymphocytes. It leads to a decrease in the number of T-lymphocytes and their influence on B-lymphocytes, inhibits the production of immunoglobulins. Reduces formation and increases the breakdown of the components of the compliment system.

The antiallergic effect is associated with inhibition of the synthesis of allergy mediators and inhibition of the release of mediators of allergy, and therefore it is effective in allergic reactions of immediate type.

Restores the sensitivity of adrenoreceptors to catecholamines. Accelerates the breakdown of proteins and reduces their concentration in the plasma, inhibits the utilization of glucose by peripheral tissues and stimulates gluconeogenesis in the liver, potentiates the formation of enzyme proteins in the liver, erythropoietin, fibrinogen, surfactant, lipomodulin. It leads to the redistribution of fat, increases the formation of triglycerides and higher fatty acids. Reduces absorption and potentiates the excretion of calcium; delays sodium and water.

The mechanism of anti-shock effect of dexamethasone is associated with a decrease in the synthesis of the platelet activating factor (a shock mediator), as well as a decrease in extra-neuronal capture and an increase in the pressor effect of catecholamines.

Pharmacokinetics:

After oral administration, it is quickly and completely absorbed from the gastrointestinal tract, T_max - 1-2 hours.

The maximum concentration of dexamethasone in the blood plasma is reached only 5 minutes after intravenous administration and 1 hour after intramuscular injection. Penetrates through the blood-brain and placental barrier. Blood is bound (60-70%) with a specific transporter protein - transcortin. Metabolized in the liver, half-life is 36-54 hours. Excreted by the kidneys and through the gastrointestinal tract.

Indications:

Acute and subacute thyroiditis, Progressive ophthalmopathy, rheumatoid arthritis in the exacerbation phase, Addison-Birmer disease, hypothyroidism, bronchial asthma, connective tissue diseases, thrombocytopenia, autoimmune hemolytic anemias, agranulocytosis, aplasia and hypoplasia of hemopoiesis, serum sickness, cerebral edema, shock of various origins (burn, anaphylactic, posttraumatic, postoperative, toxic, cardiogenic, hemotransfusion, etc.)cerebral hemorrhage, brain tumors, encephalitis, asthmatic status, meningitis, serum transfusion, insufficiency of the adrenal cortex, neural and allergic conjunctivitis, blepharoconjunctivitis, keratoconjunctivitis without epithelial damage, inflammation after eye injuries and operative ophthalmic interventions, keratitis, sympathetic ophthalmia.

ICD-10

I.A00-A09.A09 Diarrhea and gastroenteritis of allegedly infectious origin

I.A15-A19.A16 Tuberculosis of respiratory organs, not confirmed bacteriologically or histologically

I.A15-A19.A17.0 Tuberculous meningitis (G01 *)

I.A30-A49.A48.3 Toxic shock syndrome

II.C30-C39.C34 Malignant neoplasm of bronchi and lungs

II.C81-C96.C81 Hodgkin's disease [lymphogranulomatosis]

II.C81-C96.C82 Follicular [nodular] non-Hodgkin's lymphoma

II.C81-C96.C83 Diffuse non-Hodgkin's lymphoma

II.C81-C96.C85 Other and unspecified types of non-Hodgkin's lymphoma

II.C81-C96.C91 Lymphoid leukemia [lymphocytic leukemia]

II.C81-C96.C92 Myeloid leukemia [myeloid leukemia]

III.D55-D59.D59.1 Other autoimmune hemolytic anemia

III.D60-D64.D60.9 Acquired pure red cell aplasia, unspecified

III.D60-D64.D61.0 Constitutional aplastic anemia

III.D60-D64.D61.9 Aplastic anemia, unspecified

III.D65-D69.D69.3 Idiopathic thrombocytopenic purpura

III.D65-D69.D69.5 Secondary thrombocytopenia

III.D70-D77.D70 Agranulocytosis

III.D80-D89.D86.0 Lung sarcoidosis

IV.E00-E07.E05.5 Thyroid crisis or coma

IV.E00-E07.E06.1 Subacute thyroiditis

IV.E20-E35.E27.1 Primary insufficiency of the adrenal cortex

IV.E20-E35.E27.4 Other and unspecified adrenocortical insufficiency

IV.E20-E35.E27.8 Other specified disorders of the adrenal gland

VI.G35-G37.G35 Multiple sclerosis

VI.G90-G99.G93.6 Edema of the brain

VII.H00-H06.H01.0 Blepharitis

VII.H10-H13.H10.1 Acute atopic conjunctivitis

VII.H10-H13.H10.5 Blepharoconjunctivitis

VII.H10-H13.H10.9 Conjunctivitis, unspecified

VII.H15-H22.H15.0 Sclerite

VII.H15-H22.H15.1 Episcleritis

VII.H15-H22.H16 Keratite

VII.H15-H22.H16.0 Corneal ulcer

VII.H15-H22.H16.2 Keratoconjunctivitis

VII.H15-H22.H16.8 Other forms of keratitis

VII.H15-H22.H20 Iridocyclitis

VII.H30-H36.H30 Chorioretinal inflammation

VII.H43-H45.H44.1 Other endophthalmitis

VII.H43-H45.H45.1 * Endophthalmitis in diseases classified elsewhere

VII.H46-H48.H46 Optic neuritis

VIII.H60-H62.H60 External otitis media

VIII.H65-H75.H65 Pulmonary otitis media

IX.I00-I02.I00 Rheumatic fever without mention of involvement of the heart

IX.I00-I02.I01 Rheumatic fever with involvement of the heart

X.J10-J18.J18.9 Pneumonia, unspecified

X.J30-J39.J30 Vasomotor and allergic rhinitis

X.J40-J47.J45 Asthma

X.J40-J47.J46 Asthmatic status [status asthmaticus]

X.J60-J70.J63.2 Berylliosis

X.J60-J70.J69.0 Pneumonitis caused by food and vomit

X.J80-J84.J82 Pulmonary eosinophilia, not elsewhere classified

X.J80-J84.J84.9 Interstitial pulmonary disease, unspecified

XI.K50-K52.K50 Crohn's disease [regional enteritis]

XI.K50-K52.K51 Ulcerative colitis

XI.K70-K77.K72.9 Hepatic failure, unspecified

XI.K70-K77.K73.9 Chronic hepatitis, unspecified

XII.L10-L14.L10 Pemphigus [pemphigus]

XII.L10-L14.L13.9 Bullous changes, unspecified

XII.L20-L30.L20 Atopic dermatitis

XII.L20-L30.L21 Seborrheic dermatitis

XII.L20-L30.L25.9 Unspecified contact dermatitis, cause not specified

XII.L20-L30.L26 Exfoliative dermatitis

XII.L20-L30.L30.9 Dermatitis, unspecified

XII.L40-L45.L40 Psoriasis

XII.L40-L45.L40.5 Psoriasis arthropathic (M07.0-M07.3 *, M09.0 *)

XII.L50-L54.L50 Hives

XII.L50-L54.L51.2 Toxic epidermal necrolysis [Lyell's]

XII.L80-L99.L98.8 Other specified diseases of skin and subcutaneous tissue

XIII.M00-M03.M02.3 Reiter's disease

XIII.M05-M14.M06.1 Still's disease, developed in adults

XIII.M05-M14.M06.9 Rheumatoid arthritis, unspecified

XIII.M05-M14.M08 Juvenile [juvenile] arthritis

XIII.M05-M14.M10.0 Idiopathic Gout

XIII.M05-M14.M13.0 Polyarthritis, unspecified

XIII.M15-M19.M19.9 Osteoarthritis, unspecified

XIII.M30-M36.M30.0 Nodular polyarteritis

XIII.M30-M36.M32 Systemic lupus erythematosus

XIII.M30-M36.M33.2 Poliomyositis

XIII.M30-M36.M34.9 Systemic sclerosis, unspecified

XIII.M45-M49.M45 Ankylosing spondylitis

XIII.M65-M68.M65.9 Synovitis and tenosynovitis, unspecified

XIII.M65-M68.M67.9 Lesion of synovium and tendon, unspecified

XIII.M70-M79.M71.9 Bursopathy, unspecified

XIII.M70-M79.M75.0 Adhesive shoulder capsulitis

XIII.M70-M79.M77.9 Other specified intesopathy

XIV.N00-N08.N00 Acute nephritic syndrome

XIV.N00-N08.N04 Nephrotic syndrome

XVIII.R10-R19.R11 Nausea and vomiting

XVIII.R20-R23.R21 Rash and other nonspecific skin rashes

XVIII.R50-R69.R57.0 Cardiogenic shock

XIX.S00-S09.S05 Injury of the eye and orbit

XIX.S00-S09.S05.0 Injury of the conjunctiva and corneal abrasion without mention of the foreign body

XIX.S00-S09.S05.9 Injury of unspecified part of eye and orbit

XIX.T36-T50.T49.8 Poisoning by other topical agents

XIX.T66-T78.T78.0 Anaphylactic shock caused by a pathological reaction to food

XIX.T66-T78.T78.1 Other manifestations of a pathological reaction to food

XIX.T66-T78.T78.2 Anaphylactic shock, unspecified

XIX.T66-T78.T78.3 Angioedema

XIX.T66-T78.T78.4 Allergy, unspecified

XIX.T79.T79.4 Traumatic shock

XIX.T80-T88.T80.6 Other serum reactions

XIX.T80-T88.T81.1 Shock during or after the procedure, not elsewhere classified

XX.Y40-Y59.Y57 Other and unspecified medicines and medicines

XXI.Z80-Z99.Z94 Presence of transplanted organs and tissues

Contraindications:

- Hypersensitivity (with systemic administration);

- Joint deformity, joint instability due to arthritis, inflammatory processes in the joint, transgressive bone fracture, arthroplasty, pathological hemorrhage (with intra-articular injection);

- Purulent infection of the mucous membrane of the eye, viral conjunctivitis, glaucoma, trachoma, damage to the integrity of the corneal epithelium.

Carefully:

- parasitic and infectious diseases of a viral, fungal or bacterial nature (currently or recently transferred, including recent contact with a patient): herpes simplex, herpes zoster (viremic phase), chicken pox, measles; amoebiasis, strongyloidiasis (or suspected); systemic mycosis; active and latent tuberculosis. The use in severe infectious diseases is permissible only against the background of specific therapy;

- the vaccination period, lymphadenitis after BCG vaccination. Immunodeficiency conditions (including HIV or HIV infection);

- Gastrointestinal diseases: peptic ulcer and duodenal ulcer, esophagitis, gastritis, peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with perforation or abscessing threat, diverticulitis;

- liver failure;

- hypoalbuminemia;

- diseases of the cardiovascular system, including the recently transferred myocardial infarction, decompensated chronic heart failure, hypertension, hyperlipidemia;

- endocrine diseases - diabetes, thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease, obesity III-IV degree;

- severe chronic renal failure, urolithiasis disease;

- systemic osteoporosis, myasthenia gravis, poliomyelitis, epilepsy, "steroid" myopathy;

- Acute psychosis, severe affective disorders;

- open and closed angle glaucoma;

- Pregnancy;

- elderly patients - due to a high risk of osteoporosis and hypertension;

- in children during the period of growth the drug should be used only under absolute indications and under especially careful supervision of the doctor.

Pregnancy and lactation:

Category FDA - C. Adequate and well-controlled studies on humans have not been conducted. In pharmacological doses, the drug can cause placental insufficiency, fetal body weight deficiency, stillbirth. Teratogenic effect is not confirmed.Hormone replacement therapy does not adversely affect the fetus and the newborn. Penetrates into breast milk. Violations are not registered. The appointment of physiological or low pharmacological doses (equivalent to ~ 25 mg of cortisone or 5 mg of prednisolone) does not cause abnormalities on the part of the child. The appointment of higher doses is not recommended due to possible violations on the part of the child (stunting, disruption of the production of its own glucocorticoids).

In pregnancy (especially in the first trimester), as well as during lactation dexamethasone apply taking into account the expected therapeutic effect and negative impact on the fetus. With prolonged therapy during pregnancy, the possibility of fetal growth disorders is not ruled out. In case of application at the end of pregnancy, there is a risk of atrophy of the adrenal cortex in the fetus, which may require replacement therapy in the newborn.

Dosing and Administration:

When oral admission - from 2-3 to 4-6 mg (10-15 mg) per day, after the therapeutic effect of the dose is gradually reduced. Children - 0,0833-0,3333 mg / kg.

When intraarticular introduction - adults and adolescents - 0.2-6 mg with an interval of 3 days for three weeks, the maximum dose to 80 mg.

Locally: 3-4 drops 2-3 times a day.

Parenteral: intramuscularly 4-20 mg (up to 80 mg) 3-4 times a day, supporting doses - 0.2-9 mg per day, course 3-4 days, then - ingestion. Children - intramuscularly 0,02776-0,16665 mg / kg every 12-24 hours.

Conjunctival: acute conditions - 1-2 drops every 1-2 hours, then after 4-6 hours; in other cases - 1-2 drops 3-4 times a day; duration of treatment - from 1-2 days to several weeks, depending on the patient's condition.

Side effects:

From the endocrine system: impaired glucose tolerance, steroid diabetes, or manifestation of latent diabetes mellitus, adrenal suppression, Cushing's syndrome (including moon face, obesity, pituitary type, hirsutism, hypertension, dysmenorrhea, amenorrhea, myasthenia gravis, striae), sexual delay development in children.

From the side of metabolism: increased excretion of calcium ions, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating, hypernatremia, hypokalemia.

From the side of the central nervous system: delirium, disorientation, euphoria, hallucinations, manic-depressive psychosis, depression, paranoia, increased intracranial pressure, nervousness or anxiety, insomnia, dizziness, vertigo, pseudotumor, cerebral palsy, headache, convulsions.

From the cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed patients) or increased severity of chronic heart failure, changes in ECG, characteristic of hypokalemia, increased blood pressure, hypercoagulation, thrombosis. In patients with acute and subacute myocardial infarction - the spread of the focus of necrosis, slowing the formation of scar tissue, which can lead to rupture of the heart muscle; when intracranial introduction - nosebleeds.

From the digestive system: nausea, vomiting, pancreatitis, steroid ulcer of the stomach and duodenum, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increase or decrease in appetite, flatulence, hiccough; rarely - increased activity of hepatic transaminases and alkaline phosphatase.

From the sense organs: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, a tendency to develop secondary bacterial, fungal or viral infections of the eyes, trophic changes in the cornea, exophthalmos.

From the musculoskeletal system: slowing the growth and processes of ossification in children (premature closure of the epiphyseal growth zones), osteoporosis (very rarely - pathological bone fractures, aseptic necrosis of the head of the humerus and thigh bone), rupture of muscle tendons, steroid myopathy, muscle loss (atrophy).

Dermatological reactions: delayed wound healing, petechiae, ecchymoses, skin thinning, hyper- or hypopigmentation, steroid acne, striae, propensity to develop pyoderma and candidiasis.

Allergic reactions: generalized (including skin rash, skin itching, anaphylactic shock) and with topical application.

Effects associated with immunosuppressive action: development or exacerbation of infections (the emergence of this side effect is facilitated by jointly used immunosuppressants and vaccination).

Local reactions: when parenteral introduction - tissue necrosis.

For external use: rarely - itching, flushing, burning, dryness, folliculitis, acne, hypopigmentation, perioral dermatitis, allergic dermatitis, skin maceration, secondary infection, skin atrophy, striae, sweating. With prolonged use or application to large areas of the skin, it is possible to develop systemic side effects, characteristic of glucocorticoids.

Overdose:

Vomiting, nausea, agitation, depression, euphoria, sleep disorders, osteoporosis, fluid retention in the body, increased blood pressure and other signs of hypercorticism, including Itenko-Cushing syndrome, secondary adrenal insufficiency.

Treatment. Against the background of a gradual discontinuation of the drug maintenance of vital functions, correction of electrolyte balance, antacids, phenothiazines, drugs Li⁺; with the syndrome of Itenko-Cushing - aminoglutethimide.

Interaction:

Decrease in the effect of the drug when administered together with inducers of microsomal liver enzymes (phenytoin, rifampicin, barbiturates).

Decrease in the effect of the drug when taken together with somatropin, antacids (decrease in absorption).

Increase in the effect of the drug with simultaneous use with oral contraceptives containing estrogen.

When administered simultaneously with attenuated antiviral vaccines and against other forms of immunization, the risk of infection is high. The drug weakens the effect of insulin, antidiabetics, anticoagulants, diuretics.

The drug worsens the tolerability of cardiac glycosides, salicylates and praziquantel.

The risk of arrhythmias and hypokalemia is cardiac glycosides and diuretics.

The likelihood of edema and arterial hypertension - sodium-containing drugs or supplements, severe hypokalemia, heart failure and osteoporosis - amphotericin B and inhibitors of carbonic anhydrase, the risk of erosive-ulcerative lesions and bleeding from GIT non-steroidal anti-inflammatory drugs.

Weaken the hypoglycemic activity of insulin and oral antidiabetics, anticoagulant - coumarins, diuretic - diuretic, immunotropic - vaccination (suppresses the formation of antibodies).

Special instructions:

The effect of the drug is enhanced with hypothyroidism, liver cirrhosis. Termination of therapy is only gradual.Care must be taken with infectious diseases during the administration of the drug.

It is not recommended during the application of the drug to drive vehicles or other mechanisms.

Instructions

Dexamethasone (Dexamethasonum)