Methylprednisolone - instructions for use, dosage, side effects, contraindications

Interaction with intracellular glucocorticoid receptors - the formation of dimers of the glucocorticoid-glucocorticoid receptor complex (release of the receptor from the bonds with heat shock proteins 70 and 90 and immunophilin). Penetration of the activated receptor into the nucleus, binding to glucocorticoid-sensitive regulatory elements of DNA - a specific effect on gene expression (activation and suppression). Interaction with other protein transcription factors,regulating the expression of many proteins of the immune system, which leads to suppression of the expression of genes encoding some cytokines, collagenase and stromelysins.

Pharmacokinetics:

The connection with plasma proteins is 78 ± 3%, a decrease with liver cirrhosis. Biotransformation in the liver to inactive metabolites (CYP3A4). Half-life 2,3 ± 0,5 h, increase with obesity, decrease in women. It is excreted by the kidneys mainly in unchanged form - 4.9 ± 2.3%.

Indications:

Systemic connective tissue diseases (exacerbation or maintenance therapy): systemic lupus erythematosus, systemic necrotizing vasculitis, acute rheumatic carditis, systemic dermatomyositis (polymyositis).

Allergic reactions (severe course): urticaria, Quincke's edema, toxic epidermal necrolysis (Lyell's syndrome), drug exanthema, pollinosis, allergic rhinitis, severe bronchial asthma, serum sickness, anaphylactic shock, anaphylactoid reactions; atopic dermatitis, contact dermatitis (with the defeat of a large surface of the skin), granulomatous skin diseases.

Skin diseases: pemphigus, bullous herpetiform dermatitis, Stevens-Johnson syndrome, exfoliative dermatitis, mycoses, psoriasis, seborrheic dermatitis.

Interstitial lung diseases (acute alveolitis, pulmonary fibrosis, sarcoidosis of II-III stages), pulmonary tuberculosis, aspiration pneumonia.

Ulcerative colitis, Crohn's disease (does not prevent relapse), local enteritis, hepatitis (chronic hepatitis B).

Autoimmune diseases of the kidneys and liver.

Acute lymphoblastic and myeloid leukemia, agranulocytosis, panmyelopathy, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura of adults, secondary thrombocytopenia in adults, erythroblastopenia (erythrocyte anemia), congenital (erythroid) hypoplastic anemia; lymphoma, myeloma.

Multiple sclerosis, tuberculous meningitis.

Eye diseases: herpes, anterior segment inflammation, diffuse uveitis and choroiditis, sympathetic ophthalmia, keratitis, chorioretinitis, optic neuritis, iritis and iridocyclitis.

Palliative treatment in combination therapy - leukemia, lymphoma; allergic eye diseases (allergic corneal ulcers, allergic conjunctivitis); respiratory diseases: berylliosis, Leffler's syndrome (not amenable to other therapy); lung cancer (in combination with cytostatics).

Organ transplantation.

Edema of the brain due to a tumor, associated with surgery, radiation therapy or head trauma

Shock due to adrenal insufficiency.

Shock (burn, traumatic, cardiogenic), non-parenteral thyroiditis, multiple sclerosis, adrenal insufficiency (Addison's syndrome, adrenogenital syndrome, congenital adrenal hypoplasia, condition after removal of the adrenal glands).

Hypercalcemia associated with the cancer process, nausea and vomiting during cytostatic therapy.

Acute spinal cord injury.

Pain in the neck.

ICD-10

XII.L40-L45.L40 Psoriasis

I.A15-A19.A16.2 Tuberculosis of the lungs without mention of bacteriological or histological confirmation

II.C81-C96.C95.9 Leukemia, unspecified

IV.E70-E90.E88.1 Lipodystrophy, not elsewhere classified

X.J60-J70.J69.8 Pneumonitis caused by other solids and liquids

XII.L60-L75.L63.2 Nesting baldness (ribbon shape)

XII.L80-L99.L92 Granulomatous changes in the skin and subcutaneous tissue

XIX.T80-T88.T80 Complications associated with infusion, transfusion and medical injection

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

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

Contraindications:

· Individual intolerance.

· Relative: gastric ulcer and duodenal ulcer, esophagitis, gastritis, acute or latent peptic ulcer, diabetes mellitus, myasthenia gravis, osteoporosis, hypothyroidism, mental illness (in history), herpes simplex, herpes zoster (viremic phase), chicken pox; post-vaccination period (8 weeks before and 2 weeks after vaccination), amoebiasis, systemic mycosis, active tuberculosis, AIDS, latent tuberculosis, intestinal anastomosis (in the nearest history), congestive heart failure, arterial hypertension, severe impairment of liver or kidney function, Poliomyelitis (except for the form of bulbar encephalitis), lymphoma after vaccination.

· The use in severe infectious diseases is permissible only against the background of specific therapy.

· For intraarticular application: previous arthroplasty, pathological bleeding (endogenous or caused by the use of anticoagulants), intraarticular bone fracture, infectious (septic) inflammatory process in the joint and periarticular infections (including in the anamnesis),as well as general infectious disease, expressed near-joint osteoporosis, the absence of signs of inflammation in the joint (the so-called dry joint, for example, in osteoarthrosis without synovitis), severe bone destruction and joint deformation (a sharp narrowing of the joint gap, ankylosis), joint instability as the outcome of arthritis , aseptic necrosis of the joints forming the epiphyses of bones.

· In the neonatal period for the prevention of distress syndrome in children: amnionitis, placental insufficiency, premature rupture of the amniotic fluid; bleeding, fever of unclear etiology, infection, tuberculosis, herpes simplex, viral keratitis in the mother.

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.

· Post-vaccination period (8 weeks before and 2 weeks after vaccination), lymphadenitis after BCG vaccination. Immunodeficiency conditions (including AIDS or HIV infection).

· Diseases of the gastrointestinal tract: peptic ulcer of stomach and duodenum, esophagitis, gastritis, acute or latent peptic ulcer, newly created intestinal anastomosis, ulcerative colitis with perforation or abscessing, diverticulitis.

· Diseases of the cardiovascular system, including the recently transferred myocardial infarction (in patients with acute and subacute myocardial infarction, a foci of necrosis, a delay in the formation of scar tissue and, as a consequence, a rupture of the heart muscle), decompensated chronic heart failure, arterial hypertension, hyperlipidemia.

· Endocrine diseases: diabetes mellitus (including a violation of carbohydrate tolerance), thyrotoxicosis, hypothyroidism, Itenko-Cushing's disease.

· Severe chronic renal and / or hepatic insufficiency, nephrolithiasis.

· Hypoalbuminemia and conditions predisposing to its occurrence.

· Pregnancy and lactation.

Pregnancy and lactation:

Recommendations FDA category C. Potential benefits associated with the use of the drug in pregnant women may justify its use, despite the risk.

Dosing and Administration:

The dosage of the drug is selected individually in each case, depending on the disease and age of the patient.

Side effects:

Systemic application

The frequency of development and severity of side effects depend on the duration of application, the amount of dose used and the possibility of observing the circadian rhythm of the appointment.

The endocrine system: reduction of glucose tolerance, "steroid" diabetes or a manifestation of latent diabetes mellitus, adrenal suppression, Cushing's syndrome (moon face, obesity, pituitary type, hirsutism, increased blood pressure, dysmenorrhea, amenorrhea, myasthenia gravis, striae), delay sexual development in children.

Digestive system: nausea, vomiting, pancreatitis, "steroid" stomach ulcers and duodenal ulcers, erosive esophagitis, bleeding and perforation of the gastrointestinal tract, increased or decreased appetite, flatulence, hiccups.In rare cases - increased activity of hepatic transaminases and alkaline phosphatase.

Cardiovascular system: arrhythmias, bradycardia (up to cardiac arrest); development (in predisposed individuals) or increased severity of chronic heart failure, changes in the electrocardiogram, 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.

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.

Sensory organs: posterior subcapsular cataract, increased intraocular pressure with possible damage to the optic nerve, propensity to develop secondary bacterial, fungal or viral eye infections, trophic corneal changes, exophthalmos.

Metabolism: increased excretion of Ca²⁺, hypocalcemia, weight gain, negative nitrogen balance (increased protein breakdown), increased sweating.

Caused by mineralocorticoid activity - fluid retention and Na⁺ (peripheral edema), hypernatremia, hypokalemic syndrome (hypokalemia, arrhythmia, myalgia or muscle spasm, unusual weakness and fatigue).

Musculoskeletal system: slowing growth and ossification in children (premature closure of the epiphyseal growth zones), osteoporosis (very rare - pathological fractures, aseptic necrosis of the humeral head and femur), rupture of tendons of muscles, "steroid" myopathy, reduced muscle mass (atrophy).

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

Allergic reactions: generalized (skin rash, itching, anaphylactic shock), local allergic reactions.

Others: the development or exacerbation of infections (the appearance of this side effect is facilitated by concomitantly used immunosuppressants and vaccination), leukocyturia, withdrawal syndrome.

Local with parenteral administration: burning, numbness, pain, paresthesia at the injection site, infections at the injection site, rarely - necrosis of surrounding tissues, scar formation at the injection site; atrophy of the skin and subcutaneous tissue with intramuscular injection (especially dangerous is the introduction to the deltoid muscle).

With intravenous administration: arrhythmias, hot flashes, convulsions.

With intracranial injection, nosebleeds.

With parenteral administration in the region of the head, neck, nasal concha, and scalp, the crystals of the drug may be deposited, in the vessels of the eye - a sudden loss of vision.

Intra-articular injection - increased pain in the joint.

Local application

"Steroid" acne, purpura, telangiectasia, burning and itching of the skin, irritation and dry skin. With long-term use and / or when applied to large surfaces, systemic side effects are possible.

Application in ophthalmology

With prolonged use: increased intraocular pressure, optic nerve damage, subcapsular cataracts, impaired acuity and narrowing of the visual field (blurred vision or loss of vision, eye pain, nausea, dizziness).

When thinning the cornea - the danger of perforation.

Rarely, the spread of viral or fungal eye diseases.

Overdose:

In case of an overdose, nausea, vomiting, sleep disorders, euphoria, agitation, depression are observed. With prolonged use in high doses - 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:

Alcohol, NSAIDs - increased risk of bleeding (including hemorrhagic stroke) and ulceration of the gastric mucosa.

Aminoglutethimide^¤ - oppression of the adrenal glands (additional administration of glucocorticosteroids is required).

Amphotericin B (parenterally), inhibitors of carbonic anhydrase - the risk of severe hypokalemia.

Antiglaucoma means - correction of the dose due to glaucoma of the GC.

Anticholinergics, especially atropine, - risk of intraocular hypertension.

Acetazolamide - the risk of hypernatremia, edema, hypocalcemia (osteoporosis).

Anabolic steroids, androgens - the risk of edema, severe acne.

Antidepressants tricyclics - aggravation of steroid-dependent disorders of the psyche. Do not apply!

Anticoagulants indirect (coumarin and indanedione derivatives), anticoagulants direct, thrombolytics - risk of hemorrhagic stroke.

Antithyroid drugs, thyroid hormones - correction of the dose of glucocorticoid due to reduced clearance in hypothyroidism and elevated - in the hyperthyroid state.

Asparaginase - increasing its toxic effects.

Vaccines, live viruses or other immunization - pharmacological (immunosuppressive) doses of HA lead to stimulation of replication of live viruses, an increased risk of developing viral diseases, a decrease in the formation of antibodies to the vaccine.

Diuretics - reduction of their natriuretic and diuretic effects, hypokalemia.

Inhibitors of acetylcholinesterase - a risk of severe weakness in myasthenia gravis (cancellation 24 hours before the beginning of GK therapy).

Isoniazid, mexiletine - Increase in clearance of isoniazid, mexiletine, decrease in plasma concentration (dose adjustment).

Immunosuppressants, others - the risk of infection.

Carbamazepine, ephedrine, phenobarbital, phenytoin, rifampicin - increased clearance of glucocorticoids.

Ketoconazole - reduced clearance of glucocorticoids (increased risk of side effects).

Contact lenses - increased risk of infection.

Macrolides - reduced clearance of glucocorticoids.

Mitotan - an increase in the dose of glucocorticoids.

Non-depolarizing muscle relaxants - the risk of respiratory depression (due to hypokalemia induced by glucocorticoids).

Oral antidiabetic agents and insulin - dose adjustment of one or both drugs in combination. Correction of an antidiabetic remedy after cessation of glucocorticoid therapy.

Cardiac glycosides - the risk of their overdose and arrhythmia due to hypokalemia.

Somatotropin - depression of the growth stimulating response to somatotropin (prednisolone in a daily dose of less than 2.5-3.75 mg / m² (by mouth) and 1.25-1.88 mg / m² body surface (parenteral)).

Means or products that contain large amounts of sodium - the risk of edema and hypertension.

Means that induce enzymes of the liver, an increase in the clearance of glucocorticoids.

The drugs that stimulate the activity of liver enzymes are a decrease in the effects of glucocorticoids by increasing their metabolism.

Folic acid - increased demand for folate with long-term therapy with glucocorticoids.

Estrogen-containing oral contraceptives - increased clearance and reduced half-life of glucocorticoids (dose adjustment).

Special instructions:

Use strictly according to the doctor's prescription to avoid complications.

Instructions

Methylprednisolone (Methylprednisolonum)