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PREDNISONE

Pharmacodynamics:

Glucocorticosteroid, has anti-inflammatory, anti-allergic, anti-shock, immunosuppressive effect. Interaction with intracellular glucocorticoid receptors leads to the formation of dimers of the glucocorticoid-glucocorticoid receptor complex. The complex of the steroid hormone with the receptor is transported to the cell nucleus. In the nucleus, this complex interacts with effector elements localized on the acceptor sites of chromatin (genes). As a result of the interaction, stimulation or inhibition of gene expression occurs; this leads to a change in the synthesis of messenger RNA and proteins. The anti-inflammatory effect of prednisone is due to several factors.
1. The drug induces the synthesis of lipocortin, which inhibits the activity of phospholipase A2. Inhibition of phospholipase A2-mediated hydrolysis of membrane phospholipids of damaged tissues prevents the formation of arachidonic acid. Violation of the formation of arachidonic acid actually means inhibition of prostaglandin synthesis, since arachidonic acid is a substrate for further metabolism along the cyclooxygenase pathway, as well as along the lipoxygenase pathway with a corresponding inhibition of leukotriene synthesis.
2. The anti-inflammatory effect of prednisone is potentiated by its ability to inhibit the expression of COX-2 genes, which also leads to a decrease in the synthesis of prostaglandins in the focus of inflammation, including pro-inflammatory prostaglandins E 2 and I 2 .
3.Prednisoneinhibits the expression of intercellular adhesion molecules in the endothelium of blood vessels, disrupting 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 is noted (due to their receipt from the bone marrow and due to the restriction of migration from the blood vessels). This causes a decrease in the number of neutrophils at the site of inflammation.
Prednisone inhibits 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 noted is a decrease in the rate of transcription and increased degradation of IL-1 and IL-2 receptor genes, inhibition of transcription of genes for metalloproteinases (collagenase, elastase, and others) involved in increasing the permeability of the vascular wall, in the processes of scarring and destruction of cartilage tissue in diseases of the joints.
The immunosuppressive effect is due to the inhibition of transcription of DNA encoding the major histocompatibility complex, pro-inflammatory cytokines (IL-1, IL-2) and inhibition of T-lymphocyte proliferation. It leads to a decrease in the number of T-lymphocytes and their effect on B-lymphocytes, inhibits the production of immunoglobulins. Reduces the 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, degranulation of mast cells and the release of allergy mediators, and therefore it is effective in immediate allergic reactions.
Restores the sensitivity of adrenergic receptors to catecholamines. Accelerates the breakdown of proteins and reduces their concentration in 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; retains sodium and water.
The mechanism of the anti-shock effect of prednisolone is associated with a decrease in the synthesis of platelet activating factor (shock mediator), as well as with a decrease in extraneuronal uptake and an increase in the pressor effect of catecholamines.
It affects various types of metabolism: it increases the level of glucose in the blood, promotes the redistribution of adipose tissue, promotes the retention of sodium and water ions, and increases blood pressure. Modulates inflammatory processes in the connective tissue and reduces the likelihood of scar tissue formation.

Pharmacokinetics:

RAbsorbed in the gastrointestinal tract. Bioavailability - 80 ± 11%. The volume of distribution is 0.97 ± 0.11 l / kg. The maximum concentration in blood plasma is observed after 1-2 hours. It is metabolized in the liver to the active metabolite, prednisolone. Communication with plasma proteins is 90%, it is biotransformed in the liver, bronchi and kidneys. It is excreted by the kidneys mainly unchanged.
With rectal administration, more than 20% of the drug is absorbed. This number may increase in the presence of inflammation or damage to the rectal mucosa.

Indications:

  • Rheumatism, rheumatoid arthritis.
  • Dermatomyositis.
  • Nodular periarteritis.
  • Bechterew's disease.
  • Scleroderma.
  • Bronchial asthma , allergic diseases.
  • False croup in children.
  • Acute insufficiency of the adrenal cortex.
  • Addison's disease.
  • adrenogenital syndrome.
  • Hepatitis.
  • Hypoglycemic conditions.
  • Hepatic coma.
  • Lipoid nephrosis.
  • Agranulocytosis.
  • Lymphogranulomatosis.
  • Various forms of leukemia.
  • thrombocytopenic purpura.
  • Chorea.
  • hemolytic anemia.
  • Pemphigus.
  • Itching.
  • Eczema.
  • exfoliative dermatitis.
  • Scabies.
  • Psoriasis.
  • Seborrheic dermatitis.
  • Erythroderma.
  • Lupus erythematosus.
  • Alopecia.
  • Contraindications

  • Peptic ulcer of the stomach and duodenum in the acute phase
  • Itsenko-Cushing's disease
  • Osteoporosis
  • Tendency to thromboembolism
  • kidney failure
  • Systemic mycoses
  • Severe arterial hypertension
  • Vaccination period
  • Active form of tuberculosis
  • Viral infections
  • Active form of tuberculosis
  • Productive symptoms in mental illness
  • Glaucoma
  • Hypersensitivity
  • Carefully:

    There may be a withdrawal syndrome, as well as an exacerbation of the disease for which the drug is prescribed; diabetes mellitus, nonspecific infections, latent forms of tuberculosis, pregnancy (especially the first trimester).

    Pregnancy and lactation:

    Category FDA - C. _ Adequate and well-controlled studies in humans have not been conducted. In pharmacological doses causes placental insufficiency, fetal weight loss, stillbirth. Teratogenic effect has not been confirmed. Hormone replacement therapy does not adversely affect the fetus and newborn. Animal studies have found an increase in the incidence of cleft palate, placental insufficiency, spontaneous abortion, and intrauterine growth retardation.
    Penetrates into breast milk. There are no violations. When prescribing physiological or low pharmacological doses (equivalent to no more than 25 mg of cortisone or 5 mg of prednisone), they do not cause disturbances in the development of the child. It is not recommended to prescribe higher doses due to possible disorders in the development of the child (growth retardation, impaired production of its own glucocorticoids).

    Dosage and administration:

    Dosing regimen is individual. The initial dose for adults is 20-30 mg (if necessary, it can be from 15-100 mg) per day, the maintenance dose is 5-10 mg (5-15 mg) per day. Reducing the daily dose should be gradual. The initial dose for children is 1-2 mg / kg per day in 4-6 doses, the maintenance dose is 300-600 mcg / kg per day.
    Rectally: for the relief of coughing and choking attacks, children are administered one suppository per day (corresponding to 100 mg of prednisolone). If necessary, another administration of the suppository is possible on this day or on the second day. The total dose should not exceed two suppositories per day (corresponding to 200 mg prednisone).

    Side effects:

    From the nervous system: steroid cataract, mental disorders, latent glaucoma.
    From the endocrine system: weight gain, Itsenko-Cushing's syndrome, depletion of the adrenal cortex, steroid diabetes, negative nitrogen balance, hyperglycemia.
    From the side of water and electrolyte balance: hypokalemia, hypernatremia.
    From the side of the cardiovascular system: arterial hypertension.
    From the gastrointestinal tract: ulcerogenic effect, increased acidity of gastric juice.
    From the musculoskeletal system: aseptic bone necrosis, osteoporosis.
    When administered rectally: itching, burning, irritation at the injection site. Allergic reactions are possible.

    Overdose:

    Symptoms: increased side effects, vomiting, nausea, sleep disturbances, euphoria, depression, agitation.
    Treatment: gradual withdrawal of the drug.

    Interaction:

    Salicylates - increase the likelihood of bleeding.
    Diuretics are electrolyte disturbances.
    Hypoglycemic drugs - reducing the rate of decrease in blood glucose levels.
    Cardiac glycosides - risk of glycoside intoxication.
    Enzyme inducers (barbiturates,phenytoin,primidone,rifampicin) may reduce the effect of glucocorticosteroids.
    Antihypertensive drugs - reducing their effectiveness.
    rapampicin, barbiturates andphenytoin- decrease in the effect of the drug.
    Hormonal contraceptives, estrogens - enhancing the effect of the drug.
    Glucocorticosteroids can reduce the concentration of salicylates and praziquantel in the blood.
    antipsychotics,azathioprine,carbutamide- risk of developing cataracts.
    M-anticholinergics, nitrates, antihistamines, tricyclic antidepressants - an increase in intraocular pressure.
    The action of insulin, oral hypoglycemic and antihypertensive drugs, as well as oral anticoagulants (coumarin derivatives) can be weakened with the simultaneous use of prednisone.
    Increase the risk of side effects of glucocorticosteroids: non-steroidal anti-inflammatory drugs (erosive and ulcerative lesions and bleeding from the gastrointestinal tract), androgens, estrogens, oral contraceptives, steroid anabolics (hirsutism, acne); diuretics and laxatives (hypokalemia).
    In the case of simultaneous use with ACE inhibitors, changes in the blood count are possible. Possible weakening of the action of somatotropin.Chloroquine, hydroxochloroquine,mefloquine- increased risk of myopathies and cardiomyopathies.
    Cyclosporine - increased risk of cerebral seizures.

    Special instructions:

    During treatment, it is necessary to observe an ophthalmologist, control blood pressure and water-electrolyte balance, and peripheral blood pictures.
    With psoriasis - take under the strict supervision of a physician.
    In diabetes mellitus, use only with absolute indications.
    Influence on the ability to drive vehicles and control mechanismsnot found.