Corticosteroid anti-inflammatory drugs

The mechanism of action of glucocorticoid drugs is primarily due to the effect on the transcription of target cell genes via glucocorticoid receptors.

In recent years, it has been established that the basis of immunoregulation and the development of inflammation is the cytokine system. Glucocorticoids are able to suppress transcription and translation of anti-inflammatory cytokine genes – interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor (TNF), interleukin-8 (IL-8), in addition, glucocorticoids increase degradation genes IL-2 and IL-2 receptors.These effects provide the anti-inflammatory effect of glucocorticoids .

In the development of inflammatory reactions, lipocortin plays an important role , which is found in leukocytes and epithelial cells and prevents the mobilization of arachidonic acid from membrane phospholipids by suppressing their hydrolysis by A2 phospholipase and thus inhibits the synthesis of prostacyclin, thromboxane, leukotrienes. Antibodies to lipocortin have been found in patients with RA, which can suppress its action.

Glucocorticoids induce lipocortin synthesis, which leads to the suppression of the activity of phospholipase A2 and inhibition of the synthesis of anti-inflammatory prostaglandins and leukotrienes, as a result, the inflammatory process is suppressed.

  1. Glucocorticoids suppress the transcription of metalloproteinase genes (collagenase, sgromelysin) involved in the final stages of cartilage destruction in RA, therefore, glucocorticoids are able to slow down the destruction of cartilage.
  2. Glucocorticoids reduce the permeability of capillaries and lysosomal membranes, the output from lysosomes of proteolytic lysosomal enzymes, thereby reducing their damaging effect and the severity of inflammatory reactions.
  3. Glucocorticoids suppress phagocytosis and neutrophil migration to the inflammatory focus, which reduces the activity of inflammation.
  4. Glucocorticoids block the components of complement C1-C3, which inhibits inflammation.
  5. Glucocorticoids have a pronounced immunosuppressive effect, and T helper lymphocytes are much more sensitive to the action of glucocorticoids than suppressor T lymphocytes ;production of antibodies and autoantibodies is blocked in RA.
  6. Glucocorticoids inhibit the activity of fibroblasts and the development of connective tissue, inhibit the process of fibrosis.

When treating patients with RA, the following options for glucocorticoid therapy are used:

  1. Local (intra-articular) administration of glucocorticoids.
  2. Local (percutaneous) use of glucocorticoids in the form of ointments.
  3. Systemic use of glucocorticoids :
  • Daily intake of glucocorticoids inside;
  • Alternating mode of glucocorticoid use;
  • Pulse therapy with methylprednisolone;
  • Combined use of glucocorticoids with basic antirheumatic drugs (primarily with cytostatics).

This section will be considered   systemic glucocorticosteroids   with RA. Other options for glucocorticoid therapy will be discussed below.

The following drugs are used for systemic treatment:

  • prednisone( prednisone) – tablets of 0.005 g, ampoules in 1 ml of 30 mg (intravenously, intramuscularly);
  • triamcinolone( Polcortolone , Berlicort , Ke Nakort ) – tablets of 0.004 g;
  • kenalog-40- for intramuscular administration (40 ml of triamcinolone is contained in 1 ml of the preparation );
  • dexamethasone( dexazone , dexon ) – tablets of 0.0005 and 0.00075 g (i.e. 0.5 and 0.75 mg), ampoules for intramuscular and intravenous administration (1 ml contains 4 mg of dexamethasone-21-phosphate in as sodium salt);
  • methylprednisolone- tablets of 0.004 g, ampoules for intravenous and intramuscular administration of 20, 40 and 80 mg of sodium succinate methylprednisolone with the application of ampoules with a solvent. For long-term use the drug is convenient.   medrol   (manufactured by Upjohn ), in tablets of 4, 16, 32 and 100 mg;
  • solu medrol- is sodium succinate methylprednisolone , available in bottles of 40, 125, 250, 500, 1000 and 2000 mg;
  • depot medrol- a prolonged preparation of methylprednisolone acetate, in 1 ml of the suspension contains 0.04 g of the substance, is injected intramuscularly.
  • phosterone- suspension, in 1 ml of which contains 2 mg of betamezon disodium phosphate and 5 mg of betamezon dipropionate. The first is a readily soluble glucocorticoid , which is well absorbed in the tissue and provides a quick effect; absorption of the second glucocorticoid component occurs slowly, thereby increasing the duration of the drug. Phlesterone is administered intramuscularly (1 ml every 2-4 weeks) or intra-articular, it acts for a long time;
  • betamethasone- 9a-fluoro-16v-methylprednisolone;
  • diprophos – An analogue of phosterone (USA).

Side effects of glucocorticoids develop mainly with their long-term systemic use (long-term oral therapy), especially when prescribing large doses. With short courses of glucocorticoid therapy, side effects are rare.

Main side effects:

  • Damage to the gastrointestinal tract: the development of chronic gastritis with increased secretory function, erosions and ulcers of the stomach and duodenum, often complicated by bleeding;
  • Cushingoid syndrome: obesity with predominant deposition of fat in the face (moon-shaped, round face), chest, abdomen;the appearance of purple-violet strii (stretch bands) in the thighs, lower abdomen, in the armpits; hypertrichosis in women;
  • arterial hypertension;
  • Steroid diabetes mellitus (overt, manifest or latent – i.e. impaired glucose tolerance);
  • Atrophy of the skin and muscles (as a manifestation of the catabolic effect) and a decrease in muscle strength;
  • Osteoporosis of the bones and spine (in rare cases even fractures and aseptic necrosis of the bones);
  • Retention of sodium and body water;
  • Increased excretion of potassium and calcium from the body;
  • Exacerbation of chronic infections (primarily tuberculosis);
  • With long-term treatment of children, growth retardation, ossification processes, delayed sexual development;
  • Violation of the menstrual cycle;
  • In rare cases of psychosis, cataracts, skin hemorrhages;
  • With long-term, especially long-term treatment with glucocorticoids , adrenal cortex insufficiency develops and with a sudden decrease or cancellation of glucocorticoids , an adrenal crisis develops.

Considering the side effects of glucocorticoid therapy, it is contraindicated in gastric ulcer and duodenal ulcer, hypertension II and III, circulatory failure II and III, diabetes, active tuberculosis and other active forms of infection, marked osteoporosis, thromboembolic syndrome.

There are strict indications for systemic treatment with glucocorticoids in RA.

  • Severe forms of RA with systemic manifestations, viscerite , high fever, maximum activity of the process;in this case, glucocorticoids are often combined with cytostatics (the therapeutic effect is enhanced, side effects decrease);
  • The ineffectiveness of all other methods of treatment of active rheumatoid inflammation in articular RA;
  • Social indications for prescribing glucocorticoids in small doses in the morning, if the patient is the sole breadwinner of the family and is forced to continue working.

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