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Steroidal anti-inflammatory drugs.pptx

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Steroidal anti-inflammatory drugs.pptx

  1. 1. Steroidal anti-inflammatory drugs LECTURE № 10
  2. 2. Steroidal anti-inflammatory drugs - drugs are glucocorticoid hormones Biogenic drugs glucocorticoid hormones have little mineralocorticoid activity and, therefore, cause a delay of salt and water in the body. Currently, the synthetic hormones, which have only glucocorticoid activity: They are almost completely devoid of mineralocorticoid activity. Glucocorticoids
  3. 3. Glucocorticoids are released in response to stress, adapting organism mobilizing and increasing its resistance. Therefore, glucocorticoids have diverse effects on all types of metabolism: protein, carbohydrate, fat. Glucocorticoid effects on carbohydrate metabolism:  in the liver stimulates the synthesis of glucose from amino acids (gluconeogenesis), protein synthesis in the liver and kidneys is reduced;  reduced absorption, assimilation and utilization of blood glucose (hyperglycemia), decreased resorption of carbohydrates in the digestive tract. Effect of glucocorticoids on protein metabolism:  Glucocorticoids enhance the mobilization of amino acids from tissues, especially skeletal muscle, and inhibit protein synthesis, particularly in the bones (osteoporosis)
  4. 4. Glucocorticoid effects on lipid metabolism:  Glucocorticoids play a "resolution" role in the mobilization of fat from the depots. With prolonged use of hormones is a redistribution of fat.  In some tissues there is a strengthening process of lipolysis (limbs), while increasing the amount of free fatty acids in blood plasma  In other tissues, there is a strengthening process of lipogenesis (upper torso, his face - "moon face, neck -" buffalo hump "). In the blood there hypercholesterolemia. Glucocorticoid effects on water and electrolyte metabolism:  Natural and the first synthetic glucocorticoids have little sodium delayed, as well as calcium and potassium deducing action. Therefore, when assigning a patient large doses (300 mg / day) there is sufficient sodium retention. New synthetic analogues of natural glucocorticoids do not possess this activity and even, on the contrary, can cause significant loss of sodium ions in the urine. Glucocorticoid effects on the blood system  Glucocorticoid hormones induce rapid lysis of lymphoid tissue and lymphopenia in the background of a general leukocytosis. A reduction in the number of eosinophils.  Glucocorticoid promotes platelet and red blood cells.
  5. 5. Effect of glucocorticoids (GC) on inflammation The mechanism of anti-inflammatory action  GC stabilizes cell membranes and lysosomes (membrane stabilizing effect), thereby limiting the output of these enzymes, resulting in tissue damage  GC enhance the synthesis of lipomoduline - endogenous inhibitor of phospholipase A-2, inhibiting its activity this. Phospholipase A-2 facilitates the mobilization of arachidonic acid from phospholipids of cell membranes and the formation of the acid metabolites (prostaglandins and leukotrienes), which play a key role in inflammation.  GC stimulates the synthesis of intercellular substance - hyaluronic acid, which lowers the permeability of the vascular wall. The decrease of exudation are also associated with decreased secretion of histamine, as well as change the sensitivity of adrenergic receptors to catecholamines (adrenaline). Vascular tone increases as permeability decreases.  Inhibition of glucocorticoid-proliferation associated with a reduction in protein synthesis and a decrease in revenue of leukocytes into the tissues. Restriction occurs chemotaxis, spontaneous migration.  Thus, corticosteroids have no effect on the cause of inflammation, so their anti-inflammatory activity is nonspecific and is observed both at the system, and at the local to use them.  In this case, GC inhibit all three phases of inflammation (alteration, exudation, proliferation).
  6. 6. Antiallergic and immunosuppressive action of glucocorticoids  GC cause both absolute and relative T- lymphocytopenia, i.e. inhibit cell-mediated immunity.  GC inhibit the reaction of graft rejection as well as suppress the delayed-type hypersensitivity reaction.  At the same hormones in this group do not alter the production of antibodies of B- lymphocytes, as well as the formation of immune complexes.  GC inhibit the activity of phagocytes and digestive function microphages and macrophages.  Immunosuppressive effect of GC associated with the action at various stages of the immune response contributes to the susceptibility of the organism to a variety of bacterial, fungal, viral and parasitic infections.
  7. 7. Indications for use drugs glucocorticoids: 1. As a means of substitution therapy in adrenal insufficiency (Addison's disease) in combination with mineralocorticoids. 2. As a means of anti-inflammatory therapy:  at Collagenose (diffuse connective tissue diseases such as rheumatism, rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus);  - In severe forms of glomerulonephritis;  - In severe forms of hepatitis;  - In eye diseases of inflammatory etiology (interstitial keratitis, conjunctivitis, iritis, iridocyclitis, sympathetic ophthalmia, etc.);  - Skin diseases (inflammatory dermatoses, eczema, psoriasis, etc) 3. As a means of anti-allergic therapies: - Asthma; - with autoimmune hemolytic anemia, thrombocytopenia. 4. In order to reduce the permeability of vascular walls and membranes in general: - acute swelling of the brain and lungs; - at toxic and toxic-septic form of pneumonia (particularly children); - toxic, toxic-septic gastrointestinal lesions of staphylococcal and viral etiology; - for the treatment of shock (any). 5. With the purpose of influencing the blood system: - with anemia, thrombocytopenia; - with lymphoid leukemia, lymphoma; - To suppress the reaction of graft rejection in transplantation of organs and tissues.
  8. 8. The tactics of therapy with glucocorticoids By the time of treatment are two types of therapy, GC:  Short-term (intensive) glucocorticosteroid therapy. Drugs are introduced singly or within a few days.  Use of GC in case of emergency allows us to treat them as ordinary drugs.  Long-term (maintenance) glucocorticosteroid therapy. This type of therapy used in the treatment of patients with subacute or chronic disease course, with exacerbation of chronic disease. Prolonged use of GC is only justified in cases of severe pathology. When you assign a tablet dosage forms need to be considered chronobiological features and regularities. We must strive to administration of drugs through the day, which reduces the risk of adrenal suppression and non-specific resistance to infection. In the case of inadmissibility of such a method of administration, it is best to introduce single daily dose in the morning.
  9. 9. Complications, side effects of glucocorticosteroid therapy  The phenomenon of hyperglycemia ("steroid diabetes")  Reduction of protein synthesis, which occurs in the form - Muscle pain, increased muscle fatigue; - Osteoporosis; - Delayed wound healing; - Teratogenic effects; - The backlog of children in the development and growth (when using GC for six months or more); - Reducing the absorbability (suffers gastric mucosa) of calcium and phosphorus, which in children leads to rickets; - Exacerbation or appearance of new expressions of intestinal mucosa (inhibition of proliferation); cataract and cataract development.  Especially with prolonged use GC in children; increased irritability in children; AP increase, the delay of salt and fluids, especially among teenagers; Redistribution of fat ("moon face", "buffalo hump"); Decrease in immunity, immunosuppressive effect, which occurs increasing frequency of colds. May develop a withdrawal syndrome, particularly when abrupt cancellation of drugs (adrenal insufficiency). Therefore, after long-term use of glucocorticoids, the dosage should be reduced very slowly.
  10. 10. Contraindications to corticosteroids:  Diabetes mellitus  Osteoporosis  Pregnancy  Peptic ulcer disease  The presence of wound healing  Hypertonic disease  Epilepsy
  11. 11. Thank you for your attention!

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