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Adrenal steroids

Adrenal steroids. Dr Sanjeewani Fonseka Department of Pharmacology. Objectives. Recall the physiological effect of adrenocortical steroids Describe the anti- inflammatory and immunosuppressive effects of glucocorticoids

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Adrenal steroids

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  1. Adrenal steroids Dr SanjeewaniFonseka Department of Pharmacology

  2. Objectives • Recall the physiological effect of adrenocortical steroids • Describe the anti- inflammatory and immunosuppressive effects of glucocorticoids • Compare the relative potency, glucocorticoid/mineralocorticoid activity and duration of action of commonly available steroid drugs • List clinical uses and adverse effects of glucocorticoid drugs • Explain the principles underling replacement therapy in adrenocortical insufficiency • Describe the precautions that can be taken to minimize the adverse effects of long-term steroid therapy

  3. Endogenous Glucocorticoids Hydrocortisone Corticosterone

  4. Corticosteroids are Gene-Active

  5. Glucocorticoids Kinetics: • Well absorbed orally • Bound to corticosteroid-binding globulin and albumin • Distributed all over the body & passes the BBB • In the liver, cortisol is reversibly converted to cortisone & conjugated with glucuronic & sulfuric acid • Excreted in urine as 17-hydroxy corticosteroids

  6. Action of glucocorticoids • Metabolic • Anti-inflammatory • Immunosuppressive

  7. Actions • Carbohydrate • Protein • Lipid • Electrolyte and H2O • CVS • Skeletal Muscle • CNS • Stomach • Blood • Anti-inflammatory • Immunosuppressant • Growth and Cell Division • Calcium metabolism

  8. Carbohydrate metabolism • Gluconeogenesis • Peripheral actions (mobilize glucose and glycogen) • Hepatic actions • Peripheral utilization of glucose • Glycogen deposition in liver (activation of hepatic glycogen synthase) hyperglycemia

  9. protein metabolism Negative nitrogen balance • Decreased protein synthesis • Increased protein breakdown

  10. Skeletal Muscles Needed for maintaining the normal function of Skeletal muscle Addison's disease: weakness and fatigue is due to Prolonged use: inadequacy of circulatory system Steroid myopathy

  11. Lipid metabolism • Redistribution of Fat

  12. Electrolyte and water balance Act on DT and CD of kidney • Na+ reabsorption • Urinary excretion of K+ and H+

  13. CNS • Direct • Mood • Behavior • Brain excitability • Indirect • maintain glucose, circulation and electrolyte balance

  14. Stomach • Acid and pepsin secretion • immune response to H.Pylori

  15. Blood RBC: Hb and RBC content (erythrophagocytosis) WBC: Lymphocytes, eosinophils, monocytes, basophils Polymorphonucleocytes

  16. Actions on inflammatory cells • Recruitment of N, monocytes, macrophage into affected area • Action of fibroblasts • T helper action • Osteoblast • osteoclast

  17. Inflammatory mediators • Reduced cytokines • Reduced complement • Reduced histamine

  18. Anti-inflammatory actions of corticosteroids Corticosteroid inhibitory effect

  19. Growth and Cell division • Inhibit cell division or synthesis of DNA • Delay the process of healing • Retard the growth of children

  20. Calcium metabolism • Intestinal absorption • Renal excretion • Excessive loss of calcium from bones (e.g., vertebrae, ribs, etc) • Osteoporosis

  21. Pharmacological Actions • synthetic glucocorticoids are used because they have a higher affinity for the receptor • have little or no salt-retaining properties.

  22. Clinical uses • Replacement therapy • Immunosuppressive / anti-inflammatory therapy • Neoplastic disease

  23. Types of Steroids Replacement Therapy • glucocorticoid (hydrocortisone) • mineralocorticoid (fludrocortisone)

  24. Anti-inflammatory Therapy • Short acting: hydrocortisone • Intermediate acting: prednisolone, methylprednisolone, triamcinolone • Long acting: dexamethasone

  25. Side effects • Not seen in replacement therapy • Seen if used for anti-inflammatory property • Excess of physiological actions

  26. Iatrogenic Cushing’s syndrome

  27. Adverse effects (long term) • Glucose intolerance • Acne • Hypertension, edema • Susceptibility to infection (TB, fungal) • Myopathy • Behavior & mood changes

  28. Adverse effects (long term) • Avascular necrosis of bone • Cataract • Peptic ulcer • Skin atrophy, delayed wound healing • Growth retardation (children) • Suppression of HPA axis

  29. Drug interactions • Estrogens - decrease prednisone clearance • Phenobarbital, phenytoin, and rifampicin - increase metabolism of glucocorticoids • May cause digitalis toxicity secondary to hypokalemia • Monitor for hypokalemia with co-administration of diuretics

  30. Read Monitoring while on steroids Pregnancy and steroids Infections and long term steroid Surgery and steroids

  31. Summary

  32. long term steroids • Monitor BP, electrolyte and blood sugar • Advise moderate exercise • Bone protection measures • Gastric protection if needed

  33. Give morning dose • Every other day • Minimum effective dose • Steroid sparing agents

  34. Read • Mineralocorticoids – action, side effects, clinical uses

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