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Adrenal steroids Dr Sanjeewani Fonseka Department of Pharmacology.

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Presentation on theme: "Adrenal steroids Dr Sanjeewani Fonseka Department of Pharmacology."— Presentation transcript:

1 Adrenal steroids Dr Sanjeewani Fonseka 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

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5 Endogenous Glucocorticoids Hydrocortisone Corticosterone

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7 Corticosteroids are Gene-Active

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10 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

11 Action of glucocorticoids Metabolic Anti-inflammatory Immunosuppressive

12 Actions 1.Carbohydrate 2.Protein 3.Lipid 4.Electrolyte and H 2 O 5.CVS 6.Skeletal Muscle 7.CNS 8.Stomach 9. Blood 10. Anti-inflammatory 11. Immunosuppressant 12.Growth and Cell Division 13. Calcium metabolism

13 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

14 protein metabolism Negative nitrogen balance Decreased protein synthesis Increased protein breakdown

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

16 Redistribution of Fat Lipid metabolism

17 Electrolyte and water balance Act on DT and CD of kidney – Na + reabsorption – Urinary excretion of K + and H +

18 Direct –Mood –Behavior –Brain excitability Indirect –maintain glucose, circulation and electrolyte balance CNS

19 – Acid and pepsin secretion – immune response to H.Pylori Stomach

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

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

22 Inflammatory mediators Reduced cytokines Reduced complement Reduced histamine

23 Anti-inflammatory actions of corticosteroids Corticosteroid inhibitory effect

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

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

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

27 Clinical uses Replacement therapy Immunosuppressive / anti-inflammatory therapy Neoplastic disease

28 Types of Steroids Replacement Therapy glucocorticoid (hydrocortisone) mineralocorticoid (fludrocortisone)

29 Anti-inflammatory Therapy Short acting: hydrocortisone Intermediate acting: prednisolone, methylprednisolone, triamcinolone Long acting: dexamethasone

30 Preparations DrugAnti-inflam.Salt retainingTopical Cortisol Cortisone Prednisone Prednisolone Methylpredni- solone 505 Intermediate acting Triamcinolone 505 Paramethasone 100- Fluprednisolone 1507

31 Preparations DrugAnti-inflam.Salt retainingTopical Long acting Betamethasone Dexamethasone Mineralocorticoids Fludrocortisone DOCA 0200

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

33 Iatrogenic Cushing’s syndrome

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

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

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40 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

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

42 Summary

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

45 Give morning dose Every other day Minimum effective dose Steroid sparing agents

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47 Read Mineralocorticoids – action, side effects, clinical uses


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