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Dr Sanjeewani Fonseka Department of Pharmacology

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1 Dr Sanjeewani Fonseka Department of Pharmacology
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



5 Endogenous Glucocorticoids
Hydrocortisone Corticosterone


7 Corticosteroids are Gene-Active



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

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 Needed for maintaining the normal function of Skeletal muscle
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

16 Lipid metabolism Redistribution of Fat

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

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

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

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

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

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

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 1 1.0 0.8 4 5 0.3 Intermediate acting 10 - 15 7 Drug
Anti-inflam. Salt retaining Topical Cortisol 1 1.0 Cortisone 0.8 Prednisone 4 Prednisolone 5 0.3 Methylpredni- solone Intermediate acting Triamcinolone Paramethasone 10 - Fluprednisolone 15 7

31 Preparations Long acting 25-40 10 30 Mineralocorticoids 250 20 Drug
Anti-inflam. Salt retaining Topical Long acting Betamethasone 25-40 10 Dexamethasone 30 Mineralocorticoids Fludrocortisone 250 DOCA 20

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




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


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


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


47 Read Mineralocorticoids – action, side effects, clinical uses

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