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