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Adrenocorticosteroids

Adrenocorticosteroids. History. 1855 – Addison's disease 1856 – Adrenal glands essential for life 1930 – Cortex Vs Medulla 1932 – Cushing’s Syndrome 1949 – Hench et al (Steroids in Rheumatoid Arthritis) 1952 – Aldosterone. Fight & Flight

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Adrenocorticosteroids

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  1. Adrenocorticosteroids

  2. History • 1855 – Addison's disease • 1856 – Adrenal glands essential for life • 1930 – Cortex Vs Medulla • 1932 – Cushing’s Syndrome • 1949 – Hench et al (Steroids in Rheumatoid Arthritis) • 1952 – Aldosterone

  3. Fight & Flight Corticosteroids Increase Serum Glucose

  4. Adrenocorticosteroids • Glucocorticoids: Cortisol • Mineralocorticoids: Aldosterone

  5. Processing of POMC to Adrenocorticotropic Hormone

  6. Circadian Rhythm of Glucocorticoids

  7. Mechanism of Action

  8. Mechanism of Action

  9. Mechanism of Action

  10. Mechanism of Action

  11. Cortisol Aldosterone Mineralocorticoid Receptor Glucocorticoid Receptor

  12. Structure Activity Relationship(SAR)

  13. Structure Activity Relationship

  14. Effect of 11β-HSD

  15. Gluco- vs Mineralo- Corticosteroides

  16. Structure Activity Relationship 6-Methyl Prednisolone

  17. Gluco- vs Mineralo- Corticosteroides

  18. Structure Activity Relationship

  19. Structure Activity Relationship Addition of Cl to Betamethasone produce Beclomethasone

  20. Gluco- vs Mineralo- Corticosteroides

  21. Clobetasol

  22. Structure Activity Relationship

  23. Structure Activity Relationship

  24. Gluco- vs Mineralo- Corticosteroides

  25. Steroid Hormones Transport Corticosteroid-Binding Globulin (CBG): 90% Albumin : 5%

  26. Physiologic Effects They influence the function of most cells in the body Glucocorticoids are named because of widespread effect on Glucose They elicit “Permissive Effects”

  27. Metabolic Effects • Gluconeogenesis & Glycogen Synthesis • Increase serum Glucose & thus Insulin release • Diabetes??

  28. Metabolic Effects • Lipolysis • Release of FFA & Glycerol into the circulation • Redistribution of Fat • Buffalo hump • Moon face

  29. Moon Face

  30. Buffalo Hump

  31. Metabolic Effects • Protein catabolism & release of AA • Muscle mass, Weakness • Thinning of the skin • Antianabolic effects in lymphoid and connective tissue • Children?

  32. Anti-Inflammatory Effect • Lymphocytes (T and B cells), Monocytes, Eosinophils & Basophils • Neutrophils? • Functions MQ & other APC

  33. RBC: Hb & RBC content (Erythrophagocytosis) Platlertes: Blood

  34. Anti-Inflammatory Effect Furthermore, Glucocorticoids reduce expression of COX-2

  35. Other Effects • Vit. D, Calcium absorption • Peptic ulcer • Surfactant production are stimulated by Glucocorticoids

  36. Other Effects • Anti stress, Insomnia, Euphoria & Depression • Negative Feedback (For ACTH, GH, TSH & LH)

  37. Reward System

  38. Pharmacokinetic • Are administered orally, IV or IM • Systemic effect after local administration such as Synovial spaces, Eye, Skin & Respiratory Tract • **Effect of occlusive dressing, large areas of skin, skin thickness …

  39. Diagnostic Use • Dexamethasone suppression test for: • Cushing's syndrome • Differential diagnosis of Depression Liddle's test (Urine is then assayed for cortisol or its metabolites)

  40. Clinical Application(Replacement Therapy)

  41. Adrenal Insufficiency

  42. Congenital Adrenal Hyperplasia (CAH) Lack of • 21β-Hydroxylase • 11- Hydroxylase • 17- Hydroxylase

  43. Cushing's syndrome • Diagnosis and replacement therapy during & after surgery

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