1. ADRENOCORTICAL PHARMACOLOGY
DR FATAI OLUYADI
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2. ADRENAL CORTEX ZONA GLOMERULOSA ZONA FASCICULATA ZONA RETICULARIS
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3. ADRENAL CORTEX
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4. ADRENAL CORTEX HORMONES
MINERALOCORTICOIDS (ALDOSTERONE)
GLUCOCORTICOIDS (CORTISOL)
ANDROGENS (ANDROSTENIDIONE, TESTOSTERONE)
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5. ADRENAL HORMONE SYNTHESIS
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6. GLUCOCORTICOIDS CORTISONE PREDNISONE PREDNISOLONE METHYLPREDNISOLONE
HYDROCORTISONE
CORTISONE
PREDNISONE
PREDNISOLONE
METHYLPREDNISOLONE
TRIAMCINOLONE
BETHAMETHASONE
DEXAMETHAOSIONE
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7. GLUCOCORTICOID FUNCTION
Increase Blood Pressure
Increase Insulin resistance
Increase Gluconeogenesis
Decrease Fibroblast activity
Decreased Inflammation
Immunosuppression
Decrease Bone formation
Weak Mineralocorticoid effects
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8. STEROID RESPONSE
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9. ANTI-INFLAMMATORY EFFECTS OF GLUCOCORTICOIDS
Inhibits production of leukotrienes and prostaglandins by blocking the Phospholipase A2 enzyme of the Arachidonic acid pathway
Inhibits leukocyte Adhesion
Blocks Mast cell degranulation
Reduces Eosinophil count
Blocks Interleukin-2 production
Inhibits the protein synthesis ( Decrease production of Cytokines and inflammatory mediators)
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10. CLINICAL USES OF GLUCOCORTICOIDS
Management of Inflammatory disrorders – Asthma, Inflammatory bowel diseases
Immunosuppresants – Autoimmune diseases
Congenital defect in steroid synthesis – 21 Hydroxylase Deficiency
Adrenal insufficiency
Fetal Lung maturity
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11. ANTI-INFLAMMATORY Asthma Inflammatory Bowel disease Gout
Glucocorticoids are used in the treatment of Inflammatory diseases e.g:
Asthma
Inflammatory Bowel disease
Gout
Vasculitis e.g Temporal /Giant cell arteritis
*Glucocorticoids can reduce inflammatory responses mediating nervous tissue swelling therefore can be used in the treatment of trauma induced cerebral edema and spinal cord injury.
*Intra-articular steroids are used in the treatment of Inflammatory Joint Diseases
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12. IMMUNOSUPPRESSANT To Prevent Transplant rejection
Treatment of Automimmune disease: SLE, Polymyositis
Cancer treatment – for Cancers of White blood cells E.g Leukemia, Lymphoma
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13. ADRENAL INSUFFICIENCY
Glucocorticoids are given as replacement in patients with adrenal insufficiency
Adrenal insufficiency can be as a result of:
Autoimmune destruction of the adrenal glands
Hemorrhagic shock
Infection – e.g Adrenal Tuberculosis
Metastatic disease e.g Lung cancer
Hypothalamic or Pituitary insufficiency
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14. FETAL LUNG MATURATION
Glucocorticoids e.g DEXAMETHASONE, BETHAMETHASONE, HYDROCORTISONE induces surfactant synthesis in the fetus promoting fetal lung maturity and is usually given to prevent Neonatal respiratory distress.
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15. ADVERSE EFFECTS OF GLUCOCORTICOIDS
Hyperglycemia
High Blood Pressure
Truncal obesity
Moon facies
Abdominal striae
Immunosuppresssion
Osteoporosis
Easy bruising
Adrenal cortical atrophy – Reason why glucocorticoids should be tapered slowly
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16. CUSHINGNOID SIDE EFFECTS OF GLUCOCORTICOIDS
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17. MINERALOCORTICOIDS
Aldosterone is the main endogenous mineralocorticoid.
Release of Aldosterone is regulated by Angiotensin II via the Renin-Angiotensin System in the regulation of Blood Pressure.
The most common clinically used Mineralocorticoid is FLUDROCORTISONE.
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18. MINERALOCORTICOID FUNCTIONS
Mineralocorticoid functions include
Increase Sodium (Na) Reabsorption - to drive Increased Water reabsorption ultimately to increase Blood Volume, Venous return, Cardiac Output and Blood Pressure.
Increase Potassium (K) excretion
Increase Hydrogen (H) excretion.
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19. CLINICAL USES OF MINERALOCORTICOIDS
FLUDROCORTISONE
Adrenal Insufficiency : Low Cortisol, Aldosterone and Androgens
Adverse effects: Hypertension
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