ADRENOCORTICAL PHARMACOLOGYDR FATAI OLUYADI

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ADRENAL CORTEX

ZONA GLOMERULOSA

ZONA FASCICULATA

ZONA RETICULARIS

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ADRENAL CORTEX

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ADRENAL CORTEX HORMONES

MINERALOCORTICOIDS (ALDOSTERONE)

GLUCOCORTICOIDS (CORTISOL)

ANDROGENS (ANDROSTENIDIONE, TESTOSTERONE)

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ADRENAL HORMONE SYNTHESIS

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GLUCOCORTICOIDS HYDROCORTISONE CORTISONE PREDNISONE PREDNISOLONE METHYLPREDNISOLONE TRIAMCINOLONE BETHAMETHASONE DEXAMETHAOSIONE

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GLUCOCORTICOID FUNCTIONIncrease Blood PressureIncrease Insulin resistanceIncrease GluconeogenesisDecrease Fibroblast activityDecreased InflammationImmunosuppressionDecrease Bone formationWeak Mineralocorticoid effects

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STEROID RESPONSE

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ANTI-INFLAMMATORY EFFECTS OF GLUCOCORTICOIDS Inhibits production of leukotrienes and prostaglandins by blocking the Phospholipase A2 enzyme of the Arachidonic acid pathwayInhibits leukocyte AdhesionBlocks Mast cell degranulationReduces Eosinophil countBlocks Interleukin-2 productionInhibits the protein synthesis ( Decrease production of Cytokines and inflammatory mediators)

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CLINICAL USES OF GLUCOCORTICOIDSManagement of Inflammatory disrorders – Asthma, Inflammatory bowel diseasesImmunosuppresants – Autoimmune diseasesCongenital defect in steroid synthesis – 21 Hydroxylase Deficiency Adrenal insufficiencyFetal Lung maturity

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ANTI-INFLAMMATORY Glucocorticoids are used in the treatment of Inflammatory diseases e.g: AsthmaInflammatory Bowel diseaseGoutVasculitis 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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IMMUNOSUPPRESSANT

To Prevent Transplant rejectionTreatment of Automimmune disease: SLE, PolymyositisCancer treatment – for Cancers of White blood cells E.g Leukemia, Lymphoma

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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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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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ADVERSE EFFECTS OF GLUCOCORTICOIDSHyperglycemiaHigh Blood PressureTruncal obesityMoon faciesAbdominal striaeImmunosuppresssionOsteoporosisEasy bruising Adrenal cortical atrophy – Reason why glucocorticoids should be tapered slowly

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CUSHINGNOID SIDE EFFECTS OF GLUCOCORTICOIDS

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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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MINERALOCORTICOID FUNCTIONS

Mineralocorticoid functions include

1.Increase Sodium (Na) Reabsorption - to drive Increased Water reabsorption ultimately to increase Blood Volume, Venous return, Cardiac Output and Blood Pressure.

2.Increase Potassium (K) excretion

3.Increase Hydrogen (H) excretion.

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CLINICAL USES OF MINERALOCORTICOIDS

FLUDROCORTISONE

Adrenal Insufficiency : Low Cortisol, Aldosterone and Androgens

Adverse effects: Hypertension

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