adrenocortical pharmacology dr fatai oluyadi usmleinclined.com 1
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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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