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Flashcards in Adrenal Pharmacology Deck (12):

Physiologic and Pharm dosing effects of cortisol

Carb: increases gluconeogenesis, increases blood glucose (increases insulin)
Excess: diabetes like state

Protein: decreases protein synthesis leads to increased aa to glucose
Excess: muscle wasting, skin CT atrophy

Fat: increases lipolysis (peripherally), increases FA
Excess: increases lipogenesis (centrally via insulin action), centripetal obesity (moon facies, buffalo hump)


Aldosterone phys vs pharm doses

increases Na reabsorption at kidney, increases blood volume and BP (loosely coupled to K and H secretion)
Excess: fluid retention, hypertension, hypokalemia


Glucocorticoids (pharm effects)

anti-inflammatory, immunosuppressive

-vacular: reduced vasodilation, decreased fluid exudation
-Effects on cellular events: decrease in accumulation and activation of inflammatory and immune cells

Effects on inflammatory and immune mediators: decrease in synthesis

Upside: GCs suppress chronic inflammation and autoimmune reactions

Downside: GCs also decrease healing and diminish immunoprotection


Metabolism of glucocorticoids

11beta-hydroxysteroid dehydrogenase (11betaHSD)
Liver: 11betaHSD1 can convert cortisone back to cortisol-- activating
Kidney: 11beta HSD2 converts cortisol to cortisone-- inactivating (less MC activity at kidney)
Fetus: 11 beta HSD2 protects fetus from effects of maternal steroids


Characteristics of adrenocorticoid agents

Dexamethasone has highest anti-inflammatory potential
Fludrocortisone ahs highest salt retaining potential


Q: adverse effects of pharmacologic doses unlikely to be seen with dexamethasone but possible with prednisone

-elevated BP


Ex of when you'd need physiologic replacement regimen

Addison's disease
-use agent with both GC and MC actions like cortisol or add fludrocortisone)


For pharm doses for anti-inflamm or immunosuppressive actions

-desirable to select an agent with minimal or no MC activity (dexamethasone)
-not possible to avoid GC metabolic side effects with the anti-inflammatory GCs currently available.


Activation of prednisone

-inactive until hepatic conversion to prednisolone (NO topical activity or parenteral activity)


Adrenocortical Insufficiency: chronic

Chronic (Addison's disease)
-oral hydrocortisone (15-25 mg/day in 2-3 divided doses- roughly mimics the normal diurnal rhythm)
-long-acting agents provide smoother physiologic effect given daily (Dexamethasone, prednisone)
-temporary dosage increase w/ illness or surgery
-Fludrocortisone can be added if need increased salt retaining activity
-DHEA supplementation may be needed in some women (mood and well being)


Acute adrenocortical insufficiency

-adrenal crisis: electrolyte abnormalities (decreased Na, Increased K) and plasma volume depletion
-Volume replenishment with NS or D5NS
-large amounts of IV hydrocortisone if previous dx
-without dx: dexamethasone
-additional MC action greater than hydrocortisone not needed unless hyperkalemic (K greater than 6 meq/L)


Adrenocortical hyperfunction: Cushing's Syndrome (hypercortisolism) tx

-Surgery is tx of choice
-Pharm: reserved for adjunctive therapy in refractory or inoperable cases, can include:
-Synthesis inhibitors:
early: miotante, *ketoconazole, aminoglutethimide, trilostane
late: metyrapone
-Glucocorticoid receptor antagonist: Mifepristone (RU-486)