Adrenal Pharmacology Flashcards
Cortisol and Cortisone in CNS, muscle, liver, adipose
Cortisone –(11beta-hydroxylase 1)-> cortisol
Cortisol and Cortisone in kidney and colon
Cortisol –(11beta-hydroxylase 2)-> cortisone
Basal cortisol levels?
limited utility because of oscillating patterns and circadian rhythm pattern
ACTH stimulation test for diagnosing hypocortisolism
Addison’s disease, iatrogenic withdrawal from glucocorticoids
Short Test - give small dose, check cortisol levels 1 hour later
Long Test - give large dose, check at intervals
- Addison’s disease (primary) -> cortisol reduced at all timepoints
- Secondary disease -> delayed response
5 Tests to establish hypercortisolism
- 24 hr urine cortisol (high cortisol confirms hypercortisolism)
- Late night salivary (>2 tests –> loss of pattern indicative of Cushings)
- Special populations (pregnancy, epilepsy)
- Once its established –> baseline ACTH (low ACTH indicates independent disease, high ACTH indicates dependent disease)
- Dex Test
Dexamethasone Challenge Test
- Low dose -> failure to suppress cortisol after dose of dexamethasone (loss of negative feedback) -> confirms
- if cortisol is lower than normal, axis is working and Cushing is ruled out - High dose -> pituitary adenoma will show some reduction to high dex, ectopic tissue tumor will NOT
Cushing syndrome caused by adrenal tumor
Low dose test –> no change
ACTH level –> low
High dose test –> not needed
Cushing syndrome caused by ectopic ACTH tumor
Low dose test –> no change
ACTH level –> high
High dose test –> no change
Cushing syndrome caused by pituitary tumor
Low dose test –> no changed
High dose test –> normal suppression
Less Used diagnostic test
CRH/F stimulation test
- CRH stimulation used to distinguish Cushings from ectopic ACTH tumor
- Cushings will respond, ectopic tumors will not
- administer CRH –> ACTH/cortisol increase
Glucocorticoid effects
CV -> positive iontropic, increase BP (Na/H2O retention -> some mineralocorticoid activity)
CNS -> lowers seizure threshold, behavioral
GI -> increase acid, suppress immune, decrease Ca absorption
Bone -> direct inhibition of osteoclasts, stim PTH
Muscle -> hypokalemia, muscle wasting
Heme -> inhibits extravasation, suppress lymphocytes
Therapeutic Uses of Glucocorticoids
substitution and replacement of adrenal insufficiency……and many more!
- anti-inflammatory
- immunosuppressants
- anti-allergic
Natural vs. Synthetic
Synthetic are higher potency, less protein bound, and longer half-life
Cortisol has equal gluco and mineral activity
Prednisone, methylprednisone, dexa have all gluc activity
Fludrocortisone has mineral activity
* Addition of side chains enhance the potency
Active vs Inactive Cortisol
Cortisol (Prednisolone) is reduced and active
Cortisone (Prednisone) is oxidized and inactive
- prednisione gets activated in liver by 11beta-hydroxylase
Substitution/Replacement of adrenal insufficiency
Acute Adrenal Insufficiency -> sudden stop in glucocorticoids meds (IV Cortisol)
Chronic Primary Adrenal Insufficiency -> addisons (cortisol/fludrocortisone if needed)
Secondary Adrenal Insufficiency -> give cortisol
Congenital Adrenal Hyperplasia -> due to 21-hydroxylase deficiency -> give cortisol and fludrocortisone
Considerations when giving glucocorticoids
can produce toxicity
dose is determined by trial and error
high doses may be used in acute situations
gradual steroid withdrawal following chronic administration
Side Effects from Glucocorticoids
Hyperglycemia --> may need insulin Infection Peptic ulcer Myopathy Osteoporosis Mineralocorticoid effects - licorice slows down conversion of cortisol to cortisone
ACTH utility
it is a protein -> half-life of 10-15 minutes
- must be injected, mostly hydrolyzed by blood and tissue enzymes
Treatment of Cushings
surgery and support with glucocorticoids until recovery of ACTH function
- radiation for poor surgery candidates
- medical treatment
Medical Treatment of Cushings
Ketoconazole -> inhibits side-chain cleavage
- antifungal -> inhibit fungal cyto P450
- blocks glucocorticoid and androgen synthesis
Aminoglutethimide -> inhibits side-chain cleavage enzyme
Etomidate -> inhibits 11beta-hydroxylase
Metyrapone -> inhibits 11beta-hydroxylase in adrenal gland
