Adrenal Corticosteroids (Konorev) Flashcards
What are the 2 broad categories of adrenal corticosteroid drugs
- Mineralocorticoids
- Glucocorticoids
What is the one mineralocorticoid
Fludrocortisone
What are the short to medium acting <12 hours glucocorticoids
- Hydrocortisone
- Cortisone
- Prednisone
- Prednisoone
- Methyprednisolone
What is the intermediate acting 12-36 hours glucocorticoid
Triamcinolone
What are the Long acting >35 hour glucocorticoids
- Betametasone
- Dexametasone
What are the 3 categories of inhibitors of adrenal corticosteroid action?
- Steroid synthesis inhibitors
- Glucocorticoid antagonists
- Aldosterone antagonists
What are the steroid synthesis inhibitors
- Aminoglutethimide
- Ketoconazole
- Metyrapone
- Mitotane
What is the glucocorticoid antagonist
Mifepristone
What are the aldosterone antagonists?
- Spironolactone
- Eplerenone
What are mineralocorticoids induced by
-Ang II and K+
What do mineralocorticoids do
-regulate electrolytes and H2O balance and blood pressure
What are glucocorticoids induced by
ACTH
What do glucocorticoids do
regulate metabolism and immunity
What is the high affinity protein that binds cortisol and aldosterone
-Transcortin, or Corticosteroid Binding Globulin
What condition is Transcortin levels high?
Low?
- pregnancy, with estrogen administration and in hyperthyroidism
- Liver disease (cirrhosis)
What protein binds corticosteroids loosely which makes them basically free even when bound
albumin
When plasma cortisol exceeds _________, the binding capacity of transcortin is saturated, and concentration of free cortisol rises rapidly
20-30 ug/dL
Describe the role of the liver in pharmacokinetics of cortisol
- liver produces transcortin
- about 80% of cortisol is metabolized by the liver
- The half live of cortisol is normally about 60-90 min and is often increased in pts with liver diseases
Describe why cortisol does not have a big effect on mineralocorticoid receptor even though it is in higher concentration in blood and has same affinity for it as aldosterone?
-it is converted to cortisone by 11 B-HSD2 in renal tubular epithelium, salivary glands, sweat glands, and colon which is inactive
What happens when 11B-HSD2 is inhibited
excessive activation of MR by cortisol . . . leads to hypertension
What are the 2 things in the powerpoint that inhibit 11B-HSD2
- Glycyrrhizin (licorice root extract)
- Carbenoxolone (approved in UK to treat esophageal ulcers)
Describe what AME (apparent mineralocorticoid excess) is
- inactivating mutations in 11B-HSD2
- presents as a form of severe juvenile hypertension
- autosomal recessive
What cells do mineralocorticoids target
-Principal cells of collecting tubule and collecting duct
What is the effect of mineralocorticoids on gene expression in principal cells
- increase epithelial sodium channels on apical membrane (ENaC)
- increase Na/K pump (basolateral membrane)
What are the electrolyte consequences of mineralocorticoids
- Na and water retention
- K loss
What non epithelial cells do mineralocorticoids target
- Heart
- vasculature
What are the effects of gene expression on mineralocorticoids on non epithelial cell types
- NADPH reductase: oxidative stress
- Collagen, TGF-B: fibrosis, cell senescence
- IL-6, cell adhesion molecules: inflammation
- PAI-1: inhibition of fibrinolysis, blood clotting
Aldosterone excess (directly) causes what?
- cardiac fibrosis and hypertrophy
- Vascular remodeling and inflammation
-why we used aldosterone antagonists in hypertension and heart failure