Adrenal Flashcards
Mineralocorticoids general
ALDOSTERONE
- increases Na+ reabsorption at renal collecting tubule
- important regulator of blood pressure
- Increases excretion of K+
Glucocorticoids
CORTISOL
- Restores homeostasis after exposure to stress such as physical/emotional trauma
describe Hypothalamus-pituitary-adrenal (HPA) axis
- Corticotropin-releasing hormone (CRH) is released from hypothalamus
- CRH activates receptors in anterior pituitary (GPCRs)
- rapid secretion of preformed ACTH/Slower increase in the synthesis of ACTH
- ACTH activates receptors in the adrenal cortex
- increase steroidogenic enzyme expression and synthesis and secretion of cortical steroids
- ACTH stimulates production of CORTISOL and adrenal androgens
- Cortisol has a negative feedback on adrenal pituitary and hypothalamus
Cortisol binding general
binds and activates both mineralocorticoid and glucocorticoid receptors
- type 2 isoform of 11beta-hydroxysteroid dehydrogenase (11B-HSD2)
- CONVERTS ACTIVE CORTISOL TO INACTIVE CORTSONE
- which inhibits binding to mineralocorticoid receptors
- Stress leads to saturation of 11B-HSD2
- Type 1 isoform of 11beta-hydroxysteroid dehydrogenase (11B-HSD1)
- converts INACTIVE CORTISONE to ACTIVE CORTISOL
*
- converts INACTIVE CORTISONE to ACTIVE CORTISOL
describe short acting glucocorticoids
- Cortisol/hydrocotrison
- Cortisone
Have both anti-inflammatory effects and salt-retaining effects
intermediate acting glucocorticoids
12-36 hours
All have longer effect and greater potency of anti-inflammatory effect
- Prednisone
- prednisolone
- methylprednisolone
- triamcinolone –> no salt-retaining effect
Long acting glucocorticoids
16-56 hrs
High potency of antiinflammatory effects
NO SALT-RETAINING EFFECTS
- Betamethasone
- dexamethasone
Fludrocortisone
Mineralocorticoids
EXTREMELY HIGH SALT-RETAINING EFFECT
has some anti-inflammatory effects
what is the importance of 11B-HSD1
activation of many prodrugs
ADDISON’S DISEASE
primary adrenal insufficiency
- Cause = autoimmune/TB
- Characteristics
- deficiency in Cortisol and aldosterone
- ACTH and CRH levels are Elevated due to lack of negative feedback
- potassium retention, sodium excretion and fluid depletion are increased
- TX: ORAL CORTISOL and FLUDROCORTISONE
- increase dosage of cortisol during times of stress
secondary adrenal insufficiency
- Pituitary disease
- decrease ACTH causes an increase in CRH
- DECREASE In cortisol
- Hypothalamic disease
- decrease in CRH causes decrease in ACTH which causes decrease in cortisol
- TX = CORTISOL ONLY
describe the testing required for determining the cause of CUSHINGS SYNDROME
- Pituitary hypersecretion of ACTH
- increase ACTH and derease CRH
- High dose of DEXAMETHASONE suppression test = reduction of cortisol by 50%
- Adernal adenoma
- Decrease CRH and ACTH
- No reducetion in cortisol in response to DEXAMETHASONE
- Ectopic ACTH production
- Decrease CRH and increase in ACTH
- No reduction in cortisol in resposne to DEXAMETHASONE
describe inhaled corticosteroids
- First line TX for pts with persistent asthma
- should be used in pts who take inhaled B2-receptor agonist more than twice weekly
- FLUTICASONE
- should be used in pts who take inhaled B2-receptor agonist more than twice weekly
- MoA
- increase epithelial integrity
- GCs decrease adhesion molecules in airway epithelial cells
- GCs can reduce growth of ASMs
- GCs reduce leaky cells caused my inflammation
describe the interaction between corticosteroids and inhaled long-acting B2-receptor agonist
- Corticosteroid effects
- increase B2-receptor expression
- prevent desensitization of beta2-receptors
- B2 agonist effects:
- increase nuclear translocation of GRs
- Increase binding of Grs to GREs on genes
Glucocorticoid pharmacokinetics
- 90% of serum cortisol is bound to protein
- remaining free cortisol represents biologically active fraction
- Dexamethasone has LOW AFFINITY, so HIGHER FREE LEVELS IN SERUM
- DECREASE of serum proteins (liver disease or chronic inflammatory disease) –> decreased dosage of some of glucocorticoids
