Adrenal agents Flashcards
what are the drug targets of corticosteroids?
17a-hydroxylase
11B-hydroxylase
17a-hydroxylase is responsible for catalyzing what reactions?
pregnenolone to 17-hydroxypregnenolone
progesterone to 17-hydroxyprogesterone
11B-hydroxylase is responsible for catalyzing what reaction?
deoxycortisone to cortisone
what enzyme is responsible for catalyzing the reactions
pregnenolone to 17-hydroxypregnenolone
progesterone to 17-hydroxyprogesterone?
17a-hydroxylase
what enzyme is responsible for catalyzing the reaction
deoxycortisone to cortisone?
11B-hydroxylase
what types of receptors are glucocorticoid and mineralocorticoid?
nuclear hormone receptors
cortisol binds to what receptors?
glucocorticoid
mineralocorticoid
does cortisone bind to mineralocorticoid receptors?
no
where is cortisone converted to cortisol? what is the enzyme?
liver
11B-HSD1
which enzyme is responsible for converting cortisol back to cortisone?
11B-HSD2
what type of drug is fludrocortisone? what effects does it have?
mineralocorticoid
heavy salt retaining
anti-inflammatory
what enzyme is important in converting prodrugs into their active forms?
11B-HSD1
what are the causes of primary adrenal insufficiency (addison’s disease)?
autoimmune
TB
what are the results of primary adrenal insufficiency (addison’s disease)?
deficiency in cortisol, aldosterone, androgens
hypotension from unresponsiveness of vascular smooth muscle to catecholamines
primary adrenal insufficiency (addison’s disease) is treated with what agents?
cortisol
fludrocortisone
secondary adrenal insufficiency are due to what causes?
pituitary - 1) decrease in ACTH causing increase in CRH, 2) decrease in cortisol
hypothalamic - 1) decrease in CRH causes increase in ACTH, 2) decrease in cortisol
secondary adrenal insufficiency (addison’s disease) is treated with what agent?
cortisol (fludrocortisone NOT needed)
chronic glucocorticoid (cortisol) excess leads to what condition?
Cushing’s syndrome
Cushing’s syndrome is a result of elevation of what compound?
chronic glucocorticoid (corticoid) excess
why does increased levels of cortisol cause HTN?
activation of mineralocorticoid receptors
determination of the cause of cushing’s syndrome is made by what compound?
dexamethasone
what will be the levels of CRH and ACTH in pituitary hypersecretion of ACTH? upon dexamethasone administration?
low CRH
high ACTH
usually 50% reduction in cortisol upon dexamethasone
what will be the levels of CRH and ACTH in adrenal adenoma? upon dexamethasone administration?
low CRH
low ACTH
no reduction in cortisol upon dexamethasone (has nothing to do with cortisol)
what will be the levels of CRH and ACTH in ectopic ACTH production? upon dexamethasone administration?
low CRH
high ACTH
no reduction in cortisol upon dexamethasone
what class of drug is ketoconazole? what is the MOA? what is it used to treat?
antifungal
inhibits 17a-hydroxylase
cushing’s syndrome
what is the adverse effect of ketoconazole?
significant liver toxicity
what is the clinical application of metyrapone? for what condition is it used to treat?
diagnostic agent used to evaluate ACTH production
cushing’s syndrome
what drugs are used to treat cushing’s syndrome?
ketoconazole
metyrapone
what is the MOA of mifepristone? for what condition is it used to treat?
glucocorticoid receptor antagonist
inoperable patients with ectopic ACTH secretion or adrenal carcinoma
what drug is used to treat inoperable patients with ectopic ACTH secretion or adrenal carcinoma?
mifepristone
what are the effects of glucocorticoids on the immune cells?
macrophage - decrease activation
neutrophils - stabilize lysosomal membrane
mast cells - decrease release of histamine
eosinophils - decrease release of granules
T cells - decrease number and activation
what are the anti-inflammatory mechanisms of corticosteroids?
inhibition of phospholipase A2
COX inhibition
inhaled corticosteroids are the first line treatment for what condition? when should they be used?
asthma
patients who take inhaled B2 agonists more than twice a week
what is the MOA of inhaled corticosteroids on asthma?
reduce vascular permeability
reduce growth of airway SMCs
reduce adhesion molecules in airway epithelial cells
increase epithelial integrity
what is the importance of using inhaled glucocorticoids in conjuction with B2 agonists?
corticosteroids - 1) increase B2 receptor expression, 2) prevent desensitization of B2 receptors
B2 agonists - 1) increase nuclear translocation of GRs, 2) increase binding of GRs to GREs on genes
what is the importance of dexamethasone administration for glucocorticoid effect?
dexamethasone has low affinity for blood proteins - higher free levels in serum
what is the effect of glucocorticoids on stomach acid and pepsin production?
gastic acid - stimulation
pepsin - stimulation
what is the adverse effect of glucocorticoids on the endocrine system?
HPA axis suppression
what is the effect on estrogens and androgens on glucocorticoids?
increased effect
why is it necessary to taper a patient off long term glucocorticoid therapy?
reduce HPA axis suppression
what is the mechanism by which high doses of cortisol can lead to hypotension or hypokalemia? would this same mechanism be observed with dexamethasone?
aldosterone (mineralocorticoid) receptor effects
no - no mineralocorticoid receptor action
what is the principle behind the high dose dexamethasone test?
pituitary tumor - dex has some effect of inhibiting ACTH
adrenal adenoma - dex isn’t regulated by ACTH at all
ectopic ACTH production - dex doesn’t inhibit ACTH production in lung (does not have the same responsive capabilities)
what is the therapeutic use and MOA of ketoconazole?
inhibition of 17a-hydroxylase
