Adrenal Corticosteroid drugs DSA Flashcards
mineralcorticoids
fludrocortisone
short to medium acting glucocorticoids
hydrocortisone cortisone prednisone prednisolone methyprednisolone
intermediate acting glucocorticoids
triamcinolone
long acting glucocorticoids
DBs go long
betametasone
dexametasone
steroid syntheis inhibitors
aminoglutethimide
ketoconazole
metyrapone
mitotane
glucocorticoid antagonist
mifepristone
my pristine body doesn’t need sugar
steroid hormones are transported by what
cortisol bound to ___ considered ___
protein carriers bc they are hydrophobic
- transcortin or CBG
- rest loosely bound to albumin
- albumin bound cortisol should be considered free
when is transcortin and CBG high
low?
pregnancy
low in liver failure
half life of cortisol is increased in what pts
pts with liver disease
hypothyroid pts
direct effects of mineralocorticoids on CV system:
1) effects on gene expression
2) aldosterone excess causes
gene expression: NAPDH reductase-->oxidative stress collagen, TGFB--> fibrosis IL-6, CAM-->inflammation PAI-1-->inhibition of fibrinolysis, blood clotting
Cat NIP
2) aldosterone excess:
- cardiac fibrosis and hypertophry
- vascular remodeling and inflammation
glucocorticoid effects
transactivation: effect on carb, lipid, protein metab
transrepression mech: GR-ligand complex binds other txn factor complexes and suppresses gene txn
-NF-Kb, AP-1 = anti-inflamm, immunosupp, anti growhth
what receptor may be responsible for glucocorticoid resistance
GR beta
-no ligand binding, inactive
11B-HSD type 2 role
converts cortisol into inactive cortisone so cannot bind MR
-this is how aldosterone gets effect bc aldost and cortisol bind MR with same affinity but more cortisol is produced daily
what tissues does 11B-HSD type 2 convert cortisol to cortisone
renal tubular epithelium
salivary glands
sweat glands
colon epithelium
inhibtion of 11B-HSD type 2 results in
hypertension and edema with excess MR stim by cortisol
what may inhibit 11B-HSD2
glycyrrhizin (licorice root extract)
carbenoxolone
glucocorticoid effect on carb metabolism
3 enzymes
transporter
development of what
increase PEPC–>increased gluconeogenesis
increased glucose 6 phosphatase = more glucose in circulation
increased glycogen synthase
decreased GLUT4
development of hyperglycemia
glucocorticoid effect on lipid metabolism
promote stimulation of HSL
increasedd FFA and glycerol into gluconeogenic pathway
increased insulin secretion
increase fat deposition and chane in fat distribution
glucocorticoids in skeletal muscle
suppressed protein synthesis will lead to myopathy and muscle wasting
gluocorticoids and phospholipase A2 and COX
decrease production
= less prostaglandins and leukotriens
glucocorticoids on CVS
increased Epi and ?Ne
increased HR and CO
increased BP
residual mineralocorticoid activity (Na+/H20+ retention)
glucocorticoids on GI
decreased gastroprotective prostaglandins
decrease immune response H pylori
increase gastric acid and pepsin secretion
glucocort on CNS
insomnia
irritanility
euprhoia then depression
decreased libido in males
glucocort in bones/growth
decreased intest absorption calcium
increase osteoclast activity (osteoporis)
growth retardation in children
glucocort in skin
dfragile and thin skin with stretch marks
treatment addisons
hydrocortisone and fludrocortisone
cataracts, peptic ulcers, glaucoma in what steroid
glucocortioids
a prodrug activated by esterases present in bronchial epithelial cells; systemically absoerbed active drug bound to serum proteins
ciclesonide
pt populations in which systemic glucocorticoids administration is problematic
immunocompromidsed diabetics pts with infections pts with peptic ulcer pts with CV conditions pts with psychiatric condistions pts with osteoporosis children
aminoglutethimide MOA
- indication
- side effects
blocks conversion of cholesterol to pregnenolone
reduces all steroid hormones
adrenocortical cancer
drowsiness
GI upset
ketocanzole
MOA
indication
AE
p450 inhibition, reduces adrenal and sex hormones
prostate cancer
antifungal
cushing syndrome
stops androgenic hair loss
PACH of keys
hepatotox and gynecomastia in males
metyrapone
MOA
indication
AE
inhibtion of steroid 11 hydroxylation
stops cortisol and corticosterone
cushing syndrome (only drug for this in pregnancy) (tyra banks pregnant)
accumulation 11 deoxycortisol = increased aldosterone = more sodium and water retention
-also increased androgens = hirsutism in women
GI upset
dizziness
mitotane
MOA
indication
AE
sodium and calcium ionophore
PKC and AC inhibitor
cytotoxic action on adrenal cortex
adrenal carcinoma
depression, somnolence
GI upset
rashes
too tan gets rashes, GI problems bc he eats, and depression from eating too much/being fat
mifepristone
MOA
indications
AE
glucocorticoid receptor antagonist
stabilizes hsp90-GR complex in cytosol, no nuclear translocation
-progest receptor antagonist
endogenous cushings
anti progest action for termination intrauterine preg
dizziness
GI upset
fatigue
spirnonolactone MOA
indications
side effects
aldosterone receptor antagonist
also antagonist at androgen receptors
primary hyperaldost
hirsutism in women
diuretic for HF and HTN
hyperkalemia
gynecomastia and impotence in men
menstrual abnormalty in women
eplerenone
MOA
indications
side effects
antag of aldosterone at mineralocorticoid receptors
lower affinity for androgen recept than spironolact
HTN
HF
hyperkalemia
