Corticosteroids Flashcards
When are ACTH and cortisol mostly secreted
morning when you wake up
bind to cytoplasmic receptor
Corticosteroids
acts as transcription factor, regulates the transcription leading to mRNA and protein synthesis
GRE - glucocorticoid response elements
4 things to remember about corticosteroids
1) give in the morning
2) give as single dose in morning
3) takes 14 days to work
4) make sure to taper and takes 1 month for adrenals to recover
1) reduced synthesis of COX2 and cytokines
2) inhibit fxn of macrophage and antigen presenting cells
3) increase lymphocyte apoptosis
4) inhibit neutrophil migration to tissue
5) inhibit phospholipase A2
6) decrease capillary permeability
physiological effects of glucocorticoids
1) stimulate glycogen deposition in liver
2) gluconeogenesis
3) decrease peripheral utilization of glucose
Results = hyperglycemia and decreased insulin sensitivity
carbohydrate metabolism effects of glucocorticoids
1) redistribution of body fat
2) moon face, buffalo hump, fish mouth, thin limbs, lemon on stick appearance
lipid metabolism effects of glucocorticoids
protein breakdown
muscle wasting
tanning of skin
healing delayed
protein metabolism effect of glucocorticoids
sodium and water retention
edema and hypertension on prolonged use
electrolyte and water effects of corticosteroids
decrease calcium levels in blood by inhibiting calcium absorption from gut and increasing its renal excretion
prolong use causes osteoporosis
calcium effects of corticosteroids
responsible for HTN associated with cushings
cortisols mineralocorticoids
hypertension and worsening of congestive symptoms of heart failure due to sodium and water retention
CVS effects of corticosteroids
inhibit prostaglandin synthesis, increased gastric acid synthesis
CI in peptic ulcer
GIT effects of corticosteroids
hyperpigmentation, ACTH increase, hypotension, hyperkalemia, increase blood eosinophils count and fasting hypoglycemia
Addison’s dz
treatment for Addisons
Hydrocortisone + fludrocortisone
female newborn with ambiguous external genitalia
dehydration
hypotension
21 beta hydroxylase def
treatment for 21 beta hydroxylase def
fludrocortisone + cortisol
dexamethasone test results
1) blood cortisol suppression >50% means inhibition
pituitary cushings syndrome
dexamethasone test results
1) blood cortisol suppression < 50% means no inhibition
2) ACTH increase
lung cancer
dexamethasone test results
1) blood cortisol suppression < 50% means no inhibition
2) ACTH decrease
adrenal tumor
short acting glucocorticoids
t half less than 12 hrs
hydrocortisone
prednisolone
used in emergency
equal glucose and mineral corticoid activity
Hydrocortisone
active drug
4x more potent
single dose in morning mimics normal circadian rhythm of cortisol
prednisolone
intermediate acting
t half 12-36 hrs
triamcinolone
no mineralocorticoid activity
no salt retaining
triamcinolone
long acting
t half 36 hrs
dexamethasone
no mineralocorticoid activity
never given as replacement
used in hospital only
not used long term
dexamethasone
inhalation steroid preparations
fluticasone
beclomethasone
budesonide
triamcinolone
topical steroid preparations
betamethasone
triamcinolone
hydrocortisone
Cushing features
cataract ulcer skin thinner hypertension/hirsutism infection necrosis of femoral head glycosuria osteoporosis/obesity immunosuppression diabetes
CI for glucocorticoids
peptic ulcer heart dz HTN with heart failure varicella TB psychosis diabetes osteoporosis glaucoma
adrenal suppression
Osteoporosis
femur head avascular osteonecrosis
muscle wasting
some ADR of glucocorticoids
Uses for glucocorticoids
1) adrenal insufficiency
2) congenital adrenal hyperplasia
3) asthma
4) collagen vascular
5) ocular dz
6) lung maturation
7) skin dz
8) chemotherapy
9) cushings
10) cerebral edema
11) anti inflammatory
abrupt stoppage of glucocorticoids therapy after prolonged use causing:
1) flaring up of underlying dz
2) with drawl sx - fever, myalgia, malaise, athralgia
3) acute adrenal insufficiency
low dose should be used and tapered slowly without abrupt stopping to avoid ADR
HPA axis suppression
Inhibits CYP450 (desmolase), which catalyze rate limiting step conversion of cholesterol to pregnenolone
Aminoglutethimide
Reduces biosynthesis of all physiological steroids
Used to decrease hypersecretion of cortisol in px with Cushing’s syndrome
Used to reduce estrogen production in tx with great cancer with dexamethasone
Aminoglutethimide
Inhibits CYP450 11 hydroxylase enzymes
Metyrapone
Used to test adrenal fxn (insufficiency)
- if pit and adrenal are normal will cause increase ACTH and atrophy of adrenal cortex
- tumor suppresses ACTH and atrophy of adrenal cortex (not caused by adrenal tumor)
Only adrenocorticoid antagonist that can be used for cushings in pregnacy
Metyrapone
Antifungal
Inhibits steroid synthesis in high doses except 21 hydroxylase
Treatment for Cushing’s syndrome
Ketoconazole
Antiprogestin activity
High doses block glucocorticoid receptors
Mainly used as contraceptive, abortificient (+ misoprostol)
Mifepristone
Major minerocorticoid
Secretion controlled by aldosterone and RAAS (increase BP)
Acts on renal tubule cells to increase reabsorption of Na, bicarb, H2O in exchange for K excretion
Aldosterone
Primarily used for replacement therapy after adrenalectomy or for primary and secondary adrenocortical insufficiency
Fludrocortisone
ADR: hypokalemia and congestive heart failure due to volume overload
Fludrocortisone
Aldosterone receptor antagonist - inhibits 17 alpha hydroxylase (competes with DHT)
Treats: primary hyperaldosteronism and baldness in men due to excessive androgen
Spironolactone
