Adrenocortical Antagonists

Adrenocorticosteroids & Adrenocortical Antagonists
adrenocorticosteroids
glucocorticoids
intermediate metab & immune func
naturally occuring
major : cortisol (hydrocortisone)
synthesized from cholesterol
synthesis/ secretion regulated by CNS
metab by liver
pharmacokinetics
secretion governed by corticotropin (ACTH)
corticosteroid- binding globulin (CBG)- alpha2 globulin made by liver- binds 90%
remainder is free or loosly bound to albumin & avail to act...consider free
CBC inc in prego, estrogen stim, hyperthyroidism
CBC dec in hypothyroidism, genetic defects in synthesis, protein deficiency states
MOA
physiologic
vascular/ bronchial sm myo response to catecholamines is diminished if cortisol missing & restored by glucocorticoid
lipolytic response to fat cells to catecholamines, ACTH, GH are dec if glucocorticoids absent
metabolic
stimulate/ req'd for gluconeogenesis & glycogen synthesis in fasting state
inc glucose levels therefore stim insulin release & inhib lipolysis (inc fat)
catabolic/antianabolic
supra levels lead to dec myo mass, weakness, & thinning of the skin
osteoporosis in Cushings syn...avoid long term use
in children- reduce growth
can be prevented by admin GH in high doses
antiinflamm/ immunosupp
due to effects on conc, distrib, and funct of peripheral leukocytes & suppressive effects on inflam cytokines and chemokines
after dose of SA glucocorticosteroid, conc of neutophils inc, while lymphocytes, monocytes, eosinophils, basophils dec
inhib funct of tissue macrophages and other antigen-presenting cells
influence inflamm response by reducing the prostaglandin, leukotriene, and platelet-activating factor synthesis resulting from activ phospholipase A2
reduce expression of cyclooxygenase-2, reducing prostaglandins
cause vasoconstriction, & dec capillary permeability by reducing the amt of histamine prod
SE
insomnia, euphoria, depression
inc intracranial pressure
supress the pituitary release of ACTH, GH, thyroid stim hormone, LH if given chronically
peptic ulcer, fat redistribution, dec calcium absorption
inc # of platelets and RBC
deficiency
impaired renal func, augmented vasopression secretion, & diminished ability to excrete a water load
synthetic
Short/ medium acting
hydrocortisone
tx: chronic Addisons disease (chronic adrenocortical insuff) w/ fludorcortisone
tx: acute Addison's disease (parenteral) + fluids/electolytes
tx: congenital adrenal hyperplasia + prednisone + fludrocortisone + salt
tx: Cushing's syndrome
cortisone
prednisone
prodrug
prednisolone
methylprednisone
intermed acting
triamcinolone
long acting
betamethasone
used to stim fetal lung maturation
inc transfer across placenta than others
dexamethasone
tx to prevent congenital adrenal hyperplasia (given to mother)
used for diagnostic purposes : Cushings syn, depressive psych states (pseudo-cushings syn)
used for tx of transplant rejection
dose must be tapered down
prolonged therapy: perform x-ray & TB test
contraindicated
peptic ulcer, heart disease, HTN w/ heart failure, varicella, TB, phycoses, diabetes, osteoporosis, glaucoma
mineralcorticoids
salt-retaining activity
major: aldosterone
fludrocortisone
tx: Addison's disease w/ hydrocortisone
tx: aldosteronism
androgenic
major: dehydoepiandrosterone (DHEA)
estrogenic
adrenocortical antagonists
aminoglutethimide
blocks conversion of cholesterol to prenenolone and causes reduction of all hormonally active steroids
used w/ hydrocortisone or dexamethasone to reduce/eliminate estrogen production in breast cancer
tx cushings syn
ketoconazole
antifungual imadazole deriv
potent/ non-selective inhib of adrenal & gonadal steroid synthesis
tx cushings syn
metyrapone
selective inhib of steroid 11-hydroxylation (interfere w/ cortisol & corticosterone synthesis)
tx: Cushings syn
can be admin to prego wm
abiraterone
blocks 17a-hydroxylase and 17,20 lyase & reduces synthesis of cortisol and gonadal steroids
tx: refractive prostate cancer
mifeprostone (ru-48)
antagonist at the steroid receptor
strong anti-progestin activ
tx: inoperable pts w/ ectopic ACTH secretion or adrenal carcinoma
mineralcorticoid antagonists
spirinolactone
eplerenone
has no effect on androgen receptors
drospirenone
progestin on oral contraceptives
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