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Adrenocorticosteroids & Adrenocortical Antagonists

By catrina1.ellis

Added: July 08, 2011 01:09:33

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Adrenocorticosteroids & Adrenocortical Antagonists

Adrenocorticosteroids & Adrenocortical Antagonists
1 adrenocorticosteroids
1.1 glucocorticoids
1.1.1 intermediate metab & immune func
1.1.2 naturally occuring
1.1.2.1 major : cortisol (hydrocortisone)
1.1.2.1.1 synthesized from cholesterol
1.1.2.2 synthesis/ secretion regulated by CNS
1.1.2.3 metab by liver
1.1.2.4 pharmacokinetics
1.1.2.4.1 secretion governed by corticotropin (ACTH)
1.1.2.4.2 corticosteroid- binding globulin (CBG)- alpha2 globulin made by liver- binds 90%
1.1.2.4.3 remainder is free or loosly bound to albumin & avail to act...consider free
1.1.2.4.4 CBC inc in prego, estrogen stim, hyperthyroidism
1.1.2.4.5 CBC dec in hypothyroidism, genetic defects in synthesis, protein deficiency states
1.1.2.5 MOA
1.1.2.5.1 physiologic
1.1.2.5.1.1 vascular/ bronchial sm myo response to catecholamines is diminished if cortisol missing & restored by glucocorticoid
1.1.2.5.1.2 lipolytic response to fat cells to catecholamines, ACTH, GH are dec if glucocorticoids absent
1.1.2.5.2 metabolic
1.1.2.5.2.1 stimulate/ req'd for gluconeogenesis & glycogen synthesis in fasting state
1.1.2.5.2.2 inc glucose levels therefore stim insulin release & inhib lipolysis (inc fat)
1.1.2.5.3 catabolic/antianabolic
1.1.2.5.3.1 supra levels lead to dec myo mass, weakness, & thinning of the skin
1.1.2.5.3.2 osteoporosis in Cushings syn...avoid long term use
1.1.2.5.3.3 in children- reduce growth
1.1.2.5.3.3.1 can be prevented by admin GH in high doses
1.1.2.5.4 antiinflamm/ immunosupp
1.1.2.5.4.1 due to effects on conc, distrib, and funct of peripheral leukocytes & suppressive effects on inflam cytokines and chemokines
1.1.2.5.4.2 after dose of SA glucocorticosteroid, conc of neutophils inc, while lymphocytes, monocytes, eosinophils, basophils dec
1.1.2.5.4.3 inhib funct of tissue macrophages and other antigen-presenting cells
1.1.2.5.4.4 influence inflamm response by reducing the prostaglandin, leukotriene, and platelet-activating factor synthesis resulting from activ phospholipase A2
1.1.2.5.4.5 reduce expression of cyclooxygenase-2, reducing prostaglandins
1.1.2.5.4.6 cause vasoconstriction, & dec capillary permeability by reducing the amt of histamine prod
1.1.2.6 SE
1.1.2.6.1 insomnia, euphoria, depression
1.1.2.6.2 inc intracranial pressure
1.1.2.6.3 supress the pituitary release of ACTH, GH, thyroid stim hormone, LH if given chronically
1.1.2.6.3.1 peptic ulcer, fat redistribution, dec calcium absorption
1.1.2.6.4 inc # of platelets and RBC
1.1.2.7 deficiency
1.1.2.7.1 impaired renal func, augmented vasopression secretion, & diminished ability to excrete a water load
1.1.3 synthetic
1.1.3.1 Short/ medium acting
1.1.3.1.1 hydrocortisone
1.1.3.1.1.1 tx: chronic Addisons disease (chronic adrenocortical insuff) w/ fludorcortisone
1.1.3.1.1.2 tx: acute Addison's disease (parenteral) + fluids/electolytes
1.1.3.1.1.3 tx: congenital adrenal hyperplasia + prednisone + fludrocortisone + salt
1.1.3.1.1.4 tx: Cushing's syndrome
1.1.3.1.2 cortisone
1.1.3.1.3 prednisone
1.1.3.1.3.1 prodrug
1.1.3.1.4 prednisolone
1.1.3.1.5 methylprednisone
1.1.3.2 intermed acting
1.1.3.2.1 triamcinolone
1.1.3.3 long acting
1.1.3.3.1 betamethasone
1.1.3.3.1.1 used to stim fetal lung maturation
1.1.3.3.1.1.1 inc transfer across placenta than others
1.1.3.3.2 dexamethasone
1.1.3.3.2.1 tx to prevent congenital adrenal hyperplasia (given to mother)
1.1.3.3.2.2 used for diagnostic purposes : Cushings syn, depressive psych states (pseudo-cushings syn)
1.1.4 used for tx of transplant rejection
1.1.5 dose must be tapered down
1.1.6 prolonged therapy: perform x-ray & TB test
1.1.7 contraindicated
1.1.7.1 peptic ulcer, heart disease, HTN w/ heart failure, varicella, TB, phycoses, diabetes, osteoporosis, glaucoma
1.2 mineralcorticoids
1.2.1 salt-retaining activity
1.2.2 major: aldosterone
1.2.3 fludrocortisone
1.2.3.1 tx: Addison's disease w/ hydrocortisone
1.2.3.2 tx: aldosteronism
1.3 androgenic
1.3.1 major: dehydoepiandrosterone (DHEA)
1.4 estrogenic
2 adrenocortical antagonists
2.1 aminoglutethimide
2.1.1 blocks conversion of cholesterol to prenenolone and causes reduction of all hormonally active steroids
2.1.2 used w/ hydrocortisone or dexamethasone to reduce/eliminate estrogen production in breast cancer
2.1.3 tx cushings syn
2.2 ketoconazole
2.2.1 antifungual imadazole deriv
2.2.2 potent/ non-selective inhib of adrenal & gonadal steroid synthesis
2.2.3 tx cushings syn
2.3 metyrapone
2.3.1 selective inhib of steroid 11-hydroxylation (interfere w/ cortisol & corticosterone synthesis)
2.3.2 tx: Cushings syn
2.3.3 can be admin to prego wm
2.4 abiraterone
2.4.1 blocks 17a-hydroxylase and 17,20 lyase & reduces synthesis of cortisol and gonadal steroids
2.4.2 tx: refractive prostate cancer
2.5 mifeprostone (ru-48)
2.5.1 antagonist at the steroid receptor
2.5.2 strong anti-progestin activ
2.5.3 tx: inoperable pts w/ ectopic ACTH secretion or adrenal carcinoma
3 mineralcorticoid antagonists
3.1 spirinolactone
3.2 eplerenone
3.2.1 has no effect on androgen receptors
3.3 drospirenone
3.3.1 progestin on oral contraceptives