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37 Cards in this Set
- Front
- Back
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Anatomy of adenal gland
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Medulla (epi) & Cortex: Aldosterone (primary mineralcorticoid), Cortisol (primary glucocorticoid), Androgens (& some estrogens)
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Fcn of cortisol
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Glucose, AA & lipid metabolism. Anti-inflammatory & immunosuppressive
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Fcn of aldosterone
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Salt & water balance
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Effects of androgen production
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Can be sig in females especially postmenopausal. Enzyme deficiencies in gluco or mineralo-corticoid biosynthesis can result in overproduction
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Chemistry of corticosteriods
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Start w/ cholesterol-> pregnenolone (rate limiting). Rxn catalyzed by mixed fcn oxidases (require NADPH & oxygen).
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Charac of steroids
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Corticosteriods = 21 carbons. Androgens =19 C. Are lipid soluble so not stored in vesicles. Blood is a reservoir corticosteriods
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Charac of cortisol
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90% bound to corticosteriod binding globulin. 10-20mg secreted daily (follows circadian rhythm c ontrolled by ACTH & varies w/ stress). t1/2=60-90min. Metabolism via oxidation of 4-5 double bonds in liver
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Steriod receptor binding
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Most bind intracell receptor & entire cmplx transported to nuc-> turn on genes-> changes in almost all cells & tissues. Alter GF, pro-inflammatory cytokines, suppress immune response
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3 modes of reg of HPA axis?
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Diurnal rhythm in steroidogenesis, neg feedback by adrenal corticosteriods, & inc steroidogenesis in response to stress
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Describe HPA axis
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CRH released from hypothal into median eminence-> pituitary release ACTH-> stim adrenal to release cortisol.
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Explain feedback inhibition of HPA axis?
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Cortisol production inhibits CRH & ACTH release from hypothal & pituitary.
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Importance of steroid treatment & adrenal suppression
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Steriod treatment inhibits ACTH production & release-> adrenal suppression (correlates w/ dose & duration)-> can take wks -mths to recover
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MOA of ACTH
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Binds membrane receptor-> Gs->adenylate cuclase-> cAMP-> PKA-> gene transcription. T1/2= 15min
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Diagnostic test for adrenal insuficiency
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Admin ACTH-> rapid rise in plasma cortisol. Failure todo so indicates adrenal steroidogenesis is suppressed
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Fcn of ACTH
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Stim cells in fasciculata & reticularis to groe & produce steriods, inc transport of choles, inc conversion of choles to preg, permissive efect on aldosterone production, & primary reg of cortisol production
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What is pregnisone?
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Synthetic steriod used when GC activity is needed w/ a little MC activity. (eg In addison's w/ adrenal suppression due to long term therapy). Low MC allows high doses w/o affecting electrolyte & fluids. Inactive prodrug converted to pregnisolone
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General physiology of steriods?
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Essential for homeostasis. Permissive effects on catecholaminesGC= glucose, carb, anti-inflammatory. MC= salt & water balance.
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Physiology of cortisol
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Stim glucogenesis & glycogenolysis. Blocks all step in inflam process & immune cells migrate from inflam to plasma. Stim protein breakdown (except in liver-inc & AA conversion to glucose. Inc lipid catabolism
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What is addison's disease?
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The adrenal glands don't produce enough adrenocorticosteriod hormones (both GC & MC). Treated w/ oral hydrocortisone, if fails then add fludrocortisone (w/ primary MC activity)
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Mech of corticsteriod use?
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Feedback inhibition & tropic effect via HPA axis. Only treats symptoms & doesn't cure. Single dose no problem but short-term must tapper off (must supplement w/ hydrocortisone/pregnisone during adrenal suppression). & long-term can't quite
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General principles of use of corticosteriod treatment
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Treat target tissue, min systemic absorption, give least amt for shortest time.
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Charac of Bethamethsone & dexamethasone
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More potent anti-inflamm, long t1/2, dex is potent inhibitor of ACTH
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What is used to diagnose Cushing's?
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Dexamethasone
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Charac of Beclomethasone, flunisolide, mometasone?
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Topical anti-inflamm, seasonal allergies, asthma (nasal spray/inhalers), poorly absorbed so systemic effect are min
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Toxicity of cortisol & analogs
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Fluid-electrolyte disturbances, hyperglycemia, infections, peptic ulcers, osteoporosis, Cushing's, insomnia/euphoria/psychosis, rapid suppression of HPA axis & adrenal insuff on w/d
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What can cause adrenal insufficiency? How is it diagnosed?
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Overuse of GC (dose pack). Diagnosed via measuring plasma cortisol -/+ ACTH admin
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What is Cushing's disease?
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Usually results from bilat adrenal hyperplasia secondary to ACTH secreting pituitary adenoma. Diagnosed w/ 1mg of Dex @ bedtime (failure to suppress ACTH by 8am-> dysfcnal HPA axis)
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Mitotane
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Similar to DDT. Reduces production of corticsteriods
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Amohenone B
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More potent & toxic than mitotane
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Metyrapone
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Blocks 11-hydroxylation to prevent synthesis of cortisol & corticosterone. 11-deoxycortisol doesn't inhibit pituitary
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Aminoglutethimide
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Blocks conversion of choles to preg. Blocks production of all adrenal steriods
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Ketoconazole
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Antifungal. Non-selective inhibitor of steriod synthesis
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Mifepristone
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Antag progesterone>glucocorticoid>sex steroid receptors. W/ or w/o misoprostol (prostaglandin E2 analog) used to promote spontaneous abortion
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Mineralocorticoids
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Aldosterone (natural), Desoxycorticosterone (produced in zona fasciculata), Fludrocorticosterone (synthentic, most commonly used, potent MC, low GC)
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MOA of aldosterone
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Inc # of NA channels in apical membrane of distal tubule. Promotes NA reabsorption @ expense of K; activates NA/K pump-> may cause hypokalemia. Promotes reabsorption of H2O & HCO3-> inc body fluid vol
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Theropeutic uses of aldosterone
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Replacement therapy in Addison's disease
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MC antagonists
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Spironolactone, Eplerenone: Compete for receptors, prevents aldosterone action, K sparing diuretic. Spiron acts on androgen receptors
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