Adrenal Hormones and their Antagonists Flashcards
What are the 3 types of steroid hormones produced by adrenal cortex?
mineralocorticoids (salt)
glucocorticoids (sugar)
androgens (sex0
What is the major form of adrenal adrogens?
Dehydroepiandrosterone (DHEA-S)
What is the first FDA-approved medication contianing DHEA & what is its use?
DHEA or Prasterone
Vaginal inserts as treatment of vulvovaginal atrophy —> Decline in Estrogen production after menopause
Tx painful sexual itnercourse due to dryness and thinning of vaginal tissue
What are the 2 kinds of endogenous corticosteroids?
Mineralococrticoids and Glucocorticoids
What is the site of synthesis of GLucocorticoids & Mineralocorticoids?
Mineralocorticoids = Glomerulosa
Glucocorticoids = Fasciculata
Whata re the naturally-occuring/Endogenous hormones of these corticosteroids?
Mineralocorticoids = Aldosterone
Glucocorticoids = Cortisol
What are synthetic analogs/Exogenous corticosteroids?
Mineralocorticoids = Fludrocortisone
Glucocorticoids = Prednisone, Prednisolone, Betamethasone, Dexamethasone
What ist the precursor of Aldosterone?
11-Deoxycorticosterone
What stimulates release of Aldosterone & Cortisol?
Aldosterone = Angiotensin II, HIGH levels of serum K+, ACTH
Cortisol = ACTH
What is the MOA of Aldosterone?
Binds to mineralocorticoid receptor (nuclear) in DCT & CT of kidneys —> receptor activation, gene transcription, protein synthesis —> INC expression of Na/K ATPase & ENaC
What is the MOA of Cortisol?
Binds to glucocorticoid receptors —> receptor activation, gene transcription, protein synthesis —> effects
What are the effects of Aldosterone & Cortisol?
Aldosterone = Salt-retention, Excretion of K, H, SEcretion of bicarbonate
Cortisol = Gluconeogenesis, Glycogenesis, Muscle protein catabolism, Lipolysis, Fat redistribution, Anti-inflammatory & immunosuppressive effects: FTLM
What hormone stimulates secretion of Aldosterone?
Angiotensin II
What happens to the acid base balance once Aldosterone has excessive excretion of K & H
Hypokalemia
Metabolic alkalosis
What is the only synthetic minteralocorticoid? WHat is its clinical use?
FludroCORTISONE
Use: Adrenocortical insufficiency assoc w/ mineralocorticoid deficiency
What are the 3 mechanisms of neuroendocrine control?
Episodeic secretion & circadian rhythm of ACTH
Stress responsiveness of hypothalamic-pituitary-adrenal axis
Feedback inhibition of ACTH secretion by cortisol
What is the only steroid that participates in the HPA axis?
Cortisol
What are the 2 components of stress response
Fast response: EPI or Adrenaline
Slow response: HPA Axis (Cortisol)
What can happen if there is chronic exposure to stress?
Maladaptive stress response
How does Cortisol suppress inflammatory and immune response?
- Inhibits migration of leukocytes to the site of the inflammation
- Inhibits function of macraphage, production of inflam cytokines
- INhibits inflam mediators (Eicosanoid)
Does cortisol have mineracorticoid acitivity?
Yes, but minimally since if has 11-B-hydroxysteroid dehydrogenase type 2
What is the best way to administer synthetic glucocorticoids?
Oral administration (faster, complete)
What is the inactive form of Cortisol?
Cortisone
That’s why prednisone is converted to Prednisolone (active form)
Aside from Fludrocortisone, what is another corticosteroid?
Hydrocortisone
Hydrocortisone + Cortisone = shortest half-life (least potent)
Is Fludrocortisone also used for anti-inflammatory conditions?
NO, its only indications is for mineralocorticoid deficiency
What are the non-adrenal uses of Glucocorticoids?
Nasal spray for allergic rhinitis
Budesonide inhaler for asthma
Topical glucocorticoids for dermatitis
Ophthalmic solns for eye diseases
Enema and rectal suppositories for inflammaotry bowel dis (Crohn’s & ulcerative colitis)
What is the purpose of Prednisone?
Anti-inflammatory effect + Immunosuppression
DEC Ca absorption
In what conditions is Prednisone used?
RA, SLE, Graves opthalmopathy, Subacute thyroiditis, Nephrotic syndrome, Leukemia and Lymphoma
Tx for translant rejection
Tx for hyeprcalcemia
What is the purpose of Dexamethasone?
Antiemetic
DEC permeability of BBB to Na —> reduce cerebral edema
Surfacntant production for FLM
What are the 2 important glucocorticoids used for non-adrenal conditions?
Prednisone
Dexamethasone
What are the 3 main adrenal uses of glucocorticoids?
Chrousos syndrome
Hormone replacement
Congenital adrenal hyperplasia
What condition has a decreased senstiivity to glucocorticoids & INC ACTH resulting to excess production of mineraolcorticoid & Androgen effects?
Chrousous syndrome
What is the treatment for Chrousos syndrome?
Dexamethasone —> suppresses ACTH
What hormone replacement is given in Congenital adrehnal hyperplasia, chronic adrenal insufficiency, maintenance after adrenalactomy?
Hormone replcement of
Hydrocortisone +/- Fludrocortisone
What hormone replacement therapy is given in acute adrenal insufficiency during and immediately after adrenalectomy?
High dose IV hydrocortisone
What enzyme is deficient in congenital adrenal hyperpllasia?
21-a-hydroxylase
What is the tx for congenital adrenal hyperplasia?
Hydrocortisone
What is the glucocorticoid of choice in pregnancy bcos it readily crosses the placenta?
Dexamtheosone
What are the uses of dexamethasone in preggos?
- at risk of preterm labor (<34 wks)
- CAH
- Respiratory distress syndrome
- genital abnormalities
How should dexamethasone be administred to mothers at risk of preterm labor?
Short-course of Dexamethasone to accelerate fetal lung maturation
What do we do if parents are both carriers of CAH?
If fetus is female, they are more at risk of developing genital abnormalities as early as 1st trim. Mothers should start on Dexamethasone as soon as pregnancy is confirmed.
What condition results from chronic exposure to excess glucocorticoids?
Cushing syndrome
What test is done to detect Cushing syndrome?
Dexamethasone suppression test
What is the difference between Cushing & Pseudo-Cushing syndrome?
Pseudo-Cushing = caused by alcohol or psychiatric disorders
How do you localize tumor that causes Cushing syndrome?
tumor is @ APG —> suppress stimulation of Cortisol secretion
tumor @ adrenal gland —> suppress pitutary secretion of ACTH
tumor is ectopic & ACTH source is external —> Total ACTH will be high & not respond to the suppression effect of DXM
What can happen if Corticosteroids are administered >2 wks?
Iatrogenic Cushing syndrome
Adrenal suppression
What are the clin manifesations of Cushing syndrome?
IMPORTANT:
Blindness, weight gain, at risk for DM, short stature, HTN, HTN, HF, Psychosisis, Osteoporosis, Peptic ulcer (H. Pylori)
What are certain req before administreing Corticosteroids?
Px should be on high-protein & K enriched diets
Receive adequate doses of Vit D
Consider co-morbidities
Obtain CXR & tuberculin test
What are the 2 major grps of Adrenocortical antagonists?
Synthesis inhibitors
Receptor antagonists
What are the diff Adrencocortical antagonists, synthesis inibitors?
Aminoglutethimide
Ketoconazole
Abiraterone
Trilostane
Etomidate
Metyrapone
Mitotane
What are the diffrent Adrencocortical antagonists, receptor antagonists?
Mifepristone
Spironolactone
Eplerenone
