Adrenal Flashcards by tcarlso 3

What are the chemicals that are synthesized by the adrenal cortex?

Mineralocorticoids
Glucocorticoids
Androgens

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What are the two chemicals that are secreted by the medulla of the adrenal glands?

Epi and norepi (catecholamines)

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What is the function of the mineralocorticoids (aldosterone)? (3)

Increases Na reabsorption in the collecting tubule

Increases K excretion

Increase BP

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What are the physiological effects of glucocorticoids?

Restoring homeostasis after exposure to stress:

Increases BG levels
Counterbalance immune system

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What are the two glucocorticoids?

Cortisol, hydrocortisone

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What are the two drug targets of corticosteroid biosynthesis?

17 alpha hydroxlaye

11 beta hydroxylase

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What are the relative levels of aldosterone and cortisol in the blood normally?

High cortisol, low aldosterone

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What is the effect of ACTH that is release from the anterior pituitary on the adrenal cortex?

Increased steroidogenic enzyme expression

Stimulates production of cortisol and adrenal androgens

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What is the problem with long term use of corticosteroids?

Steroid rebound

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What is the MOA of glucocorticoids and mineralocorticoids?

Freely cross the lipid membrane, and interact with receptors in the cytoplasm, and then enter the nucleus to alter expression

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What is the intracellular messenger that is inhibited in glucocorticoid/mineralocorticoid use, to immune suppress pts?

NfKappaB

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True or false: cortisol binds and activates mineralocorticoids and glucocorticoids

True

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What enzyme activates cortisol into inactive cortisone?

11beta HSD1

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What is the enzyme that converts cortisone into cortisol?

11beta-HSD2

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What is the function of 11beta HSD1?

Activates cortisone to cortisol

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What is the function of 11beta HSD2?

Inactivates cortisol into cortisone

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What are the two short acting glucocorticoids? Which effect is predominant: anti inflammatory or salt retention?

Hydrocortisone
Cortisone

Both equally

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What are the four intermediate acting corticosteroids? Which effect is predominant: anti inflammatory or salt retention?

Prednisone
Prednisolone
Methylprednisolone
Triamcinolone

Anti inflammatory

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What are the two long acting corticosteroids? Which effect is predominant: anti inflammatory or salt retention?

Betamethasone
Dexamethasone

No salt retention

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What is the use of fludrocortisone?

Increase salt retention (BP)

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What makes the glucocorticoids prodrugs?

Adding a hydroxyl group to the ring

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Is dexamethasone a prodrug? Prednisolone? cortisone? Prednisone?

Prednisone and cortisone are.

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What are the causes the Addison’s disease?

Autoimmune or TB causes deficiency in cortisol, aldosterone, and androgens

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What happens to ACTH and CRH levels in primary (Addison’s) adrenal insufficiency? Aldosterone? Why? What does this lead to?

Elevated– adrenal cortex is lacking a mechanism for feedback

Aldosterone decreases, leading to K retention and Na loss

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What is the treatment for Addison's? (2)

Fludrocortisone and oral cortisol

What are the effects of Addison's?

Hypotension from unresponsiveness of vascular smooth muscle to catecholamines

What are the two causes of secondary adrenal insufficiency? What are CRH and ACTH levels in these?

Either decrease in ACTH from pituitary, causing an increase in CRH, and a decrease in cortisol OR No CRH from the hypothalamus, lowering ACTH, and lower cortisol

What is the treatment for secondary adrenal insufficiency? Why?

Cortisol | NOT fludrocortisone, since aldosterone function is still retained

When is Glucocorticoid levels highest physiologically? What is the effect on the dosing regimen with this?

In the morning Higher doses then

What is the cause of Cushing's syndrome?

Chronic glucocorticoid excess - Iatrogenic - Pituitary tumor that secretes ACTH - SCLC secretion of ACTH - Adrenal tumor that hypersecrete cortisol

What are the ssx of Cushing's?

- Buffalo hump - Increased abdominal fat - Muscle wasting - Moon facies - Poor wound healing - Thinning of the skin

What happens to bones in Cushing's?

Osteoporosis

What happens to BP with Cushing's? Why?

Increased d/t increased cortisol levels in the adrenal cortex (swamped 11bHSD2)

What happens with CRH and ACTH with: pituitary hypersecretion of ACTH

Increased ACTH | Decreased CRH

What happens with CRH and ACTH with: adrenal adenoma?

Decreased in both ACTH and CRh

What happens with CRH and ACTH with: ectopic ACTH production

Decreased CRH | Increased ACTH from ectopic production

What happens if dexamethasone is injected into a pt wit pituitary hypersecretion of ACTH? Why?

Usually around 50% reduction in cortisol The pituitary is still somewhat responsive to dexamethasone.

What happens if dexamethasone is injected into a pt with ectopic production of ACTH? Why?

No reduction in cortisol ACTH secreting adenoma has no regulatory function like the pituitary

What happens if dexamethasone is injected into a pt with adrenal adenoma? Why?

No reduction is cortisol Tumors in the adrenal cortex would have no regulatory function with dexamethasone

What is the MOA of ketoconazole in treating Cushing's?

Inhibits 17 alpha hydroxylase, which can lower cortisol production.

What is the major side effect of Ketoconazole?

Hepatotoxic

What is the MOA of Metyrapone in treating Cushings?

Inhibits 11beta hydroxylase leading to decreased aldosterone and cortisol production

Draw out aldosterone pathway

***

What is the MOA of Mifepristone? What is it normally used for? What is its basis for the use in cushing's?

Anti-progestin effects (abortion) Glucocorticoid receptor antagonist at high doses

What is the main use of glucocorticoids?

Anti-inflammatory effects Reduce histamine release Treats hypersensitivity

What is the use of glucocorticoids in preterms?

Increased lung maturation

What is the effect of glucocorticoids on: macrophages?

Decrease activation | Decrease cytokine release

What is the effect of glucocorticoids on: PMNs?

Stabilize lysosomal membrane Prevent release of catabolic enzymes

What is the effect of glucocorticoids on: mast cells?

Inhibit release of histamine, prostaglandins Increase annexin 1

What is the effect of glucocorticoids on: eosinophils?

Inhibit release of histamine, prostaglandins

What is the effect of glucocorticoids on: T cells?

Suppress activation | Decrease cytokine release

What is the effect of inhibition of phospholipase A2 by glucocorticoids?

Decreased production of lipid mediators

What is the effect of inhibition of COX by glucocorticoids?

Decreased prostaglandin release

What is the effect of inhibition of Cytokine production by glucocorticoids?

Suppression of cell mediated inflammation

What is the effects of corticosteroids on vessels?

Vasoconstriction

What is the use of inhaled corticosteroids?

Asthma treatment

What are the four inhaled corticosteroids?

Budesonide Fluticasone Mometasone Triamcinolone

Why should you treat asthma with glucocorticoids and not just beta2 receptor agonists?

Beta 2 use will downregulate the receptors, but glucocorticoids will increase it back

What is the MOA of glucocorticoids in the asthma? (3)

Decreased cell leakiness Decreased proliferation of airway smooth muscle Decrease mucus secretion

What is the effect of beta2 agonists on Glucocorticoid receptors?

Increase translocation of GRs, and increase binding of GR to GRE on genes

What is Advair?

Fluticasone + salmeterol

What percent of glucocorticoids are bound to albumin? Is this active?

greater than 90% | This is inactive

What is the effect of glucocorticoid on liver disease?

Lower albumin means more available to work

What is the relative affinity of dexamethasone for albumin? What is the significance of this?

Low Those with liver disease need lower dosages

What are the adverse effects of inhaled glucocorticoids?

Dysphonia Oropharyngeal candidiasis Cough

True or false: inhaled glucocorticoids have a high first pass effect

True--most is swallowed

What is the effect of glucocorticoids on: K levels

Decreased

What is the effect of glucocorticoids on:BP

Increased

What is the effect of glucocorticoids on: growth in children

Decreased

What is the effect of glucocorticoids on: glaucoma

Increased risk

What is the effect of glucocorticoids on: appetite?

Increased

Why does high doses of glucocorticoids cause hypokalemia? Does this happen with dexamethasone?

Hits the glucocorticoid receptor in the kidneys Does not occur with dexamethasone

HPA axis suppression may not return for how long?

Over 12 months

What are the measures to minimize the HPA axis suppression?

Use short acting compounds Low dose Short duration

What is the effect of long term HPA suppression that may lead to death?

Times of stress will not increase BP, with vasodilation, causing death

What are the drugs that induce p450s and thus increase degradation of glucocorticoids?

barbs Carbamazepine Rifampin

What are the drugs that increase the effect of glucocorticoids? Why?

Estrogens/androgen d/t competition for p450s

What is the interaction between cyclosporine and glucocorticoids?

Increase levels by inhibiting each other's metabolism

Why is coadministering glucocorticoid with NSAIDs bad?

Increases the risk of PUDs

Which drugs can glucocorticoids reduce the effects of?

Hypoglycemic drugs BP meds Glaucoma meds

What is the MOA of high dose glucocorticoid causing hypertension/hypokalemia? Would this be caused by dexamethasone?

Oversaturation of 11beta-HSD2, leading to inactivation of

What is the therapeutic use and MOA of ketoconazole?

Inhibits 17 beta hydroxylase

The adrenal cortex regulates what?

BP Na K metabolism

Steroid hormones are secreted by what organ? What are these?

Adrenal cortex Glucocorticoids Mineralocorticoids Androgens

Catecholamines are what? What organ secretes this?

Adrenal medulla | Epi and NE

What is cholesterol converted into once inside the mitochondria? What enzyme converts this?

Pregnenolone via cholesterol desmolase

After pregnenolone is converted from cholesterol by cholesterol desmolase, what is it next converted to? What enzyme does this?

17alpha-hydroxylase converts it to 17alpha-hydroxypregnenolone

17-alpha-hydroxyPregnenolone is converted to what by what enzyme?

Converted into 17 hydroxyprogesterone via 3beta-HSD

17 hydroxyproGesterone is converted to what by what?

11-beta-(OH) | 21-hydroxylase

What is the primary molecule that regulates aldosterone synthesis?

Angiotensin II

Describe the HPA axis in terms of cortisol production?

Diurnal rhythms send signals to the hypothalamus to secrete CRH via the corticotroph cells. CRH causes ACTH release from the pituitary

ACTH binds to what receptor? Where is this located? What does this cause?

MCR2 on the surface of the adrenal cortex, causing an increase in cholesterol import.

Describe the events of the renin-angiotensin axis?

Renin released by kidneys Cleaves angiotensinogen to ang I. ACE converts ang I to II.

How is the HPA axis inhibited with cortisol?

Cortisol will bind to glucocorticoid receptor on corticotrophs

What is the effect of glucocorticoids on plasma glucose levels?

Increases

What is the effect of glucocorticoids on liver gluconeogenesis?

Increases gluconeogenesis enzymes

What is the effect of glucocorticoids on protein synthesis?

Reduces

What is the effect of glucocorticoids on lipolysis?

increases

What is the effect of glucocorticoids on insulin like action?

Inhibits insulin's effects except in the brain and heart

Both cortisol and aldosterone activate the same mineralocorticoid receptor in the adrenal cortex, but cortisol levels are always much higher? How does aldosterone exert its effects? What happens with high exogenous cortisol use?

11beta-HSD2 converts cortisol into inactive cortisone High cortisol levels can saturate the 11beta-HSD2 enzyme, allowing cortisol to bind to the mineralocorticoid receptor, and allowing HTN and hypokalemia

What happens to aldosterone levels in secondary adrenal insufficiency? What is the significance of this?

Stays normal. Does not lead to K retention and Na loss like primary

What is the effect of corticosteroids on the following: phospholipase, COX, NO synthase, cytokine production

All decreases

Adrenal Flashcards

(102 cards)