Glucocorticoids and Mineralocorticoids

Question 1

Where are the following produced?

1. Mineralocorticoids (Aldosterone)
2. Glucocorticoids (Cortisol)
3. Androgens

Answer 1

1. Zona glomerulosa
2. Zona Fasciculata
3. Zona reticularis

Question 2

What are the two main effects of glucocorticoids (cortisol)?

Answer 2

1. Decr inflammation
2. Incr Glucose

Question 3

Physiological Effects of glucocorticoids (Cortisol effects)

1. Increases ____ by ___
2. _____ of skin, muscle, blood vessels –> ___ –>_____
3. how do they make fatty acids for cellular fuel?
4. Has a role in your ___

Answer 3

1. cellular fuel sources, gluconeogenesis
2. proteolysis , amino acids, gluconeogenesis
3. lipolysis
4. appetite

Question 4

What are the symptoms of deficiency of cortisol (glucocorticoids)?

Name 2

Answer 4

1. tendency for hypoglycemia
2. weight loss, nausea, anorexia

Question 5

Sx’s of excess of cortisol (glucocorticoids)?

Name 4 !

Answer 5

1. Insulin resistance and insulinemia ; tendency for hyperglycemia
2. stria in skin, limb muscle wasting, bruising
3. central deposition of fat
4. weight gain

Question 6

Name the normal organ functions for Cortisol effects (4)

Name (3) things that happen when you’re deficient of cortisol

Name (4) things that happen when you’re in excess of cortisol

Answer 6

1. Maintains Alpha receptor expression
2. RBC formation
3. Bone formation and maintenance
4. Muscle function
5. hypotension
6. anemia
7. weakness
8. mild hypertension
9. easy bruising
10. poor growth or osteoporosis
11. muscle weakness due to wasting

Question 7

Name the usual cortisol anti inflam effects (2)

Name 2 symptoms of deficiency

Name 2 symptoms of excess

Answer 7

1. decr production of inflamm mediators (pro inflamm cytokines, PLA2)
2. decr T cell response
3. exaggerated immune response
4. fever
5. decr immune response
6. incr susceptibility to infections

Question 8

How do glucocorticoids incr gene expression?

Answer 8

glucocorticoid comes and binds to GR (nuclear receptor) which is in cytosol
GR is bound to HSP, but when cortisol binds the HSP goes away and then the complex goes to nucleus.
It then binds DNA –> dimerizes –> acts as a TF

Question 9

How do glucocorticoids decr gene expression?

Answer 9

Cortisol binds GR. HSP goes away. Goes to nucleus where NFKB (TF for inflammatory cytokine genes) has co-activator bound. Transcription is activated, GR+cortisol competes to push out the coactivator –> Transcription now suppressed

Question 10

explain the regulation of aldosterone release?

Include AGT, ANG1, ANG 2, and aldosterone in answer. Include neg feedback regulation and how serum K affects aldosterone

Answer 10

RAAS system activated by decrease in blood pressure. If BP goes down, increase renin which converts angiotensinogen to ANG1, then ACE converts ANG1 to ANG2 which binds AT1 receptors in adrenal cortex –> ALDOSTERONE!

ANG 2 has neg feedback on renin to decrease it.
High serum K increases aldosterone. Aldosterone works to decr serum K by incr K excretion and incr Na/H2O retention to raise BP

Question 11

Aldosterone effects :
1. Increases ___ and with ___ present, ___ follows

2. Increases ____
3. Symptoms of deficiency? (3)
4. Symptoms of excess? (3)

Answer 11

1. sodium reabsorption, ADH, water
2. potassium excretion
3. hypotension ; compensatory high ADH –> hyponatremia ; hyperkalemia
4. Hypertension ; compensatory low ADH –> hyPERnatremia ; HYPOkalemia

Question 12

How does aldosterone ( a mineralocorticoid) act on ENAC, SGK1, and the Na/K ATPase?

Answer 12

1. Increases SGK1 expression (Ub ligase)
2. Inhibits proteasomal degradation of ENAC which incr Na reabs, and incr K excretion in urine
3. activates Na/K ATPase –> more K inside cell that can leave through ROMK channel –> excrete more potassium

Question 13

Overall, the net effect of mineralocorticoids is? (2)

Answer 13

1. INCR na reabsorption
2. INCR K+ excretion

Question 14

What’s cortisol’s (glucocorticoid) activity at the MR and GR?

What happens when cortisol acts at both of these receptors?

What ensures that aldosterone can act at MR without cortisol interfering?

Answer 14

Cortisol has equal activity at both MR and GR

Aldosterone may not have equal opportunity to act at the MR

B-11-HSD2 (11 beta hydroxysteroid dehydrogenase) makes cortisone (inactive) from cortisol! Cortisol now inactive , cant act on MR

Question 15

Indications for Corticosteroids : Addison’s (replacement therapy)

What happens in this disease?

Answer 15

Primary adrenal insufficiency (damaged adrenal gland)

• does not make enough cortisol, no negative feedback, so INCR ACTH and CRH
• Very little mineralocorticoids (Aldosterone), cortisol, AND sex steroids (androgens)

Question 16

What are the symptoms of addison’s disease? (4)

Answer 16

1. hypoglycemia
2. postural hypotension
3. weight loss
4. weakness

Question 17

Indications for corticosteroids : Congenital Adrenal disorder (replacement therapy)

What is it? what is incr or decr?

Answer 17

Several enzyme defects that do not allow you to make cortisol. Consequence –> ACTH and CRH are increased.

As ACTH is up, adrenal gland also grows .

Question 18

What does the dexamethasone test do?

Answer 18

It mimics cortisol. Give dexamethasone to see if CRH and ACTH go down (it should).

If CRH and ACTH go down, so should cortisol.
If your cortisol is still elevated, u have an issue with HPA axis

Question 19

Corticosteroids : Adverse effects

Generally develop with?

Even large doses have ?

Answer 19

Extended use

minimal AE’s when administered once or twice

Question 20

What are the side effects of corticosteroids in clinical use? (10)

M + I, M, I, F, O, H, N, T, A, T +P+B

Answer 20

1. mood disturbances and insomnia
2. moon face
3. incr susceptibiity to infection
4. fat deposit on face and back of shoulders
5. osteoporosis
6. HYPERGLYCEMIA
7. Na and Fluid retention
8. Thin extremities
9. Abdominal fat deposits
10. thin skin, purple striae, bruises+petechiae

Question 21

For the following corticosteroid ae’s, describe the management techniques?

1. HPA suppression
2. weight gain
3. glucose intolerance
4. edema/hypertension
5. hypokalemia
6. osteoporosis
7. ulcer/gi bleeding

Answer 21

1. tapering and alternate day therapy
2. monitor daily caloric intake
3. diabetic diet
4. restrict sodium intake
5. K+ suppls
6. Calcium/Vit D, Biphosphanates
7. Avoid nsaids

Question 22

Why must you taper your patient off of corticosteroids instead of just stopping the dosing all together (cold turkey)?

Answer 22

Prednisone (corticosteroid) works at receptors in pituitary and hypothalamus. CRH and ACTH BOTH GO DOWN so the adrenal gland shrinks and makes very little endog androgens, cortisol, and aldost.

Question 23

What is another endocrine disorder that is an indication for corticosteroid use?

What are the inflammatory disorders (non endocrine) that are indications for corticosteroid use? (4)

Corticosteroids used as immunosuppressant therapy in which disease states? (3)

Answer 23

Diagnosis of cushing’s syndrome (primary hyper cortisolism)

1. osteoarthritis
2. ulcerative colitis + Crohn’s
3. RHINITIS
4. asthma
5. Rheumatoid arthritis
6. Multiple schlerosis
7. organ transplant

Question 24

CI and precautions for corticosteroid usage?
(8)
S,D,P,O,H,C,P,C

Answer 24

Systemic infections (Tb , herpes lesions)
Diabetes mellitus, peptic ulcer, osteoporosis , heart failure + hypertension, cataracts and glaucoma, pregnancy, CNS disorders (psychosis)

Question 25

Corticosteroids interactions with? 1. Nsaids 2. Diabetic agents 3. Drugs affecting potassium levels 4. anti hypertensive medications

Answer 25

1. Associated with GI irritation and ulcerations 2. hyperglycemia associated with glucocorticoids requires close monitoring 3. diuretics + digoxin 4. Corticosteroids may cause incr in BP due to sodium and water retention

Question 26

Interactions of corticosteroids with CYP inducers like phenytoin and phenobarb? CYP inhibitors like ritonavir + ketoconazole? Also has interactions with?

Answer 26

1. enhance clearance of corticosteroids 2. incr plasma levels of corticosteroids 3. live vaccines

Question 27

Dosing considerations for corticosteroids?

Answer 27

Dose first thing in morning before 9AM bc adrenal glands secrete most of corticosteroids in morning

Question 28

1. You should only treat your patient with Glucocorticoids in the following? (3) 2. treat your pt with gluco + mineralocorticoids in the following?

Answer 28

Non endocrine disorders such as : Inflammatory disorders + immunological disorders Endocrine disorders : Diagnosis of cushing's syndrome 2. Endocrine disorders that need replacement therapy like the treatment of adrenal insufficiency, and congenital hyperplasia

Question 29

Speak about the glucocorticoid (anti inflamm potency) and mineralocorticoid potency (Na retaining potency) for the following 1. Hydrocortisone + cortisone 2. Fludrocortisone 3. Prednisone + Methylprednisolone 4. Triamcinolone, betamethasone, dexamethasone

Answer 29

1. weak gluco + weak mineralo 2. potent gluco + potent mineralo 3. potent gluco + Weak mineralo 4. Potent gluco + NO MINERALO

Question 30

Routes of admin : 1. parenteral used for? 2. oral used for? 3. Non systemic like topical/inhaled/intranasal?

Answer 30

1. used for emergencies 2. chronic therapy 3. used to minimize systemic effects like inhalation for asthma, topical for inflamm skin disorders

Question 31

For the following state their routes of admin? 1. hydrocortisone 2. cortisone 3. fludrocortisone 4. prednisone 5. methylprednisolone 6. triamcinolone 7. betamethasone 8. dexamethasone

Answer 31

1. po, injectable, topical 2-4 --> oral , po 5. po + injectable 6. po, injectable, topical, inhalatioon 7. po, injection, topical 8. po, injection, topical

Question 32

For Parenteral glucocorticoids like : hydrocort, methylpred, triam, beta, and dexa, what are they mainly used for? Agent of choice?

Answer 32

1. mainly used for emergencies (acute adrenal crisis) 2. hydrocortisone bc has both GC and MC activity

Question 33

Oral Glucocorticoids : Hydrocortisone , prednisone, methylpred, dexameth --> Used for 1. ___ insufficiency 2. __ and __ diseases (Asthma, IBD,RA) 3. Solid ____ for ___ 4. C___ especially for certain lymphoid malignancies

Answer 33

1. adrenal 2. inflamm and autoimmune 3. organ transplantation , immunosuppression 4. chemotherapy

Question 34

Inhaled Glucocorticoids : triamcinolone Clinical uses (3)? Specific AE"s for Triamcinolone?

Answer 34

1. Asthma, inhaled 2. allergic and non allergic rhinitis (nasal inhalation) 3. COPD , inhaled Oropharyngeal candidiasis throat irritation

Question 35

Topical Glucocorticoids : Hydrocorti, triam, beta, dexa In general, safest for ___ Clinical use? (2)

Answer 35

1. chronic application 2. inflamm dermatoses (Eczema and psoriasis)

Question 36

Mineralocorticoid Agonists: FLUDROCORTISONE 1. clinical use? 2. MOA? 3. AE's? (3)

Answer 36

1. adrenal insufficiency (Addison's ) 2. V potent Mineralocorticoid ; primary used for its mineralocorticoid effects 3. salt and fluid retention, hypertension, HF

Question 37

MC Receptor Antagonist : Spironolactone 1. Clinical uses , (3)? 2. MOA? 3. Ae's (3) ?

Answer 37

1. Primary Hyperaldosteronism hypokalemia, HF 2. Antag at Mineralocorticoid receptor 3. Hyperkalemia, hyponatremia, Gynecomastia