Glucocorticoids

Question 1

Where is exogenous corticosteroid absorbed?

Answer 1

Jejunum

Question 2

What is the spectrum of glucocorticoid to mineralocorticoid effects for short, intermediate, and long-acting corticosteroids

Answer 2

Short: decreased glucocorticoid and increased mineralocorticoid (hydrocortisone and cortisone)

Intermediate: as compared to short, increased glucocorticoid and decreased mineralocorticoid activity Prednisone, prednisolone, methylprednisolone, and triamcinolone)

Long: More increased glucocorticoid and the least amount of mineralocorticoid effect.

Question 3

What effect does food consumption have on oral steroid absorption?

Answer 3

It slows down absorption but does not decrease the amount absorbed

Question 4

Where in the cell does systemic steroid drugs bind, and where is the effect exerted?

Answer 4

Glucocorticoid receptor binds the drug in the cytoplasm, then translocates to the nucleus where it binds to nuclear DNA and affects gene regulation/transcription (acts as a transcription factor)

Question 5

What is the main carrier protein for systemic steroids, and when drug is bound is it inactive or active?

Answer 5

Cortisol-binding globulin is the main protein carrier. When steroids are bound to this they are inactive

Question 6

What things increase cortisol binding protein (thereby decreasing free corticosteroid fraction)?

Answer 6

Estrogen therapy, pregnancy, and hyperthyroidism

Question 7

What things decrease cortisol binding protein, thereby increasing free corticosteroid fraction?

Answer 7

hypothyroidism, liver disease, renal disease, and obesity

Question 8

What is the enzyme in the liver that converts steroids to active forms?

Answer 8

11beta-hydroxysteroid dehydrogenase

Question 9

What are some examples of inactive/active corticosteroid pairs?

Answer 9

Cortisone (inactive) to cortisol (active)

Prednisone to prednisolone (active form)

[The ol indicated that active form]

These are the two systemic active steroids used

Question 10

Which systemic steroid should be used in a patient with liver disease?

Answer 10

Likely prednisolone as it is in its active form

Question 11

What is the primary alteration that corticosteroids induce to affect immunosuppression and antiinflammatory processes?

Answer 11

Mediated via cytokine alteration (decrease proinflammatory cytokines and increase anti-inflammatory cytokines)

Question 12

What things are decreased in corticosteroid use?

Answer 12

NFkappaB signally, AP-1, phospholipase A2, eicosanoids (e.g., leukotrienes, prostaglandins, 12-HETE, and 15-HETE), cox-2, the activity of all types of WBC’s, fibroblast activity and prostaglandin production

Question 13

What things are increased in corticosteroid use molecularly?

Answer 13

Increased IL-10 (down-regulation of cell-mediated immunity), antiinflammatory proteins (vasocortin, lipocortin, vasoregulin), increased apoptosis of lymphocytes and eosinophils

Question 14

What is a physiologic level of prednisone?

Answer 14

5-7.5mg/day

Anything more than this is pharmacologic therapy

Question 15

What is the conversion of cortisone to cortisol (hydrocortisone), prednisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, betamethasone?

Answer 15

25mg cortisone = 20mg cortisol (hydrocortisone) = 5mg (prednisone/prednisolone)=4mg (methylprednisolone/priamcinolone) = 0.75mg (dexamethasone)=0.6-0.75mg (betamethasone)

Question 16

If you keep somebody on long-term corticosteroid therapy and induce exogenous adrenal insufficiency is the mineralocorticoid axis affected?

Answer 16

No! So it is very rare to get a true Addisonian adrenal crisis with hypotension, coma etc

Question 17

What is the maximal stress production of endogenous corticosteroid in prednisone equivalents?

Answer 17

60mg

Question 18

When corticosteroid is given, what part of the HPA axis is the fastest and slowest to be suppressed?

Answer 18

The hypothalamus is the fastest and the adrenal gland is the slowest

Question 19

What components of the HPA axis recover first when corticosteroid medications are removed? recover last?

Answer 19

Hypthalmus is the quickest to recover, adrenals are the slowest to recover

Question 20

How long does someone usually have to be on corticosteroid therapy before exogenous adrenal insufficiency is seen?

Answer 20

>3 to 4 weeks

Question 21

What are some risk factors for exogenous adrenal insufficiency?

Answer 21

Abrupt cessation (always taper if course is >4weeks)

Major stressor (surgery, trauma, illness)

Divided dosing (BID/TID)

Daily doses given at any time other than morning

Question 22

What type of corticosteroid dosing can be given to decrease the risk of complications?

Answer 22

Every other day dosing decreases the risk of complications including HPA axis suppression, growth suppression, HTN, opportunistic infections and electrolyte disturbances

Question 23

What two corticosteroid complications are not reduced by every other day dosing?

Answer 23

Osteoporosis and cataracts

Question 24

What two clinical presentations of exogenous adrenal insufficiency are seen?

Answer 24

Steroid withdrawal syndrome (most common): Presents with arthralgias, myalgias, mood changes, headache, fatigue, anorexia, nausea/vomiting. No change in serum cortisol levels but there is decreased intracellular corticosteroid

Adrenal (Addisonian) crisis: Very uncommon. Life-threatening and has sx’s of the withdrawal syndrome above plus hypotension. Decreased levels of cortisol in serum

Question 25

What are some glucose-based side effects of corticosteroids?

Answer 25

Hyperglycemia and increased appetite/weight gain (stress hormone, increases gluconeogenesis, increases insulin resistance)

Question 26

What are the lipid effects seen in corticosteroid therapy?

Answer 26

Hypertriglyceridemia (careful for pancreatitis), cushingoid changes (lipodystrophy, stores are mobilized and then deposited elsewhere like the face, posterior neck, and central obesity), menstrual irregularities

Question 27

Important pediatric concern with glucocorticoid therapy?

Answer 27

Growth impairment (results from decreased growth hormone and IGF-1 production) ## Footnote *This risk can be decreased by every other day dosing*

Question 28

What are some bone effects of corticosteroid therapy?

Answer 28

Osteoporosis: Risk does not go down with every other day dosing. Osteonecrosis: proximal femur most common area Hypocalcemia

Question 29

When does the greatest reduction in bone density occur during corticosteroid therapy?

Answer 29

During the first 6 months

Question 30

Who loses the most bone mass and who is at the highest risk for fracture during corticosteroid therapy?

Answer 30

Increased fracture risk in post-menopausal women; greatest absolute loss of bone mass in young men as they have the highest baseline bone mass

Question 31

How long does it take for osteonecrosis to occur with glucocorticoid therapy usually?

Answer 31

2-3 month courses is when this occurs usually

Question 32

What are some gastrointestinal side effects of corticosteroid therapy?

Answer 32

Bowel perforation, peptic ulcer disease (mostly if total dose is \>1g), H2 inhibitors or PPI can help, fatty liver changes, esophageal reflux, and nausea/vomiting

Question 33

What are some ocular side effects seen with chronic corticosteroid use?

Answer 33

Cataracts (risk not changed with every other day dosing), glaucoma, infections, and refraction changes

Question 34

Psychiatric side effects of glucocorticoid therapy?

Answer 34

Psychoisis, hypomania, insomnia, agitations and depression

Question 35

Neurologic side effects of glucocorticoids?

Answer 35

Pseudotumor cerebri, seizures, epidural lipomatosis, and peripheral neuropathy

Question 36

Risk of infection with corticosteroid therapy?

Answer 36

Increased risk of tuberculosis reactivation, deep fungi, prolonged herpes virus infections, and pneumocystis jiroveci pneumonia ## Footnote *decreased risk with every other day dosing*

Question 37

Muscular side effects of corticosteroid therapy?

Answer 37

Myopathy (proximal lower extremity \> others) and muscular atrophy

Question 38

Cutaneous side effects of corticosteroid therapy?

Answer 38

Decreased wound healing, striae, atrophy, telangiectasia, steroid acne, purpura, infections (staph/HSV), telogen effluvium, hirsutism, pustular psoriasis flare upon withdrawal, perioral dermatitis, contact dermatitis, and hypopigmentation

Question 39

Safety of corticosteroids in pregnancy?

Answer 39

Category C, likely safe for short courses if needed for severe PUPP or gestational pemphigus

Question 40

What does every other day dosing have a lower side effect profile?

Answer 40

The anti-inflammatory effects last longer than the HPA axis inhibition ## Footnote *good for maintenance once acute disease is controlled but systemics are still needed*

Question 41

What is the advantage and disadvantage of divided daily doses of corticosteroid?

Answer 41

They are more effective, but higher risk of side effect

Question 42

What are the unique side effects to IM corticosteroid?

Answer 42

Cold abscesses, subcutaneous fat atrophy, crystal deposition, menstrual irrgularities adn purpura

Question 43

Why do IM corticosteroids lead to greater HPA axis suppression?

Answer 43

Levels are constant through the day, so you get the levels present at night/morning

Question 44

How many times per year does Wolverton suggest a IM corticosteroid be used max?

Answer 44

For long-acting ones like Kenalog, 3-4x/year max

Question 45

What is the dosing for pulse dose steroids and which corticosteroid is used?

Answer 45

Usually Methylprednisolone, 500-1000mg (roughly 10-15mg/kg) given over 60 minutes (at least). This is done for 5 consecutive days

Question 46

What are the indications for pulse dose methylprednisolone?

Answer 46

Systemic vasculitis, systemic lupus erythematosus, pyoderma gangrenosum, and bullous pemphigoid

Question 47

What monitoring should be performed during a pulse dose of steroids and why?

Answer 47

Cardiac monitoring is recommended: there is a risk for sudden cardiac death, atrial fibrillation Also, BMP (electrolyte shifts) Clinically for seizures and anaphylaxis

Question 48

What is the target layer of the skin for intralesional Kenalog?

Answer 48

The goal is to inject in the dermis, otherwise can get atrophy more commonly

Question 49

What two patient populations are at high risk of bowel perforation with corticosteroid use?

Answer 49

Bowel anastomosis and patients with active diverticulosis

Question 50

What patients are at higher risk for getting the peptic ulcer perforation for systemic corticosteroids?

Answer 50

Most likely with adjunctive non-steroidal anti-inflammatory drugs (NSAIDs)s and patients w/ history of peptic ulcer disease. ## Footnote *Consider H2 blocker or PPI if using in someone w/ sx's or history of PUD*

Question 51

After how long on pharmacologic level of therapy with systemic corticosteroids does osteonecrosis become more worrisome?

Answer 51

Usually for at least 2-3 months

Question 52

At what point do you implement interventions to prevent bone loss for corticosteroid treatment?

Answer 52

Preventative measures to prevent bone demineralization should be instituted in any patient with a plan to be on corticosteroid for longer than 4 weeks.

Question 53

Do betamethasone and dexamethasone need the 11beta hydroxysteroid dehydrogenase enzyme to be active?

Answer 53

No, these are active independently from this enzyme

Question 54

What laps can be considered for monitoring in systemic corticosteroid use \>1 month?

Answer 54

Can consider BMP (potassium), fasting lipids (watch the tri's), height/weight for children, DEXA scan, TB test/CXR, and MRI of the hip/should/knee if there is pain during long term (\>3month) therapy).