Glucocorticoids Flashcards
Where is exogenous corticosteroid absorbed?
Jejunum
What is the spectrum of glucocorticoid to mineralocorticoid effects for short, intermediate, and long-acting corticosteroids
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.
What effect does food consumption have on oral steroid absorption?
It slows down absorption but does not decrease the amount absorbed
Where in the cell does systemic steroid drugs bind, and where is the effect exerted?
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)
What is the main carrier protein for systemic steroids, and when drug is bound is it inactive or active?
Cortisol-binding globulin is the main protein carrier. When steroids are bound to this they are inactive
What things increase cortisol binding protein (thereby decreasing free corticosteroid fraction)?
Estrogen therapy, pregnancy, and hyperthyroidism
What things decrease cortisol binding protein, thereby increasing free corticosteroid fraction?
hypothyroidism, liver disease, renal disease, and obesity
What is the enzyme in the liver that converts steroids to active forms?
11beta-hydroxysteroid dehydrogenase
What are some examples of inactive/active corticosteroid pairs?
Cortisone (inactive) to cortisol (active)
Prednisone to prednisolone (active form)
[The ol indicated that active form]
These are the two systemic active steroids used
Which systemic steroid should be used in a patient with liver disease?
Likely prednisolone as it is in its active form
What is the primary alteration that corticosteroids induce to affect immunosuppression and antiinflammatory processes?
Mediated via cytokine alteration (decrease proinflammatory cytokines and increase anti-inflammatory cytokines)
What things are decreased in corticosteroid use?
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
What things are increased in corticosteroid use molecularly?
Increased IL-10 (down-regulation of cell-mediated immunity), antiinflammatory proteins (vasocortin, lipocortin, vasoregulin), increased apoptosis of lymphocytes and eosinophils
What is a physiologic level of prednisone?
5-7.5mg/day
Anything more than this is pharmacologic therapy
What is the conversion of cortisone to cortisol (hydrocortisone), prednisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, betamethasone?
25mg cortisone = 20mg cortisol (hydrocortisone) = 5mg (prednisone/prednisolone)=4mg (methylprednisolone/priamcinolone) = 0.75mg (dexamethasone)=0.6-0.75mg (betamethasone)
If you keep somebody on long-term corticosteroid therapy and induce exogenous adrenal insufficiency is the mineralocorticoid axis affected?
No! So it is very rare to get a true Addisonian adrenal crisis with hypotension, coma etc
What is the maximal stress production of endogenous corticosteroid in prednisone equivalents?
60mg
When corticosteroid is given, what part of the HPA axis is the fastest and slowest to be suppressed?
The hypothalamus is the fastest and the adrenal gland is the slowest
What components of the HPA axis recover first when corticosteroid medications are removed? recover last?
Hypthalmus is the quickest to recover, adrenals are the slowest to recover
How long does someone usually have to be on corticosteroid therapy before exogenous adrenal insufficiency is seen?
>3 to 4 weeks
What are some risk factors for exogenous adrenal insufficiency?
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
What type of corticosteroid dosing can be given to decrease the risk of complications?
Every other day dosing decreases the risk of complications including HPA axis suppression, growth suppression, HTN, opportunistic infections and electrolyte disturbances
What two corticosteroid complications are not reduced by every other day dosing?
Osteoporosis and cataracts
What two clinical presentations of exogenous adrenal insufficiency are seen?
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
What are some glucose-based side effects of corticosteroids?
Hyperglycemia and increased appetite/weight gain (stress hormone, increases gluconeogenesis, increases insulin resistance)
What are the lipid effects seen in corticosteroid therapy?
Hypertriglyceridemia (careful for pancreatitis), cushingoid changes (lipodystrophy, stores are mobilized and then deposited elsewhere like the face, posterior neck, and central obesity), menstrual irregularities
Important pediatric concern with glucocorticoid therapy?
Growth impairment (results from decreased growth hormone and IGF-1 production)
This risk can be decreased by every other day dosing
What are some bone effects of corticosteroid therapy?
Osteoporosis: Risk does not go down with every other day dosing.
Osteonecrosis: proximal femur most common area
Hypocalcemia
When does the greatest reduction in bone density occur during corticosteroid therapy?
During the first 6 months
Who loses the most bone mass and who is at the highest risk for fracture during corticosteroid therapy?
Increased fracture risk in post-menopausal women; greatest absolute loss of bone mass in young men as they have the highest baseline bone mass
How long does it take for osteonecrosis to occur with glucocorticoid therapy usually?
2-3 month courses is when this occurs usually
What are some gastrointestinal side effects of corticosteroid therapy?
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
What are some ocular side effects seen with chronic corticosteroid use?
Cataracts (risk not changed with every other day dosing), glaucoma, infections, and refraction changes
Psychiatric side effects of glucocorticoid therapy?
Psychoisis, hypomania, insomnia, agitations and depression
Neurologic side effects of glucocorticoids?
Pseudotumor cerebri, seizures, epidural lipomatosis, and peripheral neuropathy
Risk of infection with corticosteroid therapy?
Increased risk of tuberculosis reactivation, deep fungi, prolonged herpes virus infections, and pneumocystis jiroveci pneumonia
decreased risk with every other day dosing
Muscular side effects of corticosteroid therapy?
Myopathy (proximal lower extremity > others) and muscular atrophy
Cutaneous side effects of corticosteroid therapy?
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
Safety of corticosteroids in pregnancy?
Category C, likely safe for short courses if needed for severe PUPP or gestational pemphigus
What does every other day dosing have a lower side effect profile?
The anti-inflammatory effects last longer than the HPA axis inhibition
good for maintenance once acute disease is controlled but systemics are still needed
What is the advantage and disadvantage of divided daily doses of corticosteroid?
They are more effective, but higher risk of side effect
What are the unique side effects to IM corticosteroid?
Cold abscesses, subcutaneous fat atrophy, crystal deposition, menstrual irrgularities adn purpura
Why do IM corticosteroids lead to greater HPA axis suppression?
Levels are constant through the day, so you get the levels present at night/morning
How many times per year does Wolverton suggest a IM corticosteroid be used max?
For long-acting ones like Kenalog, 3-4x/year max
What is the dosing for pulse dose steroids and which corticosteroid is used?
Usually Methylprednisolone, 500-1000mg (roughly 10-15mg/kg) given over 60 minutes (at least). This is done for 5 consecutive days
What are the indications for pulse dose methylprednisolone?
Systemic vasculitis, systemic lupus erythematosus, pyoderma gangrenosum, and bullous pemphigoid
What monitoring should be performed during a pulse dose of steroids and why?
Cardiac monitoring is recommended: there is a risk for sudden cardiac death, atrial fibrillation
Also, BMP (electrolyte shifts)
Clinically for seizures and anaphylaxis
What is the target layer of the skin for intralesional Kenalog?
The goal is to inject in the dermis, otherwise can get atrophy more commonly
What two patient populations are at high risk of bowel perforation with corticosteroid use?
Bowel anastomosis and patients with active diverticulosis
What patients are at higher risk for getting the peptic ulcer perforation for systemic corticosteroids?
Most likely with adjunctive non-steroidal anti-inflammatory drugs (NSAIDs)s and patients w/ history of peptic ulcer disease.
Consider H2 blocker or PPI if using in someone w/ sx’s or history of PUD
After how long on pharmacologic level of therapy with systemic corticosteroids does osteonecrosis become more worrisome?
Usually for at least 2-3 months
At what point do you implement interventions to prevent bone loss for corticosteroid treatment?
Preventative measures to prevent bone demineralization should be instituted in any patient with a plan to be on corticosteroid for longer than 4 weeks.
Do betamethasone and dexamethasone need the 11beta hydroxysteroid dehydrogenase enzyme to be active?
No, these are active independently from this enzyme
What laps can be considered for monitoring in systemic corticosteroid use >1 month?
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).
