Glucocorticoid Pharm Flashcards
(17 cards)
GC’s with potent antiinflammatory activity but minimal mineralocorticoid activity
Prednisone, Prednisolone (antiinflamm = 4, mc = 0.8); DEXAMETHASONE (Antiinflamm = 30, MC = 0), Triamcinolone (antiinflamm = 5, mc = 0)
Concerns with pre-operative steroid therapy/previous steroid use
- suppression of HPA axis
- impaired wound healing/increased risk of infection
- inc fragility of skin/blood vessels/CT/bone =
- inc risk GI hemorrhage, ulcers, fracture
- hyperglycemia
- HTN
- fluid retention
+ Endogenous cortisol will increase post Sx already!! – additive
difference b/t physiologic and pharmacologic Rx dose/cortisol?
Endogenous «_space;Exogenous ?
Potency, dose/timing, duration, variation in metabolism concerns for GCs?
- high dose parentral tx should NOT cause AE’s
- chronic use = ONLY w/ good evidence of effectiveness
- measure outcomes QUANTITATIVELY
- dose/time = lowest dose/least time
- use non-systemically if possible! – some will always go systemic though! Topical/inhalar GCs = still have systemic adrenal suppression!
Side effects of GC / Length of HPA suppression after steroid use…
IDIOSYNCRATIC! — suppression recovery varies by patient! (weeks to months)
– HPA suppression: suppression of ACTH and TSH production from pituitary
– Osteoporosis, diabetes, peptic ulcers, CNS SE’s
- Men: xGnRH ie hypogonadism
- Women: dysmenorrhea/xOvulation
- Children: impair linear growth rate (xGH/IGF1)
Dexamethasone Suppression Test
Assesing pituitary corticotroph cell response to GC negative feedback
- Low dose = inhibits ACTH / no effect on adrenals
- High dose = ACTH + not effected by dex = ectopic
Why taper GC use?
Avoid acute adrenal insufficiency — atrophied during long term GC use
Addison’s treatment
LIFE THREATENING! – treat and don’t wait for tests
acute = dexamethasone, subacute = acth stim test/tapper GC dose and begin MC tx, Chronic = hydorcortisone @ lowr dose
How do you evaluate HPA axis?
- stop GC for 24 hours
- morning serum cortisol < 5 mcg/dL = impaired, > 10 = continue current GC replacement dose on day of surgery
- 5-10 mcg/dL = do ACTH stimulation – measure cortisol 30 minutes after 250 mcg ACTH administration > 18 mcg/dL = adequate adrenal reserve
Fludrocortisone acetate
- – Aldosterone analog
- SEs: HTN, HypoK+/ electrolyte imbalance, CHF, Cardiomegaly
- Uses: addisons, adrenocortical inssuficiency, adrenogenital syndrome
**GC effects may appear w/ long term use!!
Spironolactone and Epleronone
- – K+ sparing!! — use for CONN’S SYNDROME (hyperaldo which causes HTN and hypoK)
- – Spironolactone: Aldosterone antagonist (MC receptor analog) + anti-androgen effects
- Epleronone = > specificity for MC receptor
- AEs: hyperK+, renal failure
Mifepristone
- GC receptor antagonist
- high doses to tx cushings patients w/ inoperable ectopic ACTH secreting neoplasia / adrenal carcinoma or wo have failed to respond to therapeutic manipulations
Glucocorticoids and DM patients
Can further increase hyperglycemia (dec glucose utilization, inc gluconeogenesis/glycogenolysis in liver)
Systemic effects of GCs
- Redistribution of body fat (truncal)
- CV: HTN (inc Na retention)
- Skeletal muscle: steroid myopathy/muscle weakness due to proteolysis
- CNS: GC tx – euphoria, addisons – apathy, cushings – neuroses/psychoses
- Antiinflammatory: xPhospholipase A2, xCytokine release (IL2, IL6, IL1, TNF), xHistamine release
Most used systemic steroids
Hydrocortisone (skin, GI)
Methylpredinsone (severe allergy)
Dexamethasone (ocular, chronic adrenal insufficiency)
Adrenal cortical Steroid Inhibitors
Ketoconazole
- xCortisol production in Cushings
- uses: adrenal carcinoma, breast/prostate cancer, hirsuitism
- AEs: hepatotoxicity/adrenal insufficiency
Aminoglutethimide
- xp450 + xOverproduction of cortisol + xSteroid production
** both blocks cholesterol –> pregnenolone
minimize GC AE’s?
- local administration
- alternate day therapy
- tapering dose after therapeutic response achieved
