Glucocorticoids Flashcards
Mechanism of GC action (2)
- turns off COX2 synthesis
2. turns on synthesis of product that inhibits PLA2
The long term administration of large doses of prednisone will cause the least reduction in the synthesis of….
a. cortisol
b. ACTH
c. CRF
d. Aldosterone
e. GH
D. aldosterone
GCs effects of vascular events?
reduced vasodilation
decreased fluid exudation
GCs effects on cellular events?
decrease in accumulation / activation of inflammatory immune cells
GCs effects on inflmmatory immune mediators
decrease
GC block (immune elements?
T cell activation
Cytokine production
eosinophil mediator release
mast cell mediator release
GC and 11 keto vs 11 hydroxyl?
11 keto can’t be topical because must be activate in liver to 11 hydroxyl
which two glucocorticoids are 11keto
prednisone
cortisone
A patient with dehydration and hyponatremia would most benefit from?
a. dexamethasone
b. prednisone
c. prenisolone
d. fludrocortisone
e. triamcinolone
fludrocortisone because increases MC activity
liver GC metabolism?
activating converts cortisone to cortisol 11b-hsd1
kidney GC metabolism
inactivating converts cortisol to cortisone 11b-hsd2
fetus GC metabolism
only has 11B-HSD2 (inactivator)
adverse effects of pharmacologic doses unlikely to be seen with dexamethasone but possible with prednisone are? (2)
fluid retention and
hypokalemia
because prednisone has some MC activity whereas dexamethasone has none
hydrocortisone
GC effect? IS effect? Topical? MC? Potency? Forms?
hydrocortisone is basically cortisol
it’s anti-inflammatory effect is the reference - 1 GC/IS; it’s topical activity is 1; its salt retaining activity is 1; and its potency is 20;
comes in oral, injectable, and topical forms
thus must be 11ox
cortisone relative to hydrocortisione?
slightly less AI (GC/IS) activity 0.8; no topical activity (11=o); slightly less MC 0.8; Potency 25eod; only oral
prednisone relative to hydrocortisone?
4x AI (GC/IS)
No topical (11=O)
0.3 MC
Potency 5 eod (relative to 20)
methylprednisone relative to hydrocortisone
5x AI (GC/IS) 5x topical (11-oh) MC = 0 Potency = 4 relative to 20 oral/injectable
triamicinolone relative to hydrocortisone
5X AI (GC/IS) Topical 5^3 No MC Potency 4 relative to 20 oral/injectable/topical
dexmethasone
30x AI (GC/IS) 10x topical 0 MC potency 0.75 relative to 20 oral/injectable/topical
fludrocortisone
what is it?
mineralocorticoid
10x AI (GC/IS)
0 topical
250 MC
Cortisol
when used?
GC:MC?
Admin
physiologic doses –> replacement therapy - emergencies
GC:MC 1:1
Administered orally and parenterally
Prednisone
when?
GC:MC
Admin?
Most commonly used oral agent for steroid burst therapy
GC:MC (5:1)
Activated to prednisolone in liver (no topical activity)
Methylprednisolone IV = Oral = use? benefit?
IV = solu-medrol
Oral = medrol
for steroid burst
minimal MC action
Dexamethasone
use?
GC:MC
Unique?
Most potent anti-inflammatory
use: cerebral edema; chemo nausea
minimal MC
Greatest suppression of ACTH
Tramcinolone
use?
GC:MC?
potent systemic agent with excellent topical activity
no MC action
Wasp reaction; which corticosteroid admin would be appropriate?
Gradually decreasing doses over several days
What is rationale behind alternate day schedule?
minimize adrenal suppression - anti-inflammatory action outlasts HPA suppression
What is rationale behind gradual termination?
minimize disease rebound and potential for symptoms of adrenal insufficiency
what is the primary clinical advantage to alternate day gc therapy?
minimizes gc block of acth release, which can reduce adrenal atrophy
which two steroids we considered would not be appropriate for derm?
cortisone
prednisone
adverse effects of GC use?
adrenal gland suppression
iatrogenic cushings
adverse mc effects
adverse mc effects
hypertension
hypokalemia
metabolic alkalosis
acute, short course, high dose mc effects
salt and water retention –> edema –> hypertension and hypokalemia
acute, short course, high dose gc effects
glucose intolerance in diabeteics, mood changes, insomnia, gi upset
high dose sustained therapy gc effects (4)
iatrogenic cushings
hpa axis suppression
mood disturbance
impaired wound healing / increased susceptibilty to infection
iatrogenic cushing?
hyperglycemia, protein wasting, lipid deposition, diabetes like state
hpa-axis suppression –>
insufficient stress response
more suppression with dexamethasone and betamethason
may also cause decrease in acth, gh, tsh, lh, sex steroids
osteoperosis is possible with large cumulative doses of GC, how would we treat?
bisphosphonates
peptic ulcers are possible with large cumulative doses of GC, how would we minimize risk?
antacids
which of the following is a pharmacologic effect of exogenous glucocorticoids?
a. increased muscle mass
b. hypoglycemia
c. inhibition of leukotriene synthesis
d. improved wound healing
e. increased excretion of salt and water
c
