Corticosteroids Flashcards
glucocorticoids
stress hormones
increase glucose concentrations
anti-inflammatory effects
mineralocorticoids
Na+ retention
increase blood volume
increase blood pressure
cortisol (hydrocortisone)
binds glucocorticoid receptor
long term persistent response
inhibit inflammatory processes
increase energy levels
2 mechanisms of action glucocorticoids
anti inflammatory and immunosupression
glucocorticoid effect in liver
increase gluconeogenesis and glycogen storage
glucocorticoid effect in muscle
promote protein degradation
decrease protein synthesis
decrease sensitivity to insulin
glucocorticoid effect in adipose tissue
promote lipolysis, decrease sensitivity to insulin
glucocorticoid effect on immune system
block cytokine synthesis and inhibit production eicosanoids
immunosuppression and anti-inflammation
Addisons Disease
destruction of the cortex by tuberculosis or atrophy, decreased cortisol and aldosterone production, increased ACTH and CRH
addisons disease symptoms (adrenal insufficiency)
weakness, anorexia, low blood pressure, depression
cessation of long term glucocorticoid therapy can lead to ____
addisonian symptoms
Cushing’s Disease (hyperadrenalism)
tumors in adrenal cortex (adrenal)
pituitary carcinoma (increased ACTH)
non pituitary carcinoma (increased ectopic ACTH)
cushings disease symptoms
increased protein catabolism (brusing, delayed wound healing, muscle wasting)
osteoporosis
infections
long term use of glucocorticoids can lead to ___
cushings symptoms
use of corticosteroids
allerigic reactions, inflammation, autoimmune disease, asthma, immunosuppressive
cortisol active form structure and name
11 beta hydroxy , hydrocortisone
fludrocortisone (structure and use)
mineralocorticoid therapy, 9 alpha F
prednisone/prednisolone (strucutre, activity)
extra double bond 1,2, greater glucocorticoid activity and increased selectivity
methylprednisolone (structure, activity)
6 alpha methyl group, greater glucocorticoid activity, reduced mineralocorticoid activity
triamcinolone (structure, activity)
9 alpha F and 16 alpha OH, powerful glucocorticoid, OH reduces MR, F enhances GR potency
dexamethasone (structure, activity)
16 alpha methyl group, increased lipophillicity, increased receptor binding, reduced MR activity
betamethasone (strucutre and activity)
16 beta methyl, enantiomer dexamethasone
21 esters modifications
acetate - COCH3, -COC3H7, lipophillic
succinate - -COCH2CH2COO, soluble
phosphate - PO2, increased solubility for emergencies
triamcinolone acetonide
resistant to hydrolysis, 8 x more potent prednisolone
beclomethasone dipropionate
converted rapidly during hydrolysis
14x more potent than dexamethasone
flunisolide
rapid first pass metabolism by liver, minimal systemic adverse effects
budesonide
low oral bioavailability, first pass metabolism
mometasone furoate
highly potent, rapid metabolism
fluticasone propionate
rapid first pass metabolism, lipophillic not soluble
desired properties of inhaled glucocorticoids
high potency, minimal systemic effects, prolonged action
glucocorticoids with ___ potency are safest for chronic application
low
triamcinolone acetonide (topical, good lipophillicity, esters)
fluocinonide (topical, good lipophilicity, esters)
betamethasone valerate (medium potency, good lipophillicity, esters)
what groups make topical glucocorticoids more potent
halogenated
21 chlorocorticoids
enhanced topical anti inflammatory activity
