Lecture 8 - Corticosteroids Flashcards
Cortisol affects: what is the acronym?
where is it produced?
A BIG FIB;
adrenal zonula fasiculata
A BIG FIB: A = B = I = G =
increase Appetite;
increase Blood pressure
increase Insulin resistance
increase Gluocneogeneisis, lipolysis, proteolysis (catabolic)
FIB:
F =
I =
B -
decrease Fibroblast activity
decrease Inflammation/Immune response
decrease Bone formation
cortisol release is increased by the action of ____, which is produced by the ___ ____. that hormone is stimulated to be released by ____, which is produced in the ____
ACTH, anterior pituitary;
CRH, hypothalmus
glucocorticoids and ____ are transported in the blood by _____ (______)
progesterone;
corticoid-binding globulin (transcortin)
the first step in steroid hormone synthesis is conversion of cholesterol to _____ via what enzyme? ____ stimulates this enzyme, ____ inhibits it
progenolone;
cholesterol desmoloase;
ACTH, ketoconazole
glucocorticoids receptor is _____. upon binding, the glucocorticoid-receptor complex enters the ____, forms a ____ and becomes a ____ ____, causing an increase in gene transcription
intracellular;
nucleus, dimer;
transcription factor
activated glucocorticoid-receptor dimers bind to DNA sequences called ____. these increase the rate of ____.
GRE’s (glucocorticoid receptor elements);
transcription
glucocroticoids cause an increase in the production of ______, which inhibits ______. this causes a decrease in arachadonic acid production and a decrease in _____
lipocortin;
PLA2;
inflammation
glucorticoids also inhibit the transcription factor ____, causing a decrease in cytokine production. it inhibits IT by _____ it from its DNA binding protein
NFKB;
sequestering
cortisol:
increases glycogen ____.
storage
in ___, the 11B-hydroxyl group and C17-OH group is required for activity. in _____, these groups are less important
cortisol (hydroxycortisone);
mineralcorticoids
corticosteroids end in “___”
sone
hydrocortisone and cortisone are ____ acting
short (half life 10 hours)
dexamethasone and betamethasone are ____ acting
long (48 hours), used for severe inflammation
prednisone, _____, _____, and triamcinolone are interemediate acting (half life ___ hrs)
prednisolone, methylprednisolone; 24
which corticosteroid has large mineralcorticoid activity?
fludrocortisone (can see HTN)
dexa and betamethasone are more _____, accounting for their long half life
lipophillic (increased receptor binding)
triamcinolone has increased _____ and ____ oral bioavailability
hydrophilicity, low
the ____ group at 21 can be modified to make 21-esters. these are ____
hyrdoxyl;
prodrugs
21 ester corticosteroids are usually ____ soluble and/or have increased ____
more;
lipophilicity
21 ____ esters have very high solubility and are used for emergency IV
phosphate
topical glucocorticoids are typically ____ analogues. they have high ____ for fast absorption and minimal ____ _____
halogenated;
lipophillicity (ie acetonide or ester forms)
systemic effects
substitution of a ____ atom for the 21-hyrdoxyl group greatly enhances topical anti-inflammatory activity. often end in _____
chlorine;
propionate (ie clobetasol, halobetasol)
