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)
fluticasone propionate and mometason furorate are usually used as _____ forms due to poor ____
inhaled (or intranasal);
solubility
inhaled glucocorticoids usually have ___ lipophilicity, ____ oral bioavailability, and _____ clearance
high, low (due avoid systemic effects);
rapid
flunisolide and budesonide have extensive ____ ____ _____ and are used as inhaled glucocorticoids
first pass metabolism
mometasone and fluticasone are similar
corticoid side effects:
______emia; wasting of ______; reduced ____ ____ growth; osteoporosis due to inhibition of _____
hyperglyc;
muscles;
long bone;
osteoblasts
cortisol side effects:
fat redistribution leading to _____, ____, and _____;
can unmask _____
central adiposity, moon face, buffalo hump;
type 2 DM
cortisol side effects:
supression of immune system, can cause _____ with inhaled forms;
in GI, increased ____ risk;
CNS ____
oral thrush (candida);
peptic ulcer;
psychosis/depression
2 irreversible side effects of corticosteroids:
cataracts, redistribution of fat
____ disease is adrenal sufficiency.
primary causes = destruction of the ____ ____ by atrophy or Tb.
secondary causes = decreased secretion of _____ due to diseases of the _____.
tertiary disease = due to ____ dysfunction
addison’s;
adrenal cortex;
ACTH, anterior pituitary;
hypothalmic
cushing’s = _____
primary cushings: tumor in ____ cortex
secondary cushings: tumor in ____ = increase in _____
ectopic production of _____
increase in cortisol
adrenal;
pituitary, ACTH;
ACTH
corticosteroids can cause ____ upon withdrawl, causing weakness, ___ blood pressure
adrenal insufficiency;
decreased
