Lecture 8 - Corticosteroids

Question 1

Cortisol affects: what is the acronym?

where is it produced?

Answer 1

A BIG FIB;

adrenal zonula fasiculata

Question 2

A BIG FIB:
A = 
B =
I = 
G =

Answer 2

increase Appetite;
increase Blood pressure
increase Insulin resistance
increase Gluocneogeneisis, lipolysis, proteolysis (catabolic)

Question 3

FIB:
F =
I =
B -

Answer 3

decrease Fibroblast activity
decrease Inflammation/Immune response
decrease Bone formation

Question 4

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 ____

Answer 4

ACTH, anterior pituitary;

CRH, hypothalmus

Question 5

glucocorticoids and ____ are transported in the blood by _____ (______)

Answer 5

progesterone;

corticoid-binding globulin (transcortin)

Question 6

the first step in steroid hormone synthesis is conversion of cholesterol to _____ via what enzyme? ____ stimulates this enzyme, ____ inhibits it

Answer 6

progenolone;
cholesterol desmoloase;

ACTH, ketoconazole

Question 7

glucocorticoids receptor is _____. upon binding, the glucocorticoid-receptor complex enters the ____, forms a ____ and becomes a ____ ____, causing an increase in gene transcription

Answer 7

intracellular;
nucleus, dimer;
transcription factor

Question 8

activated glucocorticoid-receptor dimers bind to DNA sequences called ____. these increase the rate of ____.

Answer 8

GRE’s (glucocorticoid receptor elements);

transcription

Question 9

glucocroticoids cause an increase in the production of ______, which inhibits ______. this causes a decrease in arachadonic acid production and a decrease in _____

Answer 9

lipocortin;
PLA2;
inflammation

Question 10

glucorticoids also inhibit the transcription factor ____, causing a decrease in cytokine production. it inhibits IT by _____ it from its DNA binding protein

Answer 10

NFKB;

sequestering

Question 11

cortisol:

increases glycogen ____.

Answer 11

storage

Question 12

in ___, the 11B-hydroxyl group and C17-OH group is required for activity. in _____, these groups are less important

Answer 12

cortisol (hydroxycortisone);

mineralcorticoids

Question 13

corticosteroids end in “___”

Answer 13

sone

Question 14

hydrocortisone and cortisone are ____ acting

Answer 14

short (half life 10 hours)

Question 15

dexamethasone and betamethasone are ____ acting

Answer 15

long (48 hours), used for severe inflammation

Question 16

prednisone, _____, _____, and triamcinolone are interemediate acting (half life ___ hrs)

Answer 16

prednisolone, methylprednisolone; 24

Question 17

which corticosteroid has large mineralcorticoid activity?

Answer 17

fludrocortisone (can see HTN)

Question 18

dexa and betamethasone are more _____, accounting for their long half life

Answer 18

lipophillic (increased receptor binding)

Question 19

triamcinolone has increased _____ and ____ oral bioavailability

Answer 19

hydrophilicity, low

Question 20

the ____ group at 21 can be modified to make 21-esters. these are ____

Answer 20

hyrdoxyl;

prodrugs

Question 21

21 ester corticosteroids are usually ____ soluble and/or have increased ____

Answer 21

more;

lipophilicity

Question 22

21 ____ esters have very high solubility and are used for emergency IV

Answer 22

phosphate

Question 23

topical glucocorticoids are typically ____ analogues. they have high ____ for fast absorption and minimal ____ _____

Answer 23

halogenated;
lipophillicity (ie acetonide or ester forms)
systemic effects

Question 24

substitution of a ____ atom for the 21-hyrdoxyl group greatly enhances topical anti-inflammatory activity. often end in _____

Answer 24

chlorine;

propionate (ie clobetasol, halobetasol)

Question 25

fluticasone propionate and mometason furorate are usually used as _____ forms due to poor ____

Answer 25

inhaled (or intranasal);

solubility

Question 26

inhaled glucocorticoids usually have ___ lipophilicity, ____ oral bioavailability, and _____ clearance

Answer 26

high, low (due avoid systemic effects);

rapid

Question 27

flunisolide and budesonide have extensive ____ ____ _____ and are used as inhaled glucocorticoids

Answer 27

first pass metabolism

mometasone and fluticasone are similar

Question 28

corticoid side effects:

______emia; wasting of ______; reduced ____ ____ growth; osteoporosis due to inhibition of _____

Answer 28

hyperglyc;
muscles;
long bone;
osteoblasts

Question 29

cortisol side effects:
fat redistribution leading to _____, ____, and _____;
can unmask _____

Answer 29

central adiposity, moon face, buffalo hump;

type 2 DM

Question 30

cortisol side effects:
supression of immune system, can cause _____ with inhaled forms;
in GI, increased ____ risk;
CNS ____

Answer 30

oral thrush (candida);
peptic ulcer;
psychosis/depression

Question 31

2 irreversible side effects of corticosteroids:

Answer 31

cataracts, redistribution of fat

Question 32

____ 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

Answer 32

addison’s;
adrenal cortex;
ACTH, anterior pituitary;
hypothalmic

Question 33

cushing’s = _____
primary cushings: tumor in ____ cortex
secondary cushings: tumor in ____ = increase in _____
ectopic production of _____

Answer 33

increase in cortisol
adrenal;
pituitary, ACTH;
ACTH

Question 34

corticosteroids can cause ____ upon withdrawl, causing weakness, ___ blood pressure

Answer 34

adrenal insufficiency;

decreased