Test 2: 26 steroids

Question 1

glucocorticoids will block — synthesis.
will stimulate synthesis of —
will inhibit — induction

Answer 1

eicosanoid synthesis (Leukotrienes and prostaglandins)

lipocortin I/annexin I (which inhibit PLA2)

NFκB dependent COX2 induction

Question 2

what are some functions of glucocorticorids in the body

Answer 2

cortisol and corticosterone

– Regulate blood sugar levels (keeps brain fed)
– Regulate protein, fat, carbohydrate metabolism
– Suppress inflammatory response
– Regulated by ACTH from adenohypophysis (anterior pituitary)

Question 3

what are some functions of mineralcorticoids

Answer 3

aldosterone

retain Na and water
excrete potassium
raise BP

Question 4

how do glucocorticoids maintain adequate glucose supply to brain

Answer 4

will make glucose from other tissues
increases liver glycogen deposition
increased insulin secretion
decreased cellular uptake of glucose
inhibit glucose uptake by peripheral fat cells
increased fat deposition at abdomen

natural GC have some mineralocorticoid activity= Na retention and K and H excretion

Question 5

how does HPA axis work

Answer 5

Question 6

what will GC drugs do to HPA axis

Answer 6

the steroids will tell the pituitary and the hypothalamus to stop releasing CRH and ACTH

a decrease in ACTH will lead to adrenal atrophy from dissuse

Question 7

how do GC work

Answer 7

float around blood as bound or unbound

unbound steroids will diffuse into cell, bind with intracellular receptor

this will dimerize and cause DNA activation- leading to formation of protein

Question 8

GCs will lead to the formation of — that are anti-inflammatory genes

Answer 8

lipocortin 1/ annexin
MAP kinase ppase
NFKB inhibitor

Question 9

GC will lead to downregulation of what pro inflammatory genes?

Answer 9

IL1, IL2
POMC-ACTH

Question 10

what does lipocortin1/ annexin A1 do

Answer 10

Binds to and inhibits phospholipase A2 (lowers arachidonic acid production)- anti-inflammatory

production is stimulated by GCs

Question 11

GC will do what to neutrophils and lymphocytes

Answer 11

neutrophils:
* decrease in # at site of inflammation
* increase in over number in the blood

lymphocytes
* decrease in number in the blood
* cause lymphoid cells to move to lymphoid organs and get stuck there

CG will suppress the immune system

Question 12

cortisol is made from

Answer 12

cholesterol

short 1/2 life (60-90 mins)

80% bound to plasma proteins (CBG)
20% free or loosely bound to albumin

CBG made by liver, if pt has liver failure there will be more free cortisol in the system

Question 13

half life of cortisol

Answer 13

short acting
60-90 mins

cortisol, pred and methylpred are all short acting

Question 14

how is cortisol metabolized

Answer 14

small amount excreted in urine unchanged

20% converted to cortisone in kidney

most inactivated and metabolized in the liver by glucuronic acid (cats can not do this) →then excreted in the urine

60-90 min half life in plasma (short)

Question 15

hypercorticism will suppress — release from the HPA axis

Answer 15

ACTH

will cause atrophy of the adrenal gland = addisons

Question 16

hypercorticism will do what to sugar, fat and protein?

Answer 16

will cause hyperglycemia and increased insulin requirements

will cause weight gain in the trunk

will eat away at muscles and bone and skin for sources of glucose

Question 17

GC will act as a immunosuppression and will cause — wound repair

Answer 17

slow

infections may persist, cause Neutrophils can’t leave blood and lymphoid cells are stuck in lymphoid organs

Question 18

— is a short acting synthetic GC with a reduced mineralcorticoid activity and 4-5 x more potent then cortisol

Answer 18

prednisolone

(0.3 Na and water retention)

Question 19

— is a long acting synthetic steroid

Answer 19

dexmethasone (1/2 life over 48 hours)
30x more potent
no salt retention

Question 20

— is an intermediate synthetic GC

Answer 20

triamcinolone
5 x more potent oral
100 x more potent topical
no salt retention

Question 21

what are the short acting GC

Answer 21

cortisol
prednisone (4 x more potent, 0.3 salt retention)
prednisolone (4-5 x more potent, 0.3 salt retention)
methylprednisolone (4-5 x more potent, no salt retention)

Question 22

which GC can be used as topical antinflammatory with 5-100x activity compared to cortisol

Answer 22

triamcinolone

5x oral antinflammatory

acetonide is lipophilic = 5-100x more potent as topical

intermediate acting
(little salt retention)

Question 23

water soluble esters will be — acting

Answer 23

rapid

phosphate
succinate ester of drug

can give oral, IV, or IM

Question 24

poorly water souble esters like — will have slower uptake

Answer 24

acetate and diacetate

if oral - rapid uptake cause ester is removed in GI
IM- slower- increases 1/2 life and duration

Question 25

non water soluble drugs with — will have the slowest uptake

Answer 25

acetonide and diproprionate

slowest - if given IM

if oral- will have fast uptake cause esters are removed in GI tract

In general, the lower the water solubility the GC-ester, the longer drug half life/duration in tissues; Poorly soluble and insoluble GCs are slower acting and longer lasting than water soluble GCs – due to slow cellular uptake

Question 26

In general, the lower the water solubility the GC-ester, the — drug half life/duration in tissues.

Answer 26

longer

Poorly soluble and insoluble GCs are slower acting and longer lasting than water soluble GCs – due to slow cellular uptake

triamcinolone has acetonide that makes it lipophilic → intermediate 1/2 life

Question 27

Most common side effects of short term glucocorticoid therapy

Answer 27

Increased susceptibility to infection
* Increased urination (polyuria) and thirst (polydipsia)
* Increased appetite (polyphagia)
* Behavioral -mood changes (depression, aggression, panting)
* Diarrhea
* Development of pancreatitis
* Dogs- hepatomegaly (from increased glycogen production)

Question 28

Side effects of long term GC therapy:

Answer 28

Suppression of HPA axis / adrenal atrophy
Cushing’s syndrome (high GC levels)

Question 29

symptoms of cushings

Answer 29

supression of immune system
poor wound healing
dull/dry hair coat, dry thin skin
decreased muscle mass and tone

Question 30

repositol

Answer 30

way to give GC to cats that are hard to pill

IM/SC injections

methylprednisolone acetate, triamcinolone acetonide

long lasting (weeks to months)

Question 31

— are water soluble esters

Answer 31

phosphate
succinate esters

cause rapid uptake, any way it is given

Question 32

— are poorly water soluble esters

Answer 32

acetate
diacetate

will have slow uptake if given IM or SQ

Question 33

— are non water soluble esters

Answer 33

acetonide (lipophilic)
diproprionate

will have very slow uptake if given IM or SQ