Test 2: 26 steroids Flashcards
glucocorticoids will block — synthesis.
will stimulate synthesis of —
will inhibit — induction
eicosanoid synthesis (Leukotrienes and prostaglandins)
lipocortin I/annexin I (which inhibit PLA2)
NFκB dependent COX2 induction
what are some functions of glucocorticorids in the body
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)
what are some functions of mineralcorticoids
aldosterone
retain Na and water
excrete potassium
raise BP
how do glucocorticoids maintain adequate glucose supply to brain
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
how does HPA axis work
what will GC drugs do to HPA axis
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
how do GC work
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
GCs will lead to the formation of — that are anti-inflammatory genes
lipocortin 1/ annexin
MAP kinase ppase
NFKB inhibitor
GC will lead to downregulation of what pro inflammatory genes?
IL1, IL2
POMC-ACTH
what does lipocortin1/ annexin A1 do
Binds to and inhibits phospholipase A2 (lowers arachidonic acid production)- anti-inflammatory
production is stimulated by GCs
GC will do what to neutrophils and lymphocytes
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
cortisol is made from
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
half life of cortisol
short acting
60-90 mins
cortisol, pred and methylpred are all short acting
how is cortisol metabolized
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)
hypercorticism will suppress — release from the HPA axis
ACTH
will cause atrophy of the adrenal gland = addisons
hypercorticism will do what to sugar, fat and protein?
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
GC will act as a immunosuppression and will cause — wound repair
slow
infections may persist, cause Neutrophils can’t leave blood and lymphoid cells are stuck in lymphoid organs
— is a short acting synthetic GC with a reduced mineralcorticoid activity and 4-5 x more potent then cortisol
prednisolone
(0.3 Na and water retention)
— is a long acting synthetic steroid
dexmethasone (1/2 life over 48 hours)
30x more potent
no salt retention
— is an intermediate synthetic GC
triamcinolone
5 x more potent oral
100 x more potent topical
no salt retention
what are the short acting GC
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)
which GC can be used as topical antinflammatory with 5-100x activity compared to cortisol
triamcinolone
5x oral antinflammatory
acetonide is lipophilic = 5-100x more potent as topical
intermediate acting
(little salt retention)
water soluble esters will be — acting
rapid
phosphate
succinate ester of drug
can give oral, IV, or IM
poorly water souble esters like — will have slower uptake
acetate and diacetate
if oral - rapid uptake cause ester is removed in GI
IM- slower- increases 1/2 life and duration
non water soluble drugs with — will have the slowest uptake
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
In general, the lower the water solubility the GC-ester, the — drug half life/duration in tissues.
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
Most common side effects of short term glucocorticoid therapy
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)
Side effects of long term GC therapy:
Suppression of HPA axis / adrenal atrophy
Cushing’s syndrome (high GC levels)
symptoms of cushings
supression of immune system
poor wound healing
dull/dry hair coat, dry thin skin
decreased muscle mass and tone
repositol
way to give GC to cats that are hard to pill
IM/SC injections
methylprednisolone acetate, triamcinolone acetonide
long lasting (weeks to months)
— are water soluble esters
phosphate
succinate esters
cause rapid uptake, any way it is given
— are poorly water soluble esters
acetate
diacetate
will have slow uptake if given IM or SQ
— are non water soluble esters
acetonide (lipophilic)
diproprionate
will have very slow uptake if given IM or SQ
