Glucocorticoids and Mineralocorticoids Flashcards
what are some of the sex steroids?
estrogens
progesterone
testosterone
what do anabolic steroids promote?
protein synthesis and hence muscle mass
marginal success in stimulating bone marrow in anemic animals
do synthesized anabolic steroids used in medicine have reproductive side effects?
yes- fewer than testosterone
what are corticosteroids?
name implies steroids derived from adrenal cortex
mineralocorticoids and glucocorticoids
what are the two main steroid groups derived from the cortex?
mineralocorticoids: aldosterone
glucocorticoids: cortisol
when is cortisol released?
response to stress and low blood glucocorticoid levels
what are the functions of cortisol?
increase blood sugar through gluconeogenesis
suppress immune system
aid in fat, carbohydrate, and protein metabolism
reduce bone formation
what does an excess of cortisol lead to?
Cushing’s disease
what does a deficiency of cortisol lead to?
Addison’s disease
where does aldosterone act?
acts on distal tubules and collecting ducts of the nephron to resorb sodium and excrete potassium
what is the net effect of aldosterone?
increased water retention and blood pressure
what are two drugs that are intended for use as mineralocorticoids?
fludrocortisone
desoxycorticosterone pivalate
what drugs have pure glucocorticoid effects?
dexamethasone
betamethasone
flumethasone
what drugs have incidental or additive mineralocorticoid effects?
prednisolone
predef 2X (isoflupredone)
how do you convert a predisone dose to dexamethasone dose?
divide your pred dose by 7
the potency factor of pred is _____ times cortisol and dex is _____ times
4
30
what is the biological half-life of predisolone?
12-36 hours (intermediate)
what is the biological half-life of dexamethasone?
26-54 hours (long)
what describes IV drugs?
water soluble
can be given IV
duration controlled by biological half-life
what describes IM drugs?
water insoluble
given IM
duration controlled by rate of absorption (usually lasts 2-4 weeks)
what are the expected side effects of glucocorticoids?
PU/PD/PP (polyphasia)
panting
alopecia/hair thinning
increased ALP and vacuolar hepatopathy
what are unusual (important) adverse effects of glucocorticoids?
inhibit wound healing
increased susceptibility to infection
diabetes
laminitis in horses
GI ulceration
may cause abortion
in which species do we expect ALP to increase with glucocorticoids?
dogs
not cats
what is budesonide?
glucocorticoid
what does budesonide do?
dissolves in duodenum to provide local anti-inflammatory activity
suppresses HPA axis
what is oral budesonide good for orally?
gastrointestinal and potentially hepatic disease
what is fluticasone?
inhaled glucocorticoid in dogs and cats
what is important to think about with dosing cats on glucocorticoids?
much more resistant to side effects
require 2x dose as dog for same anti-inflammatory effect
dose not absorb predisone well (use prednisolone)
what is important to think about with horses on glucocorticoids?
does not absorb predisone well (use prednisolone)
certain steroids are more prone to predispose to laminitis
what is important to think about with cattle on glucocorticoids?
prone to abortion/induction of parturition from certain steroids in last half of gestation and especially in last month of gestation
what is desoxycorticosterone pivalate?
pure mineralocorticoid
how do you dose desoxycorticosterone pivalate?
pivalate repository formulation allows dosing every 21-30 days
what is desoxycorticosterone pivalate used to treat?
hypoadrenocorticism
what is fludrocortisone acetate (Florinef) used for?
oral mineralocorticoid as alternative to DOCP
also glucocorticoid action: PU/PD
hypoadrenocorticism
what are the adverse effects of mineralocorticoids?
few
PU/PD
hypertension
hypokalemia
DOCP, rare: anemia, anaphylaxis, injection site reaction
what happens in Addison’s disease?
adrenals do not produce enough of their intended steroid products: glucocorticoids, mineralocorticoids
often both, sometimes isolated
what do we supplement with Addison’s disease?
mineralocorticoids
glucocorticoids
what does mineralocorticoid supplementation replace?
aldosterone
what does glucocorticoid supplementation mimic?
cortisol
what can be given during initial stabilization of Addison’s disease that does not react with the cortisol assay?
dexamethasone
what drug is preferred for glucocorticoid supplementation?
prednisolone
what is the dosing range for prednisolone for Addison’s?
0.1-0.4 mg/kg
taper to no signs PU/PD/PP
how are mineralocorticoid dosages adjusted for an addisonian?
based on serum Na and K
what are glucocorticoid dosage adjustments based on in an addisonian?
clinical signs
do you ever need to change the glucocorticoid dose for an Addison’s disease animal after finding a good dose?
yes: more glucocorticoids during times of stress
2-3x maintenance dose
how do glucocorticoids have an anti-inflammatory effect?
increase production of inhibitory protein lipocortin which inhibits phospholipase A2 within arachidonic acid cascade
reduces inflammatory gene transcription
reduces macrophage phagocytosis
inhibits complement
how do you dose dogs for anti-inflammatory therapy using glucocorticoids?
begin at 1 mg/kg/day, taper down until signs controlled
0.5-1 mg/kg pred usually
what dose of prednisolone do cats usually need to accomplish anti-inflammatory therapy?
1-2 mg/kg
what is immunosuppressive dosing used for?
used to treat most immune-mediated diseases
when treating for immunosuppression, how do you dose a dog and a cat?
begin 2 mg/kg/day pred and taper over weeks to months
cats 2-4 mg/kg prednisolone may be needed to accomplish same thing
why must a steroid be reduced gradually after being used for longer than a couple of weeks?
to avoid iatrogenic hypoadrenocorticism crisis
how are steroids used for antineoplastic effects?
prednisone/prednisolone can be sole palliative treatment for lymphoma (different if doing chemo)
effective against other round cell tumors like multiple myeloma and mast cell tumor
palliative for other neoplasias, though NSAIDs often recommended for carcinomas
when should you not give a patient steroids?
fungal and viral infections
gastrointestinal ulceration
osteoporosis
late pregnancy
corneal ulcers
diabetes mellitus (relative)
procoagulant states (relative)
why should we not use steroids for a patient with a fungal infection (systemic mycoses)?
diseases held in check by cell-mediated immunity: severely inhibited by steroids
why should we not use steroids in patients with gastrointestinal ulceration?
may result in ulcer development or aggravate an existing ulcer
is it okay to use NSAIDs and steroids together?
no
significant risk of ulceration/perforation if used together
what animals are most prone to steroid-induced abortion?
cattle
mid-gestation on, especially last month
why should you be hesitant to use steroids in a patient with diabetes mellitus?
glucocorticoids have an anti-insulin effect
regulation of diabetic difficult
what is an aldosterone antagonist?
spironolactone
what antagonizes cortisol synthesis?
trilostane (vetoryl): inhibits enzyme in cortisol synthesis pathway
mitotane (lysodren): adrenolytic; cytotoxic to adrenal zona fasciculata and reticularis
what is a dopamine agonist?
pergolide mesylate
dexamethasone is __________ as potent as prednisone
7 times
true/false: steroids are used to enhance wound healing
false
are mineralocorticoids or glucocorticoids used primarily for hypoadrenocorticism?
mineralocorticoids
what does corticotropin releasing hormone lead to?
adrenocorticotropic hormone and then cortisol
what is aldosterone involved in?
maintaining electrolyte and fluid balance
what is the potency of predisolone?
glucocorticoid: 4
mineralocorticoid: 0.8
what is the potency of dexamethasone?
glucocorticoid: 30
mineralocorticoid: 0
what is the biological half-life of prednisolone?
12-36hr
what is the biological half-life of dexamethasone?
36-54hr
what are some base words to show drugs are IM repository?
acetate
pivalate
what are some other adverse effects of glucocorticoids? other than pu/pd/pp, panting, alopecia, increased ALP
inhibit wound healing
increased susceptibility to infection
decreased response to vaccination
diabetes
laminitis in horses
GI ulceration
may cause abortion
muscular weakness
calcinosis cutis
hypertension
CHF
worsen proteinuria
pancreatitis?
what are the positives of budesonide as an alternative glucocorticoid?
potentially fewer systemic side effects
still suppresses HPA axis
fluticasone causes suppression of HPA axis in _________________________
dogs, but not cats
what diseases should you consider fluticasone for?
feline asthma
canine chronic bronchitis
why do we think some steroids cause laminitis in horses?
not sure, but may be due to sensitization of alpha receptors in hoof wall
what drugs are less likely to cause abortion in cattle?
prednisolone
isoflupredone
does potency play a role in choosing a steroid for anti-inflammatory or immunosuppressive purposes?
no
what should you choose a steroid for anti-inflammatory or immunosuppressive purposes by?
whether or not want mineralocorticoid effects
duration of action desired
if tissue distribution is an issue
species differences
what mineralocorticoids are used in addison’s disease?
DOCP
fludrocortisone
why is prednisolone preferred for the glucocorticoid in addison’s?
has mineralocorticoid activity: can reduce dose of DOCP or fludrocortisone
what drugs increase production of lipocortin (which inhibits phospholipase A2)?
glucocorticoids
what is the duration of therapy for anti-inflammatory therapy (short)?
2-3 days: control pruritis
single dose dexamethasone
one week of prednisolone
what are the positives of doing alternate day therapy with long-term anti-inflammatory therapy?
less immunosuppression
less pituitary-adrenal axis suppression
any nonrepository steroid can be used early one
why do we try to avoid repository injections?
highs are too high, lows too low
less control
more adrenal suppression
repeating infections prone to cause iatrogenic hyperadrenocorticism in dogs
what is the dose of prednisolone for horses?
50-100mg IM/IV per horse
PO similar to dogs
what is the dose of dexamethasone for cows?
5-20 mg IM/IV per cow
0.02-0.04 mg/kg IM for many indications
how many half-lives should you wait between NSAIDs and steroids?
5 half-lives
if cannot: consider misoprostal
what can happen with a pregnant bitch placed on high doses of steroids?
fetal death
reabsorption in first half of gestation or abortion thereafter
why should you avoid steroids in animals predisposed to thromboembolism?
animals with hyperadrenocorticism are predisposed to sudden death from thromboembolism: evidence that this occurs with exogenous steroids as well
what should you treat hyperaldosteronism with?
spironolactone: aldosterone antagonist
what is the drug of choice for canine and feline cushings?
trilostane
how is equine cushings treated?
dopamine agonists
pergolide mesylate
