Glucocorticoids Flashcards
Why do steroids have global effects on the body
they get in most cells through the cell membrane and act/suppress the nucleus
Once steroids get into the cell and cause nuclear transcription/repression of glucocorticoid-sensitive genes, what does protein synthesis of Annexin A1 do?
It affects neutrophils
1) Increased L-selectin shedding
2) Decrease endothelial adherence
3) Decrease endothelial tranigration
What does Annexin A1 do
It affects neutrophils
1) Increased L-selectin shedding
2) Decrease endothelial adherence
3) Decrease endothelial tranigration
If steroids supress cell lines, why do you see an increase in neutrophils
Neutrophilia from decreased extravasation
How do steroids affect macrophages
inhibit phagocytosis, cytokine release (IL-1, IL-2, TNFa)
How do steroids affect b-cells
decrease antibody production
How do steroids affect fibrogenesis
decrease
How do steroids affect the arachidonic acid cascade
reduced prostaglandin/keukotriens
With steroids, how are t-cells inhibited
IL-2 inhibition
T/F: steroids do pain control
true
Are steroids good for acute or chronic management
acute
What are examples of short-acting steroids
cortisone
hydrocortisone
about 8-12 hours
What are examples of intermediate-acting steroids
Prednisone
Prednisolone
Methylpredisolone
all are about 12-36h
What steroids is less likely to cause PU/PD because it has no mineralocorticoid potency
Methylprednisolone
Do cats tolerate prednisone or prednisolone better
Prednisolone
What are the long acting steroids
Triamcinolone
Flumethasone
Dexamethasone
Betamethasone
all about 35-54 hours (expect trimcinolone 12-36)
What are the steroids with mineralocorticoid potency
Hydrocortisone (2)
Prednisone (1)
Prednisolone (1)
What is the preferred route for steroid dosing
Oral*
The onset of effect of systemic corticoisteroids is often delayed for ________, regardless of the route of administration
3-8 hours
T/F: IV is the fastest method of steroid absorption
True
T/F: IM is faster at absorbing steroids than oral
False
rapidly diminishing response to a drug
Tachyphlyaxis
What are the potency factors of steroids
1) Polarity (aqeuous vs lipophilic)
2) Protein binding
3) Liver metabolism (prednisone to prednisolone)
4) Cellular metabolism
5) Receptor affinity
Potency changes with species, tissue, patient, and application method
What steroids are insoluble esters that stay in the tissue a long time
1) Vetalog (triamcinolone acetonide) - last about a week SQ/IM
2) Depo-Medrol (methylprednisolone acetate) - lasts 3-12 weeks (SQ/IM)
bad because you cant take it out if something goes wrong
Why does Vetalong (Triamcinolone acetonide) and Depo-Medrol last a long time in the tissue
because they are suspensions of insoluble esters
-Acetate, Privalate, Acetonide
What makes steroids short-acting
because they are suspension of water soluble (salt, phosphate) esters
Why is dexamethasone a short-acting steroid
becuae it is water soluble (salt, phosphate) esters
lasts 1-3 days (dose-dependent)
giving this injectables orally changes bioavailability and duration
How do you rank the steroids based on relative potency
1) Hydrocortisone
2) Prednisone
3) Dexamethasone
4) Betamethasone, Mometasone, Triamcinolone
5) Fluocinolone
a potent new generation glucocorticoid
thats double esterificiation of HCA makes it ideal
30x more potent than hydrocortisone
Lipophilic for skin penetration
Locally metabolized dermal metabolism
Hydrocortisone aceponate
topical corticosteroids can be used as effectively as systemics for
focal inflammatory lesions
Even a single dose of topical or systemic steroids will
Suppress the HPA acis (dose/formulation dependent)
With systemic steroids, longer tx duration, the greater
wash-out
-4-8 weeks for many protocols (dexamethasone)
-Cutaneous changes due to steroids can take months to resolved
The wash-out of topical steroids depends on
the formulation
-Mometasone, hydrocortisone aceponate less effect
can get systemic signs with topical absorption (patient dependent)
T/F: we can get systemic signs with topical steroid absorption
True
Steroids affects the skin and fur long-term. What changes are seen
-Hair loss
-Increased susceptibility to infection
-Thinning of skin
-Calcinosis cutis
How do steroids affect muscle
-Weakness (short-term)
-Pendulous abdomen (long term)
-Thinning (long term)
-Temporal muscle atrophy (long term)
What does steroids affect the CNS short term
Polydipsia
Polyphagia
Mood change/aggression
How do steroids affect the kidneys
Polyuria
Protein-losing glomerulonephropathy
Altered electrolyte balance
What are the cutaneous adverse effects of steroids due to catabolism + immunosuppression
1) Scale (weeks to months)- common
2) Truncal alopecia- months; common
3) Demodex overgrowth- any point, uncommon
4) Comedones- weeks to months, uncommon (check for Demodex)
5) Calcinosis cutis- months, uncommon
6) Hyperfragility syndrome (cats)- months, rare
7) Opportinistic infections- depends on tissue location/infection
8) Curling ear tips (cartilage)- cat; rare
9) Delayed wound healing - days to weeks, common
What parasite is likely to overgrow with steroid usage, caused comedones
Demodex
What systemic effects are seen with steroids
1) PU/PD -ADH deficiency?
2) Polyphagia (days)
3) Food aggression - days to weeks
4) Insomnia (humans)
5) Weight gain (polyphagia)
6) Gastric ulceration-inhibits prostaglandins
7) Ligament rupture (catabolism)
8) Laminitis in horses
9) Diabetes mellitus (decreased insulin response)
10) Heart failure (increased circulatory volume)
11) Hypertension (increased circulatory volume)
How can steroids lead to gastric ulceration
inhibits protective prostaglandins
What can steroids cause in horses
Laminitis
Triamcinolone > Dexamethasone > Prednisolone
How can steroids cause diabetes mellitus
decreased insulin response, increased gluconeogenesis - PEPCK enzyme
How can steroids cause heart failure and/or hypertension
increased circulatory volume
a type of skin scarring that appear as irregular bands, lines, or stripes
can occur secondary to steroids
striae
dermal calcium deposition that is secondary to steroids or cushings
leads to inflammatory response
calcinosis cutis
If hairs are in telogen due to steroids there will be
No growth phase
What changes to the cat’s ears can be seen with steroids
pinnal laxity
(topical or oral)
What CBC changes is seen with steroids
1) Neutrophilia
decreased extravasation from circulation
2) Monocytosis
decreased extravasation from circulation
3) Lymphopenia (immunosuppression)
4) Thrombocytosis (hypercoagulopathy, increased productio)
“Stress leukogram”
What CHEM changes are seen with steroids
1) Hyperglycemia (decreased insulin response)
2) Steroid hepatopathy (increased ALP, ALT, GGT) - largely induced and expected
3) Decreased thyroid hormone (FT4 less affected)
What UA changes are seen with steroids
1) Isosthenuria / Hyposthenuria
2) Occult UTI- things are harder to find when theyre dilutes
T/F: routine anti-inflammatory doses do not appear to impede a protective response to vaccination
True
Steroid hepatopathy, what induced liver enzyme elevations are expected
ALP, ALT, GGT
ALP > ALT
In a dog on steroids with an elevated BUN and normal Creatinine, what are you suspicious for
Gastric ulceration? GI bleed?
What is the physiologic dose of prednisolone for a dog/horse
0.2-0.3 mg/kg/day
What is the anti-inflammatory (anti-pruritic) dose of prednisolone for a dog/horse
0.5-1 mg/kg/day
What is the immunomodulatory dose of prednisolone for a dog/horse
2 mg/kg/day
What is the physiologic dose of prednisolone for a cat
0.5 mg/kg/day
What is the anti-inflammatory dose of prednisolone for a cat
1-2 mg/kg/day
What is the immunomodulatory dose of prednisolone for a cat
3+ mg/kg/day
How often should you dose prednisolone
total daily dose can be separated out (a24 hours, BID)
How do you dose Triamcinolone / Dexamethasone
it is about 7-10x as potent as prednisolone
assume 10x and move the decimal point
Ex: Immunomodulatory for dog would be 0.2mg/kg
Cats typically have _________ the steroid dose as dogs do
twice
With steroids most dermatological diseases can be in remission in
1-2 weeks and then taper to effect
hit them hard and then get out
“lowest effective dose’ is paramount
What is up with steroid maintenance
long-term disease control is not necessarily 100% disease resolution- it is about quality of life/management
Goal is physiologic dose EOD
if you cant get there: Azathioprine, Cyclosporine, Chlorambucil, Mycophenolate, Leflunomide, Topical Tacrolimus
What are common pitfalls with steroid tapering
1) Using injectables- still take hours, even parenterally, not necessarily more efficacious, overdose can lead to adverse side effections
2) x for 3d, x for 3d, x for 1.5 days
you dont give it a chance to work
3) Not tapering fast enough- steroid adverse effects are progressively dose and time dependent
-Serious infection of adverse eent (gastric ulcer, calcinosis cutis) might necessitate a significant decrease in a short period of time
-Depends on duration and dose but short term steroids can be tapered within 1-2 weeks (or not at all if <two weeks)
-Adrenal hibernation is not instaneous
-Long term (months) requires tapering for at least 4 weeks
