Corticosteriods Flashcards
MOA
inhibits phospholipase which decreased arachidonic acid. This suppresses COX1/2 and LOX synthesis and therefore decreases PGs and leukotrienes
Hypothalamusc (CRH) –> pituitary gland )ACTH) –> adrenal gland –> cortisol (negative feed back on the hypothalamus)
exogenous glucocorticoids e.g. prednisone enhances the -ve feedback loop shutting down the HPA. Over time this will cause atrophy of the glands.
SO if you abruptly stop the red you get a HYPOADRENOCORTICOL crisis.
decrease cell mediated immunity (CMI)
glucocorticoids reduce CMI (WBC) first because it is more energy intensive. This only leaves you with humeral (plasma bodies that spew out antibodies.
info about corticosteroids
hormones (endocrine) highly affect metabolism
they are potent
have many different effects on the body
LONG DOA
The MOA is very different to most drugs. An increase in a dose of corticosteroids amplify the effect considerably.
Cortisols function is to ensure glucose is supplied to the brain in short and long term.
Cortisol will sacrifice the rest of the body to support the brain.
Exogenous glucocorticoids have supra-physiologic activity
A single measured conservative dose of a short acting glucocorticoids will usually be safe un an otherwise healthy animal - except in exotics
Clinical Applications - major uses
(remember you must change doses for your use!)
Supraphysiologocal to suppress
ALLERGY
- Atopy (=enviromental allergies) types 1 & 4 hypersensitivity (0.5mg/kg/day)
- insect bite = type 1 hypersensitivity
INFLAMMATION
- general inflammation, often inappropriate used for every type of ‘it is’ ‘band-aid solution’ (1mg/kg/day)
- acute asthma
- neoplasia (pallative, but also cytotoxic to lymphocytes)
IMMUNE DISEASE
-eg autoimmune disorders (2mg/kg/day)
immune-mediated haemolytic anaemia (IMHA), immune mediated thrombocytopenia (ITP), rheumatoid arthritis, lupus, crowns disease.
Other:
equine airway disease - inhalant corticosteriods
ophthalmology - may allow for the infection to take-off
** use of corticosteroids for shock is controversial
Clinical application - minor use
replacement in adrenal insufficiency
- addisons (=underactive adrenal cortex)
- induction of parturition in some species
Glucocorticoid side effects 1/
NEVER give concurrent with NSAIDs because of the synergistic side effects
All NSAIDS side affects (cox inhibition)
- GIT ulceration (decreased PGE, decreased PGI2), decreased mucosal blood flow
- kidney failure (decreased PGE, decreased PGI2)
-altereed platelet function (decreased PGI2 and TXA2)
Glucocorticoid side effects 2/
METABOLIC
many predictable, based on supraphysiologic cortisol - sudden cessation may lead to hypoadrenocortocal crisis
Glucocorticoid side effects 3/
IMMUNE SYSTEM
more prone to infections, this infections will be more severe
Glucocorticoid side effects 4/
CARDIOVASCULAR
hypotension
Alternate Day therapy (ADT=EOD)
whats its purpose?
A method for achieving lowest possible dose that is still therapeutic
The dose (i.e pred) is given every 2nd day meaning there is a period of time where cortisol is not circulating in the system so the HPA axis kicks in to release cortisol. This keeps the HPA axis kicking over.
Clinical application:
treating a patient with prednisone for its atopy
> must wean the patient off linger term steroids to prevent hypoA crisis.
Numerous protocols - name one
3-3-3 protocol
higher anti-pruritc: 3 days bid
maintenance anti-pruritic: 3 days SID
lower possible anti-prutitic: 3 weeks EOD
gradual reduce dose down, you can maintain a dog for a number of years
prednisolone - most widely used glucocorticoid
(used in many chronic skin conditions)
IV
- most rapid onset action
- plasma half life <24hrs
- DOA 24-36hrs
Oral liquid formation for difficult to pill animals
Granules: indeed med for horses
Dexamethasone (30 x more potent than cortisol)
= potent and long lasting
DOA ~72 hrs
Ears/eyes contraindications
Eyes: never use corticosteroids if a corneal ulcer is present
- do a fluroscene stain first!
ears: if you keep using a glucocorticoid in the ear it will suppress the immune system and bacteria will run a muck
