Glucocorticoids – use in clinical practice Flashcards
(24 cards)
indications for glucocorticoids
allergic disease immune-mediated disease replacement therapy (hypoadrenocorticism ) neoplasia (lymphoma, mastocytoma) shock (controversial) cerebral and spinal cord oedema (controversial) profound inflammatory disorders hypercalcemia
What is the difference between a corticosteroid and a glucocorticoid ?
glucocorticoids are a type of corticosteroid
inappropriate uses of glucocorticoids
appetite stimulant
non-specific treatment in lieu of a diagnosis
suppression of pyrexia + infl without knowledge of its cause
use before investigative process has concluded
action of glucocorticoids at cellular level
bind to specific intracellular receptors
alter gene expression
alter the regulation of many cellular processes – enzyme synthesis, membrane permeability, transport processes, structure, tachyphylaxis (quick reaction to drug) – ⇑ their own metabolism
effects of glucocorticoids
immunomodification protein metabolism carbohydrate metabolism lipid metabolism endocrine function psychogenic effects
mechanism of action of glucocorticoids
stop cell membrane phospholipids being converted to arachidonic acid
arachidonic acid can’t then be made into prostagladins or leukotrienes
prostaglandins effect mucosal protection, renal blood flow, hemostasis, Inflammation, pain & fever
leukotrienes - infl
net effects - inhibition of which processes
oedema formation fibrin deposition capillary dilatation leukocyte migration phagocytic activity capillary and fibroblast proliferation collagen deposition
Why are glucocorticoids better at suppressing inflammation than NSAIDs?
Suppress T-lymphocyte functions
Inhibit monocyte-macrophage activities
Suppress fibroblast functions and collagen deposition
Reduce histamine release from mast cells
Decr synthesis of lymphokines – decr release of proteases
block leukotriene formation as well as prostaglandins
effect on immune response
Inhibit antigen processing by macrophages
Inhibit cell-mediated immunity
Suppress the inflammatory response by antigen-antibody union
So unlike NSAIDs they suppress the immune response
How are glucocorticoids different?
Differ in their anti-inflammatory potency
Differ in their duration of activity
They have no separation between their anti-inflammatory and/or immunosuppressive effects and their metabolic effects
Short acting (less than 12 hours)
Cortisone
Hydrocortisone
Intermediate acting (12-36 hours)
Prednisone
Prednisilone
Methylprednisilone
Triamcinolone (up to 48 hours)
Long acting (more than 48 hours)
Flumethasone
Dexamethasone
Betamethasone
effect of solubility
less soluble = longer duration of release
duration of action affected by which 3 factors
half-life of drug itself
effect of the formulation (ester’s solubility)
dose of the drug
sustained release injections
prolongation of effect
Adrenal suppression duration > duration of anti-inflammatory effect - adrenal supression lasts longer
inhaled glucocorticoid uses
immune-mediated bronchial inflammation
asthmatic infl
which drug to use for asthmatic infl + why
fluticasone proprionate
v.potent - incr glucocorticoid receptor affinity
2 phases of treating immune-mediated disease
induction of remission - high dose once daily
maintenance of remission - alternate day glucocorticoids + synergistic immunosupressant
Glucocorticoid therapy in treating immune-mediated disease
use appropriate dose and the shortest acting effective agent for effect intended
prednisolone or prednisone - 2-3mg/kg/24h
this could be a non-divided dose ie think about giving it once daily not twice daily
only in exceptional circumstances should we start at a dose less than this ….almost NEVER!
induction of remision
need a non-divided dose to induce remission of an immune-mediated disease
generally for around 10 days then decrease for a further 10 days
maintenance of remission
start patients on concurrent non-steroidal immunosuppressant
same daily dose of prednisolone but given on alternate days
tapered every 2-4 weeks
glucocorticoid therapy - variation in cats
more steroid resistant
less immuno-suppresive effect only
adverse effects
a lot of variation
PU + PD
polyphagia - significant risk
