Anti-inflammatory Steroids Flashcards
Glucocorticoids help to?
maintain bp and CV function
slow the immune system’s inflammatory response
maintain levels of glucose in the blood
regulate the metabolism of proteins, carbs, fats
Cortisol acts as?
Mineralocorticoid and Glucocorticoid
GC- means to increase serum glucose levels
MC- means to increase Na levels
What are adrenal steroids bound to in the plasma?
corticosteroid binding protein (CBP) and/or plasma proteins (albumin)
Feedback inhibition of HPA axis?
feedback inhibition by cortisol
Clinical use of Steroids?
Treatment of endocrine disorders (adrenal insufficiency)
Acute inflammation/ Organ transplant/ Allergic inflammation
Cells of inflammation?
have an ability to leave the vessel into tissue (basophil- mast cell, monocyte- Macrophage, Lymphocyte- Plasma cell)
Steroids block these
dampen the cascade of inflammation, dampen effect
Steroids and inflammatory effect?
decrease arachidonic acids, decrease leukotienes and Prostaglandins
even broader anti-inflammatory effect than NSAIDs
Anti-inflammatory action?
Suppress production of cytokines, prostaglandins, leukotrienes
decrease release of proinflammatory mediators
stabilize lysosomal membranes
cause vasoconstriction and decrease capillary permeability
Immunosuppressive action?
change lymphocyte distribution
suppresses the activation of T lymphocytes
Inhibits monocyte and phagocyte production and function
Synthetic steroids?
similar to cortisol
produce same effects but have different ratios of GC and MC potency
Chemical changes affect mainly for GC and MC receptors
Differing rates of elimination (half life)
cant seperate GC and anti-inflammatory effects
Synthetic steroids? oral?
most are rapidly and completely absorbed
Synthetic steroids? other?
topical- inflammatory skin
inhalation- therapy for asthma
intraarticular injection- joint inflammation
parerntal- emergencies (septic shock, severe acute asthma)
Do you get side effects with topical?
yes
Pharmacokinetics? DOA?
-potency at GC receptor
elimination half life
Pharmacokinetics? ADT Alternate day therapy?
attempt to alleviate side effects
decreae likelihood of hypothalamic pituitary adrenal axis suppression
severe autoimmune and inflammatory disorders
Stopping therapy/ indications for glucorticoid withdrawl?
max therapeutic benefit obtained
Sub-optimal theurapeutic response
Serious/ uncontrollable side effects (lumbar spine osteoporosis, hypertension)
Why tapper drug?
flare-up of underlying disease
adrenal insufficiency due to HPA suppression
when is HPA suppression unlikely?
GC dosing for under 3 wks
Treatment with alternate day dosing
If HPA suppression is unlikey then?
wean off GCs as dictated by disease control
When is HPA suppression likely?
Mod-hight daily dose GC for >3wks
evening/bedtime GC doses for >2wks
presence of a Cushingnoid appearance
If HPA suppression is likely?
treat like secondary adrenal insufficiency (taper dose at rate to prevent both disease flare and symptoms of cortisol deficiency)
med alert bracelet, emergency med info card
preloaded syringe with decamethasone
Adverse effects?
Steroid induced morbidity is a major problem in many transplant patients
Extensive use of steroids often results in disabling and life-threatening SAEs
Skin and soft tissue adverse effects?
thinning of the skin and purpura
development of cushing like symptoms
Eye Adverse effects?
cataracts
increased intra-ocular pressure
GI tract Adverse effects?
gastritis
peptic ulcers
GI bleeding
syngergistic effect in combo with NSAIDs (prophylaxis with PPIs may be required)
Renal function and systemic hemodynamics Adverse effects?
commonly promotes fluid retention (electrolyte imbalance, not a problem for normalt pts)
can raise blood presure
MSK Adverse effects?
Osteoporosis
usually if someone has cushingoid affects and fat redistribution patient will have this
prevent/treat by following general approach for osteoporsis, ADT does not prevent bone loss
GCs on MSK?
GCs inhibit Ca absorption in the gut, bone metabolism altered by a number of different mechanisms (increase bone resorption)
-effect through GC receptors, Increae osteoclastogenesis
Bone metabolism altered by a number of different mechanisms?
increase bone formation
-inhibit osteoblast proliferation, stim apoptosis of osteoblasts and mature osteocytes, antagonism of anabolic action of PTH, decrease insulin like growth factor (IGF-1) and testosterone production
Other MSK Adverse effects?
Muscle weakness (proximal motor weakness in upper and lower extremities)
Muscular atrophy/ wasting (direct catabolic effect on skeletal m)
CNS Adverse effects?
Euphoria (slight increase in overall sense of well being commonly seen)
Pysch disorder (depression, anxiety, panic attacks, phobias)
Metabolism Adverse effects?
Carb metabolism- (Hyperglycemia
Exacerbation of preexisting diabetes
New onset diabetes)
Lipid- (dyslipidemia)
Immune system (increase susceptibility to infections)
