Iatrogenic Complications of Steroid Treatments Flashcards
What are some iatrogenic complications of glucocorticoid therapy?
Cushingoid syndrome Adrenal suppression Immunosuppression Peptic ulcers Osteoporosis Inhibition of linear growth in children
Why do you get adrenal suppression with glucocorticoid therapy?
Cortisol not released > cells atrophy > can’t produce cortisol anymore
Does everyone with Addison’s disease get a tan in the absence of sunlight?
No
Can also just get patchy discolouration
Why are people who present with cortisol deficiency often missed?
Nebulous symptoms
Gradual onset
Each patient present differently
What also occurs with a cortisol deficiency in primary adrenal hypofunction?
Mineralocorticoid deficiency
What does a mineralocorticoid deficiency present as?
Hyperkalaemia
Hyponatraemia
Acidosis
Dehydration
Why is it so important to diagnose Addison’s disease promptly?
Death follows quickly
What are the options for cortisol replacement?
Hydrocortisone
Cortisone acetate
Prednisolone
How is replacement cortisol dosed?
Divide dose to mimic physiological time course
- Large dose in morning
- Smaller dose during day
When are extra doses of replacement cortisol taken?
Infections
Periods of stress
What must be done for patients when they’re put on cortisol replacement therapy?
Have to be educated to adjust dose themselves
Why is extra cortisol needed during infections?
Stop over-activation of immune system
Does everyone with Addison’s disease require fludrocortisone?
No, but most do
What is the bioavailability of oral cortisone?
A little less than cortisol’s
Are there any side effects with cortisol replacements?
No, if it’s well-managed physiological replacement
Why do some patients prefer to use prednisolone rather than hydrocortisone or cortisone?
Prednisolone has longer half life
What happens to cortisol in the kidneys?
Quickly converted to cortisone
Why is cortisol so quickly inactivated in the kidneys?
Prevent it acting on mineralocorticoid receptor
What happens to cortisone in the liver?
Reconverted to cortisol via same enzyme as that in kidney
What is the half life of prednisolone?
Prednisone’s half life = 1 hour
Converted to prednisolone
Prednisolone’s half life = 3-4 hours
When do cortisol peaks occur?
With meal times
Why don’t patients take cortisol with each meal?
Can’t mimic short lived peaks
Therefore take big dose in morning and smaller dose later in evening
What is the major complication of glucocorticoid therapy?
Adrenal suppression
What is adrenal suppression because glucocorticoid therapy related to?
Dose and duration
- Varies between drugs
- Affected by dosing regime
Do patients all react to adrenal suppression in the same way?
No, varies in severity and duration
How do you minimise adrenal suppression?
Allow for ACTH secretion - Avoid long-lasting drugs - Alternate day dosing - Morning dose > most effectively mimics diurnal system Minimise systemic absorption - Inhaled/topical 3rd generation glucocorticoid drugs
What is ciclesonide?
3rd generation glucocorticoid
Why does ciclesonide have reduced systemic effects after inhalation?
Pro-drug activated in lungs
Lipophilic > retained in tissue
Low oral bioavailability
Highly protein bound in plasma
Do glucocorticoids cause peptic ulcers?
Causal role debatable
Mostly occur in patients taking NSAIDs
- Synergistic interaction possible
What does RANK on osteoclast precursors bind to?
RANKL
What does binding of RANK and RANKL do?
Promotes osteoclast formation
What do osteoclasts do?
Promote bone resorption
What does OPG do to osteoclasts?
Inhibits their formation by binding to RANKL
What is the effect of glucocorticoids on RANKL and OPG?
Increase RANKL
Decrease OPG
Do glucocorticoids cause osteoporosis?
Do get some bone resorption but benefit of treating asthma may be greater
Do glucocorticoids inhibit linear growth in children?
Modest effect size with moderate dosing
May be less than disease-induced stunting
