corticosteroids Flashcards
what are glucocorticoids?
the adrenal cortex produces steroid hormones (corticosteroid)
- required for regulating organ function in response to various types of stress
- mineralocorticoids: Na+ and water conversion
- glucocorticoids: increase blood glucose levels; inhibit inflammation and immune function
- affect essentially every tissue
what is the process from cholesterol to our glucocorticoids and mineralocorticoids?
what is glucocorticoid mechanism?
glucocorticoids indirectly inhibit PA
- this inhibits the synthesis of AA and therefore the synthesis of not only PGs but also leukotrienes
- leukotrienes lead to neutrophil migration and increased function, enhances cytokine production, and enhances NK cell activity
- glucocorticoids inhibit inflammation and essentially at WBC functions (i.e. immune function is inhibited)
what is the 1st mechanism by which glucocorticoids inhibit PA2?
A nuclear pathway promoting the production of proteins that inhibit the EGFR
- the epidermal growth factor receptor (EGFR) normally activates PA2 → AA production → inflammation
1. glucocorticoids (GC) bind cytoplasmic GC receptor (GR):
a) activated drug-receptor complex enters the nucleus
b) complex up-regulated synthesis of proteins that inhibit EGFR
what is the 2nd mechanism by which glucocorticoids inhibit PA2?
a cytoplasmic pathway that activates proteins that inhibit EGFR
- the epidermal growth factor receptor (EGFR) normally activates PA2 → AA production → inflammation
2. binding of GC to GR releases a peptide (src), which is normally bound to the inactive cortisol receptor
a) this peptide activates protein that inhibit EGFR
b) inhibititon of EGFR = PA2 is not activated
immune system effects of glucocorticoids
- in addition to inhibiting PA2, glucocorticoids also impact immune activity
- glucocorticoids inhibit virtually all leukocyte functions
types of inflammatory and allergic disorders
what are clinical considerations for glucocorticoid administration?
- due to significant adverse side effects, the aim of GC treatment is to achieve disease remission on the lowest dose possible
- GC administration is meant to alleviate patient’s symptoms until initial inflammatory insult is resolved
- emperical therapy: one size does not fit all
- consider risk/benefits in that patient
- does very dependent on disease severity/patient tolerance → trial and error
- endogenous GCs affect many metabolic processes nd pharmacological dosing with exogenous GCs amplifies those actions
glucocorticoid adverse effects
- central fat distribution and hair loss (excessive doses can lead to cushings syndrome)
- increased appetite, thurst and urination
- hypertension (mineralocorticoid activity, RAS, activation, etc. )
- edema
- negative calcium balance (osteoporosis)
- gastric ulcers
- infection
- psychoses/euphoria
the risk of adverse effects is related to what?
the risk of adverse effects is related to duration of therapy as well as dose
therapeutic principles for glucocorticoid use
- clinical considerations for glucocorticoid administration
- serious adverse effects are usually only seen after ~2 weeks of continuous therapy
1. re-evaluate dose and response periodically; gradually reduce dose to an acceptable minimum
2. generally, large single dose are harmless (given in crisis situations; < 1 week unlikely to be harmful)
3. with increasing time and dosage, risk of adverse effects increases
4. with chronic use, abrupt cessation can cause adrenal insufficiency (e.g. hypoglycaemia +/- hyperkalemia, hyponatremia, hypotension)
5. must wean patient of drug gradually
what is secondary to abrupt glucocorticoid cessation?
- hypoandrenocorticism secondary to abrupt glucocorticoid cessation
- may or may not be as severe as addison’s disease, depending on the drug
- drugs such as cortisone, prednisone and prednisolone which have some mineralocorticoid activity, will suppress the patients aldosterone levels during therapy
- aldosterone levels may be inadequate following abrupt cessation of the glucocorticoid, resulting in:
1. Na+ and water loss → low BP
2. K+ retention → arrhythmias - these effects may be fatal
how does the potency of different glucocorticoids compare?
clinical uses of glucocorticoids - osteoarthritis
provide GC therapy early to minimize damage from inflammation
- combine with exercise rehabilitation to slow disease progess
- caution about “masking” of pain - patient may overuse and injure affect joints (e.g. athletes)
- intra-articular injections vs. oral GC; limit the number of injections to limit side effects
clinical uses of glucocorticoids - asthma
- GC therapy provided via inhalation to control chronic symptoms and prevent asthma attacks
- occasionally provided orally for severe asthma attacks
- use injectable drug for anaphylaxis
