corticosteroids

Question 1

what are glucocorticoids?

Answer 1

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

Question 2

what is the process from cholesterol to our glucocorticoids and mineralocorticoids?

Answer 2

Question 3

what is glucocorticoid mechanism?

Answer 3

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)

Question 4

what is the 1st mechanism by which glucocorticoids inhibit PA2?

Answer 4

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

Question 5

what is the 2nd mechanism by which glucocorticoids inhibit PA2?

Answer 5

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

Question 6

immune system effects of glucocorticoids

Answer 6

• in addition to inhibiting PA2, glucocorticoids also impact immune activity
• glucocorticoids inhibit virtually all leukocyte functions

Question 7

types of inflammatory and allergic disorders

Answer 7

Question 8

what are clinical considerations for glucocorticoid administration?

Answer 8

• 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

Question 9

glucocorticoid adverse effects

Answer 9

• 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

Question 10

the risk of adverse effects is related to what?

Answer 10

the risk of adverse effects is related to duration of therapy as well as dose

Question 11

therapeutic principles for glucocorticoid use

Answer 11

• 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

Question 12

what is secondary to abrupt glucocorticoid cessation?

Answer 12

• 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

Question 13

how does the potency of different glucocorticoids compare?

Answer 13

Question 14

clinical uses of glucocorticoids - osteoarthritis

Answer 14

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

Question 15

clinical uses of glucocorticoids - asthma

Answer 15

• 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

Question 16

clinical uses of glucocorticoids - lymphoma

Answer 16

• many chemotherpay regimens to treat lympoma (a blood cancer) include prednisone (or sometimes other GCs)
• GCs decrease number of circulating lymphocytes (lymphosuppression)
• administered alongside other drugs to kill cancer cells