243. Glucocorticoids

Question 1

What are the 5 signs of inflammation

Answer 1

Pain, redness, warmth, swelling, loss of function

Question 2

What pathway regulates signalling by the GC receptor? What signals are normally involved?

Answer 2

Hypothalamic-Pituitary-Adrenal Axis

Hypothalamus secretes CRH to pituitary secretes corticotrophin to adrenal cortex secretes cortisol

Question 3

What two ways does cortisol perform its function?

Answer 3

1. nongenomic: activates antiinflammatory proteins (FAST)
2. genomic: (SLOW) transcription of antiinflammatory proteins, downregulate transcription of proinflammatory cytokines by blocking NF-kB

Question 4

What two ways does the GC receptor perform its function?

Answer 4

1. nongenomic: activates c-Src (GC receptor accessory protein) - decreases production of Arachidonic Acid
2. genomic: decrease inflammation transcription (NF-kB), decrease arachidonic acid synthesis

Question 5

Cushing’s Syndrome vs. Addison’s disease

Answer 5

CS: hyperactive cortisol release = immunosuppression and high infection risk

AD: hypoactive cortisol release = needs supplemental GC during inflammation/infection to modulate

Question 6

What disease is GCs primary and initial tx?

Answer 6

Polymyalgia rheumatica!!

Question 7

What are the adverse effects of GCs?

Answer 7

1. Decreased cortisol following use
2. Osteoporosis: VERTEBRAL FRACTURES (can permenantly reduce height) by increasing osteoclast activity
3. Transient increase in blood sugar
4. HTN in long term use (renal Na retention and potentiated response to Ang II)
5. GC Resistance (acquired with long term use)
6. Osteonecrosis at femoral head, esp with chronic use