SM 243a - Glucocorticoids Flashcards
What is the role of annexin 1 in inflammation?
How is annexin 1 affected by corticosteroids?
-
Phosphorylated annexin 1 inhibits cPLA2-alpha, thus reducing the production of arachidonic acid
- Annexin 1 is phosphorylated by cytosolic steroid (glucocorticoid) receptor activation
- Production of annexin 1 is also increased due to genomic effects of glucocorticoids
What disorders result in adrenal insufficiency?
Addison’s disease
What are the common adverse effects of glucocorticoid use?
- Osteoporosis
- Elevated blood sugar
- Hypertension
- Acquired glucocorticoid resistance
Describe the genomic and non-genomic cortisol/gluicocorticoid mechanisms of action
- Non-genomic
- Anti-inflammatory proteins inhibit inflammatory proteins
- Genomic
- Induces transcription of anti-inflammatory proteins
- Blocks transcription of pro-inflammatory factors (es: NF-KB)
Which of the following is most likely to be treated with oral glucocorticoids as the initial and primary treatment?
a. Rheumatoid arthritis
b. Knee osteoarthritis
c. Polymyalgia rheumatica
d. Gout
c. Polymyalgia rheumatica
- Can use corticosteroids to treat RA, but it is not the primary treatmet; need to use DMARD too
- MTX
- Biologis targeting IL-1, IL-6, or TNF-alpha
What is the treatment for polymyalgia rheumatica?
Oral glucocorticoids – prednisone
Use initially, taper for discontinuation
Add methotrexate in high-risk patients
Which enzyme catalyzes the production of arachidonic acid?
From what precursor?
- Cytosolic phospholipase A2-alpha (cPLA2-alpha) catalyzes the production of arachidonic acid from triglycerides (phospholipids)
What is the role of glucocorticoids in the treatment of tendinopathy?
No role!
Tendinopathy is not inflammatory, and glucocorticoids may weaken the tendon
Peridendinous injection may be useful if superimposed inflammation is present
What is the role of cPLA2-alpha in inflammation?
How is cPLA2-alpha affected by glucocorticoids?
cPLA2-alpha is the enzyme that catalyzes the synthesis of arachadonic acic from triglyceride precursors
Increased cPLA2-alpha = increased inflammation
- cPLA2-alpha is inhibited by phosphorylation of annexin 1
- Annexin 1 is phosphorylated in response to glucocorticoids binding to their cytosolic receptors (nongenomic)
- Increaed annexin 1 synthesis due to glucocorticoids binding to their nuclear receptors (genomic)
Decreaed cPLA2-alpha activity due to glucocorticoids, mediated by increased annexin 1 activity
Describe the hypothalamic-pituitary-adrenal axis for cortisol
- Hypothalmus secretes corticotropin-releasing hormone (CRH)
- CRH stimulates pituitary to release corticotropin
- Corticotropin induces the adrenal cortex to syntesize and secrete cortisol
Which fractures are most commonly associated with glucocorticoids?
Vertebral fracture
Hip fracture
Associated with oral glucocorticoids, high doses of epidural spine injections
How do glucocorticoids affect blood sugar?
Increase blood sugar after injection or daily long-term oral use
Which disorders result in hyperactivity of the hypothalamic-pituitary-adrenal axis?
What is the effect?
- Cushing’s syndrome
- Physical pain
- Emotional trauma
- Caloric restriction
-> Immunosuppression, increased susceptibility to infection
What is the role of corticosteroids for the treatment of knee osteoarthritis?
May help with acute pain, but worse outcomes long-term
How do glucocorticoids affect blood pressure? Which mode of delivery?
Increase blood pressure
- Renal sodium retention -> increase blood volume -> increase BP
- Associated with long-term oral use
