SM 243a - Glucocorticoids Flashcards

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1
Q

What is the role of annexin 1 in inflammation?

How is annexin 1 affected by corticosteroids?

A
  • 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
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2
Q

What disorders result in adrenal insufficiency?

A

Addison’s disease

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3
Q

What are the common adverse effects of glucocorticoid use?

A
  • Osteoporosis
  • Elevated blood sugar
  • Hypertension
  • Acquired glucocorticoid resistance
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4
Q

Describe the genomic and non-genomic cortisol/gluicocorticoid mechanisms of action

A
  • Non-genomic
    • Anti-inflammatory proteins inhibit inflammatory proteins
  • Genomic
    • Induces transcription of anti-inflammatory proteins
    • Blocks transcription of pro-inflammatory factors (es: NF-KB)
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5
Q

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

A

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
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6
Q

What is the treatment for polymyalgia rheumatica?

A

Oral glucocorticoids – prednisone

Use initially, taper for discontinuation

Add methotrexate in high-risk patients

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7
Q

Which enzyme catalyzes the production of arachidonic acid?

From what precursor?

A
  • Cytosolic phospholipase A2-alpha (cPLA2-alpha) catalyzes the production of arachidonic acid from triglycerides (phospholipids)
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8
Q

What is the role of glucocorticoids in the treatment of tendinopathy?

A

No role!

Tendinopathy is not inflammatory, and glucocorticoids may weaken the tendon

Peridendinous injection may be useful if superimposed inflammation is present

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9
Q

What is the role of cPLA2-alpha in inflammation?

How is cPLA2-alpha affected by glucocorticoids?

A

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

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10
Q

Describe the hypothalamic-pituitary-adrenal axis for cortisol

A
  • Hypothalmus secretes corticotropin-releasing hormone (CRH)
  • CRH stimulates pituitary to release corticotropin
  • Corticotropin induces the adrenal cortex to syntesize and secrete cortisol
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11
Q

Which fractures are most commonly associated with glucocorticoids?

A

Vertebral fracture

Hip fracture

Associated with oral glucocorticoids, high doses of epidural spine injections

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12
Q

How do glucocorticoids affect blood sugar?

A

Increase blood sugar after injection or daily long-term oral use

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13
Q

Which disorders result in hyperactivity of the hypothalamic-pituitary-adrenal axis?

What is the effect?

A
  • Cushing’s syndrome
  • Physical pain
  • Emotional trauma
  • Caloric restriction

-> Immunosuppression, increased susceptibility to infection

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14
Q

What is the role of corticosteroids for the treatment of knee osteoarthritis?

A

May help with acute pain, but worse outcomes long-term

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15
Q

How do glucocorticoids affect blood pressure? Which mode of delivery?

A

Increase blood pressure

  • Renal sodium retention -> increase blood volume -> increase BP
  • Associated with long-term oral use
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16
Q

Which populations are most likely to develop glucocorticoid resistance?

A

Patients wtih severe rheumatoid arthritis

17
Q

How do glucocorticoids cause osteoporosis?

Describe the effect of glucocorticoids on bone cells

A

Increase number of osteoclasts

Increased apoptosis of osteocytes

-> Decreased integrity of bone, worse circulation