Corticosteroids & antagonists

Question 1

Prednisone

Answer 1

• Glucocorticoid agonist
• MOA
• activation of GR
• Clinical
• inflammatory conditions, organ transplant, hematologic cancers
• Kinetics, tox, int.
• well absorbed orally
• tox: adrenal supression, growth inhibition, muscle wasting, osteoporosis, salt retention, glucose intolerance, behavioural changes

Question 2

Fludrocortisone

Answer 2

• Mineralocorticoid agonist
• MOA
• strong agonist at MR and moderate activation of GR
• Clinical
• Addison’s
• Kinetics, tox, int.
• long duration of action
• tox: salt & fluid retention, congestive heart failure, signs and symptoms of glucocorticoid excess

Question 3

Mifepristone

Answer 3

• MOA
• pharmacologic GR & progesterone receptor antagonist
• Clinical
• medical abortion
• Kinetics, tox, int.
• oral
• tox: vaginal bleeding, abdominal pain, GI-upset, diarrhea, headache

Question 4

Spironolactone

Answer 4

• MOA
• pharmacologic MR antagonist, weak antagonism of androgen receptors
• eplerenone is similar, but more selective for MR
• Clinical
• aldosteronism from any cause
• hypokalemia due to other diuretcs
• post-MI
• Kinetics, tox, int.
• slow onset and offset, duration 24-48h
• tox: hyperkalemia, gynecomastia, additive with other K-retaining drugs

Question 5

Ketoconazole

Answer 5

• Synthesis inhibitor
• MOA
• blocks CYP450 enzymes involved in synthesis
• Clinical
• inhibits steroid hormone synthesis (the table doesn’t have any more than that)
• Kinetics, tox, int.
• oral, topical
• tox: hepatic dysfunction, many drug-drug CYP450 interactions