Adrenal Corticosteroid Drugs Iszard

Question 1

What enzyme converts inert steroids into active steroids?

Answer 1

• 11 Beta-HSD1 11 ketoreductase
• cortisol, corticosterone, prednisilone are active

Question 2

What enzyme converts active steroids to inert steroids?

Answer 2

• 11B- HSD2 11B-dehydrogenase
• cortisone, 11-dehydrocorticosterone, prednisone are inert

Question 3

Primary therapeutic effects of glucocorticoids?

Answer 3

• Immunosuppression and Anti-inflammatory
• anti-allergy
• pain relief
• decrease blood vessel permeabilty

Question 4

Glucocorticoid AE’s?

Answer 4

• htn
• cataracts and glaucoma
• HPA insufficiency
• hyperglycemia/weight gain/fluid retention/ cushingoid appearance
• skin thinning
• osteoporosis
• infection

Question 5

What makes the difference betwen therapeutic and AE of steroids?

Answer 5

• potency
• pharmacokinetics
• daily dose and timing of the dose
• duration of treatement

Question 6

Application of adrenal corticosteroids?

Answer 6

• endocrine conditions → replacement therapy
  
  • primary adrenal insufficiency (addisons) use comno of glucocorticoid like hydrocortisone and mineralocorticoid like fludrocortisone
  • CAH use hydrocortisone and fludrocortisone
• Non endocrine conditions:
  
  • immunosuppression
  • inflammatory & alleric conditions

Question 7

How should steroids be used in a medical emergency?

Answer 7

• high doses can be given for few days with little risk
• should NOT be given for more than a few days
• use cant replace or delay specific primary therapies

Question 8

How should steroids be used for chronic therapy?

Answer 8

• cannot be given chronically without the risk of AE’s
• need to consider dose frequency administration route

Question 9

Guidelines for corticosteroid therapy?

Answer 9

• only start if there is published evidence of objective theapeutic benefit
• only after other therapies have failed
• don’t use longer than necessary
• stop use if therapeutic benefit is not observed, complications occur, or max benefit has been reached

Question 10

How do glucocorticoids impact carb metabolism?

Answer 10

• inc. gluconeogenesis
• inc. glucose output
• inc. glycogen synthesis
• dec. glucose uptake → hyperglycemia

Question 11

Effects of glucocorticoids on lipid metabolism?

Answer 11

• inc. lipolysis
• inc. FFA and glycerol into gluconeogenic path
• inc. lipogenesis
• inc. fat deposition
• change in fat distribution

Question 12

How do glucocorticoids impact protein metabolism?

Answer 12

• decreased AA uptake
• dec protein synthesis
• dev of myopathy and muscle wasting

Question 13

In what patient populations would systemic glucocorticoid administration be an issue?

Answer 13

• HIV
• diabetic
• patients with infection
• peptic ulcers
• CV conditions
• psychiatric conditions
• osteoporosis → postmenopausal women
• kids

Question 14

What results if there is decreased activity of 11B HSD2? What are known inhibitors of this enzyme? (WILL BE ON EXAM)

Answer 14

• excessive activation of mineralocorticoid mediated by cortisol, results in an inc. in sodium and water retention and incr in K loss leading to increased BP
• glycyrrhizin (found in licorice root extract)
• carbenoxolone (used for tx of esophageal ulcers in UK)

Question 15

What is the anti-insulin activity of glucocorticoids?

Answer 15

• inc. gluconeogenesis in the liver
• dec. of glucose intake and glycogen synthetase activity and increase in proteolysis in muslce
• dec glucose uptake and incr lypolysis in adipose tissue
• all leads to hyperglycemia

Question 16

What are the short-med acting (<12 hrs)

Answer 16

• hydrocortisone (cortisol)
• cortisone

Question 17

Intermediate acting (12-36 hr)

Answer 17

• prednisone
• prednisolone
• Methylprednisolone
• Triamcinolone

Question 18

Long acting (>36hrs)

Answer 18

• betamethasone
• dexamethasone

Question 19

What can treat cancer of the adrenal glands?

Answer 19

Mitotane

Question 20

Desscribe the glucocorticoid, Prednisolone’s MOA, application, & pharmacokinetics?

Answer 20

• activation of GR alters gene transcription
• inflammatory conditions, organ transplants, hematologic cancer
• intermediate length acting

Question 21

Glucocorticoid Receptor Antagonist Mifepristone use MOA pharmacokinetics AE’s?

Answer 21

• antagonist of glucocorticoid and progesterone receptor
• used for medical abortions and rarely cushing syndrome
• PO
• vaginal bleeding, abd pain, diarrhea, HA

Question 22

Mineralocorticoid influences?

Answer 22

influences salt and water balance, can cause sodium and water retention and active excretion of potassium and protons

Question 23

Describe the mineralocorticoid agonist Fludrocortisone’s MOA, use, pharmacokinetics, and AE’s.

Answer 23

• agonist at MR receptors and activation of glucocorticoid receptors
• used in adrenal insufficiency (Addison’s Disease)
• long duration of action
• salt and fluid retention, CHF, glucocorticoid excess symptoms

Question 24

What is Metyrapone used for?

Answer 24

used in diagnosis of adrenal insufficiency and occasionally in tx of cushings

Question 25

What are the MR receptor antagonists Spironolactone and Eplerenone used for, MOA, pharmacokinetcs and AE’s?

Answer 25

• antagonist of MR receptor and weak androgen receptors
• used for aldosteronism and hypokalemia due to diuretic effect,
  
  • eplerenone used for lowering BP
• slow onset of action and offset 24-48 hrs
  
  • eplerenone cleared by CYP 3A4
• hyperkalemia, gynecomastia, interacts wtih other K sparing drugs

Question 26

Ketoconazole aes?

Answer 26

Hepatic dysfunction and many drug drug interactions with CYP450

Question 27

Ketoconazole MOA?

Answer 27

blocks fungal and mammalian CYP450