Corticosteroids

Question 1

Where are corticosteroids synthesized and stored and what are they made with?

Answer 1

adrenal cortex, cholesterol

Question 2

What are the two types of corticosteroids?

Answer 2

glucocorticoids, mineralocorticoids

Question 3

Which is the primary example of glucocorticoid?

Answer 3

Cortisol

Question 4

Which is the primary example of mineralocorticoid?

Answer 4

Aldosterone

Question 5

What does Aldosterone do?

Answer 5

Na retention

Question 6

What effects does Cortisol have (3)?

Answer 6

metabolism, anti-inflammatory, immunosuppression

Question 7

Do Mineralocorticoids have any effect on glucocorticoid receptors?

Answer 7

No!

Question 8

Do glucocorticoids have affinity for mineralocorticoid receptor?

Answer 8

Yes! cross-reactivity (side effects)

Question 9

Hypothalamic-Pituitary-Adrenal (HPA) Axis: what hormone is released from hypothalamus?

Answer 9

Corticotropin releasing hormone (CRH)

Question 10

HPA axis: Which hormone is released from anterior pituitary?

Answer 10

Adrenocorticotropic hormone (ACTH)

Question 11

HPA axis: Which hormone is released from adrenal cortex?

Answer 11

Cortisol

Question 12

What is the regulatory mechanism of cortisol release?

Answer 12

negative feedback by cortisol at hypothalamus AND anterior pituitary (increases of cortisol is due to decreased negative feedback!)

Question 13

What is an example of a hypo-secretion pathology (cortisol)?

Answer 13

Addisons Disease

Question 14

What is an example of a hyper-secretion (cortisol) pathology?

Answer 14

Cushings Syndrome

Question 15

What are the corticosteroids to know (7)?

Answer 15

hydrocortisone, Prednisone, Triamcinolone, Dexamethasone, Betamethasone, Fluticasone, Fluocinonide

Question 16

Which corticosteroid is a prodrug?

Answer 16

prednisone

Question 17

Which corticosteroid is inhaled?

Answer 17

Fluticasone

Question 18

Which corticosteroid is topical?

Answer 18

fluocinonide

Question 19

Which corticosteroid is actually cortisol?

Answer 19

hydrocortisone

Question 20

What are the physiological actions of cortisol (5)?

Answer 20

1) activated gluconeogenesis and hyperglycemia (increase liver production of glucose)
2) activates catabolism of protein and lipids (permissive) (increase amino acids for gluconeogenesis)
3) maintains blood volume (activated mineralocorticoid receptors, just like aldosterone)
4) maintains vascular function (blood pressure) (enhance effect of catecholamines)
5) anti-inflammatory/immunosuppression (higher doses)

Question 21

What are the “activation” effects of glucocorticoids?

Answer 21

increase: gluconeogenesis genes, protein catabolism genes, and lipid catabolism genes…metabolism genes

Question 22

What are the “repression” effects of glucocorticoid?

Answer 22

decrease: prostaglandins, leukotrienes, cytokines…inflammatory-response genes

Question 23

What are 2 effects of corticosteroids on immune cells?

Answer 23

1) inhibition of migration from vascular space to site of injury (decrease endothelial intracellular adhesion molecules for leukocyte localization)
2) inhibition of phospholipase A2 and cycooxygenase-2 (decrease prostaglandins and leukotrienes)

Question 24

What is effect of corticosteroids on mast cells and basophils?

Answer 24

decrease histamine release

Question 25

What is effect of corticosteroids on monocytes and macrophages (3)?

Answer 25

decrease production of proinflammatory cytikines, decrease chemotaxis response, decrease differentiation into macrophages

Question 26

What is effect of corticosteroids on lymphocytes (3)?

Answer 26

decrease T cell response to antigens, mitogens, decrease proliferation, decrease proinflammatory cytokine gene expression

Question 27

What is the net effect of corticosteroids?

Answer 27

immunosuppression, anti-inflammatory, decreased pain and tissue destruction

Question 28

Are the anti-inflammatory effects of corticosteroids curative or palliative?

Answer 28

Palliative!

Question 29

What is the short-acting corticosteroid?

Answer 29

hydrocortisone

Question 30

What are the intermediate acting corticosteroids?

Answer 30

prednisone, triamcinolone

Question 31

What are the long acting corticosteroids?

Answer 31

dexamethasone, betamethasone

Question 32

Which ones don't cause any Na retention?

Answer 32

Triamcinolone, Dexamethasone, Betametasone

Question 33

What are the two other corticosteroids and what's unique about them?

Answer 33

Fluticasone (inhaled, reduced systemic effects), Fluocinonide (topical)

Question 34

What is the toxicity of corticosteroids with continued use?

Answer 34

Iatrogenic Cushing's Disease

Question 35

What are the toxicities of chronic use of corticosteroids (Iatrogenic Cushing's Disease) (8)?

Answer 35

hypertension (mineralocorticoid receptors and vasoconstriction), hyperglycemia (diabetes), susceptibility to infection/poor wound healing, osteoporosis (calcium loss), muscle myopathy/weakness, GI ulcers (NSAIDs), cataracts, psychosis

Question 36

What does withdrawal of corticosteroids cause?

Answer 36

iatrogenic adrenal insufficiency

Question 37

What are the characteristics of iatrogenic adrenal insufficiency?

Answer 37

adrenal-pituitary suppression due to feedback inhibition and adrenal atrophy...therefore suppresses normal response to stress. (ACTH and Cortisol release inhibited by prednisone)

Question 38

What are the symptoms of iatrogenic adrenal insufficiency? how long to restore hormone levels?

Answer 38

decreased response to stress: nausea, fatigue, weight loss, hypotension, shock. may require 2-6 months to restore normal ACTH/cortisol production

Question 39

What are the two dosage schedules for systemic oral corticosteroids?

Answer 39

Tapering dose, alternate day therapy

Question 40

What are the characteristics of tapering dose schedule (3)?

Answer 40

gradual reduction in dose over 2-3 months. prevents flare of inflammatory process. may allow recovery of adrenal-pituitary suppression

Question 41

What are characteristics of alternate day therapy (2)?

Answer 41

reduces side effects with chronic therapy metabolism/infection/growth. may prevent adrenal-pituitary suppression

Question 42

What are the therapeutic indications of corticosteroids (10)?

Answer 42

adrenal insufficiency, rheumatic disorders, renal disease, allergic disease, asthma, ocular, skin disease, GI diseases, organ transplantation, spinal injury

Question 43

Should you go look at the lecture practice problems?

Answer 43

probably.