Steroids - Konorev

Question 1

Renal functions of MC receptor activation

Answer 1

Increased ENaC + Increased Na/K pump

= Water and Na+ retention, K+ wasting

Question 2

Excess MC effects on cardiovascular system

Answer 2

Cardiac fibrosis and hypertrophy (increased collagen and TGF-beta)
Vascular remodeling and inflammation (increased IL-6, adhesion molecules)

Question 3

GC have effects on metabolism of _________

Answer 3

Carbs, lipids, and proteins

Question 4

GC have suppressive effects on ________

Answer 4

Inflammation and growth

Question 5

Genetics of GC resistance

Answer 5

Overexpression of GR-beta isoform (inactive) – due to TNF-alpha

Question 6

11-beta-hydroxysteroid dehydrogenase type 2 (11 b-HSD2)

Why is it needed?

Answer 6

Inactivates cortisol and prednisolone at MC receptor (MR), allowing for appropriate level of MC responsiveness

Cortisol and Aldosterone otherwise bind to MC receptor equally

Question 7

11-beta-hydroxysteroid inhibition

What can do this?

Answer 7

Increased MR activation by cortisol –> HTN, edema

Licorice root extract

Question 8

Apparent mineralocorticoid excess syndrome (AME)

Answer 8

Mutated 11-beta-hydroxysteroid –> HTN, edema

Question 9

Effects of GC on carbohydrate metabolism

RESULT?

Answer 9

• Increased gluconeogenesis, glycogen synthesis, glucose release into blood
• Decreased glucose uptake by tissues

RESULT = HYPERGLYCEMIA

Question 10

Effects of GC on lipid metabolism

RESULT?

Answer 10

Change in fat distribution (insulin vs. cortisol)

RESULT = FAT ACCUMULATION in upper body and face, thinning of extremities

Question 11

Effect of GC on protein metabolism

RESULT?

Answer 11

Decreased AA uptake and protein synthesis

RESULT= myopathy, MUSCLE WASTING

Question 12

Effects of GC on immune system

RESULT?

Answer 12

Decreased PLA2, COX2, immune cell reproduction, cytokines, adhesion molecules, transmigration into tissues

RESULT = decreased inflammation, increased INFECTIONS

Question 13

Effects of GC on CV system

RESULT?

Answer 13

Increased sympathetics, increased MC activity

RESULT = Tachycardia, HTN, increased cardiac output

Question 14

Effects of GC on GI system

RESULT?

Answer 14

Decreased prostaglandins, immune response to H. pylori
Increased gastric acid and pepsin

RESULT = peptic ULCERS

Question 15

Effects of GC on bones/growth

RESULT?

Answer 15

Increased osteoclastic activity, decreased osteoblasts

RESULT = growth retardation, osteoporosis, fractures

Question 16

Effects of GC on skin

RESULT?

Answer 16

Decreased collagen, fibroblasts, wound healing

RESULT = thin skin, purple STRIAE

Question 17

Addison’s disease - treatment

Answer 17

Glucocorticoid drug (Hydrocortisone, prednisone, etc.) + Mineralocorticoid drug (Fludrocortisone)

Question 18

Immunosuppression (transplant, MS, leukemia) - drug?

Answer 18

Corticosteroid

Question 19

RA, IBD, asthma, COPD, psoriasis, hypersensitivity - treatment?

Answer 19

Corticosteroid

Question 20

Fludrocortisone - adverse effects

Answer 20

Edema, HTN, CHF, hypokalemia, alkalosis

Question 21

Glucocorticoids - adverse effects

Answer 21

Opportunistic infections, hyperglycemia, striae/easy bruising, muscle wasting, HTN, glaucoma, ulcers, euphoria/mania/anxiety, weight gain, osteoporosis, growth retardation (kids)

Question 22

How to dose corticosteroids? (4)

Answer 22

• Lowest dose, shortest duration
• Reduce systemic distribution
• Pulse therapy administration
• Dose tapering

Question 23

Contraindications to corticosteroids

Answer 23

• Immunocompromised
• Diabetes
• Infections
• Peptic ulcers
• CV conditions
• Psych conditions
• Osteoporosis
• CHILDREN

Question 24

Aminoglutethimide - MoA (what is reduced?)

Answer 24

Corticosteroid inhibitor - blocks conversion of cholesterol to pregnenolone (ALL STEROIDS REDUCED)

Question 25

Aminoglutethimide - indication

Answer 25

Adrenocortical cancer

Question 26

Ketoconazole - MoA (what is reduced?)

Answer 26

Corticosteroid inhibitor - P450 inhibition (ADRENAL AND SEX HORMONES REDUCED)

Question 27

Ketoconazole - indications (4)

Answer 27

Fungal infections, Cushing’s syndrome, androgenic hair loss, prostate cancer

Question 28

Ketoconazole - adverse effects

Answer 28

Hepatotoxicity, Gynecomastia (males)

Question 29

Metyrapone - MoA (what is reduced?)

Answer 29

Corticosteroid inhibitor - 11-beta-hydroxylase inhibitor (CORTISOL REDUCED)

Question 30

Metyrapone - indications

Answer 30

Cushing’s syndrome (IN PREGNANCY too)

Question 31

Metyrapone - adverse effects

Answer 31

• HTN, edema (more aldosterone from built-up precursor)

- Hirsutism (women) (more androgens from precursor)

Question 32

Mitotant - MoA

Answer 32

Adrenal cortex killer - Ionophore, PKC and AC inhibitor

Question 33

Mitotant - indication

Answer 33

Adrenal carcinoma

Question 34

Mitotant - adverse effects

Answer 34

Depression/somnolence, skin rashes

Question 35

Mifepristone - MoAs (3)

Answer 35

• GC receptor antagonist
• Prevents HSP90-GR complex nuclear translocation
• Progesterone receptor antagonist

Question 36

Mifepristone - indications (2)

Answer 36

Cushing’s syndrome, intrauterine abortion

Question 37

Spironolactone - MoA (2)

Answer 37

• Aldosterone receptor antagonist

- Androgen receptor antagonist

Question 38

Spironolactone - indications (3)

Answer 38

• Primary hyperaldosteronism
• Hirsutism (women)
• HF/HTN diuretic

Question 39

Spironolactone - adverse effects

Answer 39

Hyperkalemia, gynecomastia/impotence (men), menstrual abnormalities (women)

Question 40

Eplerenone - MoA

Answer 40

Competitive antagonist of aldosterone at MC receptors

Question 41

Eplerenone - indications

Answer 41

Diuretic (HTN, HF)

Question 42

Eplerenone - adverse effect

Answer 42

Hyperkalemia