Corticosteroids

Question 1

When is cortisol secretion maximal in 24 hours?

Answer 1

In the morning

Question 2

Why do we give a single dose of prednisone in the morning?

Answer 2

To mimic normal circadian rhythm of cortisol

Question 3

Where is the corticosteroid receptor located in the cell?

Answer 3

cytoplasmic receptor

Question 4

MoA of corticosteroids?

Answer 4

corticosteroids bind cytoplasmic receptor, drug-receptor complex enters nucleus binds glucocorticoid response elements (GRE) which regulate transcription leading to mRNA and protein synthesis.

Question 5

What are the major effects of glucocorticoids?

Answer 5

Anti-inflammatory and immunosuppressant (reduce synthesis of COX2, inhibit function of macrophage and APC, increase lymphocyte apoptosis, inhibit neutrophil migration, PlA2 and  decrease capillary permeability).
Precipitate diabetes (hyperglycemia and decrease insulin sensitivity).
Lipid metabolism (moon face, thin limbs , lemon on stick appearance).
Protein metabolism (muscle wasting, thinning of skin and delayed healing).
Electrolytes and water (edema and hypertension on prolonged use).
Calcium (inhibit its resorption increase its excretion, osteoporosis and fractures on prolonged use).
Aggravates peptic ulcer (increase acid synthesis).

Question 6

Why does prednisone have salt retention as a side effect?

Answer 6

Because it has mineralocorticoid activity (aldosterone)

Question 7

Does dexamethasone have salt retention effect?

Answer 7

No because it has no mineralocorticoid activity (aldosterone)

Question 8

What is the anti-inflammation potency sequence for corticosteroid?

Answer 8

Cortisol < prednisone < methylprednisolone = triamcinolone < dexamethasone

Question 9

How many days do we use methylprednisolone intensive therapy?

Answer 9

3-5 days

Question 10

Which test is used to differentiate primary and secondary adrenal failure?

Answer 10

Measure blood/urine cortisol levels before and after IV ACTH (cosyntropin). If cortisol does not double- primary adrenal insufficiency. If cortisol doubles- secondary adrenal insufficiency.

Question 11

What are the contraindications for corticosteroids?

Answer 11

peptic ulcer, heart disease, hypertension with heart failure, varicella, TB, psychosis, diabetes, osteoporosis and glaucoma

Question 12

What is the mechanism of aminoglutethimide?

Answer 12

Adrenocorticosteroid antagonist. inhibits CYP450 desmolase which is rate limiting step in conversion of cholesterol to pregnenolone. Decreases hypersecretion of cortisol in Cushing’s.

Question 13

Why can antifungal drug ketoconazole, treat Cushing’s syndrome?

Answer 13

Because inhibits steroid synthesis, all but 21 hydroxylase

Question 14

Which receptors are blocked by mifepristone?

Answer 14

Block glucocorticoid receptor.

Question 15

Fludrocortisone mimics cortisol or aldosterone?

Answer 15

Mimics aldosterone

Question 16

How many days are required for prednisone to suppress adrenal?

Answer 16

More than 2 weeks

Question 17

How do we stop prednisone after 2 weeks use?

Answer 17

Low dose should be used and tapered slowly without abrupt stopping.

Question 18

What are the side effects of glucocorticoid?

Answer 18

Adrenal suppression, diabetes, muscle wasting, osteoporosis (femur head avascular necrosis), peptic ulcer, inhibit wound healing, Cushing’s, decreased immunity, cataract, dermal atrophy and psychosis.

Question 19

What are the symptoms of acute and chronic adrenal failure? How is it treated?

Answer 19

Acute adrenal failure- fever, myalgia, malaise. Tx- low dose tapered slowly.
Chronic adrenal failure- hyper pigmentation, ACTH increase, hypotension, hyperkalemia, increase blood eosinophil and fasting hypoglycemia. Tx- hydrocortisone and fludrocortisone