Antiinflammatory Steroids

Question 1

Mineralocorticoids - general function

Answer 1

water, electrolyte balance

Question 2

Glucocorticoids general function

Answer 2

Carbohydrate/Protein metabolism

Inflammation

Question 3

Basic corticosteroid, used for comparison of relative potency

Answer 3

Cortisol

Question 4

Most potent corticosteroids

Answer 4

Betamethasone, Dexamethasone

Question 5

Steroids are synthesized endogenously in response to

Answer 5

Stress, Trauma, Surgery, Hemorrhage, infection, cold, pain, fear.

Question 6

Regulation of steroid synthesis

Answer 6

Corticotropin Releasing Hormone (CRH) is released from the hypothalamus, and stimulates the anterior pituitary to release Adrenocortotropic Hormone (ACTH), which stimulates the fasciculata cells of the adrenal cortex to release cortisol.

Question 7

Glucocorticoid effects on carbohydrate and protein metabolism

Answer 7

Increase liver synthesis of glucose, glycogen deposition.

Increases protein breakdown and decreases glucose utilization by peripheral tissues.

The overall effect is to conserve glucose.

Question 8

Glucocorticoid effects on lipid metabolism

Answer 8

Increase in free fatty acids

Question 9

Glucocorticoid effects on cardiovascular, nervous, and muscle systems

Answer 9

Hypertension

Alterations in mood/behavior

Muscle Wasting (due to protein catabolism)

Question 10

How do glucocorticoids reduce inflammation?

Answer 10

Alter lymphocyte activity

Alter cytokine release and synthesis by macrophages and monocytes

Decrease production of leukotrienes and prostaglandins.

Question 11

Do steroids prevent or suppress the underlying disease process causing the inflammation?

Answer 11

No

Question 12

Where do glucocorticoids act in the cell?

Answer 12

At receptors in the cytosol. They bind ligands and induce the expression of new proteins.

Question 13

Mineralocorticoid behavior at cortisol receptor

Answer 13

High affinity, long duration binding.

Question 14

Why doesn’t cortisol stimulate mineralocorticoid receptors in the kidney?

Answer 14

Mineralocorticoid tissues avoid being stimulated by cortisol by converting cortisol to cortisone using 11-betahydroxysteroid dehydrogenase 2.

Question 15

What happens if you inactivate 11-betahydroxysteroid dehydrogenase 2? What can cause this?

Answer 15

Cortisol acts like aldosterone in the kidney, causing fluid retention and hypertension. This can be caused by eating licorice.

Question 16

Why is cortisol production important during an inflammatory response?

Answer 16

Cortisol protects against the life threatening consequences of an uncontrolled inflammatory response (think septic shock)

Question 17

Glucocorticoid receptor - 4 functions

Answer 17

Increased Annexin 1

Decreased prostaglandin/leukotrienes

Decreased COX-2

Decreased TNF-alpha

Question 18

Annexin 1 function

Answer 18

Inhibits phospholipase A2, a necessary enzyme for production of Arachidonic Acid, necessary for prostaglandins/leukotrienes

Question 19

COX 2 function

Answer 19

Conversion of Arachidonic acid to prostaglandins

Question 20

TNF alpha function

Answer 20

Increases epithelial permeability, releases proteinases, chemokines, interferon, and something called NFkB - All of these help macrophages, lymphocytes and NK cells kill infected cells as part of the inflammatory process.

Question 21

Steroids ADME

Answer 21

PO, IV, IM, Topical
Good systemic distribution (lipid soluble)
Hepatic Metabolism
Renal Excretion

Question 22

Steroid toxicity

Answer 22

Cessation - adrenal involution due to prolonged high dose, can no longer produce enough.

High doses - mimics Cushing’s Syndrome

Question 23

How do you withdraw steroid therapy without causing toxicity?

Answer 23

By slowly tapering the dose

Question 24

Therapeutic Principles

Answer 24

Short course is unlikely to be harmful

The longer the therapy, the higher the risk of adverse effects

Use the lowest dose possible!