Corticosteroids

Question 1

MOA of glucocorticoids

Answer 1

binds GC Receptor in cell and forms hormone-receptor complex that alters gene expression: incr. lipocortin- inhibits PLA 2a- inhibits AA metabolites prostaglandins, leukotrienes, PAF and inhibit production of mediators- cytokines, IL (1 & 4), TNF-a, adhesion molecules, enzyme e.g. collagenase

Question 2

What corticosteroid is the shortest acting?

Answer 2

cortisol/hydrocortisone

Question 3

What carbon on the coticosteroid structure is usually modified to create different drugs w/ different water/lipid solubility?

Answer 3

C-21

Question 4

Esterification with a yields water-insoluble drugs.

Answer 4

monoacid- acetic acid (e.g. methylprednisolone acetate)

Question 5

Esterification with a yields hydro-soluble drugs.

Answer 5

diacid- succinate acid (methylprednisolone sodium succinate)

phosphate esters

Question 6

Why would a corticosteroid administered parenteral be longer acting than via PO?

Answer 6

PO- ester prodrug is activated via pancreatic esterases

parenteral- needs to be activated since it is in prodrug form when administered

Question 7

which corticosteroid has a higher mineralcorticoid action than GC?

Answer 7

fludrocortisone

Question 8

Differentiate plasma half-life and biological half-life?

Answer 8

plasma T1/2: time for 50% drug to be eliminated

biological T1/2: time for 50% effects of drug to wear off

Question 9

Describe the biological half-life difference between alcohol/highly soluble esters, moderately soluble esters, & poorly soluble esters?

Answer 9

1. alcohol/highly soluble esters: minutes to hours
2. moderately soluble esters: days to weeks
3. poorly soluble esters: weeks to months

Question 10

What are the alcohol/highly soluble esters?

Answer 10

methylprednisolone sodium succinate (solu-medrol)

dexamethasone sodium phosphate (decadron)

Question 11

Name the moderately soluble esters?

Answer 11

methylprednisolone acetate (depo-medrol)

fludrocortisone (florinef)

Question 12

Name the poorly soluble esters.

Answer 12

triamcinolone acetonide (Vetalog)

betamethasone diproprionate (Otomax)

Question 13

Describe the prednisone equivalents for physiological, anti-inflammatory, and immune suppression effects?

Answer 13

physiologic: 0.2 mg/kg/d

anti-inflammatory: 0.5-1 mg/kg/d

immune suppression: >2 mg/kg/d

Question 14

How many times is dexamethasone more potent than prednisone?

Answer 14

7-10x

Question 15

Is I have a Addison’s patient (not producing enough MC), what does of prednisone do they need?

Answer 15

physiologic: 0.2 mg/kg/d

Question 16

Describe the physiologic effects corticosteroids have on the body?

Answer 16

increase gluconeogenesis in liver

stimulate lipolysis & protein catabolism

inhibit insulin & cause insuline resistance (cells decrease uptake of glucose)

non-fluorinated effects on water & electrolyte balance (MC effects)

Question 17

What corticosteroid are fluorinated and have no MC activity?

What special effect do they have on the kidneys?

Answer 17

dexamethasone & triamcinolone

PU/PD effect: inhibit ADH secretion and decrease renal sensitivity to ADH

Question 18

How do GC affect Calcium homeostasis?

Answer 18

enhance renal excretion & inhibit GI absorption of Ca-deplete Ca

inhibit osteoblasts, stimulate osteoclasts, increase PTH secretion-affect bone healing

Question 19

What anti-inflammatory actions do GC have during acute inflammation?

Answer 19

decrease vascular permeabolity

inhibit migration lymphocytes neutrophils

induce lymphocyte apoptosis

reduce circulating eosinophils, basophils, monocytes

inhibit phagocytosis and free-radical production macrophages

inhibit fibroblasts

Question 20

What salts adjuncts to coticosteroids are used in emegency situations w/ allergic rxns?

Answer 20

sodium phosphate & succinate (highly water soluble-rapid onset of action)

Question 21

long term administration of supraphysiologic levels of corticosteroids may result in what condition?

Answer 21

iatrogenic Cushing’s syndrome (hyperadrenocorticism)

Question 22

Describe the signs of Cushing’s

Answer 22

PU/PD

alopecia

suceptible to infection

myopathy & muscle atrophy- pendulous abdomen

redistribution of body fat

Question 23

Abrupt disruption of corticosteroid treatment causes what?

Answer 23

Addisonian Crisis: lethargy, weakness, vomiting, diarrhea (severe cases- circulatory shock & death)

Question 24

What drug is contraindicated with corticosteroids?

Answer 24

NSAIDs

Question 25

What condition are we concerned about in horses treated with corticosteroids?

Answer 25

laminitis