Steroids

Question 1

Corticosteroids

Answer 1

-from adrenal cortex:

1.zona fasciculata= glucocorticoids (eg.cortisol)

2. Zona glomerulosa= mineralocorticoids (eg. aldosterone)
3. Zona reticularis= sex steroids

Question 2

Glucocorticoid effects

Answer 2

-impacts metabolism, fat stores, and protein stores

Question 3

How do glucocorticoids (cortisol) effect metabolism?

Answer 3

-Increases blood glucose (increased gluconeogenesis and antagonizes insulin/glucose uptake)

Results in increase in fat breakdown (lipolysis) and proteolysis.

Question 4

Cortisols impact on immune system

Answer 4

1. Reduces inflammation (low to moderate dose) so helpful with allergic rxns and musculoskeletal inflammation
   **NO help with any pain/analgesia
2. Immunosuppression (high dose)- for immune mediated conditions
3. White blood cell changes (neutrophilia-high, lymphopenia-low) =stress leukogram

Question 5

Inflammation pathway

Answer 5

Glucocorticoids will result in stopping production of arachidonic acid therefore preventing both prostacyclin, thromboxane, and leukotrienes
**leukotrienes needed for immune response

Question 6

Glucocorticoid effects

Answer 6

1.Polyuria/polydipsia
2.Weak mineralocorticoid (aldosterone-like) effect
3. Increased plasma volume
4. Suppress hypothalamo-pituitary-adrenal (HPA) axis

Question 7

Polyuria/polydipsia from glucocorticoids

Answer 7

-not a clear mechanism

Possibilites:
1. steroids cause decrease in ADH release from posterior pituitary (central diabetes insipidus)
2. Steroids block ADH binding to V2 receptor on principle cell (nephrogenic diabetes insipidus)

Question 8

Weak mineralocorticoid (aldosterone-like) effect

Answer 8

Increase Na reabsorption from distal nephron therefore decrease in Na loss in urine

**Can lead to K wasting= increase K loss in urine

Question 9

Mineralocorticoid deficiency and glucocorticoids

Answer 9

Glucocorticoids are not sufficient! Need to use other drugs which mimic aldosterone

Question 10

Role in suppression of hypothalamo-pituitary-adrenal (HPA) axis

Answer 10

Glucocorticoids are basically heavily increased cortisol therefore large suppression of CRH and ACTH

Question 11

Glucocorticoid injectable

Answer 11

-Can be phosphate or succinate esters OR acetate/acetonide esters

Question 12

Phosphate or succinate ester glucocorticoid injectables

Answer 12

FAST ACTING
-IV or IM injections

Ex. Dexamethasone sodium phosphate

Question 13

Acetate/acetonide ester glucocorticoid injectables

Answer 13

SLOW ABSORPTION
-IM/SC.intra articular

Ex. Methylprenisolone acetate (Depo-Medrol)- used in dogs and cats

Ex. Prednisolone acetate

Question 14

Oral formulations of glucocorticoid formulations

Answer 14

-Prenisone/prenisolone
-Dexamethasone tabletes/powder

Question 15

Other glucocorticoid formulation types

Answer 15

-topical (does not always stay where you put them, some systemic absorption; often combined with antifungals and antibiotics)

-inhalant steroids (discussed in respiratory drugs)

-ophthalmic drops

Question 16

Glucocorticoid pharmacokinetics

Answer 16

-generally good oral bioavailability
-high volume of distribution >low plasma concentration but might be high tissue concentration
>plasma half life does not correlate with biological effect
>hepatic metabolism

Question 17

Hepatic metabolism of glucocorticoid pharmacokinetics

Answer 17

-Prednisone and cortisone are pro-drugs (prednisolone and cortisol are active forms)

-horses and cats have poor metabolism of prednisone to prednisolone conversion

Question 18

Prednisone in Cats

Answer 18

-if given prednisone then conversion to prednisolone is much lower and therefore less active in the blood

**still will work, but may need higher dose to have same effect

Question 18

Dosing glucocorticoids

Answer 18

1. Use smallest possible dose
   *potency of different steroids varies although dosage is different (ex. Hydrocortisone= 1 potency vs. Prednisone= 4 potency… therefore 1mg/kg is not the same)
   -anti-inflammatory=5-10x physiological dose
   -immunosuppressive= 20x
   -shock doses= 100-200x
2. Avoid HOA suppression
   -need to taper slowly (use lower doses, or longer dosing interval)

Question 19

Glucocorticoid adverse effects

Answer 19

-Metabolic effects
-hemodynamic effects
-muscle atrophy
-delayed wound healing
-Inflammation and damage
-laminitis
-polyuria/polydipsia
-abortion
-polyphagia and weight gain
-immune suppression
-HPA suppression

Question 20

Metabolic effects of glucocorticoids

Answer 20

-Hyperadrenocorticism
>”cushingoid”- pot bellied, lack of fur, sagging skin

-Hyperglycemia
>diabetes in cats from increased blood glucose (esp. Depo-medrol)

Question 21

Hemodynamic effects of glucocorticoids

Answer 21

-Plasma volume expansion leads to increase in glucose or Na

-See decrease in RBC, PCV, Hb
-See left shift

Question 22

muscle atrophy of glucocorticoids

Answer 22

-See proteolysis

Question 23

Delayed wound healing of glucocorticoids

Answer 23

-Thin skin appearance
-decrease in immune function

Question 24

Inflammation and damage of glucocorticoids

Answer 24

**prostaglandins are cytoprotective (increase in mucosal blood flow, bicarbonate and mucous production) and when inhibited, results in
-GI ulceration
-pancreatitis
-Renal damage

Question 25

Laminitis from glucocorticoids

Answer 25

Causality not confirmed!

-altered hoof vascular flow, weakened coffin bone to support laminae
-insulin resistance