Steroids Flashcards
Corticosteroids
-from adrenal cortex:
1.zona fasciculata= glucocorticoids (eg.cortisol)
- Zona glomerulosa= mineralocorticoids (eg. aldosterone)
- Zona reticularis= sex steroids
Glucocorticoid effects
-impacts metabolism, fat stores, and protein stores
How do glucocorticoids (cortisol) effect metabolism?
-Increases blood glucose (increased gluconeogenesis and antagonizes insulin/glucose uptake)
Results in increase in fat breakdown (lipolysis) and proteolysis.
Cortisols impact on immune system
- Reduces inflammation (low to moderate dose) so helpful with allergic rxns and musculoskeletal inflammation
**NO help with any pain/analgesia - Immunosuppression (high dose)- for immune mediated conditions
- White blood cell changes (neutrophilia-high, lymphopenia-low) =stress leukogram
Inflammation pathway
Glucocorticoids will result in stopping production of arachidonic acid therefore preventing both prostacyclin, thromboxane, and leukotrienes
**leukotrienes needed for immune response
Glucocorticoid effects
1.Polyuria/polydipsia
2.Weak mineralocorticoid (aldosterone-like) effect
3. Increased plasma volume
4. Suppress hypothalamo-pituitary-adrenal (HPA) axis
Polyuria/polydipsia from glucocorticoids
-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)
Weak mineralocorticoid (aldosterone-like) effect
Increase Na reabsorption from distal nephron therefore decrease in Na loss in urine
**Can lead to K wasting= increase K loss in urine
Mineralocorticoid deficiency and glucocorticoids
Glucocorticoids are not sufficient! Need to use other drugs which mimic aldosterone
Role in suppression of hypothalamo-pituitary-adrenal (HPA) axis
Glucocorticoids are basically heavily increased cortisol therefore large suppression of CRH and ACTH
Glucocorticoid injectable
-Can be phosphate or succinate esters OR acetate/acetonide esters
Phosphate or succinate ester glucocorticoid injectables
FAST ACTING
-IV or IM injections
Ex. Dexamethasone sodium phosphate
Acetate/acetonide ester glucocorticoid injectables
SLOW ABSORPTION
-IM/SC.intra articular
Ex. Methylprenisolone acetate (Depo-Medrol)- used in dogs and cats
Ex. Prednisolone acetate
Oral formulations of glucocorticoid formulations
-Prednisone/prednisolone
-Dexamethasone tabletes/powder
Other glucocorticoid formulation types
-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
Glucocorticoid pharmacokinetics
-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
Hepatic metabolism of glucocorticoid pharmacokinetics
-Prednisone and cortisone are pro-drugs (prednisolone and cortisol are active forms)
-horses and cats have poor metabolism of prednisone to prednisolone conversion
Prednisone in Cats
-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
Dosing glucocorticoids
- 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 - Avoid HOA suppression
-need to taper slowly (use lower doses, or longer dosing interval)
Glucocorticoid adverse effects
-Metabolic effects
-hemodynamic effects
-muscle atrophy
-delayed wound healing
-Inflammation and damage
-laminitis
-polyuria/polydipsia
-abortion
-polyphagia and weight gain
-immune suppression
-HPA suppression
Metabolic effects of glucocorticoids
-Hyperadrenocorticism
>”cushingoid”- pot bellied, lack of fur, sagging skin
-Hyperglycemia
>diabetes in cats from increased blood glucose (esp. Depo-medrol)
Hemodynamic effects of glucocorticoids
-Plasma volume expansion leads to increase in glucose or Na
-See decrease in RBC, PCV, Hb
-See left shift
muscle atrophy of glucocorticoids
-See proteolysis
Delayed wound healing of glucocorticoids
-Thin skin appearance
-decrease in immune function
Inflammation and damage of glucocorticoids
**prostaglandins are cytoprotective (increase in mucosal blood flow, bicarbonate and mucous production) and when inhibited, results in
-GI ulceration
-pancreatitis
-Renal damage
Laminitis from glucocorticoids
Causality not confirmed!
-altered hoof vascular flow, weakened coffin bone to support laminae
-insulin resistance
