12 – Steroids Flashcards
Where are corticosteroids produced?
- Adrenal cortex
o Zona fasciculata=glucocorticoids (ex. cortisol)
o Zona glomerulosa=mineralocorticoids (ex. aldosterone)
o Zona reticularis=sex steroids
Glucocorticoid effects on metabolism?
- Increase blood glucose
- Lipolysis
- Proteolysis
Glucocorticoids increase blood glucose
- increase gluconeogenesis, antagonizing insulin (decrease glucose uptake)
o why they are good therapy for ketosis(animals in a negative energy balance)=good
o why diabetes mellitus can occur with chronic GC use=bad
Glucocorticoid effects on the immune system: low to moderate dose
- reduce inflammation
o use for allergic reactions and musculoskeletal inflammation
o NOT necessarily helpful for pain due to musculoskeletal disease
Glucocorticoid effects on the immune system: high dose
- Immunosuppression
o For immune-mediate conditions
Glucocorticoid effects on the immune system
- White blood cell changes (neutrophilia, lymphopenia
o ‘stress leukogram’
Inflammation pathway - peripheral (glucocorticoids)
- Phospholipids broken down into AA=BLOCKED by glucocorticoids
o Prostaglandins, prostacyclins, thromboxane, leukotrienes - *block the same pathway of NSAIDs but different enzymes=slightly different results
o Steroids=produces less leukotrienes (don’t see that with NSAIDs)
Glucocorticoid effects on water and electrolyte balance
- Polyuria/polydipsia
- Weak mineralocorticoid (aldosterone) effect
- Increase plasma volume?
Polyuria/polydipsia: possible physiological mechanisms (glucocorticoid)
- Cause decrease ADH release from P. pituitary=’central diabetes insipidus’
- MORE LIKELY: Block ADH binding to the V2 receptor on principal cells=’nephrogenic diabetes insipidus’
Weak mineralocorticoid (aldosterone-like) effect
- Increase Na+ reabsorption from distal nephron
o Decrease Na+ loss in urine - Can lead to potassium wasting
o Increase K+ loss in urine
*cannot use it to treat mineralocorticoid deficiency in hypoadrenocorticism (Addison’s disease)
Glucocorticoid effect on HPA axis
- SUPPRESSES
- *impacts steroid dosing regimens
Glucocorticoid formulations: injectable products
- Phosphate or succinate esters=’fast-acting’
- Acetate/acetonide esters=slow
**SALTS matter
Phosphate or succinate esters
- ‘fast-acting’
- IV or IM injections
- Different formulations
o *Dexamethasone sodium phosphate
Acetate/acetonide esters
- SLOW absorption
- IM/SC/Intra-articular
- Ex. methylprednisolone acetate (Depo-Medrol: ‘long-acting’ steroid used mostly in dogs/cats)
- Ex. prednisolone acetate
Other routes of administration
- Oral formulations: vet or human products
- Topical
- Inhalant steroids
- Ophthalmic drops
Oral formulations examples
- Prednisone/prednisolone
- Dexamethasone tablets/powder
Topical
- Some systemic absorption
- Often combined with antifungals and antibiotics
High volume of distribution
- Low plasma concentration, but might be high concentration in tissues
- Plasma half-life does NOT correlate with biological effect
Glucocorticoid pharmacokinetics
- Generally good oral bioavailability
- High volume of distribution
- Hepatic metabolism
Hepatic metabolism
- Prednisone and cortisone=PRO-DRUGS
o prednisOLone and cortisOL=ACTIVE forms - horses and cats have POOR metabolism of prednisone to prednisolone
Prednisone PK in cats: clinical relevance
- it does work, but dose needs to be higher or effect is NOT as obvious
- rather give them the active drug (prednisolone)
Dosing glucocorticoids
- use SMALLEST POSSIBLE dose
- avoid HPA suppression
- *potency is NOT an issue (need to be careful when dosing)
Smallest possible dose
- anti-inflammatory: 5-10x physiological dose (lower)
- Immunosuppressive: 20x (moderate)
- ‘shock’ doses: 100-200x (no longer used, dangerous)
Avoid HPA suppression
- Don’t stop ‘cold turkey’
- *Taper slowly: use lower doses OR longer dose intervals
- The body thinks there is still lots of steroids in the body=animal not producing their own steroid, NEED time to get back on track
Glucocorticoid adverse metabolic effects
- Hyperadrenocorticism (‘cushingoid’: pot belly, lack of fur on ventral abdomen)
- Hyperglycemia
o Diabetes in cats (Especially Depo-Medrol=long acting)
Glucocorticoid adverse hemodynamic effects
- Plasma volume expansion: increase glucose or Na+
- Blood work: decrease in RBC, PCV, Hb
o ‘dilution-effect’
Prostaglandins are cytoprotective (adverse effects)
- Increase mucosal blood flow
- Increase bicarbonate and mucus production
- *anti-inflammatory drugs (prostaglandin INHIBITION, ex. steroids) can lead to GI ulceration, pancreatitis, renal damage
- BE CAREFULEWITH CONCURRENT USE OF NSAIDs
- *Do NOT mix steroids with other anti-inflammatories
Other glucocorticoid adverse effects
- Muscle atrophy: proteolysis
- Delayed wound healing
- Laminitis
- Polyuria/polydipsia
- Abortion
- Polyphagia and weight gain (may be beneficial?)
- Immune suppression (increase infection risk)
- HPA suppression
Laminitis (controversial)
- Altered hoof vascular flow?
- Weakened coffin bone support to laminae?
- Insulin resistance?
