Steroids Flashcards
How big is dosage range for steroids?
150-fold difference!
Where do corticosteroids come from?
adrenal ctx
where do glucocorticoids come from and what is an ex?
zona fasciculata, ex: cortisol
What are the effects of glucocorticoids on metabolism?
- increase blood glucose (increased gluconeogenesis, antagonize insulin (decreased glucose uptake); why they are effective therapy for ketosis (good!); why diabetes mellitus can occur w/ chronic use (bad!)
- lipolysis
- proteolysis
(increases all of these mcs in bloodstream - mobilization of metabolic fuels & building blocks -> naturally occurs as adaptation to stress)
How does the immune system respond to glucocorticoids?
- reduce inflammation (low-moderate dose): useful for allergic reactions & musculoskeletal inflammation, but NOT necessarily helpful for pain due to musculoskeletal disease (like osteoarthritis)
- immunosuppressive (high dose): for immune-mediated conditions
- wht blood cell changes (neutrophilia, lymphopenia): “Stress leukogram”
Why are glucocorticoids immunosuppressive?
Glucocorticoids inhibit the synthesis of arachidonic acid from diacylglycerol or phospholipid, leading to reduction in leukotrienes (which modulate immune responses & resolve inflammation)
What are the effects of glucocorticoids on water & electrolyte balance?
- PU/PD: physiological mech isnt really clear (maybe steroids cause decreased ADH release from posterior pituitary - “central diabetes insipidus” or maybe steroids block binding of ADH to V2 receptor on principal cell - “nephrogenic diabetes insipidus”)
- weak mineralcorticoid (aldosterone-like) effect:
- increased sodium reabsorption from distal nephron (decreased loss of sodium in urine)
- can lead to potassium wasting (increased loss of potassium in urine)
so, increased blood glucose &/or sodium:
- possible increased plasma volume or impact on BP? (Note: hyperglycemia &/or hypernatremia generally not significant enough to cause polyuria)
- Note: for treating MINERALOcorticoid deficiency in hypoadrenocorticism (Addison’s), glucocorticoids are not sufficient. instead, use drugs that better mimic aldosterone!
What is another effect of glucocorticoids?
suppress hypothalamo-pituitary-adrenal (HPA) axis (b/c cortisol inhibits (negative feedback loop) both anterior pituitary & hypothalamus)
- important concept for steroid dosing regimens!
What options are there for glucocorticoid formulations as injectable products?
- phosphate or succinate esters = FAST-ACTING
- IV or IM injections
- formulation: Dexamethasone sodium phosphate (multiple vet products) - acetate/acetonide esters = SLOW ABSORPTION
- IM/SC/ intra-articular
- methylprednisolone acetate (DepoMedrol) -> long acting steroid used mostly in Ca/Fe
- prednisolone acetate (multiple generic versions)
Routes of glucocorticoid formulation administration other than injectable?
- oral - vet & human products (prednisone/prednisolone, dexamethasone tablets/powder)
- topical - some systemic absorption (often combined w/ antifungals & antibiotics)
- inhalant steroids
- ophthalmic drops
What are the pharmacokinetics of glucocorticoids?
- generally good oral bioavailability
- high vol of distribution
> low [plasma] - but might be high [tissue]
> plasma half-life DOESNT correlate w/ biological effect - hepatic metabolism
> prednisone & cortisone are pro-drugs (prednisolone & cortisol are active forms)
>Eq & Fe have poor metabolism of prednisone to prednisolone
How do you dose glucocorticoids?
- use smallest possible dose
> anti-inflammatory = 5-10x physiological dose
> immunosuppressive = 20 x
> “shock” doses = 100-200x (no longer used?) - avoid HPA suppression
> dont stop “cold turkey”
> taper slowly: use lower doses or longer dosing intervals
What are the adverse effects of glucocorticoids?
- metabolic effects
- hyperadrenocorticism (cushingoid)
- hyperglycemia (diabetes in Fe - esp: DepoMedrol) - hemodynamic effects
- plasma vol expansion (increased glucose or sodium)
- RBC, PCV, Hb decrease (dilution effect) - muscle atrophy (proteolysis)
- delayed wound healing
- block production of prostaglandins
- prostaglandins are cytoprotective (increase mucosal blood flow, bicarb, & mucus production)
- anti-inflammatory drugs can lead to: GI ulceration, pancreatitis, renal damage
- be very careful with concurrent use of NSAIDS (washout periods when switching anti-inflammatories - laminitis (controversial)
- potential altered hoof vascular flow, weakened coffin bone support to laminae, or insulin resistance? - PU/PD
- abortion (depends on spp, gestation stage, dose)
- polyphagia & weight gain (may be beneficial?)
- immune suppression (increased infection risk)
- HPA suppression
