Ch.27: Corticosteroids (Vickroy) Flashcards
What are corticosteroids
group of natural and synthetic substances that mimic in-part or wholly the actions of the adrenal hormone cortisol
*widely used and misused
Are most therapeutic uses of corticosteroids based on glucocorticoid or mineralocorticoid actions?
glucocorticoid (affects hypothalamic-pituitary-adrenal (HPA) axis to affect metabolic processes in many cells)
What do mineralocorticoid receptors control?
electrolyte handling/water retention. Control sodium retention and potassium loss
major physiological effects of corticosteroids*
- anti-inflamm.
- immunosuppressive
- metabolic changes (ie. metabolism)
- electrolyte balance
- CV homeostasis
low dose corticosteroids primarily affect:*
adrenal insufficiency
medium dose corticosteroids primarily cause:*
anti-inflamm.
high dose corticosteroids primarily cause:*
immunosuppression
Major clinical uses of corticosteroids (CCS)
- allergy/anti-inflamm.
- replacement therapy
- metabolic therapy
- immune suppression
- cancer
- circulatory shock
HPA axis
1) stressors stimulate hypothalamus to release CRH
2) CRH acts on pituitary gland to release ACTH
3) ACTH acts on adrenal glands to release cortisol
4) cortisol negatively feeds back to hypothalamus and pituitary gland
* exogenous glucocorticoids act like cortisol in this process to negatively feedback
examples of stressors
- fear/pain/cold/injury
- hemorrhage
- major sx
- severe infection
- hypoglycemia
what 2 main classes of receptors mediate effects of CCS?
glucocorticoid and mineralocorticoid receptors
which usually requires a higher dose: pharmacological or physiologic dose?
pharmacological
How do glucocorticoids (GC) evoke their actions?
- GENOMIC responses via cytosolics GCRs (slow)
- NON-GENOMIC responses via cytosolic or membrane-bound GCRs (fast)
main GC actions
- inc. carb. metabolism
- protein catabolism (aa shunted into gluconeogenesis)
- mobilization of fatty acids from adipose
- blockade of inflamm. cascade (higher doses)
- altered electrolyte and water balance
- CNS effects
how do GCs increase carb. metabolism?
inc. gluconeogenesis –> dec. cellular glucose use –> acute hyperglycemia
how do GCs block inflammatory cascade?
- dec. vasoactive/chemoattractive factors
- dec. lipolytic/proteolytic enzyme secretion
- dec. leukocyte infiltration
- dec. COX-2/NOS expression
How do GCs alter electrolyte and water balance
by activation of mineralocorticoid receptors, Na is retained, K and Ca are lost. Intestinal Ca absorption decreases, ADH decreases –> PUPD
adverse effects of GCs correlate with:**
DOSE and DURATION of treatment
Main GC adverse effects
- HPA axis suppression*
- GI ulceration (especially if combined with an NSAID)*
- muscle wasting
- immunosuppression
- hematopoietic changes
- behavioral changes
- diabetes
- hypothyroidism
- retarded growth
- electrolyte imbalance
- corneal ulceration
- abortion
- many effects overlap with NSAIDs.
hematopoietic changes assoc. with GCs
increased platelets/neuts/RBC
decreased platelet aggregation/lymphos/monos/eos
how to dampen HPA axis suppression effect of GCs
withdraw from GC tx SLOWLY
GC –> urine glucose
inc.
GC –> serum cholesterol
inc.
GC –> serum K+
dec.
GC –> thyroid function
dec.
precautions for GC therapy*
- NOT curative
- use topicals to lessen negative systemic imbalances
- use minimal dose
- withdraw tx slowly
GC contraindications
- pre-existing infections
- high dose in late pregnancy
- diabetes
- renal dz (due to fluid overload)
- CHF (due to fluid overload)
- young animals
- GI ulcers/hypersecretory disorders
4 types of administration routes for GCs
1) Topical (skin, eye, MM)
2) Inhaled (nasal mucosa, sinuses, bronchii, lungs)
3) Oral (include prednisone, prednisolone)
4) Systemic (IV, IM, SC, Intra-articular)
Pharmacokinetics of GCs
- actions last longer than drug lvls in plasma
- hepatic metabolism
- certain side chains delay metabolism and inc. duration of action
- many systemic agents NOT bound to transcortin, which enhances cellular penetration
Hydrocortisone
natural adrenal hormone that exhibits both gluco and mineralocorticoid activities*
- admin. via all routes
- anti-inflamm. at higher dose
- downside: affects body’s fluid balance
- used in SA and LA
most widely used GC agent across species
dexamethasone
dexamethasone (selectivity, dur. of action, potency, routes, species used in, side effects, etc.)
- most widely used GC agent across species
- GCR selective*
- long-acting, synthetic
- potent (30x more than cortisol)
- anti-inflammatory with rapid onset*
- routes: PO, IM, IV, topical
- used a lot in cattle
- can cause colonic perf. and laminitis in horses
Triamcinolone
- GCR selective*
- intermediate duration of action
- 4-5x more potent than cortisol
- routes: PO, parenteral, topical, inhalation
Prednisone/Prednisolone
- mineralocorticoid selective*
- synthetic
- 4-5x more potent than cortisol
- pred converts to prednisolone in liver
- use PREDNISOLONE in cats/horses, not prednisone because they don’t convert it well in the liver
- effects fluid balance
Methyl-prednisolone**
-GCR selective
-synthetic
-lipid antioxidant action
-dur. of action formulation-dependent:
Sodium succinate: water soluble, rapid effect*
Acetate: insoluble, long acting*
Order GCs in order of decreasing duration of action*
dexomethasone > triamcinolone > Prednisolone, Prednisone, Hydrocortisone
