Corticosteroids Flashcards
MOA of glucocorticoids
binds GC Receptor in cell and forms hormone-receptor complex that alters gene expression: incr. lipocortin- inhibits PLA 2a- inhibits AA metabolites prostaglandins, leukotrienes, PAF and inhibit production of mediators- cytokines, IL (1 & 4), TNF-a, adhesion molecules, enzyme e.g. collagenase
What corticosteroid is the shortest acting?
cortisol/hydrocortisone
What carbon on the coticosteroid structure is usually modified to create different drugs w/ different water/lipid solubility?
C-21
Esterification with a yields water-insoluble drugs.
monoacid- acetic acid (e.g. methylprednisolone acetate)
Esterification with a yields hydro-soluble drugs.
diacid- succinate acid (methylprednisolone sodium succinate)
phosphate esters
Why would a corticosteroid administered parenteral be longer acting than via PO?
PO- ester prodrug is activated via pancreatic esterases
parenteral- needs to be activated since it is in prodrug form when administered
which corticosteroid has a higher mineralcorticoid action than GC?
fludrocortisone
Differentiate plasma half-life and biological half-life?
plasma T1/2: time for 50% drug to be eliminated
biological T1/2: time for 50% effects of drug to wear off
Describe the biological half-life difference between alcohol/highly soluble esters, moderately soluble esters, & poorly soluble esters?
- alcohol/highly soluble esters: minutes to hours
- moderately soluble esters: days to weeks
- poorly soluble esters: weeks to months
What are the alcohol/highly soluble esters?
methylprednisolone sodium succinate (solu-medrol)
dexamethasone sodium phosphate (decadron)
Name the moderately soluble esters?
methylprednisolone acetate (depo-medrol)
fludrocortisone (florinef)
Name the poorly soluble esters.
triamcinolone acetonide (Vetalog)
betamethasone diproprionate (Otomax)
Describe the prednisone equivalents for physiological, anti-inflammatory, and immune suppression effects?
physiologic: 0.2 mg/kg/d
anti-inflammatory: 0.5-1 mg/kg/d
immune suppression: >2 mg/kg/d
How many times is dexamethasone more potent than prednisone?
7-10x
Is I have a Addison’s patient (not producing enough MC), what does of prednisone do they need?
physiologic: 0.2 mg/kg/d
Describe the physiologic effects corticosteroids have on the body?
increase gluconeogenesis in liver
stimulate lipolysis & protein catabolism
inhibit insulin & cause insuline resistance (cells decrease uptake of glucose)
non-fluorinated effects on water & electrolyte balance (MC effects)
What corticosteroid are fluorinated and have no MC activity?
What special effect do they have on the kidneys?
dexamethasone & triamcinolone
PU/PD effect: inhibit ADH secretion and decrease renal sensitivity to ADH
How do GC affect Calcium homeostasis?
enhance renal excretion & inhibit GI absorption of Ca-deplete Ca
inhibit osteoblasts, stimulate osteoclasts, increase PTH secretion-affect bone healing
What anti-inflammatory actions do GC have during acute inflammation?
decrease vascular permeabolity
inhibit migration lymphocytes neutrophils
induce lymphocyte apoptosis
reduce circulating eosinophils, basophils, monocytes
inhibit phagocytosis and free-radical production macrophages
inhibit fibroblasts
What salts adjuncts to coticosteroids are used in emegency situations w/ allergic rxns?
sodium phosphate & succinate (highly water soluble-rapid onset of action)
long term administration of supraphysiologic levels of corticosteroids may result in what condition?
iatrogenic Cushing’s syndrome (hyperadrenocorticism)
Describe the signs of Cushing’s
PU/PD
alopecia
suceptible to infection
myopathy & muscle atrophy- pendulous abdomen
redistribution of body fat
Abrupt disruption of corticosteroid treatment causes what?
Addisonian Crisis: lethargy, weakness, vomiting, diarrhea (severe cases- circulatory shock & death)
What drug is contraindicated with corticosteroids?
NSAIDs
What condition are we concerned about in horses treated with corticosteroids?
laminitis
