GLUCOCORTICOID Flashcards
cortisol moa
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glucocorticoid receptor subtypes
type 1 - mineralocorticoid (misnomer) - kidney, colon, salivary glands, sweat glands; type 2 - glucocorticoid - broad tissue distribution
glucocorticoid response elements
effectuate all changes in gene expression - contained in ~10% of all human genes -> huge impact
cortisol effects, ideally
keep humoral/local inflammatory response reasonable; protect glucose-dependent tissue from starvation; switch to catabolism -> preserve electrolytes/water; improve mood
cortisol metabolic effects: protect glucose-dependent tissues from starvation
stimulate gluconeogenesis from AA, glycerol; stimulate liver glycogen; dec gluc use in periphery; stimulate insulin secretion - bring gluc to cells; stimulate lipolysis; NET EFFECT - inc plasma gluc
cortisol metabolic effects: increase nutrient availability for the brain
stim gluconeogenesis from AA, glycerol; stimulate liver glycogen storage; dec gluc use peripherally; stim insulin secretion; stim lipolysis -> NET EFFECT - inc plasma gluc/TGs -> HYPERGLYCEMIC; protein CATABOLISM, mainly muscle -> inc plasma AA
cortisol metabolic effects: electrolyte, water balance
aldosterone-like effects; NET EFFECTS - positive na-balance, ecv expansion, hypokalemia, alkalosis; dec body ca++ stores (dec intestinal absorption, inc renal excretion)
adrenal crisis metabolic imbalances
caused by abrupt discontinuation of exogenous GC; hyponatremia, hypovolemia, hyperkalemia, acidosis (low bicarb), hypoglycemia, inc BUN
adrenal crisis symptoms
dehydration, hypotension, abdominal complaints, “pseudo-peritonitis”, hypothermia -> dehydration-related fever, delirium, coma; tx w/cortisol, cortisone
cortisol effects: immunosuppressive/anti-inflammatory
down-reg stress from injury; interfere w/peripheral leukocyte fxn; move leukocytes to lymphatics; suppress inflammation mediators; suppress mast cell degranulation; inhibit lipoxygenase; inhibit COX-2; inhibit complement effects (not activation); antibody production inhibited (high doses only)
cortisol effects: cns
variable effects on mood, behavior, excitability, insomnia, euphoria -> depression; may inc icp (large doses); improve mood, appetite in terminally ill pt’s
cortisol effects: fetal lung maturation
critically important b4 gestational wk 34; preterm: inject 2 doses -> mature lungs, stim pulmonary surfactant production
corticosteroids used as aerosol inhalants
for asthma - beclomethasone, budesonide; high first pass metabolism
glucocorticoids adverse effects
low dose inhalant/topical - local ae’s, none systemic; high dose inhalant/topical - local ae’s, minor systemic; prolonged systemic use - severe -> only use if not alternatives; single ultrahigh dose bolus - inc risk of pre-existing infection, aggravation of DM, inc risk of stress ulcers
glucocorticoids adverse effects: prolonged systemic use
similar to cushing’s syndrome - affects skin, bone, sk muscle, eyes, GI, cv system, blood, electrolytes, endocrine sys, immunological status, mental status
interactions during prolonged systemic tx: cardiac glycosides
inc toxicity due to hypokalemia
interactions during prolonged systemic tx: loop diuretics, thiazides, irritant laxatives
inc potassium loss
interactions during prolonged systemic tx: NSAIDs
inc peptic ulcers, GI bleeding
interactions during prolonged systemic tx: antidiabetics
dec antidiabetic effects
interactions during prolonged systemic tx: ACE-inhibitors
inc risk of blood dyscrasias (unspecified blood disorder)
interactions during prolonged systemic tx: chloroquine, mefloquine
inc risk of myopathy, cardiomyopathy
interactions during prolonged systemic tx: atropine, anticholinergics
inc rise in intraocular pressure
how to minimize GC toxicity
use topical when possible; adapt systemic use to diurnal rhythm (8am); vary daily dose; taper dose asap; use other immunomodulator as sub or in combo
glucocorticoids indications
allergic rxn (asthma, angioneurotic edema, drug rxns, envenomations); collagen disorders (rheumatoid arthritis, polymyosistis); ophthalmologic (allergic uveitis, conjunctivitis); GI (bowel inflammatory dz); hematologic (acute allergic purpura, leukemia); infections (gram- septic shock); joint, bone (arthritis, bursitis, tendosynovitis); neurologic (cerebral edema, MS); pulmonary (COPD, infant RDS); renal (nephrotic syndrome); dermatologic (atopic dermatitis); thyroid (subacute thyroiditis); surgery/EM (acute severe trauma)
drugs used to minimize glucocorticoid use
leukotriene-receptor antagonist (asthma, allergy); lipoxygenase inhibitors; anti-IgE-antibodies; cyclosporin (bowel inflammatory dz); tacrolimus (rheumatism, dermatology); methotrexate; azathioprine; etanercept; remicade (BID); thalidomide; activated protein C (septic shock)
