GLUCOCORTICOID

Question 1

cortisol moa

Answer 1

http://o.quizlet.com/FVJbYZgkmlK0WzLgsl6NXw.png

Question 2

glucocorticoid receptor subtypes

Answer 2

type 1 - mineralocorticoid (misnomer) - kidney, colon, salivary glands, sweat glands; type 2 - glucocorticoid - broad tissue distribution

Question 3

glucocorticoid response elements

Answer 3

effectuate all changes in gene expression - contained in ~10% of all human genes -> huge impact

Question 4

cortisol effects, ideally

Answer 4

keep humoral/local inflammatory response reasonable; protect glucose-dependent tissue from starvation; switch to catabolism -> preserve electrolytes/water; improve mood

Question 5

cortisol metabolic effects: protect glucose-dependent tissues from starvation

Answer 5

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

Question 6

cortisol metabolic effects: increase nutrient availability for the brain

Answer 6

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

Question 7

cortisol metabolic effects: electrolyte, water balance

Answer 7

aldosterone-like effects; NET EFFECTS - positive na-balance, ecv expansion, hypokalemia, alkalosis; dec body ca++ stores (dec intestinal absorption, inc renal excretion)

Question 8

adrenal crisis metabolic imbalances

Answer 8

caused by abrupt discontinuation of exogenous GC; hyponatremia, hypovolemia, hyperkalemia, acidosis (low bicarb), hypoglycemia, inc BUN

Question 9

adrenal crisis symptoms

Answer 9

dehydration, hypotension, abdominal complaints, “pseudo-peritonitis”, hypothermia -> dehydration-related fever, delirium, coma; tx w/cortisol, cortisone

Question 10

cortisol effects: immunosuppressive/anti-inflammatory

Answer 10

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)

Question 11

cortisol effects: cns

Answer 11

variable effects on mood, behavior, excitability, insomnia, euphoria -> depression; may inc icp (large doses); improve mood, appetite in terminally ill pt’s

Question 12

cortisol effects: fetal lung maturation

Answer 12

critically important b4 gestational wk 34; preterm: inject 2 doses -> mature lungs, stim pulmonary surfactant production

Question 13

corticosteroids used as aerosol inhalants

Answer 13

for asthma - beclomethasone, budesonide; high first pass metabolism

Question 14

glucocorticoids adverse effects

Answer 14

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

Question 15

glucocorticoids adverse effects: prolonged systemic use

Answer 15

similar to cushing’s syndrome - affects skin, bone, sk muscle, eyes, GI, cv system, blood, electrolytes, endocrine sys, immunological status, mental status

Question 16

interactions during prolonged systemic tx: cardiac glycosides

Answer 16

inc toxicity due to hypokalemia

Question 17

interactions during prolonged systemic tx: loop diuretics, thiazides, irritant laxatives

Answer 17

inc potassium loss

Question 18

interactions during prolonged systemic tx: NSAIDs

Answer 18

inc peptic ulcers, GI bleeding

Question 19

interactions during prolonged systemic tx: antidiabetics

Answer 19

dec antidiabetic effects

Question 20

interactions during prolonged systemic tx: ACE-inhibitors

Answer 20

inc risk of blood dyscrasias (unspecified blood disorder)

Question 21

interactions during prolonged systemic tx: chloroquine, mefloquine

Answer 21

inc risk of myopathy, cardiomyopathy

Question 22

interactions during prolonged systemic tx: atropine, anticholinergics

Answer 22

inc rise in intraocular pressure

Question 23

how to minimize GC toxicity

Answer 23

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

Question 24

glucocorticoids indications

Answer 24

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)

Question 25

drugs used to minimize glucocorticoid use

Answer 25

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)