Study your flashcards anywhere!

Download the official Cram app for free >

  • Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off

How to study your flashcards.

Right/Left arrow keys: Navigate between flashcards.right arrow keyleft arrow key

Up/Down arrow keys: Flip the card between the front and back.down keyup key

H key: Show hint (3rd side).h key

A key: Read text to speech.a key


Play button


Play button




Click to flip

107 Cards in this Set

  • Front
  • Back
how does cortisol increase fight or flight response (2)?
1) increase epinephrine synthesis; 2) increase sensitivity of tissues to catecholamines
what four problems will sustained increase in glucocorticoids cause?
1) diabetes (from counter-regulation of glucose); 2) CV effects; 3) osteoporosis; 4) (increased bone resorption, decreased Ca++ absorption)
what is a synthetic CRH, and what is it used for clinically?
cosyntropin, a synthetic CRH, is used to diagnose Cushing's disease
in what pattern is GC synthesis secreted?
what enzymes mediate the direct genomic effects of GC action (3)?
1) tyrosine aminotransferase (AA degradation); 2) phosphoenolpyruvate carboxykinase; 3) G-6-Phosphatase - last two involved in gluconeogenesis - dysregulation leads to diabetes
how do indirect genomic effects work?
GR binds to DNA binding proteins like NFkB and inhibits their ability to upregulate genes
what type of genes are downregulated?
those that stimulate inflammatory response - cytokines like IL-8, 12, and TNF-a
what are indirect genomic effects initiated by, and what are they important for?
interactions with membrane bound or cytoplasmic GRs, or interactions with cell membrane - important for eliciting changes in vascular tone
what actions occur first, genomic or nongenomic?
nongenomic - they occur very fast
what is the treatment for glucocorticoids increasing bone loss through interference with Ca++ uptake and vitamin D actions, in adults?
administration of oral bisphosphonate, Ca++, vitamin D
what hormones do GCs inhibit production of, that relate to growth and development?
sex steroids
what do excessive amounts of GCs or MCs do to muscle/skeleton?
can impair muscle, and cause skeletal wasting
why can large GC doses lead to ulcers?
suppress immune response against H. pylori
what is normal treatment for glucocorticoid insufficiency?
what is added if it is Addison's (both inner and outer zone destroyed)?
hydrocortisone + fludrocortisone
what drugs (3) can pharmacologically reduce cortisol synthesis (3)?
1) ketoconazole; 2) aminogluthemide; 3) metapyrone
how do glucocorticoids affect cell trafficking and adhesion molecules in innate immune response?
alter bone marrow release and infiltration and clearance of leukocytes, decrease expression of adhesion molecules, decrease chemokine release at inflammation site
in what disease do glucocorticoids prevent inflammatory response from overshooting?
what cells do they promote survival and proliferation of, and what cells do they induce apoptosis of (innate IR)?
promote survival of neutrophils, induce apoptosis of eosinophils
in what case are glucocorticoids used to prevent inflammatory response from overshooting, and how does this work on phagocytes?
enhance clearance of foreign antigens, toxins, microbes, enhance opsonization, stimulate macrophages to phagocytose
how does this affect cytokines?
increase antiinflammatory, decrease proinflammatory
how do glucocorticoids affect biochemical mediators of inflammation?
block release of arachadonic acid and thus formation of prostaglandins, thromboxanes, and leukotrienes, decrease NO release, decrease formation of free radicals
formation of what particular cell is blocked that may lead to cellular immunodeficiency?
Th1 helper T cell
how are dendritic cells affected?
can't present antigens as well or mature as well
formation of what cell is increased by glucocorticoids, and what is the result?
Th2 helper cell - stimulates humoral immune response and increased antibody formation
what may be the underlying mechanism of steroid resistant asthma and ulcerative colitis?
administration of GCs will increase IgE levels
what do glucocorticoids do to B cells and why is this useful?
inhibit proliferation and development, useful for leukemia
how else do glucocorticoids relate to IgE secretion?
prevent the release of IgE-R mediated release of inflammatory mediators, and also deplete tissue mucosal mast cells
what AE can glucocorticoids cause in the eye?
what is a recently developed drug in glucocorticoid therapy, how does it function, what is it used for, and what are its advantages?
ZK 216348 - binds GR with high affinity, represses inflammatory response, and does not appear to induce side effects such as thinning of skin and increased glucose
how is dose usually determined in glucocorticoid treatment?
trial and error
what can happen after abrupt cessation after long term use?
adrenal insufficiency (may be fatal)
what is alternate dose therapy and when is it used?
GC may suppress allergic phenomena when given every 48 hours, whereas pituitary suppression is shorter lived
what iGC is used for asthma and why?
flucitasone, because it is highly metabolized
what is an example of a GC given intravenously?
hydrocortisone Na++ succinate
what is a long acting type of GC?
intraarticular injection of crystalline, insoluble GC
what are the features of pulmonary and dermal administration both (2)?
high potency, limited systemic effect
what drug regimen with GCs is most effective for asthma?
inhaled GC coadministered with inhaled beta-2 agonists
what were said not to be considered significant risks for children (4)?
decreased growth, decreased bone mineral density, suppressed adrenal glands, cataracts (but height of children should be monitored)
what drugs must we know are sued for asthma (2)?
1) beclomethasone; 2) flucitasone
what drugs are used for allergic rhinitis (2), how are they given, and which has higher potency?
given as nasal spray - 1) beclomethasone (high potency); 2) triamcinolone (medium potency)
what are pros and cons of treating allergic rhinitis with GCs?
broad relief of symptoms, low systemic absorption, but adverse effects
what drugs are typically given topically for eczema and psoriasis (2)?
1) hydrocortisone; 2) betamethasone
what drug is given as an intralesional injection?
triamcinolone acetonide
what is done for acute eczematous reaction such as poison oak?
systemic therapy with prednisone, tapered over 21 days
what is the goal of GC therapy for MS?
ameliorate suffering during attacks (6 weeks)
what GC drugs are given for MS and how is each administered (2)?
1) prednisone oral tapering course; 2) methylprednisone IV for 3-5 days
what drugs are given for allograft rejection (2)?
prednisone, methylprednisone
what drug is typically given for rheumatic diseases, and what other drugs are used with it (non GC - 2)?
prednisolone - also NSAID and disease modifying drug
what happens to the GC, eventually, and over how long?
weaning, over as much as two years
what type of therapy is often given for RA with methylprednisone?
pulse therapy IV ofer 3-7 days
what GC drug is given as a joint injection for RA?
triamcinolone acetonide
what are GCs able to do for RA?
decrease pain/disability/inflammation in first year but not sure about long term efficacy, does not alter structural damage
what are side effects of treating RA with GCs (2)?
1) osteoporosis; 2) ulcers
in what case are GCs used in Crohn's disease, what drug is used, and why?
in patients who do not respond to conservative management - oral budesonide is used because it is better tolerated and more effective than prednisolone
what should be remembered about pharmacokinetics of oral budesonide?
11% bioavailability because it dissolves in ileum and ascending colon due to pH
what malignancy are GCs particularly used for (to induce apoptosis), and what GCs are used (3)?
lymphoid malignancies, namely ALL - drugs used: 1) prednisone; 2) methylprednisone; 3) dexamethasone
how else is it useful in cancer (2)?
potentiates effeccts of other cytotoxic agents (prednisone/vincristine/doxorubicin/cyclophosphamide for non-Hodgkin's), also treats complications associated with cancer (cerebral edema, pain)
what GC drug regimen is used in tuberculous meningitis?
prednisone for first month
what drug is a mineralocorticoid receptor antagonist, and what does it do?
spironolactone - reduces the expression of gene controlling synthesis of Na/K ATPase
what drug is an antagonist of glucocorticoid receptors, and what is it used for (2)?
RU 486 (Mifepristone) - used in: 1) Cushing's; 2) abortion
what drug inhibits the initial and rate-limiting step in the biosynthesis of all physiological steroids?
what is it used for (in conjunction with other drugs)?
to treat steroid producing adrenocortical tumor
what drug inhibits the terminal step in GC synthesis (11-B hydroxylase) and what is this drug used for?
metyrapone - used in diagnostic test of adrenal function
what drug can block all teroidogenesis and can be used for hirsutism, adrenal carcinomas, and breast cancer?
in what diseases is glucocorticoid resistance the most problematic (2)?
asthma, ALL (5% of patients have no response to 7 day therapy with prednisone)
what are three new therapeutic develpments with GCs?
1) develop drugs with transrepression >> transactivation (flucitasone pripionate, RU486, other RU's); 2) develop drugs that specifically inhibit NFkB or TNF (i.e. infliximab for RA); 3) develop retinoic acid derivatives (synergistic actions between RXR and GR)
what genes are directly regulated by aldosterone (2)?
1) CHIF - challen inducing factor; 2) epithelial sodium channel subunits
what were said to directly regulate the Na/K ATPase genes?
glucocorticoids such as dexamethasone
how strongly does aldosterone activate the MR compared to cortisol?
equal affinity
how do MR and GR compare as far as their ability to activate gene transcription via hormone response element?
stimulate it equvalently
how is specificity gained?
by location of MR and GR
where is the GR located, and where is the MR (5)?
GR - all cells; MR - kidney, gut, sweat glands, brain, and vascular smooth muscle
how else do they differ?
differential transcriptional activation
what key enzyme is expressed only in some mineralocorticoid responsive tissues?
11B-hydroxysteroid dehydrogenase type 2 (11B-HSD)
what are the two main strategies for treating mineralocorticoid excess, and what drug(s) is used for each?
1) antagonize mineralocorticoid receptor (spironolactone); 2) antagonize Na+ exchange in distal nephrone (amiloride, triamterene)
what happens when there is high concentrations of spironolactone?
inhibits androgen receptor
what other problems may spironolactone cuase (2)?
1) hyperchloremic acidosis; 2) hypokalemia
how is mineralocorticoid deficiency treated, and what is the affinity of this drug for MR and GR?
flucortisone - 10x affinity for MR compared to GR
what are side effects of flucortisone, and what should be monitored?
hypertension, hypokalemia - monitor BP and renin activity
what is the treatment for CAH (21-hydroxylase or 17-hydroxyprogesterone deficiency) (2)?
1) fludrocortisone; 2) hydrocortisone (GC)
what is the treatment for primary aldosteronism?
unilateral adrenalectomy
what is the treatment for pseudohypoaldosteronism (a rare form of mineralocorticoid resistance that presents as neonatal renal salt wasting, caused by mutations in mineralocorticoid receptor)?
sodium supplementation
what is the treatment for apparent mineralocorticoid excess (3)?
1) amiloride and/or spironolactone; 2) antihypertensive; 3) KCl supplements
what mutation can cause pregnancy induced hypertension, and why?
missense mutation (L810) in ligand binding domain of MR allows a number of steroids to act as MR agonists
what else can act as an agonist, and what does it cause?
spironolactone can act as an agonist, and allow constitutive activity of MR
what MR antagonist is more preferred than spironolactone, and why?
eplenerone - it is more selective (but has lower affinity for MR)
what are the three high potency GC agonists?
1) beclomethasone; 2) betamethasone; 3) dexamethasone
what are the three mid potency GC agonists?
1) methylprednisone; 2) prednisolone; 3) prednisone
what are three inhibitors of cortisol synthesis?
1) metyrapone; 2) ketoconazole; 3) aminoglutethimide
what MR agonist must we know?
what MR antagonists must we know (2)?
1) spironolactone; 2) eplenerone