Term
| what is hydrocortisone a synthetic form of? |
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Definition
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Term
| where is cortisol produced? what regulates it? |
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Definition
| in the adrenal cortex, regulated by adrenocorticotropic hormone (ACTH) - which regulates the synthesis AND secretion of cortisol |
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Term
| what is the *production pathway for cortisol? |
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Definition
| the hypothalamus releases corticotropin (ACTH) releasing hormone, the pituitary releases ACTH, and the adrenal cortex releases glucocorticoids, mineralocorticoids, and androgens (5% of testosterone) |
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Term
| do drugs vary more in potency or function? |
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Definition
| drugs vary more in potency, not what they do |
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Term
| what other function besides stimulation of cortisol synthesis does ACTH perform? |
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Definition
| ACTH also functions as a growth factor for the adrenal cortex (therefore a decrease in plasma ACTH reduces cortisol synthesis and causes atrophy of the adrenal cortex) |
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Term
| how do the anti-inflammatory effects and Na+ retention effects of cortisol/hydrocortisone (the glucocorticoids) compare? do other synthetic derivatives have varying levels of one or the other effect? |
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Definition
| hydrocortisone/cortisol have 1:1 anti-inflammatory and Na+ retention effects. cortisone is 8:8, prednisone is 4:.3, and all the way at the extreme end of the spectrum, betamethasone has 25-40:0 anti-inflammatory effects to Na+ retention. |
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Term
| what kind of hormone is cortisol/hydrocortisone (and the other glucocorticoids)? |
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Definition
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Term
| what are the metabolic effects of cortisol (and the other glucocorticoids)? |
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Definition
| increased gluconeogenesis, glycogenolysis, and protein catabolism. decreased *osteoblast formation, osteoblast activity, Ca+ absorption, protein synthesis, and decreased secretion of TSH |
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Term
| what are the anti-inflammatory effects of cortisol (and the other glucorticoids)? |
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Definition
| decreased production of cytokines, interleukins, prostaglandins, and decreased proliferation/migration of lymphocytes and macrophages |
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Term
| can glucocorticosteroids mask infections? |
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Definition
| yes b/c their anti-inflammatory effects are so strong |
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Term
| when glucocorticoids are administered, are they administered in pharmacologic/therapeutic or physiologic amounts? |
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Definition
| pharmacologic - an amount higher than that which the body is able to produce |
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Term
| what are some general therapeutic uses of glucocorticoids? |
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Definition
| replacement in adrenal hypofunction, anti-inflammatory, and immunosuppression (good for transplant pts, not necessarily for non-transplant pts). |
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Term
| what are some adjuvant uses of glucocorticoids? |
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Definition
| glucocorticoids can be used in myeloproliferative disease and other malignancies, like in the case of brain CA, glucocorticoids can shrink the tissue to a more surgically manageable size |
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Term
| what endocrine disorders can corticosteroids be used in? |
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Definition
| adrenocortical insufficiency (primary and secondary) and congenital adrenal hyperplasia (attempting to stimulate negative feedback loop, thus decreasing production) |
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Term
| can glucocorticosteroids be used for rheumatic disorders? |
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Definition
| yes, not consistently, but during acute exacerbations - for example, RA, bursitis, and gouty arthritis can all be treated *acutely with corticosteroids (chronically with NSAIDs) |
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Term
| do corticosteroids have a dermatologic application? |
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Definition
| yes, they can be used acutely for severe psoriasis and seborrheic dermatitis (check to make sure pt isn't using both a topical and oral steroid) |
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Term
| what are allergic states in which glucocorticoids can be administered? |
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Definition
| severe bronchial asthma, contact dermatitis, and drug hypersensitivity |
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Term
| can glucocorticoids be used in neoplastic diseases? |
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Definition
| yes, glucocorticoids can be used for palliation of child and adult leukemia and adult lymphomas |
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Term
| can glucocorticoids be used for GI disorders? |
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Definition
| yes, glucocorticoids are used for *exacerbations of ulcerative colitis |
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Term
| what are musculoskeletal ADRs associated with glucocorticoids? |
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Definition
| muscle weakness due to protein catabolism, loss of muscle mass, tendon rupture, steroid myopathy, osteoporosis (due to reduced osteoblastic formation/activity), pathologic fracture of long bones (enabled by osteoporosis), vertebral compression fractures , aseptic necrosis (femoral heads and humoral heads at risk), and decreased metabolic effects |
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Term
| how can glucocorticoid use lead to tendon rupture? do other medications interact to increase the likelihood of this ADR occuring? |
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Definition
| tendon rupture can occur as a result of protein catabolism. quinolone usage can increase the risk of achilles tendon rupture; particularly in elderly pts treated concomitantly with glucocorticoids |
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Term
| what are metabolic ADRs associated with glucocorticoids? |
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Definition
| decreased osteoblast formation, decreased osteoblast activity, decreased Ca+ absorption from the GI (even w/high concentrations of Vit D), hypocalcemia, and increased secretion of PTH to catabolize bone to elevate Ca++ (secondary effect, continuing vicious cycle) |
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Term
| what are fluid/electrolyte level ADRs associated with glucocorticoids? |
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Definition
| Na+ is retained increasing fluid retention , which can lead to HTN (mainly a serious problem for CHF pts), K+ loss (likely a compensatory measure for Na+ retention) and hypokalemic acidosis |
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Term
| what are GI tract ADRs associated with glucocorticoids? |
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Definition
| there is an increase in GI ulceration potential via peptic ulcers coupled with a higher risk of perforation in the small and large bowel - esp in pts w/inflammatory disease |
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Term
| what are dermatologic ADRs associated with glucocorticoids? |
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Definition
| thin, fragile skin, impaired wound healing and erythema (side effects may begin to mimic initial condition) |
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Term
| what are psychological ADRs associated with glucocorticoids? |
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Definition
| acute: euphoria (could be a protective mechanism to increased stress hormones). chronic: insomnia, depression, and psychosis |
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Term
| what are immunologic ADRs associated with glucocorticoids? |
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Definition
| signs of an infection may be masked, and immunosuppression may occur w/large doses (leaving pts more vulnerable to new infections - chickenpox/measles can then be fatal in children) |
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Term
| what are endocrine ADRs associated with glucocorticoids? |
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Definition
| *this is the most common side effect of chronic glucocorticoid administration (via adrenal hypothalamic suppression affecting the pituitary). children: suppression of growth (due to protein catabolism, glucocorticoids may trick the pituitary into reducing hormone production). female: menstrual irregularities, anovulation. male: decreased testosterone (due to molecular similarity w/glucocorticoids). overall: cushingoid state (overabundance of glucocorticoids, hypercortisolemia, moon face, buffalo hump) |
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Term
| what are opthalamic ADRs associated with glucocorticoids? |
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Definition
| cataracts, and increased IOP |
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Term
| what enzyme inducing drugs will commonly interact with glucocorticosteroids? |
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Definition
| phenytoin, phenobarbital, and rifampin |
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Term
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Definition
| a synthetic glucocorticoids partial antagonist which binds to glucocorticoid receptors, it can reduce some signs of cushings |
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Term
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Definition
| a synthetic adrenal cytotoxic agent (no celluar destruction) that directly suppresses the adrenal cortex (M/A unknown) - which can be used to treat inoperable *adrenal cortical carcinomas |
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Term
| can corticosteroids be used to prevent A fib after cardiac sx? are the immunosuppressive ADRs associated with them a consideration? |
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Definition
| yes, they can lower the incidence of A fib and higher rates of infection/complication due to ADRs have not been found in this application |
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Term
| can corticosteroids be used to treat pts affected by severe sepsis/septic shock? do corticosteroid ADRs factor in this application? |
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Definition
| yes, and this can be done w/out increasing the risk of GI bleeding, but there was an increased risk of hyperglycemia and hyperatrenemia. this was concluded to still be beneficial due to short term mortality/hospital stay decrease |
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Term
| does addition of fludrocortisone (mineralocorticoid) with IV corticosteroid/insulin therapy improve hospital mortality in septic shock pts? |
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Definition
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Term
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Definition
| an intranasal prodrug glucocorticoid, which doctors need to be aware can be affected by enzyme inducing drugs such as phenytoin, phenobarbital, and rifampin. it also has a high first pass metabolism |
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Term
| what is the major endogenous mineralcorticoid? where is it synthesized? what controls its release? where is its major site of action? M/A? |
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Definition
| aldosterone, which is synthesized by the adrenal cortex and controlled by the RAA and K+ conc (ACTH plays a secondary role). it has its major action on the DCT, stimulating Na+ reabsorption and K+ excretion (electrolyte monitoring is very important, CHF pts at risk) |
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Term
| what are the pharmacologic actions of mineralcorticoids? |
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Definition
| similar to corticosteroids, but there are more powerful effects on the carbohydrate metabolism and electrolyte balance |
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Term
| what are the effects on electrolytes with mineralcorticoids? |
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Definition
| increased reabsorption of Na+, excretion of K+/H+ via action on the DCT and resulting increased BP |
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Term
| what can large doses of mineralcorticoids result in? |
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Definition
| decreased adrenocortical secretion, decreased pituitary corticotropin secretion, decreased activity of the thymus, *increased deposition of liver glycogen, and increased protein catabolism (except in the presence of adequate protein intake) |
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Term
| what are therapeutic uses of mineralocorticoids? |
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Definition
| addison's disease, which is failure at the adrenal cortex level, and mineralocorticoids can be used as replacement therapy for primary/secondary adrenocortical insufficiency (mainly rectifies Na/K ratio problems) |
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Term
| can glucocorticoids be given to treat addisons? |
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Definition
| yes, and they are - mainly b/c mineralcorticoids affect Na/K for the most part |
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Term
| can mineralocorticoids be given to treat salt-losing adrenogenital syndrome/hypoaldosteronism? |
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Definition
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Term
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Definition
| a synthetic compound similar to cortisol, but with powerful mineralocorticoid properties along with strong glucocorticoid properties (effects limited to mainly glucose metabolism). it is used only as therapy for mineralocorticoid actions. |
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Term
| can fludrocortisone be used in hypoatremia associated with cerebral salt wasting in neurosurgical pts? |
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Definition
| yes, fludrocortisone can be administered to pts experiencing cerebral salt wasting associated with neurosx - esp to protect against possible vasospasms. |
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Term
| how and why does hypoatremia affect the brain primarily? |
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Definition
| when sodium levels drop in the fluids outside the cells, water will seep into the cells in an attempt to balance the concentration of salt outside the cells. the cells will swell as a result of the excess water. while most cells can accommodate this swelling, brain cells cannot, because the skull confines them. therefore, most symptoms of hyponatremia will result from brain swelling. |
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Term
| where is the major action of fludrocortisone? |
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Definition
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Term
| what do small p.o. doses of mineralocorticoids deliver? how does thi affect BP? |
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Definition
| Na+ reabsorption and K+ excretion - which will result in elevated BP (higher fluid volume, higher Na+ availability to vascular smooth muscle) |
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Term
| if someone is on fludocortisone, the core problem is thus electrolytic - therefore what other tests need to be done if on chronic mineralocorticoid therapy? |
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Definition
| consistent serum electrolyte level checks. restrictions of Na+/K+ supplementation may be necessary. |
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Term
| what can occur with larger doses of fludrocortisone? |
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Definition
| inhibition of adrenal cortical secretions, inhibition of pituitary corticotropin excretion and inhibition of thymic activity (negative feedback). increased deposition of liver glycogen and a negative nitrogen balance (due to protein loss) may also occur |
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Term
| what are indications for fludrocortisone? |
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Definition
| addisons (glucocortisone is also given) - produces effects closer to normal adrenal activity, w/fewer ADRs at a low dose and salt-losing adrenocogenital syndrome |
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Term
| what are the major ADRs associated with mineralocorticoids? |
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Definition
| edema, HTN, CHF, cardiac enlargement, K+ loss, hypokalemic acidosis, musculoskeletal (less w/mineralocorticoids: muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression, spontaneous fractures, asceptic necrosis of femoral/humeral heads), GI (peptic ulcers w/potential for perforation/hemorrhage, ulcerative colitis), dermatologic, and endocrine (suppression of growth in children, development of a cushinoid state) |
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Term
| what drugs may specifically interact with the mineralocorticoids? |
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Definition
| barbiturates, digitalis, furosemide, and the enzyme inducers: phenytion and rifampin |
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