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103 Cards in this Set
- Front
- Back
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TRH structure?
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tripeptide (pyroglutamyl-histidyl-proline amide)
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TSH structure?
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glycoprotein (~30 kD)
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TSH effects?
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stimulates both central and peripheral aspects of T4 and T3 synthesis and release
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factors controlling TRH and TSH release?
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stress (-)
heat/cold (-/+) fasting/overfeeding (-/+) increased/decreased blood iodine (-/+) high/low T3 and T4 levels (-/+) |
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iodide into follicular cells?
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have active I- transport pump
activity stimulated by TSH cell to plasma ratio of I- is 20-40:1 |
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in hyperthyroid states, cell to plasma ratio of I- may reach?
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>100:1
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ezyme responsible for oxidizing I-?
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thyroidal peroxidase (TPO)
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how is I- incorporated into thyroglobulin (Tg)?
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oxidized by TPO
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coupling?
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two DIT or one DIT and one MIT in close proximity;
in presence of TPO and H2O2; couple to form peptide-bound iodothyronines T4 and T3 |
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where does coupling occur?
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near cell-colloid interface
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T4:T3 ratio in thyroglobulin?
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15-20:1
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storage of thyroglobulin?
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mature Tg containing MIT, DIT, T3 and T4 is moved out of the follicular cell and stored in the colloid of the thyroid
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consequence of inhibition of synthesis of TH?
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no changes in plasma T3 and T4 due to large reserves;
no changes until the storage pool is significantly reduced after long onset of action |
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response to secretory stimuli?
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resorption of stored Tg back into the follicular cell
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how is TH released?
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endocytosis --> formation of phagolysosome --> enzymes lyse Tg to liberate T3, T4, MIT, and DIT --> T3 and T4 secreted to circulation while MIT and DIT are deiodinated and iodide is recycled
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how are MIT and DIT deiodinated after their liberation?
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thyroid microsomal deiodinase
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how much of T3 and T4 exists in free form?
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0.3% of T3
0.02% of T4 |
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thyroid binding proteins?
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TBG [thyroxine binding globulin (T4, T3)
TBPA [thyroxine binding prealbumin] (T4) albumin (T3, T4) |
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T3 vs T4?
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T3 is more rapid acting
T3 has shorter half life T4 only comes from thyroid T3 from thyroid and periphery T4 thought to be prohormone |
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half life of T3 and T4?
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T3 = 1-2 days
T4 = 6-7 days |
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agents that inhibit 5' deiodination of iodothyronines?
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propylthiouracil
iopanoic acid amiodarone propanolol pharmacologic doses of glucocorticoids |
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primary hypothyoidism?
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at level of thyroid:
congenital defect iodine deficiency chronic autoimmune thyroiditis (hashimotos) postablative |
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hypothyroid aka?
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myxedema
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suprathyroid causes of hypothyroid?
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secondary: panhypopitutarism
tertiary: hypothalamic |
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why should infants be screened for T4 or TSH?
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cretinism has very nonspecific early manifestations that has serious consequences to development
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manifestations of cretinism?
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neonate hypothyroid:
physiologic jaundice constipation somnolence feeding problems |
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clinical presentation of hypothyroid in young children?
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protruding tongue
broad flat nose, wide-set eyes dry skin, coarse hair impaired mental development retarded bone growth/dentition |
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manifestations of hypothyroid in older children?
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retardation of linear growth
delayed puberty poor school performance |
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adult manifestations of hypothyroid?
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fatigue, lethargy, constipation
slowing of central and muscular activity decreased appetite, increased wt deeper, hoarse voice |
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severe myxedema?
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doughy cool skin
enlarged hear can lead to coma seen with hypothyroid adults |
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why is T3 and FT3I normal in mild hypothyroidism?
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there is a compensatory increase in 5' deiodinase
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serum TSH levels in primary, secondary, and tertiary hypothyroid?
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primary: high
secondary: normal or low tertiary: normal or low |
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TRH test?
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inject synthetic TRH and measure TSH response?
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TRH test response in hypothyroid?
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primary: high with high basal levels;
secondary: low (flat) with basal levels usually low; tertiary: delayed response with low or normal basal levels |
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other indices in diagnosis of hypothyroidism?
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I123 uptake is low
elevated serum cholesterol elevated CPK and ALT pernicious anemia |
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common comorbidity with hypothyroid?
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elevated serum cholesterol
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how much iodide needed daily?
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micrograms
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iodized salt?
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0.006-0.01% KI
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treatment of endemic goiter and reasoning?
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iodid with T4 to inhibit TSH secretion and avoid acute hyperthyroid event
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why is replacement TH titrated slowly to full dose?
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patients are quite sensitive to exogenous hormone due to decreased metabolic activity - especially elderly and those with CHF
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patients that are particularly sensitive to exogenous TH?
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hypothyroid in elderly and CHF patients
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why given higher amount of replacement than produced by native gland?
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only 50-75% absorbed
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why and how much thyroid replacement be monitored?
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toxicity is directly related to hormone levels;
monitor with follow-up visits and clinical chemistry |
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organic TH extracts?
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thyroid USP
thyroglobulin USP |
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thyroid USP?
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dessicated powder of animal thyroid glands;
must contain 0.17 to 0.23% of organic iodide; many not bioassayed; 15-500 mg tablets |
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thyroglobulin USP?
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purified extract of pig thyroid;
USP standard iodide content; bioassayed; 15-300 mg tablets |
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organic vs synthetics?
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organics are cheaper;
organics have major variability and safety issues |
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drug of choice for hypothyroid?
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levothyroxine
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synthetic TH preparations?
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levothyroxine
liothyronine liotrix |
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levothyroxine?
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L isomer of synthetic T4
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advantages of levothyroxine?
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more uniform preparation than thyroid USP;
large pool of T4 for conversion to T3 so missing a dose is not as serious |
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liothyronine?
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L isomer of synthetic T3
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liotrix?
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mixture of levothyroxine and liothyronine (4:1 T4:T3);
developed to mimic thyroid output |
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hyperthyroidism aka?
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thyrotoxicosis: clinical and physiological excess of TH
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causes of primary hyperthyroid?
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graves dz
trophoblastic tumor chronic thyroiditis |
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other causes of hyperthyroid?
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pituitary tumor
contaminated food (hamburger toxicosis) |
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hamburger toxicosis?
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meat contaminated with bits of thyroid gland
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graves dz?
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autoantibodies to TSH receptors that stimulate cells to overproduce T3/T4;
most common in older women |
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symptoms of graves dz?
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thyroid enlargement
heat intolerance decrease in wt increase in appetite diarrhea tiredness, irritability heart problems ocular changes hand tremors |
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cause of exophthalmos?
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autoantibodies in graves cross react to tissue behind eyes to cause eyes to protrude
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thioamides?
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propylthiouracil (PTU)
methimazole (therapy of hyperthyroid) |
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thioamides mechanism?
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inhibit TPO to inhibit the organification and coupling steps
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absorption, Vd, and T1/2 of thioamides?
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both rapidly absorbed
high Vd short T1/2 |
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half lives of PTU and methimazole?
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PTU = 1.5 hr
methimazole = 6 h |
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why is dosing for thioamides longer than would be expected by their half lives?
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accumulate in thyroid
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dosing for PTU and methimazole?
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PTU = every 6 h
methimazole = every 24 h |
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issues with using thioamides?
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long onset of therapeutic effect
difficulty dosing therapy is palliative toxicity |
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why is dosing difficult with thioamides?
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long onset due to depleting TH storage pool;
excessive may lead to secondary hypothyroidism |
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how delayed in therapeutic effect of thioamides?
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can take 4-6 weeks
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why is thioamide therapy considered palliative?
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may require ablative therapy
high rate of relapse with long-term therapy with cross response to both |
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adverse effects and rates with thioamides?
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3-12%
maculopapular pruritic rash lupus-like symptoms agranulocystosis (most dangerous) |
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reversal of thioamide toxicity?
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reversible with cessation
cross-sensitivity ~50% |
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why isn't switching between thioamides recommended?
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cross-sensitivity
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monovalent anion inhibitors?
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competitively block iodide uptake:
perchlorate pertechnetate thiocyanate |
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why are monovalent anion inhibitors rarely used?
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overcome by large iodide doses
causes aplastic anemia |
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uses of perchlorate?
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iodide-induced thyrotoxicosis (amiodarone-induced hyperthyroidism)
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perchlorate?
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monovalent anion inhibitor
ClO4- |
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pertechnetate
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monovalent anion inhibitor
TcO4- |
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thiocyanate?
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monovalent anion inhibitor
SCN- |
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pharmacologic doses of iodide?
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mg used to treat hyperthyroidism (microgram quantities needed for T3 and T4 synthesis)
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iodide preparations?
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potassium iodide
sodium iodide potassium iodide oral solution |
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iodine is reduced to I- in GI?
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strong iodine solution
lugols solution |
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beneficial effects of pharmacologic doses of iodide?
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transiently inhibit organification of iodide;
decrease release of T3, T4; reduces vascularity of hyperfunctioning thyroid; effects are rapid |
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wolff-chaikoff effect?
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overwhelm system with iodide so little is produced
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issues with pharmacologic doses of iodide?
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transient effect with rapid recovery
inhibition of release still occurs, but less effective |
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uses of pharmacologic iodine?
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rapid relief from thyrotoxicosis
used with thiourea drugs acute thyroid crisis severe thyrocardiac disease surgical emergencies |
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why are thiourea drug and pharmacologic iodine used together?
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complementary timing of actions
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toxicity associated with pharmacologic iodine?
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uncommon and typically reversible with cessation;
acneiform rash drug fever metallic taste bleeding disorders |
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PTU mechanism?
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inhibit TPO
inhibit peripheral dediodination |
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danger of thioamides during pregnancy?
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can cross placental barrier
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predominant use of iodinated contrast media?
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diagnosis of thyroid disease
adjuvant therapy in thyroid storm |
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iodinated contrast media effects?
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inhibit peripheral deiodination
suppress T3, T4 production |
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benefit of iodinated contrast media in inhibiting peripheral deiodination?
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very rapid
can alleviate effects of thyrotoxicosis |
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radioactive iodide?
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I131 is beta emitter with half life of 8 days
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why is radioactive iodide so effective?
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selective to thyroid because taken up like normal I-;
beta particles only penetrate a small distance in tissue |
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major drawbacks of radioactive iodide?
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postradiation hypothyroid;
I131 therapy often followed by replacement therapy; crosses placental barrier; excreted in breast milk |
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mechanism of adrenoreceptor-blocking agents in hyperthyroid?
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effects of thyroid are analogous to sympathetic stimulation so blocking can prevent much of the symptoms
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propranolol?
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drug of choice in category
treat HTN, tachycardia, atrial fib of thyrotoxicosis |
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propranolol with antithyroid therapies?
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complementary mechanisms and propranolol is withdrawn as serum thryoxin levels return to normal
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thyroid storm?
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severe acute thyrotoxicosis that is life-threatening
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therapy strategy for thyroid storm?
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treat symptoms and prevent thyroid release rapidly with combined therapy:
propranolol iodine PTU |
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other therapies to treat symptoms of thyroid storm?
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antipyretics
heart failure (often caused by storm) treat cause |
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causes of thyroid storm?
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stress
infection (increased antibodies to precipitate graves dz) |
