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
Reading...
Front

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

image

Play button

image

Play button

image

Progress

1/106

Click to flip

106 Cards in this Set

  • Front
  • Back
what is important to understand about how long it will take for drugs lowering thyroid hormone levels to work?
it will take weeks bc thyroid hormone is made and stored in large quantities in the follicles.
what is the function of the thryoid?
secretion of thyroid hormones and calcitonin
what are the major roles of thyroid hormone/
growth
develpment
body temp reg
metabolic rates of cells

aides in these pathways doesn't directly cause

temp regulation is done by epinephrine from sympathetic system but it epinephrine wont cause the temperature regulation in the absence of thyroid hormone.
what does epinephrine need in order to stimulate body temperature change?
thyroid hormone.
what is the pathway for thyroid hormone release?
hypothalamus relsease TRH
stimulates release of TSH from anteriorpituitary. Which in turn stimulates synthesis and release of T3 and T4 from the thyroid gland.
what are the controls of TRH and TSH release?
stress - inhibits
heath- inhibits
cold- stimulate
-fasting- inhibits
overfeeiding-stimulates
increased iodine- inhibits
decreased iodine - stimulates
High levels of T3/4 - inhibits
low levels of T3/4- stimulates
what is the difference btw T4 and T3 structurally?
T3- has 3 Iodines
T4- has 4
what are the 5 major steps of thyoid hormone synthesis?
1.uptake of Iodine
2. oxidatino/activation of idodine
3. coupling into Tg
4. storage
5. proeolysis and release.
what is the the cell to plasma ratio of Iodine in folicular cells and how is that maintianed?
40:1

Iodine pump in follicular cell membrane which is stimulated by TSH
what is the enzyme responsible for oxidizing and incorporating Iodion into thyroglobulin(Tg)?
thyroidal peroxidase(TPO)
what are the two molecules produced by thryglobulin(Tg) attack of tyrosine? in the second step of T3/4 synthesis?
MIT and DIT
what is the couplings that occur to create T3 as opposed to T4?
MIT couples with DIT to create T3

two DITs couple to create T4

MIT never couples with itself.
what catalyzes coupling reaction in T3/4 synthesis?
TPO
what are the two ways T3 is produced IN THYROID GLAND?
MIT coupling with DIT creates T3

after proteolysis and release from storage and prior to release into the blood some T4 will be deiodinated into T3 by 5`deiodinase.
what is important about 5'deiodinase activity that takes place in the thyroid gland as oppposed to the periphery?
This 5'deiodinase is not targetable by PTU.
what are the differences btw T3 and T4? in relation to acitivty and orgin?
T3 is hormonally active but T4 is probably just a prohormone that is converted into T3.

T4 comes exclusively fromt eh thryoid gland

T3 also comes from peripheral deiodination of T4

Treating anathyroidal individuals with T4 will give near normal levels of T3
what is the difference in distribution of T4 as opposed to T3?
T4 is limited to plasma while T3 can distribute to entire body water.
what are the half lifes of T3 and T4?
T3- 1-2 days

T4- 6-7 days
what are the two indirect mechanisms of modulating T3/4 activity
affecting binding proteins

inhibiting 5'deiodinatino of iodothryonines
what are the T3/4 binding protiens/
TBG-thyroxine binding globulin, binds t3 and 4

TBPA- thyroxine binding prealbumin binds T4 only

albumin- binds just about everything including T3 and T4.
what is the effect of decreased levels of TBG?
relative hyperthyroidism bc there will be an increase in the amount of free T3/4.
what is the effect of Propylthiouracil(PTU)?
inhibits peripheral 5'deiodinase
What is the effect of propranolol on thyroid hormone?
inhibits 5'deiodination

secondary benifit when used to treat thyroid storm.

primary use is to treat the hypertension and tachycardia.
what are the drugs that can inhibit 5'deiodinase?
Propylthiouracil(PTU)

iodinated contrast media(iopanioc acid)

Amiodarone(antiarrhythmic agent)

propranolol

pharmacologic doses of glucocorticoids
what is myxedema?
hypothyroidism
what are the causes of myxedema?
congential defect of thyroid
iodine deficiency
chronic autoimmune(hashimotos) thyroiditis
postablative

panhypopitutarism(secondary hypothyroidism)

hypothalmic problems(tertiary hypothyroidism)
what are neonatal symtoms of hypothyroidism?
cretinism
usually presents firist month after birth
manifests as jaundice, constipation, somnolence, and feeding problems

this can be hard to differentiate from normal behavior and since this can lead to major developmental concerns all infants are screened for T4 and or TSH levels
what are the young child symptoms of hypothyriodism?
protruding tongue
broad flat nose, wide set eyes
dry skin, coarse hair
imparied mental development
retarded bone growth/dentition
enlarged gland
what is the presentation of hypothyroidism in older children?
retardation of linear growth
delayed puberty
poor school performance
what are the manifestation of hypothyroidism in adults?
fatigue, lethargy, constipation
slowing of the central and muscular activity
decreased appetite, increased weight
deeper, hoarse voice
severe myxedema-doughy cool skin, enlarged heart, can lead to coma
what are expected T4 and freeT4 values seen in differnt hypothyroid conditions?
T4 and FT4I are low in all conditions that induce hypothyroidism.
what is T3 and FT3I levels in hypothyroid conditions?
in most cases it will be low, but it can be normal if T4 deiodination is able to compensate in this case T4 will be low and T3 will be normal pt still considered hypothyroidic even though they will be asymptomatic.
what is serum TSH levels in the different forms of hypothyroidism?
TSH is high in primary hypothyroidism and usually results in a goiter

TSH will be normal or low in secondary or tertiary hypothyroidism.
What is TRH response?
TRH response is a test which measures TSH levels in response to TRH.

in primary hypothyroid TSH levels will be high in response to a dose of TRH

in secondary TSH levels will be low and flat even in response to TRH

in tertiary TSH levels will go up but only after a delayed response and will be low prior to dose. this is bc it takes some time for the pituitary to react to sudden TRH after going so long without it.
what are some of the indicators and lab values important in measuring and assessing hypothyroidism?
T4,FT4I
T3, FT3I
TSH
123I uptake- low in hypothyroidisms
elevated serum cholesterol(primary hypothyroidism)

elevated CPK and ALT

Pernicious anemia(autoimmune mediated hypothyroidism hashimotos)
what are the treatments for hypothyroidism?
iodide supplementation
thyroid hormone suppliementation
what is the epidemiology of iodide defiency ?
rarely seen in US since 1920 due to iodide added into salt.
what is Iodide supplementation used to treat?
endemic goiter
what is complicated about treating endemic goiter?
problem is not in the gland. its a defiency of iodine.

gland is enlarged so if you provide iodine you will actually cause massive surge in production which will cause hyperthyroidism.
how do you prevent hyperthyroidism in treatment of endemic goiter?
suppliment for a time with thyroid hormone to decrease enlargment then suppliment Iodine.
what are some concerns with administration of replacement thyroid hormone?
patients are quite sensitive to exogenous thyroid hormone due to decreased metabolic acitivy especially the elderly and those with CHF so full replacement dose is not given immediatedly but titrated up to.
what is the replacement dose of thyroid homrone?
thryoid secretes 80ug of T4/day

full replacement dose is 150-200ug/day in a 70kg male bc only 50-75% oral absorption.

must monitor regularly to ensure that dose is both adequet and not reaching toxic levels bc amount of replacement needed is directly related to severeity of deficit.
what is the pathology behind normal T3/4 with goiter?
enlarged thyroid is needed to meet demands due to problem treat this with supplimentation of TH to maintian normal levels and take stress off gland so it can shrink back to normal.
What are the organic TH extracts?
thyroid USP
Thyroglobulin USP
what are the advantages and disadvantages of organic TH use?
they are cheaper but have major variability and safetly issues mainly with immune responses
what type of TH is prefered for treatment?
synthetics
what is thyroid USP?
desiccated powder from animal thyroid glands

contains .17 to .23% of organic iodide

bc of variabliliity in batches comercially available products are not bioassayed so potency is not know.

availabe in tablets containing 15-500mg of the powder
what is Thyroglobulin USP?
purified extract of pig thyroid

contains USP standard iodide content

it is bioassayed( potency is known)

available 15-300mg tablets.
what is the drug of choice for TH replacement?
levothyroxine
what is levothyroxine?
L isomer of synthetic T4
sodium salt
what is the dosages available for levothyroxine?
25-5--ug
what are the advantages of levothyroxine?
more uniform preparation when compared to thyroid USP

provides large pool of T4 that can be converted to T3

missing a dose is not as serous as compared to supplementing T3

T3 serum profiles more uniform than with T3 administration(bc the body decided when to convert this to T3 and when to just keep it as T4)
what is the problem with Levothyroxine?
its not effective in people who can't convert T4 to T3 such as people with liver disease
Why is it hard for people with severe liver disease to convert T4 to T3?
because liver is main site of peripheral 5'deiodoninase.
what is liothyronine?
L isomer of synthetic T3
sodium salt
what is dosing for Liothyronine?
5-50ug
what is Liotrix?
mixture of levothyroxine and liothryonine

4:1 mix

developed to mimic normal thryoid releases.
what is thyrotoxicosis?
hyperthyroidism
what are the causes of hyperthyroidism?
graves disease
trophoblastic tumor
chronic thryoiditis

pituitary tumor(secondary)
nigestion of contaminated foods.
what is the most common cause of hyperthyroidism?
graves disease.
what is graves disease pathology?
autaoantibodies to receptors for TSH stimulate cells to overproduce T3/4
who is graves disease most common in?
older women
what are the symptoms of graves disease?
thyroid enlargment
heat intolerance
decreased weight, increased in appetite, diarrhea, tiredness, irritablility, heart problems, ocular changes, hand tremors.
what is the eye problem in graves disease?
eyes bug out due to muslce behind eyes that has receptors for T3/4
what are the drug therapies for hyperthyroidism?
thiourea derivatives(thioamides)

monovalent anion inhibitors

High dose iodides

iodinated contrast media

radioactive iodide

adrenoreceptor antagonists
what are the thioamides?
propylthiouracil
(PTU)
methaimazole
what are the monovalent anion inhibitors
potassium perchlorate
what are the iodinated contrast media?
ipodate
iopanoic acid
what are the adrenorecptor antagonsts?
propanolol
what is the MOA of the thioureas?
inhibit orgnification and coupling reaction by inhibiting thyroid peroxidase(TPO)

PTU also inhibits peripheral dediodination of T4 to T3.
what is the pharacokinectics of the thioureas?
both are rapidly absorbed
PTU>methimazole

both have short half-lives
PTU-1.5h
methimazole-6h

both accumulate in the thyroid

both cross placental barrier(PTU less than methimazole)
what is the doseing schedule for the thiourease?
PTU every 6hours

methimazole ever 24

this is because even though they have a short duration of action the effect of their actions last a longer time. ie takes a while for thyroid to rebuild its stores .
what are some problems with using thioamides?
long onset of therapeuitc effect. because it must deplete the thyroid hormone storage pool this can take up to 4-6 weeks

also bc of this there can be some difficulty in making dose predictions so if to high of a dose is used then you could wind up in hypothyroidism
what is the use of thioamide therapy?
palliative relieves symptoms but does not fix the problem

it allows for recover from stimulus of the hyperthyroid state

often combined with ablative therapy.
what is the toxicity associated with thioamides?
adverse effects rate of 3-12%

maculopapular pruritic rash(most common)

lupus like symptoms

most dangerous agranulocytosis(0.3-0.6%)

urusally rapidly reversible with cessation

liver toxicity

cross sensitivity btw thioamides of about 50% therefore if adverse reaction occurs not recommened to switch to other one.
what are the monovalent anion inhibitors?
perchlorate
pertechnetate
thiocyanate
what are problems of the monovalent anion inhibitors?
can be overcome by large doses of iodide

can cause aplastic anemia
what are the uses of monovalent anion inhibitors?
Usually used for acute issues rarely used for chronic therapy


perclorate sometimes used in iodide induced thyrotoxicosis such as amiodarone-induced hyperthyroidism
what is the MOA of monovalent anion inhibitors?
competitively block iodide uptake by follicle cells
what is the woff-chigot effect?
you only need a few mg of iodide a day if you get more than that into ur system it will actually inhibit thyroid peroxidase and inhibits synthesis of T3 and T4.
what are the prepartations of Iodide that are given?
lugols solution(5% Iodine, 10%KI that is reduced to I- in the GI tract)

potassium Iodide

Sodium Iodide

Potassium Iodide oral solution.
what is the MOA of Iodide treatment of hyperthyroidism?
wolff chaikoff effect
inhibition of the organification of iodide
transient

main action is to inhibit proteolysis which leads to decreased release of T3 and T4 from the thyroid this is why the onset of action is so fast and ignores the storage pools.
What are the benifits of Iodide treatment?
very fast onset of action
what are the problems with Iodide treatments?
only a transient effect. gland rapidley overcomes the wolff chiakoff effect after that inhibition still occurs but less effective.
How is iodide used in treatment?
almost always given in conjunction with thioureas which have a very long onset of action but more long lasting effects

benificial in thyoid surgury because it reduces vascularity of the hyperfunctioning thyroid.

also used in acute thyroid crisis and severe thyrocardiac disease.
what is the toxicity of iodide treatements?
uncommon and reversible with discontinuation

acneiform rash, drug fever, metalilc taste, bleeding disorders.
what is the use of iodinated contrast media?
used predominantly for diagnosis of thryoid diseases, but it is useful as an adjevant therapy in thyroid storm do to its ability to rapidly inhibit peripheral deiodination as well as suppress T3 and T4 production with longer administration(most likely by same mech as normal iodine)
what are the two curative treatments of chronic hyperthyroidism?
surgury and radioactive iodide
what is the radioactive iodide?
I131
what is the MOA of radioactive iodide?
emitts beta particles that destroy some surrounding follicular tissue. with results in deacresed hormone synthesis and destroyes some of the stores

only penetrates a small distance into the tissue and Iodine is only found in the thyroid so damage is very localized and selective.
what is the major drawbacks of usage of radioactive iodide?
postradiation hypothyroidism
-therefore radioactive therapy usually followed by replacement therapy.usually for rest of life

crosses plancetal barrier and is exreted in breast milk.
what cell type is targeted by radioactive iodide?
acinar cells
What is the role of adrenorecptor blocking agents?
effects of thryoid are analogous to symptthectic stimulation TH acts a a permissive to adrenergic stimuli

so these can be used to relieve symptoms indirectly.
what is the main adrenorecptor blocking agent?
beta blockers -mainly propranolol
what is the doseing for propranolol in thyroid conditions?
20-40mg p.o every 8 hours
what is the major use of beta blockers in thyroid conditions?
used to treat symptoms of thryotoxicosis
treates hypertension, tachycardia, atrial fib, and can inhibit peripheral deiodination

palliavtive used adjevantly with antithyroid therapies.
what is thyroid storm?
sever acute thyrotoxicosis-life threatening
what is the treatment of thyroid storm?
propranolol
iodine(saturated) 10 drops daily
PTU(250mg p.o. every 6 hours)

antipyretics
treatements of cause usually infection
what is risk after treating graves disease?
high level of relapse
what are the most serious side effects of thioamines drugs
agranulocytosis(loss of white cells)
liver toxiciy
what is the preferred thioamine?
methinazole due to less side effects
how is radioactive iodide given
one dose usually does it

given orally
what is the reccomendation of radioacitve iodide with pregancncy?
countraindicated in preg and breast feeding bc it will cross into this.

even goes farther people on this medication should stay away from children in general
why is T4 given more often then T3?
T4 has longer half life
T4 is regulated by the body to turn into T3 so less chance of causeing hyperthyroid symptoms
what is the risk of radioactive iodide with cancer?
not big risk in older people not seen.

but it is a potential reason not to give to younger people
in the US what is the main first line treatment for hyperthyroidism?
radioactive iodide