Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Endocrine and Reproductive Systems > Ph- Thyroid Drugs > Flashcards

Ph- Thyroid Drugs Flashcards

1
Q

What are iodine [SSKI] and radioactive sodium iodine given to treat?
What does each do?

A

They are both given to treat hyperthyroidism and are thyroid hormone constituents

Iodine- rapidly inhibits thyroid gland function

Radioactive sodium iodide - destroys the thyroid gland

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are the 2 thionamide therapy drugs?

A
  1. PTU- inhibits PTO, inhibits Type 1 5’-deiodinases

2. Methimazole- inhibits PTO

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the T4 analog used to treat hypothyroidism?
T3?
Natural T3/4 combo?
Synthetic T3/4 combo?

A

T4 - levothyroxine
T3- liothyronine

Natural mix- armour thyroid
Synthetic mix- thyrolar

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

In general, what are the 6 steps of thyroid hormone synthesis?

A
  1. Iodide trapping in the follicular cell
  2. Transport to colloid by pendrin
  3. Iodination of thyroglobulin
  4. coupling to MIT DIT
  5. Storage
  6. Release of T3/T4
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Describe the steps leading up to iodide trapping in the thyroid follicular cell.

A
  1. dietary intake of iodine
  2. iodine is converted to Iodide [I-] in the gut
  3. iodide gets absorbed to circulation
  4. NIS symporter takes I- into the follicular cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How does iodide get from the follicular cell to the colloid?

A

1 NIS on basolateral membrane takes it into the cell with Na/I- symporter.
2. It goes to the apical side where it is transported by pendrin into the colloid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Once I- is in the colloid, what are the steps of iodination of thyroglobulin?

A
  1. NADPH oxidase produces H2O2
  2. Thyroid peroxidase [TPO] uses the peroxide for the oxidation of I- to I [iodide to iodine]
  3. IodiNe is able to attach to tyrosine residue on thyroglobulin to for MIT and DIT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is coupling? What enzyme is necessary to carry it out?

A

TPO:

  1. forms T3 [triiodothyronine] by MIT +DIT
  2. Forms T4 [thyroxine] by DIT + DIT
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Where is thyroglobulin with T4, T3 [and also MIT, DIT] attached, stored?
How does it get released?

A

It gets stored in the colloid.

  1. pinocytosis of Tg into thyroid follicular cell
  2. fusion with lysosome with cathepsin B/C and L digest Tg
  3. T3 and T4 are released into circulation
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Once T3/T4 is released from the follicular cell into circulation what happens?

A

It is bound to various transporter proteins:

  1. TBG - 60 to 70%
  2. TTR- transthyretin
  3. albumin
  4. lipoproteins
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What is the effect of estrogen/OCPs on TBG levels?

A

Estrogen increases TBG levels so it will decrease the amount of free T4/T3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the mechanism of thyroid hormone action on the target cell?

A
  1. T3 enters the cell freely
  2. T4 needs 5’deiodinase to convert it to “active form” T3 before it enters the cell
  3. T3 in the cell interacts with nuclear receptor [THR/RXR heterodimer]
  4. THR/RXR heterodimer acts on thyroid hormone response elements [TRE] to regulate gene expression

*there are 2 forms of thyroid hormone receptors[THRs]–> TRa and TRb

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What enzyme does T4 need to become usable in the target cells?
Which form of the enzyme is in the thyroid, liver and kidney?
Which form is in the brain, pituitary, skeletal muscle and heart?

What drugs can inhibit this enzyme?

A

Type 1 5’ deiodinase [D1] is in the kidneys, liver and thyroid. It is inhibited by PTU, propanolol, some steroids

Type 2 5’ deiodinase [D2] is in the heart, skeletal muscle, brain, pituitary. It CANNOT be inhibited by drugs

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is hypothalamic regulation of thyroid hormone release?
What inhibits TRH?
What stimulates TRH secretion?

A

Hypothalamus releases thyrotropin-releasing hormone (TRH)

Release is stimulated by:
1. cold temperatures

Release is inhibited by:

  1. Dopamine
  2. SST
  3. glucocorticoids
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

What is the role of the pituitary gland in the regulation of thyroid hormone release?

A

TRH stimulates thyrotropes in the ant. pituitary to stimulate the release of TSH.

TSH acts directly on the thyroid gland by binding GCPR and activating adenylyl cyclase to increase synthesis of T3/T4 by stimulating:

  1. increased NIS synthesis
  2. Increased TPO synthesis
  3. Tg synthesis
  4. H202 production
  5. cathepsin B and L increase
  6. increased pinocytosis
  7. increased cell division of follicular cells (increased gland size)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

TSH is low and FT4 and T3 is high. What is the problem?

A

Primary hyperthyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

TSH is high and FT4/T3 is low. What is the problem?

A

Primary hypothyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

TSH is low and FT4/T3 is low. What is the problem?

A

Secondary hypothyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

TSH is low and FT4/T3 is normal. What is the problem?

A

mild primary hyperthyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

TSH is high and FT4/T3 is normal. What is the likely problem?

A

mild primary hypothyroidism

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

A patient presents with fatigue, lethargy, weight gain, heavy menstruation, cold intolerance, dry coarse skin hair and nails, myalgia/arthralgia, constipation and slow cognition. What is the problem? Who is this most common in?

A

Hypothyroidism, most common in the elderly

22
Q

What are the 3 major categories of hypothyroidism?

A
  1. Primary- failure of thyroid gland
  2. secondary- failure of pituitary to make sufficient TSH
  3. Tertiary- failure of the hypothalamus to make TRH
23
Q

What are the causes of hypothyroidism?
Which is most common in the US?
Which is most common in the world?

A

Most common in US: Hashimoto thyroditis
Most common in the world: iodine deficiency, or acute excess

Others:

  1. post-partum
  2. post-radiation/surgery
24
Q

What are the 2 main drugs used in thyroid replacement therapy for hypothyroidism?
What is the different in half life?
What are the side effects of each?

A
  1. Levothyroxine- T4, 7days to reach half life, so 6-8 weeks to steady state. Few side effects unless you over-replace [hyperthyroid effects]
  2. Liothyronine- T3. 7hour to half life so quick onset/offset of action. Causes tachycardia and jitters due to rapid onset
25
Q

What is autoimmune polyglandular syndrome [Schmidt’s syndrome]? What is the treatment?

A

It is a combination of hypothyroidism and adrenal insufficiency.
You need to treat the adrenal insufficiency first with glucocorticoids because if you try to do give thyroxine first, it will increase metabolism of the cortisol and will exacerbate the adrenal problems.

26
Q

What changes need to be made to drug dosing for a hypothyroid woman who becomes pregnant?

A

Estrogen increases levels of TBG so there is less free T4/T3. You would need to increase their dose of levothyroxine or liothyronine

27
Q

A patient presents with:

  1. weight loss despite increased appetite
  2. tremors
  3. palpitations
  4. heat intolerance and increased sweating
  5. anxiety
  6. frequent BMs

What does this person have and what are the potential causes?

A

Hyperthyroidism and the potential causes are:

  1. Graves disease
  2. toxic multinodular goiter
  3. toxic adenoma
  4. EARLY hashimotos
  5. deQ thyroiditis
  6. high iodine load/amiodarone
  7. struma ovarii
  8. germ cell tumors
28
Q

On RAIU, _____________ is going to have increased uptake whereas _________________ is going to have low uptake of I 123.

A

ongoing overproduction of T4/3 like in Graves or toxic adenoma will have increased uptake

Release of preformed thyroid hormones due to inflammation [thyroiditis] will have low uptake

29
Q

What is the purpose of using a beta-blocker in the treatment of hyperthyroidism?
When should it be started?
What are the 2 variants that are used?
What is the benefit of each?

A

It ameliorates the symptoms of hyperthyroidism caused by the increased adrenergic tone [palpitations, tachycardia, tremors, anxiety, heat intolerance].

It should be started as soon as the diagnosis of hyperthyroidism is made.

  1. atenolol - single daily dose, b1 selectivity
  2. propanolol- in high doses can decrease T4 conversion to T3 at target tissue by inhibiting type 1 5-deiodinase, but it is a slow effect
30
Q

What are the 6 possible treatments for Graves disease?

A
  1. radiotherapy [sodium iodide]
  2. thionamide [PTU, methimazole]
  3. surgery
  4. Iodine
  5. Lithium
  6. Dexamethasone
31
Q

How does radioactive sodium iodide treat Graves?
What are the side effects/drawbacks?
What are the contraindications?

A

Iodine concentrates in the thyroid gland up to 100x over the amount in circulation. This means after administration, it is all taken up into the thyroid and destroys the glands.

Side effects: mild effect on salivary gland
Drawback: since it destroys the thyroid, lifetime levothyroxine is necessary
Contraindications: not to be used in pregnant women or children

32
Q

What is the function of PTU [propylthiouracil] in the treatment of Graves?
What patients specifically should use PTU for graves?
What are the side effects?

A

It has two functions:

  1. inhibits TPO -blocks organification/coupling
  2. inhibits type 1 5 deiodinase -blocks T4->T3

It is the thionamide of choice for pregnant/nursing women

Side effects: black box warning for hepatic failure

33
Q

What is the function of methimazole?
What is the benefit of using methimazole over PTU?
When is methimazole contraindicated?
What are the side effects?

A

It inhibits TPO which blocks organification and coupling in thyroid hormone synthesis.

Methimazole does NOT have hepatic toxicity and has a longer T1/2 so it can be used once daily.

Methimazole has potential teratogenic properties so it should not be used in pregnant women in the first trimester

Side effects:

  1. rash
  2. LFT abnormalities
  3. lupus-like syndrome
  4. agranulocytosis
  5. GI distress
33
Q

What is the function of methimazole?
What is the benefit of using methimazole over PTU?
When is methimazole contraindicated?
What are the side effects?

A

It inhibits TPO which blocks organification and coupling in thyroid hormone synthesis.

Methimazole does NOT have hepatic toxicity and has a longer T1/2 so it can be used once daily.

Methimazole has potential teratogenic properties so it should not be used in pregnant women in the first trimester

Side effects:

  1. rash
  2. LFT abnormalities
  3. lupus-like syndrome
  4. agranulocytosis
  5. GI distress
34
Q

A patient on methimazole presents complaining of a sore throat and fever. What do you do?

A

This is probably caused by the medication [side effect of agranulocytosis] so stop medication and check the CBC/diff

34
Q

A patient on methimazole presents complaining of a sore throat and fever. What do you do?

A

This is probably caused by the medication [side effect of agranulocytosis] so stop medication and check the CBC/diff

35
Q

What are the 3 mechanisms by which SSKI [oral iodine] works to treat hyperthyroidism?

A
  1. blocks thyroid hormone release
  2. temporary inhibition of iodine organification in the thyroid gland [Wolf-Chaikoff effect]
  3. decreases vascularity of the gland so it can be used pre-surg
35
Q

What are the 3 mechanisms by which SSKI [oral iodine] works to treat hyperthyroidism?

A
  1. blocks thyroid hormone release
  2. temporary inhibition of iodine organification in the thyroid gland [Wolf-Chaikoff effect]
  3. decreases vascularity of the gland so it can be used pre-surg
36
Q

When are the 2 real times you would want to give SSKI?

What do you have to give first?

A
  1. Thyroid storm
  2. victims of radioactive fallout

Must give a thionamide first

36
Q

When are the 2 real times you would want to give SSKI?

What do you have to give first?

A
  1. Thyroid storm
  2. victims of radioactive fallout

Must give a thionamide first

37
Q

What is the Wolff- Chaikoff effect?

A

When the thyroid receives a big bolus of I- the gland will slow uptake as a protective mechanism

Hypertrophied glands never recover from the effect.

37
Q

After thyroid cancer treatment, what lab value is followed?

What is done 6-12 months after treatment?

A

Follow Tg levels while TSH is suppressed to make sure there are no thyroid cancer cells present.

6-12 months later, stimulate the thyroid with thyrogen [artificial TSH] to see if any cancer cells “reveal themselves’
If there are cancer cells present, use I 131 to ablate and kill the leftovers. It is taken up best when thyrogen is delivered.

38
Q

The mechanism by which lithium inhibits the thyroid is not well understood but what are 3 proposed mechanisms?

A
  1. inhibits iodide transport into the thyroid [NIS]
  2. in vitro it decreases colloid droplet formation in follicular cells [decreased pinocytosis]
  3. impairs proteolytic digestion of Tg within the phagolysosome
38
Q

The mechanism by which lithium inhibits the thyroid is not well understood but what are 3 proposed mechanisms?

A
  1. inhibits iodide transport into the thyroid [NIS]
  2. in vitro it decreases colloid droplet formation in follicular cells [decreased pinocytosis]
  3. impairs proteolytic digestion of Tg within the phagolysosome
39
Q

What is the mechanism by which dexamethasone treats hyperthyroidism?

A
  1. blocks T4–> T3

2. useful in thyroid storm

39
Q

What is the mechanism by which dexamethasone treats hyperthyroidism?

A
  1. blocks T4–> T3

2. useful in thyroid storm

40
Q

What is used to monitor for thyroid hormone recurrence after cancer treatment?

A

Thyrogen

40
Q

What is used to monitor for thyroid hormone recurrence after cancer treatment?

A

Thyrogen

41
Q

What is the 2 step treatment for most thyroid cancers?

If cancer persists past these two steps of standard treatment, what do you do?

A
  1. surgical removal
  2. I 131 to ablate any thyroid remnant and to destroy remaining cancer cells [added benefit is that I 131 allows you to see mets too because it is radioactive]
  3. provide levothyroxine to supply hormone that is missing post gland removal AND spur TSH inhibition via feedback
41
Q

What is the 2 step treatment for most thyroid cancers?

If cancer persists past these two steps of standard treatment, what do you do?

A
  1. surgical removal
  2. I 131 to ablate any thyroid remnant and to destroy remaining cancer cells [added benefit is that I 131 allows you to see mets too because it is radioactive]
  3. provide levothyroxine to supply hormone that is missing post gland removal AND spur TSH inhibition via feedback
42
Q

After thyroid cancer treatment, what lab value is followed?

What is done 6-12 months after treatment?

A

Follow Tg levels while TSH is suppressed to make sure there are no thyroid cancer cells present.

6-12 months later, stimulate the thyroid with thyrogen [artificial TSH] to see if any cancer cells “reveal themselves’
If there are cancer cells present, use I 131 to ablate and kill the leftovers

42
Q

After thyroid cancer treatment, what lab value is followed?

What is done 6-12 months after treatment?

A

Follow Tg levels while TSH is suppressed to make sure there are no thyroid cancer cells present.

6-12 months later, stimulate the thyroid with thyrogen [artificial TSH] to see if any cancer cells “reveal themselves’
If there are cancer cells present, use I 131

Endocrine and Reproductive Systems (27 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions