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Block 2 Pharmacology > Thyroid > Flashcards

Thyroid Flashcards

1
Q

most active thyroid hormone

A

T3

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2
Q

Steps in Thyroid Hormone Synthesis

A
  • TSH leads to stimulation of iodide (I-) uptake
  • I- is oxidized to I2 by a peroxidase
  • Tyrosines are then iodinated and bind to thyroglobulin
  • Condensation then occurs:
    Tyrosine + I = MIT (monoiodotyrosine)
    MIT + I = DIT (diiodotyrosine)
    MIT + DIT = T3
    DIT + DIT = T4
  • These condensates are still bound to thyroglobulin
  • The hormones are released into plasma following proteolytic cleavage of the thyroglobulin
  • Most circulating T3 and T4 are bound to thyroxine-binding globulin
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3
Q

Thyroid Hormones: MOA

A
  • T3 and T4 must dissociate from thyroxine-binding proteins prior to entry into cells (diffusion or active transport)
  • Inside the cell, T4 is deiodinated to T3
  • T3 then enters nucleus and attaches to receptors
  • Activation of these receptors promotes the function of RNA and subsequent protein synthesis
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4
Q

causes of hyperthyroidism

A

o Graves’ Disease: autoimmune Ab attack on TSH receptor ↓TSH
Ab stimulates ↑T3 & T4
o Tumor
o Thyroiditis
o Drug induced:
Ingest thyroid
Amiodarone (↓ conversion of T4->T3; contains iodide)

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5
Q

levels of TSH and T3/T4 in hyperthyroidism

A

T3/T4 is high

TSH is low

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6
Q

Hyperthyroidism (Thyrotoxicosis) Treatments:

A
  • Surgery
  • Radioactive iodine
  • Antithyroid medications
    Methimazole (Tapazole)
    Propylthiouracil (PTU)
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7
Q

Methimazole (Tapazole)

MOA

A
  • inhibits thyroid hormone synthesis
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8
Q

is Methimazole or PTU more potent?

A

Methimazole

- 10x as potent as PTU

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9
Q

does Methimazole or PTU have a faster onset and is longer acting?

A

Methimazole

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10
Q

FDA pregnancy category of Methimazole

A

D

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11
Q

what semester of pregnancy can Methimazole be taken

A

avoid in 1st trimester but favored agent in 2nd and 3rd

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12
Q

SE/ADEs of Methimazole

A
  • dermatitis, myalgia, arthralgia, jaundice, edema, nephritis, agranulocytosis, hepatotoxic

o Serious side effects are due to agranulocytosis and hepatoxicity
o Also has issues with rashes (dermatitis)

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13
Q

what do you need to check before prescribing methimazole?

A

Need to check baseline CBC with differential and liver enzymes before treating

o To monitor for granulocytes and hepatotoxicity, get baseline liver enzymes to check for hepatotoxicity
o Need differential for liver enzymes
o If someone has liver damage or low count we wouldn’t use this medication

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14
Q

Propylthiouracil (PTU)

MOA

A

Inhibits thyroid hormone synthesis and prevents peripheral conversion

PTU prevents periheral conversion of T4 to active T3

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15
Q

BBW for PTU

A
  • BBW: hepatotoxicity (including fatal) so is mainly used if methimazole fails
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16
Q

does Methimazole or PTU have higher risk of causing liver damage?

A

Propylthiouracil (PTU)

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17
Q

three reasons to use PTU over methimazole

A

1st trimester of pregnancy if they fail methimazole, and people who have more severe thyroid storm

mainly first trimester of pregnancy

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18
Q

PTU should be taken during which trimester of pregnancy?

A

favored during 1st trimester

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19
Q

SE/ADEs of Propylthiouracil (PTU)

A

o Derm, GI, arthritis, vasculitis

o Granulocytopenia, leukopenia

20
Q

why does PTU and methimazole onset of action take so lone?

A
  • There is a delay in action of these drugs
  • This delay is due to MOA and the fact that there will still be circulating thyroid hormone
  • These drugs will not work quickly for symptoms
  • can be problem for cardiac arrhythmia symptoms
  • These drugs only affect syntheses mainly- circulating thyroid hormone has to deplete which can take weeks
21
Q

Advantages of Methimazole

A
  • More rapid achievement of euthyroidism (few weeks)
  • Once-daily dosing and better compliance
  • Little or no effect on subsequent success of radioiodine therapy (unlike PTU, which is associated with an increase in radioiodine failure rates)
  • Less toxicity
22
Q

When You Might Choose PTU

A
  • In pregnant women during their first trimester
  • In patients with life-threatening thyrotoxicosis or thyroid storm (because of PTU’s ability to inhibit peripheral conversion of T4 to T3)
  • In patients with adverse reactions to methimazole (other than agranulocytosis) who are not candidates for radioiodine or surgery
23
Q
  • Pharmacologic dose of iodide inhibits the iodination of ___.
A

tyrosines

24
Q
  • Iodide is not used much now except in ______ (it decreases thyroid vascularity)
A

thyroid storm or prior to surgery

25
Q

Beta Blockers

MOA

A

beta andrenergic antagonist (B1 & 2)
o Partially block conversion of T4 to T3
o Main thing is blocking andrenergic receptors because we slow heart rate down

26
Q

BBW for beta blockers

A

Abrupt D/C: angina exacerbation, MI, ventricular arrhythmias, (only if you stop suddenly)

27
Q

contraindications for beta blockers

A

cardiogenic shock, sinus bradycardia

28
Q

take Precaution with beta blockers for the following

A

o Asthma, COPD, DM, uncompensated HF
o Abrupt withdrawal
o Pregnancy 2nd & 3rd trimester

29
Q

Beta blockers SE/ADEs

A

dizzy, bradycardia, decrease BP, sexual dysfunction, bronchospasm

30
Q

Beta Blocker Drugs

A
  • Atenolol

- Propranolol- causes more problems

31
Q

is atenolol or propranolol Selective for beta-1 receptors and is usually better tolerated than non-selective options

A

Atenolol

32
Q

atenolol advantage

A

o once daily dosing and provides more consistent symptom control

33
Q

is atenolol or propranolol non selective, so it acts on beta-1 and beta-2 receptors

A

Propranolol

34
Q

disadvantages if propranolol

A

o More poorly tolerated

o Dosed multiple times per day

35
Q

if pt has hypothyroidism what medication would you start them on?

A

levothyroxine

36
Q

how should you dose levothyroxine in patients that are elderly or have heart disease

A

Start low and go slow in elderly or heart disease

37
Q

how often would adjust levothyroxine dose?

A
  • Adjust dose Q4-8wks; base on TFTs
38
Q

should you take levothyroxine on an empty stomach

A

yes

39
Q

BBW for levothyroxine

A

do not use for weight loss

40
Q

levothyroxine contraindications

A

acute MI, thyrotoxicosis, adrenal insufficiency

41
Q

SE/ADEs if levothyroxine

A

appetite increase, tachycardia, wt loss, nervousness, insomnia, heat intolerance, tremor; arrhythmias, CHF, HTN, angina

42
Q

levothyroxine pregnancy category

A

A- pregnant people need to be on this if they have hpothyroidism

43
Q

Factors That Increase Requirements for T4

A

Drug interactions, GI problems, and hormones- like pregnancy

44
Q

Special Treatment Situations for levothyroxine- pregnancy

A

o Monitor frequently as increased need might require increase dose

45
Q

Special Treatment Situations for levothyroxine-Older (>50-60) patients and/or those with CAD or risk of same

A

o Thyroid hormone increases oxygen demand

o Start low dose of 25-50 mcg/day

46
Q

Special Treatment Situations for levothyroxine- estrogen therapy

A

o Estrogens increase serum TBG so might require higher doses and more frequent monitoring

47
Q

Special Treatment Situations for levothyroxine- Interactions

A

o Be very cautious when starting and stopping medications
o Dose T4 several hours before interfering agents
o Foods can interfere with absorption (e.g., fiber, coffee)
o Iron salts, multivitamins with calcium and zinc, drugs that can change pH of stomach like antacids

Block 2 Pharmacology (13 decks)

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