Thyroid Flashcards
most active thyroid hormone
T3
Steps in Thyroid Hormone Synthesis
- 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
Thyroid Hormones: MOA
- 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
causes of hyperthyroidism
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)
levels of TSH and T3/T4 in hyperthyroidism
T3/T4 is high
TSH is low
Hyperthyroidism (Thyrotoxicosis) Treatments:
- Surgery
- Radioactive iodine
- Antithyroid medications
Methimazole (Tapazole)
Propylthiouracil (PTU)
Methimazole (Tapazole)
MOA
- inhibits thyroid hormone synthesis
is Methimazole or PTU more potent?
Methimazole
- 10x as potent as PTU
does Methimazole or PTU have a faster onset and is longer acting?
Methimazole
FDA pregnancy category of Methimazole
D
what semester of pregnancy can Methimazole be taken
avoid in 1st trimester but favored agent in 2nd and 3rd
SE/ADEs of Methimazole
- 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)
what do you need to check before prescribing methimazole?
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
Propylthiouracil (PTU)
MOA
Inhibits thyroid hormone synthesis and prevents peripheral conversion
PTU prevents periheral conversion of T4 to active T3
BBW for PTU
- BBW: hepatotoxicity (including fatal) so is mainly used if methimazole fails
does Methimazole or PTU have higher risk of causing liver damage?
Propylthiouracil (PTU)
three reasons to use PTU over methimazole
1st trimester of pregnancy if they fail methimazole, and people who have more severe thyroid storm
mainly first trimester of pregnancy
PTU should be taken during which trimester of pregnancy?
favored during 1st trimester
SE/ADEs of Propylthiouracil (PTU)
o Derm, GI, arthritis, vasculitis
o Granulocytopenia, leukopenia
why does PTU and methimazole onset of action take so lone?
- 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
Advantages of Methimazole
- 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
When You Might Choose PTU
- 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
- Pharmacologic dose of iodide inhibits the iodination of ___.
tyrosines
- Iodide is not used much now except in ______ (it decreases thyroid vascularity)
thyroid storm or prior to surgery
Beta Blockers
MOA
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
BBW for beta blockers
Abrupt D/C: angina exacerbation, MI, ventricular arrhythmias, (only if you stop suddenly)
contraindications for beta blockers
cardiogenic shock, sinus bradycardia
take Precaution with beta blockers for the following
o Asthma, COPD, DM, uncompensated HF
o Abrupt withdrawal
o Pregnancy 2nd & 3rd trimester
Beta blockers SE/ADEs
dizzy, bradycardia, decrease BP, sexual dysfunction, bronchospasm
Beta Blocker Drugs
- Atenolol
- Propranolol- causes more problems
is atenolol or propranolol Selective for beta-1 receptors and is usually better tolerated than non-selective options
Atenolol
atenolol advantage
o once daily dosing and provides more consistent symptom control
is atenolol or propranolol non selective, so it acts on beta-1 and beta-2 receptors
Propranolol
disadvantages if propranolol
o More poorly tolerated
o Dosed multiple times per day
if pt has hypothyroidism what medication would you start them on?
levothyroxine
how should you dose levothyroxine in patients that are elderly or have heart disease
Start low and go slow in elderly or heart disease
how often would adjust levothyroxine dose?
- Adjust dose Q4-8wks; base on TFTs
should you take levothyroxine on an empty stomach
yes
BBW for levothyroxine
do not use for weight loss
levothyroxine contraindications
acute MI, thyrotoxicosis, adrenal insufficiency
SE/ADEs if levothyroxine
appetite increase, tachycardia, wt loss, nervousness, insomnia, heat intolerance, tremor; arrhythmias, CHF, HTN, angina
levothyroxine pregnancy category
A- pregnant people need to be on this if they have hpothyroidism
Factors That Increase Requirements for T4
Drug interactions, GI problems, and hormones- like pregnancy
Special Treatment Situations for levothyroxine- pregnancy
o Monitor frequently as increased need might require increase dose
Special Treatment Situations for levothyroxine-Older (>50-60) patients and/or those with CAD or risk of same
o Thyroid hormone increases oxygen demand
o Start low dose of 25-50 mcg/day
Special Treatment Situations for levothyroxine- estrogen therapy
o Estrogens increase serum TBG so might require higher doses and more frequent monitoring
Special Treatment Situations for levothyroxine- Interactions
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
