Pharmacology of Thyroid Disorders Flashcards

1
Q

What is the mechanism of amiodarone’s causing of hypo and hyperthyroidism, other than its iodine loading efffect?

A

Hypothyroid:

  1. Reduces peripheral conversion of T4 to T3
  2. Blocks T3 nuclear receptor

Direct toxic effect on thyroid follicular cells -> destructive thyroiditis -> transient hyperthyroid followed by hypothyroid

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2
Q

What is the dose-limiting side effect of levothyroxine therapy, and what is the general treatment paradigm for elderly patients?

A

Dose-limiting: Cardiac symptoms, i.e. tachycardia, AFib, risk of cardiac mortality

Treatment paradigm: Stat at a low dose and titrate up slowly (drug has a long halflife, don’t want to overdo it)

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3
Q

What are the problems with using natural iodine purified from pig/cow/sheep?

A
  1. Antigenic potential - change to become allergic
  2. Unstable bioavailability
  3. Unknown dosing / inconsistent
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4
Q

How long does it take levothyroxine to reach steady state? How often should you re-evaluate once symptoms are resolved? How does T4 clearance change as you age?

A

About 6-8 weeks

Should re-evaluate every 6-12 months once euthyroid

T4 clearance decreases as you age -> need lower dose in elderly

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5
Q

What is the most sensitive test of thyroid function overall?

A

TSH -> responds massively to small changes in T3/T4

Free T4 can also be measured.

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6
Q

When should you take levothyroxine and what should you avoid taking at the same time?

A

Take at least 30-60 minutes before breakfast, or 4 hours after the last meal

  • > need to not interfere with its absorption
  • > avoid iron-containing products, calcium-containing products which avidly bind thyroxine and reduce absorption
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7
Q

What drugs interact with levothyroxine concentrations overall?

A

Estrogens -> increase TBG
CYP Enzyme inducers -> increase clearance
Resin binders -> i.e. cholestyramine
Aluminum-containing compounds -> Aluminum hydroxide, sucralfate

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8
Q

What should you do if a patient changes brands of levothyroxine?

A

Re-assess thyroid function in 6-8 weeks -> certain brands can be a little off and fuck with your levels

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9
Q

What is the clinical definition of subclinical hyperthyroidism and what is the cause? Should you treat it?

A

Low TSH but normal free T4, asymptomatic

Normal cause is too much levothyroxine

Fix the levothyroxine dose

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10
Q

What is the clinical definition of subclinical hypothyroidism? Should you treat it?

A

High TSH but normal T4, asymptomatic

Should not be treated

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11
Q

What is the treatment for myxedema coma and why?

A
  1. IV bolus thyroxine - obviously

2. IV hydrocortisone - adrenal suppression presents similarly, and you want to treat for that too just in case.

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12
Q

What drugs inhibit thyroperoxidase and which one is different / how is it different?

A

Methimazole (MMI)

Propylthiouracil (PTU)
-> also useful in thyroid storm by inhibiting 5’ deiodinase.

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13
Q

Which of the two thioamides is preferred and why?

A

Methimazole, because it has a lower risk of hepatotoxicity. It also has a longer halflife for convenient once-daily dosing.

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14
Q

What are the adverse effects of PTU and MMI?

A

Maculopapular rash - think of the dude with a rash
Lupus-like syndrome - MMI specifically, think of the lupus wolf
Aplastic anemia - blue bones on ground
Agranulocytosis - hourglass in back
Hepatotoxicity - especially PTU

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15
Q

What should one do if PTU or MMI causes hepatotoxicity, agranulocytosis, or benign transient leukopenia (WBC<4000)?

A

Hepatotoxicity - don’t switch to the other agent! they are cross-reactive
Agranulocytosis - don’t switch to the other agent! they are cross-reactive
Benign transient leukopenia - no one cares, continue onward

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16
Q

What is the preferred pregnancy regimen for hyperthyroid patients and why?

A

1st trimester: PTU, since methimazole is a teratogen (think of the tarantula) -> cause cutis aplasia

2nd/3rd trimesters: Use MMI since PTU is more hepatotoxic

17
Q

What is the drug of choice for toxic autonomous nodules, multinodular goiters, the elderly, and those with cardiac disease in hyperthyroidism?

A

Radioactive iodine (I-131)

18
Q

What is the drug of choice for hyperthyroidism for poor surgical candidates or those for whom thioamides (PTU/MMI) failed?

A

Radioactive iodine (I-131)

lul

19
Q

What is the mechanism of action of Radioactive iodine and what are the contraindications?

A

Mechanism: Disrupts hormone synthesis, causes cellular necrosis and follicular breakdown
-> generally only need one treatment, can repeat at 6 months

Contraindications: pregnancy (hypothyroid of fetus), breastfeeding, children

20
Q

What monitoring should be done after radioactive iodine ablation?

A

Monitor thyroid function tests every 3 months for a year

Look for signs of hypothyroidism -> most common side effect

21
Q

What drugs are given pre and post thyroid surgery for malignancy to prevent thyrotoxicosis symptoms?

A

Pre:

Thionamides for 6-8 weeks until euthyroid

Iodide therapy - 10-14 days pre-op to reduce size and vascularity of thyroid gland

Post:
Propranolol - incase some cell lysis occurred

22
Q

What adjunctive rate control agent is commonly given if beta blockers are contraindicated in hyperthyroidism?

A

Verapamil or diltiazem

23
Q

What are some precipitating factors of thyroid storm?

A

Infection, trauma, or surgery

24
Q

What is the definition of agranulocytosis with MMI or PTU treatment? How will the patient present to you? What should you do?

A

Absolute neutrophil count <500 / microL

Patient will present with signs of infection: Fevere, sore throat, malaise, erythematous stomatitis, unusual bleeding / bruising

You should order a WBC with differential to see if agranulocytosis is the cause of their symptoms