Pharmacology of Thyroid Disorders Flashcards
What is the mechanism of amiodarone’s causing of hypo and hyperthyroidism, other than its iodine loading efffect?
Hypothyroid:
- Reduces peripheral conversion of T4 to T3
- Blocks T3 nuclear receptor
Direct toxic effect on thyroid follicular cells -> destructive thyroiditis -> transient hyperthyroid followed by hypothyroid
What is the dose-limiting side effect of levothyroxine therapy, and what is the general treatment paradigm for elderly patients?
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)
What are the problems with using natural iodine purified from pig/cow/sheep?
- Antigenic potential - change to become allergic
- Unstable bioavailability
- Unknown dosing / inconsistent
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?
About 6-8 weeks
Should re-evaluate every 6-12 months once euthyroid
T4 clearance decreases as you age -> need lower dose in elderly
What is the most sensitive test of thyroid function overall?
TSH -> responds massively to small changes in T3/T4
Free T4 can also be measured.
When should you take levothyroxine and what should you avoid taking at the same time?
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
What drugs interact with levothyroxine concentrations overall?
Estrogens -> increase TBG
CYP Enzyme inducers -> increase clearance
Resin binders -> i.e. cholestyramine
Aluminum-containing compounds -> Aluminum hydroxide, sucralfate
What should you do if a patient changes brands of levothyroxine?
Re-assess thyroid function in 6-8 weeks -> certain brands can be a little off and fuck with your levels
What is the clinical definition of subclinical hyperthyroidism and what is the cause? Should you treat it?
Low TSH but normal free T4, asymptomatic
Normal cause is too much levothyroxine
Fix the levothyroxine dose
What is the clinical definition of subclinical hypothyroidism? Should you treat it?
High TSH but normal T4, asymptomatic
Should not be treated
What is the treatment for myxedema coma and why?
- IV bolus thyroxine - obviously
2. IV hydrocortisone - adrenal suppression presents similarly, and you want to treat for that too just in case.
What drugs inhibit thyroperoxidase and which one is different / how is it different?
Methimazole (MMI)
Propylthiouracil (PTU)
-> also useful in thyroid storm by inhibiting 5’ deiodinase.
Which of the two thioamides is preferred and why?
Methimazole, because it has a lower risk of hepatotoxicity. It also has a longer halflife for convenient once-daily dosing.
What are the adverse effects of PTU and MMI?
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
What should one do if PTU or MMI causes hepatotoxicity, agranulocytosis, or benign transient leukopenia (WBC<4000)?
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