Thyroid/antithyroid Flashcards
6 steps of TH synthesis
1) active accumulation of iodide into gland
2) oxidation of iodide to iodine via peroxidase
3) iodination of tyrosyl residues (organification) on thyroglobulin to form MIT and DIT
4) coupling of MIT and DIT to form T3 or T4
5) proteolytic release of T3 and T4 from thyroglobulin
6) conversion of T4 to T3 via 5’ deiodinase in periphery
What is the rate limiting step of TH synthesis
The oxidation of iodide to iodine via peroxidase
What drugs work on the rate limiting step of TH synthesis
Thioamides
Propylthiouracil
- class
- mechanism (4)
- use
- side effect
- similar drugs
- Thioamide
- inhibits peroxidase (rate limiting step), inhibits iodination of tyrosyl residues (can’t form MIT or DIT), inhibits coupling of MIT and DIT, inhibits 5’ deiodinase
- uncomplicated hyperthyroid conditions
- allergies (rash), cross placenta (least of the thioamides due to protein binding), granulocytosis
- Methimazole, carbimazole
Methimazole
- class
- mechanism (3)
- use
- side effect
- similar drugs
- Thioamide
- inhibits peroxidase (rate limiting step), inhibits iodination of tyrosyl residues (can’t form MIT or DIT), inhibits coupling of MIT and DIT
- uncomplicated hyperthyroid conditions
- allergies (rash), cross placenta, granulocytosis (less than PTU)
- Propylthiouracil, carbimazole
Carbimazole
- class
- mechanism
- use
- side effect
- similar drugs
- Thioamide
- Prodrug of methimazole: inhibits peroxidase (rate limiting step), inhibits iodination of tyrosyl residues (can’t form MIT or DIT), inhibits coupling of MIT and DIT
- uncomplicated hyperthyroid conditions
- allergies (rash), cross placenta, granulocytosis (less than PTU)
- methimazole, propylthiouracil
Iodine
- examples
- use
- limitations
- potassium iodide and iodine
- thyrotoxicosis (cause negative feedback), used preoperatively to shrink gland and decrease fragility and vascularity
- can only be used for 10-14 days before the effect no longer works
131 I
- use
- limitations
- imaging, to determine if nodules are functional or non functional
- can’t be used during pregnancy
What enzyme converts T4 to T3 in the periphery
5’ deodinase
What drugs can be used to block the conversation of T4 to T3 in the periphery
propulthiouracil and propanolol
What drugs are used to manage a thyroid storm
iodide, propanolol, and propylthiouracil
Levothyroxine sodium
- class
- use
- mechanism
- side effect
- synthetic thyroid hormone, T4
- drug of choice for hypothyroidism
- converted to T3 in the liver, induces gene expression
- hyperthyroidism
Liothyronine
- class
- use
- mechanism
- side effect
- synthetic thyroid hormone, T3
- used for acute management, myxedema coma
- binds directly to TR complex
- hyperthyroidism
Liotrix
- class
- use
- synthetic T3 and T4
- thyroid replacement therapy
What can be used to inhibit the release of T3 and T4 from the thyroglobulin
iodide
