Endo - Pharm - 1-21 Thyroid Drugs

Front 1

Agents used in hypothyroidism

Back 1

Levothyroxine (which is T4 or thyroxine)

Front 2

Agents used in hyper

Back 2

Radioactive iodide

Thioureas - propylthiouracil or methimazole.

Front 3

Thyroid hormones derived from...

Back 3

iodination and coupling of tyrosine residues.

This occurs in the thyroglobulin molecule (within the thyroid gland)

Front 4

Biosynth and secretion of thyroid hormones

Back 4

Iodide transported into thyroid follicular cell by sodium iodide transporter.
Thyroglobulin protein is synth in RER and is secreted into follicular lumen.
Thyroid peroxidase enzyme (TPO) at the lumenal surface activates iodide and links it to tyrosine in the thyroglobulin protein. This rxn forms MIT and DIT.
Two iodined tyrosines are linked through ether bond and this is the storage form.
Pseudopods get thyroglobulin into the cell and digests it. The tyrosines are now present as T3 or T4.
T4 and a small amt of T3 is secreted into the blood.
MIT and DIT are recycled.

Front 5

How long can T4 be stored?

Back 5

about a month

Front 6

T4 vs. T3

Back 6

Most of stuff released by thyroid is T4

T4 has a higher concentration as total, free and bound to TBG compared to T3

T4 has a longer half life (1 week) compared to T3 (1 day)

T4 has lowerr biological activity.

Front 7

Levothyroxine

Back 7

Long half life so less fluctuations in blood levels - start with a low dose because steady state takes a while to achieve and toxicity can be bad.

Front 8

AEs of levothyroxine

Back 8

hyperthyroidism, cardiac sx.

Front 9

When would T3 be useful

Back 9

emergency therapy of hypothyroidism when a pt hasn't taken their meds in a while.

Front 10

Aim of therapy of hyperthyroidism

Back 10

Inhibit thyroid hormone secretion or reduce amt of functional thyroid tissue.

Front 11

Radioactive iodide

Back 11

It concentrates in teh thyroid and emits ionizing beta particles to damage thyroid cells.
Takes 2-3 months to work

Gets in through sodium iodide transporter.

Front 12

AEs of radioactive iodide

Back 12

Hypothyroidism (but not a big deal because then you just tx with levothyroxine)
Ablation of fetal thyroid gland if given during pregnancy.

Front 13

Propylthiouracil and methimazole

Back 13

Inhibit thyroid peroxidase and thus inhibit iodination of tyrosine residues in thyroglobulin.

Takes many weeks to work because preform thyroid hormone is already there in the gland. So you give this drug at maximal doses.

Front 14

Propylthiouracil also...

Back 14

inhibits peripheral deiodination of T4 to T3.

Front 15

Rx of radioactive iodide with propylthiouracil or methimazole?

Back 15

No!
Because if TPO is blocked, the radioactive iodide can't be incorporated into thyroid storage.

Front 16

AEs of propylthiouracil or methimazole

Back 16

Agranulocytosis (presents with sore throat - is very severe), hepatitis, jaundice, pruritis, rash.

Front 17

Diff btwn methimazole and propylthiouracil

Back 17

Methimazole has longer half-life, can be given fewer times per day.

Propylthiouracil - shorter half-life. good for pregnant or nursing pts who want to avoid drug in the baby. Can also block conversion of T4 to T3 peripherally, and thus is more effective for rapid control of severe hyperthyroidism.

Front 18

When to use propylthiouracil or methimazole

Back 18

Short term - before and after radioactive iodide therapy.
Long term - For some pts
Emergency - T4 --> T3 conversion. For someone wildly hyperthyroid.