Thyroid Hormone & Anti-thyroid Drugs Flashcards
How is thyroxine formed
Iodination & couplling of 2 tyrosineresidues
Thyroxine is know as
T4
How is thyroxine (T4) convered to T3
De-iodination of the outer ring
How can thyroxine (T4) be deactived
De-iodination of the inner ring of tyrosine
6 steps of T4 & T3 sythesis
- Iodine taken into thyroid follicular and out into the lumen where the colloid is located
- Iodine added to tyrosine residues inside thyroglobulin (peroxidase enzyme)
- T4 formed by joining of diiodotyrosines (DIT) to form tetraiodothyronine (thyroxine, T4) by thyroid peroxidase enzyme
- T3 formed by joining DIT and monoiodotyrosine (MIT) to form triiodothyronine (T3) by thyroid peroxidase enzyme
- Thyroglobin taken from lumen bought into follicular cell & undergoes proteolysisto yeild T4 & T3
- DIT & MIT can be deiodinated
Which (T4 or T3) has a longer half life
T4 - 1 week
T3 - 1 day
Which (T4 or T3) is biological active
T3 active
T4 is a reservior
Thyroid Hormone Receptor have 2 domains- name them
DNA binding
Ligand binding
How does T3 alter gene expression
T3 binds to and inactivates CoR (Corepression) to the retinoid X receptor hetrodimer
Co-activator (CoA) canbind & increases mRNA
Side Effects of thyroxine
Adverse effects of thyroxine administration: Hyperthyroidism, including cardiac symptoms such as tachycardia, arrhythmias, angina, or infarction.
Treatment options for hyperthyrodism - Radioablation
Mechanism
SE
Mechanism
- Radioactive iodine (I 131)
- Destroys functional thyroid tissues
SE
- Hypothyrodism
- Destroys fetal thyroid
- NOT carcinogenic
Treatent options for hyperthyrodism - medicinal
Mechanism How long until effects show up? How does this alter dosage? SE BBW for PTU
Methimazole and Propylthiouracil (PTU)
How long until effects are evident
- several weeks must deplete existing thyroid hormone
Dosage
- Start at high doses and then lower dose once euthyroid
SE
- Inhibit thyroid hormone sythesis by inhibiting thyroid peroxidase
BBW for PTU
- Severe liver injury
Treatment options for hyperthyrodism - radioative iodide
What isotope?
Mechanism
How long until effect?
SE (2)
Isotope
I 131
Mechanism
- Radioactive iodide concentrated in the thyroid and emits beta particle
How long until effect?
2-3 months
SE
- Hypothyrodism (treat levothyroxine)
- Ablation of fetal thyroid
Is radioactive I carcinogenic
No
Name one effect that propylthiouracil has that methimazole does not have
PTU can stop peripheral conversion of T4 to T3 so it can be used acutely
Thioureas
Mechanism
Use
SE
Mechanism
Inhibits thyroid peroxidase & stops deiodination of T4
Use - Acute states of hyperthyroidsim or thyrotoxic crisis - Can be used long term for patients with Grave's disease (causes sponatous remission in some) SE - Agranulocytosis - Hepatitis - Jaundice - Pruritis - Rash
Which (methimazole/propylthiouracil)
causes agranulocytos or hepatacoxicity
propylthiouracil
Which (methimazole/propylthiouracil) has a longer half life
methimazole
Which (methimazole/propylthiouracil) is prefered in 1st trimester of pregancy
propylthiouracil
Which (methimazole/propylthiouracil) can be used to rapidly control severe hyperthyrodism?
propylthiouracil & Thioureas
2 drugs used to treat hypothrydoism
How long until patients experece an effect
Levothyroxine
Liothyronine
6-8 weeks
2 drugs used to treat hyperthyrodism
Duration of action
Methimazole: 24 hrs given orally
Propylthiouracil: 6-8 hrs given orally
Radioactive iodine
Which isotopes
How long until onset of action
Maximum effect st
131
Onset: 6-12 weeks
Maximum effect: 3-6 months
