Thyroid & Antithyroid Drugs Flashcards
The two iodine containing hormones secreted by thyroid.
- Thyroxine (T4)
- Triiodothyronine (T3)
Synthesis of Thyroid Hormones.
- Iodine necessary to synthesise T4 and T3 comes from food or iodide supplements.
- Iodide ion is actively taken up by and is highly concentrated in the thyroid gland; it is converted to elemental iodine by thyroidal peroxidase.
- The protein Thyroglobulin serves as as scaffold for thyroid hormone synthesis; tyrosine residues in thyroglobulin are iodinated to form Monoiodotyrosine (MIT) or Diiodotyrosine (DIT) in a process known as Iodine Organification.
- Within thyroglobulin;
- 2 molecules of DIT combine to form T4.
- 1 molecule of MIT and DIT combine to form T3.
- Proteolysis of thyroglobulin liberates the T4 and T3, which are then released from the thyroid.
Thyroxine-binding globulin.
After release from the gland, T4 and T3 are transported in the blood by thyroxine-binding globulin.
Thyroxine-binding globulin is a protein synthesized in the liver.
Thyroid function is controlled by the pituitary through the release of ____ & ____.
Thyrotropin (Thyroid Stimulating Hormone [TSH]) and by availability of iodide.
____ also has a growth-promoting effect that causes thyroid cell hyperplasia and an enlarged gland. (Goiter)
Pituitary gland
High levels of thyroid hormones inhibit the release of ___, providing an effective negative feedback control mechanism.
TSH
Grave’s Disease.
- An autoimmune disorder.
- B lymphocytes produce an antibody that activates the TSH receptor, this can cause a symptom of hyperthyroidism called Thyrotoxicosis.
- B lymphocytes are not susceptible to negative feedback, patients with Grave’s disease can have very high blood concentrations of thyroid hormone and at the same time their blood concentrations of TSH are very low.
Why is T3 10 times more potent than T4?
Because T4 is converted to T3 in target cells, the liver, and the kidneys, most of the effect of circulating T4 is probably due to T3.
Thyroid hormones bind to?
They bind to intracellular receptors that control the expression of genes responsible for many metabolic processes.
Key features of thyrotoxicosis and hypothyroidism.
Clinical uses of thyroid hormones.
- Synthetic levothyroxine (T4) is the form of choice.
- Liothyronine (T3) is faster acting but has a shorter half-life and is more expensive.
Who is highly sensitive to the stimulatory effects of T4?
Older patients, those with cardiovascular disease, and those with longstanding myxedema(hypothyroidism) are highly sensitive to the stimulatory effects of T4 on the heart. Such patients should receive lower initial doses of T4.
Antithyroid Drugs
- Thioamides
- Iodide salts and iodine
- Radioactive Iodine
- Propranolol
Thioamides
>Propylthiouracil (PTU) and Methimazole.
Mecahnism of action: Inhibit thyroid peroxidase reactions, iodine organification, and peripheral conversion of T4 to T3.
Clinical Applications: Hyperthyroidism.
Pharmacokinetics: Oral administration, delayed onset of activity (3-4 weeks)
Toxicities: Nausea, gastrointestinal disturbances, rash, agranulocytosis, hepatitis, hypothyroidism.
Between Methimazole and Propylthiouracil (PTU), which one is preferred in pregnancy?
PTU is preferred in pregnancy because it is less likely than methimazole to cross the placenta and enter breast milk.
