Ans. A: Propyl-thiouracil Thioamide drugs (methyl and propyl thiouracil, methimazole and carbimazole) can also be used during pregnancy (the lowest possible dose should be used) The foetal thyroid is extremely susceptible to radiation and may be quickly destroyed. Propylthiouracil/ PTU/ 6-n-Propylthiouracil It is a thioamide drug used to treat hypehyroidism (including Graves' disease) by decreasing the amount of thyroid hormone produced by the thyroid gland. Its notable side effects include a risk of agranulocytosis. PTU inhibits the enzyme thyroperoxidase, which normally acts in thyroid hormone synthesis by oxidizing the anion iodide (I-) to iodine (10), facilitating iodine's addition to tyrosine residues on the hormone precursor thyroglobulin. This is one of the essential steps in the formation of thyroxine (T4). PTU does not inhibit the action of the sodium-dependent iodide transpoer located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors, such as perchlorate and thiocyanate. PTU also acts by inhibiting the enzyme 5'-deiodinase (tetraiodothyronine 5' deiodinase), which conves T4 to the active form T3. (This is in contrast to methimazole, which shares propylthiouracil's central mechanism, but not its peripheral one) Administration is oral, with peak serum concentrations occurring in one hour, and actively concentrated to the thyroid gland. The drug is approximately 70% protein-bound and significantly ionized at normal physiologic pH, while the antithyroid agent methimazole is substantially less protein bound. However both are equally transferred across the placenta. Less than 10% of the drug is excreted unchanged, with the remaining fraction undergoing extensive hepatic metabolism glucuronidation. One side effect is agranulocytosis, thrombocytopenia A more life threatening side effect is sudden, severe, fulminant hepatic failure occurs in up to 1 in 10,000 people taking propylthiouracil. PTU is preferred over methimazole only in the first trimester of pregnancy and in woman who may become pregnant. In the second and third trimester, methimazole is preferred.