propylthiouracil

Propylthiouracil works through two mechanisms: (1) inhibition of thyroid peroxidase, blocking the oxidation of iodide and coupling of iodotyrosines to form T3 and T4, and (2) inhibition of 5'-deiodinase, preventing peripheral conversion of T4 to the more active T3. This dual mechanism makes PTU particularly useful in thyroid storm where rapid reduction of circulating T3 is critical. PTU is preferred over methimazole in pregnancy (especially first trimester) due to lower teratogenic risk, and in thyroid storm due to its additional peripheral action. The drug crosses the placenta and enters breast milk but in smaller amounts than methimazole. Common side effects include rash, arthralgia, and rarely but seriously, agranulocytosis (monitor CBC) and hepatotoxicity (potentially fatal, more common than with methimazole). PTU has a shorter half-life than methimazole, requiring more frequent dosing (2-3 times daily vs once daily). Clinical response typically occurs within 2-4 weeks, with full therapeutic effect in 6-8 weeks.