The major action of thionamides is to reduce the formation of thyroid hormone by inhibiting oxidation and organification (incorporation into organic form) of iodine (iodotyrosines), and by inhibiting the coupling of iodotyrosines to form T4 and T3. These actions result in intrathyroidal iodine deficiency. Maximum effect is delayed until existing hormone stores are exhausted (weeks, see below). With high dosage the reduction in hormone synthesis leads to hypothyroidism.
Carbimazole and methimazole (the chief metabolite of carbimazole) (t\ 6h) and propylthiouracil (t1/, 2 h) are commonly used, but t1/, matters little since the drugs accumulate in the thyroid and act there for 30-40 h; thus a single daily dose suffices.
Propylthiouracil differs from other members of the group in that it also inhibits peripheral conversion of T4 to T3, but only at the high doses used in treatment of thyroid storm (p. 705).
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