Mechanism of Action : Anti Thyroid Drugs

The antithyroid drugs that have clinical utility are the thioureylenes, which belong to the family of thionamides. Propylthiouracil may be considered as the prototype.

Mechanism of Action-

Antithyroid drugs inhibit the formation of thyroid hormones by interfering with the incorporation of iodine into tyrosyl residues of thyroglobulin; they also inhibit the coupling of these iodotyrosyl residues to form iodothyronines. This implies that they interfere with the oxidation of iodide ion and iodotyrosyl groups.

In addition to blocking hormone synthesis, propylthiouracil inhibits the peripheral deiodination of thyroxine to triiodothyronine. Methimazole does not have this effect and can antagonize the inhibitory effect of propylthiouracil. Although the quantitative significance of this inhibition has not been established, it does provide a theoretical rationale for the choice of propylthiouracil over other antithyroid drugs in the treatment of severe hyperthyroid states or of thyroid storm. In this acute situation, a decreased rate of conversion of circulating thyroxine to triiodothyronine would be beneficial.

Measurements of the course of organification of radioactive iodine by the thyroid show that absorption of effective amounts of propylthiouracil follows within 20 to 30 minutes of an oral dose. They also show that the duration of action of the compounds used clinically is brief. The effect of a dose of 100 mg of propylthiouracil begins to wane in 2 to 3 hours, and even a 500-mg dose is completely inhibitory for only 6 to 8 hours. As little as 0.5 mg of methimazole similarly decreases the organification of radioactive iodine in the thyroid gland, but a single dose of 10 to 25 mg is needed to extend the inhibition to 24 hours.

The half-life of propylthiouracil in plasma is about 75 minutes, whereas that for methimazole is 4 to 6 hours. The drugs appear to be concentrated in the thyroid, and methimazole, derived from the metabolism of carbimazole, accumulates after carbimazole is administered. Drugs and metabolites appear largely in the urine.

Although both propylthiouracil and methimazole cross the placenta and also can be found in milk, methimazole does so to a greater degree than propylthiouracil.

Category: Pharmacology Notes