Thionamides.

• Pixorize.

▪ Drugs: Propylthiouracil, methimazole.

▪ Mechanism of action.

The two antithyroid drugs available in the United States are propylthiouracil (PTU) and methimazole. Both belong to the thionamide class. Thionamides, including methimazole and propylthiouracil, function as antithyroid medications by reducing the formation of thyroid hormones. They do this by inhibiting the enzyme thyroid peroxidase. Propylthiouracil also reduces the peripheral conversion of T4 to T3.

<aside> 💡 The enzyme thyroid peroxidase is responsible for the oxidation of inorganic iodide, the formation of monoiodotyrosine and diiodotyrosine, and the coupling of these iodotyrosines.

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▪ Clinical use.

• Hyperthyroidism. They differ in that PTU also decreases the peripheral conversion of T4 to T3, has a shorter half-life, and is the drug of choice in pregnancy, as methimazole is teratogenic.
• PTU blocks Peripheral conversion, used in Pregnancy.

▪ Side effects.

• Skin rash, aplastic anemia, and hepatotoxicity are associated with Propylthiouracil. Agranulocytosis is a rare yet severe complication of antithyroid drugs, resulting from drug-induced granulocyte destruction and subsequent neutropenia. A WBC count with a differential is necessary if a patient receiving either methimazole or PTU presents with a fever. Agranulocytosis is characterized by an absolute neutrophil count of less than 500/ml.
• Despite agranulocytosis occurring in approximately 0.5% of cases treated with antithyroid medications, it is a serious complication. Neutrophils are crucial for mounting an immune response to many pathogens. Patients typically present with fever and a sore throat. If thionamide-associated agranulocytosis is suspected, the drug is immediately discontinued, and a white blood cell count with differential is obtained. Methimazole can potentially cause aplasia cutis, making it a possible teratogen.

Radioactive iodine.