Thioamides, propylthiouracil

The available agents with antithyroid activity are the thioamides propylthiouracil, carbimazole and methimazole also known as thiamazole. Their thio-carbamide group is indispensable for antithyroid activity. The mechanism of action is complex. The most important action is the prevention of hormone synthesis by an inhibition of the thyroid peroxidase-catalyzed reactions involved in iodine organification. These agents also block the coupling of the iodoty-rosines. 

The steps in thyroid hormone synthesis and the antithyroid agents effects upon them are summarized in Table VII-2-2. The clinical uses and their potential complications are presented in greater detail for the thioamides (propylthiouracil and methimazole) and iodine. 

Thioamides Propylthiouracil (PTU) and methimazole are small sulfur-containing molecules that inhibit thyroid hormone production by several mechanisms. The most important effect is to block iodination of the tyrosine residues of thyroglobulin (Figure 38-2). In addition, these drugs may block coupling of DIT and MIT. The thioamides can be used by the oral route and are effective in most patients with uncomplicated hyperthyroidism. Since synthesis of thyroid hormone rather than release is inhibited, the onset of activity of these drugs is usually slow, of-... 

The client with hyperthyroidism is prescribed the thioamide propylthiouracil (PTU). Which laboratory data should the nurse monitor ... 

The answer is c. (Katzung, pp 651-652.) Propylthiouracil is a thioamide that interferes with the production of thyroid hormone. Its primary action is prevention of thyroid hormone synthesis by blocking thyroid peroxidase catalysis leading to interference with iodine organification. 

The most useful drugs used for this purpose are classified as thioamides. They are chemically similar and contain thiourea-like thioamide functional groups. The most preferred are propylthiouracil and methimazole, although methylthiouracil and carbimazole are widely used. 

III.b.1.2. Inhibitors of hormonogenesis thioamides. The active antithyroid compound is thio-carbamide. Methimazole, carbimazole (which is converted to methimazole in vivo) and PTU (propylthiouracil) are mostly used to treat hyperthyroidism. 

Adverse reactions to the thioamides occur in 3-12% of treated patients. Most reactions occur early, especially nausea and gastrointestinal distress. An altered sense of taste or smell may occur with methimazole. The most common adverse effect is a maculopapular pruritic rash (4-6%), at times accompanied by systemic signs such as fever. Rare adverse effects include an urticarial rash, vasculitis, a lupus-like reaction, lymphadenopathy, hypoprothrombinemia, exfoliative dermatitis, polyserositis, and acute arthralgia. Hepatitis (more common with propylthiouracil) and cholestatic jaundice (more common with methimazole) can be fatal, although asymptomatic elevations in transaminase levels also occur. 

The thioamides methimazole and propylthiouracil are major drugs for treatment of thyrotoxicosis. 

Both thioamides cross the placental barrier and are concentrated by the fetal thyroid, so that caution must be employed when using these drugs in pregnancy. Of the two, propylthiouracil is preferable in pregnancy because it is more strongly protein-bound and therefore crosses the placenta less readily. In addition, it is not secreted in sufficient quantity in breast milk to preclude breast-feeding. 

Questions A.17 When using a thioamide, either methima-zole or propylthiouracil, the most serious adverse drug reaction to monitor for is ... 

Antithyroid drugs include iodide (discussed above) and the thioamides. The principal thioamides are propylthiouracil and methimazole. Almost all patients respond to these agents. However, immunologic complications are not rare. Skin rashes are the most common. Agranulocytosis, cholestatic jaundice, hepatocellular damage, and exfoliative dermatitis are uncom-... 

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