Pharmacology
Summary
Propylthiouracil (PTU) and methimazole are thioamides that inhibit thyroid peroxidase (TPO), an enzyme crucial for T3 and T4 thyroid hormone synthesis, making them effective in treating hyperthyroidism, including Graves' disease. Specifically, PTU also diminishes the peripheral conversion of T4 to T3, indicating its use in thyroid storm management. Both are used as a preparatory measure before surgeries or radioactive thyroid ablation to minimize thyroid storm risks. Notably, they do not address the exophthalmos associated with Graves' disease. The most common side effect is pruritic rash, but can also cause urticaria, GI distress, lupus-like reaction, arthralgias, and agranulocytosis. PTU is linked to hepatotoxicity, and methimazole can be teratogenic in the first trimester. Both drugs can traverse the placenta, potentially causing neonatal hypothyroidism.
Radioactive iodine (131I) is employed for thyroid ablation in hyperthyroidism, destroying thyroid tissue and leading to permanent hypothyroidism, necessitating lifelong hormone replacement through levothyroxine, a synthetic T4 hormone replacement. Levothyroixine is indicated for all causes of hypothyroidism due to its long half-life. Synthetic T3 (liothyronine), is sparingly used due to its short half-life. Glucocorticoids are utilized to treat the exophthalmopathy in Graves’ disease, and beta-blockers are used to alleviate hyperthyroid symptoms. Some beta blockers, like propanolol, also inhibit the conversion of T4 to T3.
Lesson Outline
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FAQs
Propylthiouracil and methimazole are classified as thioamides. primary function is to inhibit thyroid peroxidase (TPO), a crucial enzyme in the synthesis of the thyroid hormones T3 and T4. These medications are instrumental in managing hyperthyroidism conditions like Graves' disease by curbing the excessive production of thyroid hormones. Unique to propylthiouracil is its capability to decelerate the peripheral conversion of T4 into the more active T3 hormone.
Patients using Propylthiouracil and Methimazole may commonly experience a pruritic rash. Other potential side effects include urticaria, a lupus-like reaction, fevers, nausea, vomiting, dermatitis, arthralgias, and specifically for Propylthiouracil, ANCA-associated vasculitis. A particularly grave side effect shared by both drugs is agranulocytosis. Propylthiouracil is linked with hepatotoxicity and the risk of hepatic failure. During the first trimester, Methimazole poses teratogenic risks. Furthermore, since both drugs can traverse the placental barrier, there's a risk of transient hypothyroidism in neonates.
Levothyroxine is a synthetic version of the T4 thyroid hormone, which undergoes conversion to T3 in peripheral tissues and is the recommended treatment for all instances of hypothyroidism. With a half-life of roughly 7 days, levothyroxine mandates periodic TSH level assessments to fine-tune dosing. Excessive levothyroxine can precipitate either subclinical or overt hyperthyroidism, manifesting symptoms such as heat intolerance, diaphoresis, tremors, tachycardia, and arrhythmias.
Both PTU and methimazole can be deployed as preparatory treatments preceding thyroid surgery or radioactive thyroid ablation. By doing so, they diminish the threat of thyroid storm, an acute and hazardous exacerbation of hyperthyroidism.
Employing radioactive iodine is a strategic move for thyroid ablation when managing hyperthyroidism. This intervention eradicates thyroid parenchyma, consequently resulting in an irreversible hypothyroid state that mandates lifelong thyroid hormone supplementation. A byproduct of this procedure might be radiation-induced thyroiditis, characterized by pain, glandular swelling, tenderness, and a paradoxical escalation of hyperthyroid symptoms. These can be mitigated using methimazole and beta blockers as a pre-treatment. Additionally, it's noteworthy that radioactive iodine treatment can exacerbate exophthalmos, a complication that can be alleviated with glucocorticoids.
