Which of the following antithyroid drugs acts primarily by inhibiting thyroid peroxidase and blocking organification of iodine?

Explanation

## Mechanism of Propylthiouracil (PTU) **Key Point:** Propylthiouracil is a thionamide antithyroid drug that has two distinct mechanisms of action: 1. **Primary:** Inhibits thyroid peroxidase (TPO), blocking organification of iodine and coupling of iodotyrosines 2. **Secondary:** Inhibits peripheral conversion of T₄ to T₃ (5'-deiodinase inhibition) ### Comparison of Antithyroid Drug Mechanisms | Drug | Primary Mechanism | Secondary Mechanism | Onset | |------|------------------|---------------------|-------| | **Propylthiouracil (PTU)** | TPO inhibition + organification block | Blocks T₄→T₃ conversion | 6–12 hours | | **Methimazole** | TPO inhibition + organification block | None | 6–12 hours | | **Iodine (Lugol's)** | Inhibits thyroid hormone release | Decreases gland vascularity | 1–3 days | | **Sodium perchlorate** | Blocks iodine uptake (competitive) | None | 1–2 weeks | | **Propranolol** | None (symptomatic only) | Blocks T₄→T₃ conversion | Minutes | **High-Yield:** PTU is the drug of choice in the **first trimester of pregnancy** because methimazole is associated with methimazole embryopathy (methimazole-induced PTU is safer early in pregnancy). Both PTU and methimazole inhibit TPO, but PTU has the added benefit of reducing peripheral T₄ conversion, making it faster-acting clinically. **Clinical Pearl:** PTU carries a risk of agranulocytosis (0.3–0.5%) and hepatotoxicity, so baseline CBC and LFTs are mandatory. Methimazole is preferred in non-pregnant patients due to lower hepatotoxicity risk. **Mnemonic:** **PTU = Peroxidase + Peripheral conversion** (two mechanisms); **Methimazole = Monofunctional** (TPO only). [cite:KD Tripathi 8e Ch 57]