## Pharmacology of Propylthiouracil (PTU) ### Mechanisms of Action **Key Point:** PTU has TWO distinct mechanisms: 1. **Central mechanism**: Inhibits thyroid peroxidase (TPO), blocking organification of iodine and coupling of iodotyrosines → prevents thyroid hormone synthesis 2. **Peripheral mechanism**: Inhibits type 1 deiodinase → blocks conversion of T₄ to T₃ in tissues Methimazole has ONLY the central mechanism (no peripheral effect). ### Onset of Action **High-Yield:** PTU has a **slower onset** (3–5 weeks) compared to methimazole (1–3 weeks), NOT faster. Both are well-absorbed from the GI tract, but PTU's slower onset is due to: - Need to deplete existing thyroid hormone stores - Slower accumulation in thyroid tissue - The dual mechanism does not accelerate initial symptom relief ### Clinical Use in Pregnancy **Clinical Pearl:** PTU is preferred in the **first trimester** because: - Methimazole is associated with methimazole embryopathy (rare but includes: methimazole-induced cutis aplasia, esophageal atresia, choanal atresia) - PTU has minimal placental transfer and lower teratogenic risk - After first trimester, methimazole is preferred (lower hepatotoxicity risk) ### Comparison Table: PTU vs Methimazole | Feature | PTU | Methimazole | | --- | --- | --- | | **Onset** | 3–5 weeks | 1–3 weeks | | **Peripheral effect** | Yes (blocks T₄→T₃) | No | | **Duration** | 6–24 hours | 36–72 hours | | **Pregnancy (1st trimester)** | Preferred | Avoid | | **Hepatotoxicity** | Rare but severe (fulminant hepatitis) | Rare, usually mild | | **Agranulocytosis** | 0.3–0.6% | 0.1–0.5% | **Warning:** The statement "faster onset of action" is INCORRECT — this is a common misconception. PTU is actually slower-acting than methimazole. **Mnemonic:** **PTU = Peripheral effect + Pregnancy + Peroxidase** (three P's for PTU's unique features) [cite:KD Tripathi 8e Ch 41]
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