Материал: 2016_Kaplan_USMLE_Step_1_Lecture_Notes_Pharmacology
Antithyroid Agents |
3 |
Learning Objectives
Describe the short-term effect of iodine on the thyroid and the most commonly used thioamides
Table VIII-3-1. The Synthesis of Thyroid Hormone and Action and Effects of Antithyroid Agents
Thyroid Hormone Synthesis |
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Effects of Antithyroid Agents |
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1. Active accumulation of iodide into gland |
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Basis for selective cell destruction by 131I |
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2. |
Oxidation of iodide to iodine by peroxidase |
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Inhibited by thioamides |
3. |
Iodination of tyrosyl residues (organification) on thyroglobulin to |
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Inhibited by thioamides |
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form MIT and DIT |
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4. |
Coupling of MIT and DIT to form T3 and T4 |
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Inhibited by thioamides |
5. |
Proteolytic release of T3 and T4 from thyroglobulin |
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Inhibited by high doses of iodide* |
6. Conversion of T4 to T3 via 5´ deiodinase in peripheral tissues |
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Inhibited by propranolol* and propylthiouracil* |
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Definition of abbreviations: MIT, monoiodotyrosine; DIT, diiodotyrosine; T3, triiodothyronine; T4, thyroxine. *Thyroid storm management may include the use of any or all of these agents.
Iodide |
2 |
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Iodine |
3 MIT |
4 |
T3 |
T4 - TG |
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DIT |
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Thyroid |
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peroxidase |
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TG |
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1 |
5 |
TG |
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Iodide |
T3 T4 |
6 T3 |
Figure VIII-3-1. Thyroid Hormone Synthesis
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Section VIII λ Endocrine Pharmacology
λThioamides: propylthiouracil and methimazole
–Use: uncomplicated hyperthyroid conditions; slow in onset
–High-dose propylthiouracil inhibits 5′ deiodinase
–Common maculopapular rash
–Both drugs cross the placental barrier, but propylthiouracil is safer in pregnancy because it is extensively protein bound
λIodide
–Potassium iodide plus iodine (Lugol’s solution) possible use in thyrotoxicosis: used preoperatively →↓ gland size, fragility, and vascularity
–No long-term use because thyroid gland “escapes” from effects after 10 to 14 days
λI131: most commonly used drug for hyperthyroidism
Chapter Summary
λThe steps in thyroid hormone synthesis and the antithyroid agents’ effects upon them are summarized in Table VIII-3-1. The clinical uses and their potential complications are presented in greater detail for the thioamides (propylthiouracil and methimazole) and iodine.
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