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Thyroid and Antithyroid Drugs

Thyroid and Antithyroid Drugs. By: Bohlooli S, PhD School of Medicine, Ardabil University of Medical Sciences (ArUMS). THYROID PHYSIOLOGY. Iodide Metabolism The recommended daily adult iodide (I-) intake is 150 mcg Biosynthesis of Thyroid Hormones Transport of Thyroid Hormones

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Thyroid and Antithyroid Drugs

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  1. Thyroid and Antithyroid Drugs By: Bohlooli S, PhD School of Medicine, Ardabil University of Medical Sciences (ArUMS)

  2. THYROID PHYSIOLOGY • Iodide Metabolism • The recommended daily adult iodide (I-) intake is 150 mcg • Biosynthesis of Thyroid Hormones • Transport of Thyroid Hormones • thyroxine-binding globulin (TBG) • about 0.04% of total T4 and 0.4% of T3 exist in the free form.

  3. Biosynthesis of thyroid hormones

  4. Peripheral metabolism of thyroxine

  5. Evaluation of Thyroid Function • THYROID-PITUITARY RELATIONSHIPS • AUTOREGULATION OF THE THYROID GLAND • ABNORMAL THYROID STIMULATORS

  6. Typical values for thyroid function tests

  7. The hypothalamic-pituitary-thyroid axis

  8. BASIC PHARMACOLOGY

  9. THYROID HORMONES • Chemistry • Are levo (L) isomers • Dextro (D) isomer of thyroxine, dextrothyroxine, has approximately 4% of the biologic activity of the L isomer • Pharmacokinetics • Mechanism of Action

  10. Summary of thyroid hormone kinetics.

  11. Model of the interaction of T3 with the T3 receptor

  12. Effects of Thyroid Hormones • The thyroid hormones are responsible for : • Optimal growth • Development • Function • Maintenance of all body tissues

  13. Manifestations of thyrotoxicosis and hypothyroidism (1)

  14. Manifestations of thyrotoxicosis and hypothyroidism (2)

  15. Manifestations of thyrotoxicosis and hypothyroidism (3)

  16. Thyroid Preparations • Synthetic: • levothyroxine, liothyronine, liotrix • Animal origin • desiccated thyroid

  17. ANTITHYROID AGENTS • Thioamides • Anion Inhibitors • Iodides • Iodinated Contrast Media • Radioactive Iodine • Adrenoceptor-Blocking Agents

  18. Thioamides

  19. Thioamides • Pharmacokinetics • Propylthiouracil is rapidly absorbed and the bioavailability is 50-80% • Methimazole is completely absorbed • Both thioamides cross the placental barrier

  20. Thioamides; Pharmacodynamics • Act by multiple mechanisms • Prevent hormone synthesis by inhibiting the thyroid peroxidase • Inhibiting the peripheral deiodination of T4 and T3 • The onset of these agents is slow, often requiring 3-4 weeks

  21. Thioamides: Toxicity: • Occur in 3-12% of treated patients • Nausea and gastrointestinal distress • The most common adverse effect is a maculopapular pruritic rash (4-6%) • Rare adverse effects include: • an urticarial rash, vasculitis, a lupus-like reaction, lymphadenopathy, hypoprothrombinemia, exfoliative dermatitis, polyserositis, and acute arthralgia. • Hepatitis can be fatal • The most dangerous complication is agranulocytosis

  22. Anion Inhibitors • Perchlorate (ClO4-) • Pertechnetate (TcO4-) • Thiocyanate (SCN-)

  23. Iodides • Inhibit organification • Hormone release • Decrease the size and vascularity of the hyperplastic gland

  24. Iodinated Contrast Media • diatrizoate • iohexol • inhibit the conversion of T4 to T3 • inhibition of hormone release

  25. Radioactive Iodine • 131I is the only isotope used for treatment of thyrotoxicosis • therapeutic effect depends on emission of  rays

  26. Adrenoceptor-Blocking Agents • Metoprolol • Propranolol • Atenolol • effective therapeutic adjuncts in the management of thyrotoxicosis

  27. CLINICAL PHARMACOLOGY OF THYROID & ANTITHYROID DRUGS HYPOTHYROIDISMHYPERTHYROIDISM Thyroid Storm OphthalmopathyDermopathy

  28. Etiology and pathogenesis of hypothyroidism

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