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Thyroid and Antithyroid Drugs

Explore the physiology, pharmacology, and clinical implications of thyroid and antithyroid drugs. Learn about thyroid hormone kinetics, effects, and manifestations of thyroid disorders, as well as the pharmacokinetics and toxicity of thioamides and other antithyroid agents.

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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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