6.-Thyroid-and-Antithyroid-Drugs_compressed_compressed

Endocrine Drugs Overview

  • Focus areas include:

    • Hypothalamic & Pituitary Hormones

    • Thyroid & Antithyroid Drugs

    • Adrenocorticoids & Adrenocortical Antagonists

    • Gonadal Hormones & Inhibitors

    • Pancreatic Hormones & Antidiabetic Drugs

    • Agents affecting Bone Mineral Homeostasis

Thyroid Hormones

  • Triiodothyronine (T3) and Thyroxine (T4):

    • Essential for normal growth, development, thermoregulation, and energy metabolism.

    • T3 contains 59% iodine, T4 contains 65%.

    • Main thyroid hormone.

  • Calcitonin:

    • Second type of thyroid hormone, regulates calcium metabolism.

Functions of Thyroid Hormones

  • Calorigenesis: Heat production in the body.

  • Regulation of cholesterol: Decreases hepatic LDL receptors, lowering total cholesterol levels.

  • Cardiovascular effects:

    • Inotropic effect by upregulating beta receptors.

    • Increases heart rate, cardiac output, and blood pressure.

  • Promotes fluid retention.

Biosynthesis of Thyroid Hormones

  • Site: biosynthesis occurs in the follicular cells of the thyroid gland.

    • Calcitonin is produced by parafollicular cells or C-cells.

Uptake of Iodide

  • Transporter: Sodium/Iodide symporter (NIS) facilitates iodide uptake into follicular cells.

    • Iodide is distinct from elemental iodine.

    • High iodide levels can inhibit its own uptake, reducing thyroid hormone production.

Peroxidase-Mediated Steps

  1. Peroxidation of Iodide: Converts iodide to iodine.

  2. Organification: Iodine binds with tyrosine within thyroglobulin, forming DIT (Diiodotyrosine) and MIT (Monoiodotyrosine).

  3. Coupling: MIT and DIT combine to form T3, while DIT and DIT combine to form T4, both still bound to thyroglobulin.

  4. Proteolysis: T3 and T4 are released from thyroglobulin; MIT and DIT are deiodinated and recycled.

  5. Exocytosis: Most released hormone is T4 (5:1 ratio of T4:T3).

  6. Deiodination: T4 is metabolized into T3 by 5' deiodinase. T3 is more potent than T4.

Thyroid Function Regulation

  • Hypothalamus: Produces TRH (Thyrotropin-releasing hormone).

  • Pituitary Gland: Releases TSH (Thyroid-stimulating hormone), stimulating the thyroid gland.

  • Iodine levels:

    • Adequate iodine stimulates thyroid hormone production.

    • Excess iodine inhibits production.

Feedback Mechanism

  • High levels of T4 and T3 inhibit further release of TRH and TSH, controlling thyroid hormone synthesis.

Thyroid Disorders

  • Hypothyroidism: Low levels of T3 and T4.

    • Primary (within the thyroid) vs. Secondary (within the pituitary).

  • Hyperthyroidism: High levels of T3 and T4.

    • Primary (overactive thyroid) vs. Secondary (excessive TSH from pituitary).

Common Causes of Hypothyroidism

  • Iodine deficiency leading to cretinism.

  • Post-surgical (iatrogenic) hypothyroidism.

  • Autoimmune diseases like Hashimoto’s thyroiditis.

  • Drug-induced (e.g., amiodarone).

Treatment Options for Hypothyroidism

  • Levothyroxine Na:

    • Synthetic T4, preferred treatment for thyroid hormone replacement and maintenance.

  • Liothyronine Na:

    • Synthetic T3, used in emergencies like myxedema coma.

  • Liotrix: Combination of T4 and T3 (4:1 ratio).

  • Desiccated thyroid: Not clinically used due to instability and variability.

Thyroid Hormone Excess

  • Thyrotoxicosis: Excessive T3 and T4 levels, symptomatic of hyperthyroidism.

  • Causes of Hyperthyroidism:

    • Solitary thyroid nodules and autoimmune diseases such as Grave’s disease.

    • Symptoms: Weight loss, tremors, palpitations.

Antithyroid Drugs

  • Used to inhibit thyroid hormone production in hyperthyroidism.

  • Types of Antithyroid Drugs:

    1. Thioamides (e.g., Propylthiouracil, Methimazole).

    2. Anion inhibitors (e.g., Thiocyanate, Perchlorate).

    3. Iodides (e.g., Potassium iodide).

    4. Radioactive iodine.

    5. Adrenoceptor-blocking agents (Beta-blockers).

Thioamides

  • Mechanism: Inhibit thyroid peroxidase, blocking steps of thyroid hormone synthesis.

  • Propylthiouracil additionally blocks the conversion of T4 to T3.

  • Used for short-term and emergent treatment of hyperthyroidism.

Iodides

  • Inhibit hormone release and organification; used pre-operatively or in specific cases of thyrotoxicosis.

Radioactive Iodine

  • Destroys functioning thyroid tissue to reduce hormone production.

Adrenoceptor-blocking Agents

  • Counteract hyperthyroid symptoms by blocking peripheral effects of thyroid hormones.

Miscellaneous Agents

  • Include radiocontrast dyes and glucocorticoids, which can affect thyroid hormone metabolism.