Thyroid and Antithyroid Drugs PDF

# Thyroid and Antithyroid Drugs ## Topic Outline - Thyroid Hormone - Disorders of Thyroid Function - Thyroid Preparations - Antithyroid Agents - Thioamides (PTU, MMI) - Iodides - Beta Blockers - RAI ## Guide Questions - Which of the following describes the mechanism...

# Thyroid and Antithyroid Drugs ## Topic Outline - Thyroid Hormone - Disorders of Thyroid Function - Thyroid Preparations - Antithyroid Agents - Thioamides (PTU, MMI) - Iodides - Beta Blockers - RAI ## Guide Questions - Which of the following describes the mechanism of action of the thioamides for the management of hyperthyroidism? - Block uptake of iodine by the follicular cells - Block the peroxidase-catalyzed reactions - Block coupling of iodotyrosines - What is the role of beta-blockers in the management of thyrotoxicosis? - Beta-blockers can inhibit the peroxidase-catalyzed reaction in the synthesis of thyroid hormones - Beta-blockers control the sympathetic symptoms of hyperthyroidism - Beta-blockers may inhibit the peripheral conversion of T4 to T3 ## Thyroid Hormone The thyroid gland releases thyroid hormones which are regulated by the hypothalamus and pituitary gland. - Thyroid hormone is synthesised, stored and released by the thyroid follicle. - The thyroid follicle is a spherical structure composed of follicular epithelial cells which line the follicle. - The follicular lumen (colloid) is filled with a protein called thyroglobulin. ### Synthesis of Thyroid Hormone - **Iodide uptake:** Thyroid gland cells take up iodide from blood - **Peroxidation of iodide to iodine:** Iodide is oxidized to iodine by thyroid peroxidase. - **Organification of iodine:** iodine is attached to tyrosyl residues on the thyroglobulin molecule. - **Coupling reaction:** MIT and DIT are coupled to produce two hormones: - T4 (thyroxine): DIT + DIT - T3 (triiodothyronine): DIT + MIT - **Proteolysis:** Thyroglobulin is broken down releasing T3 and T4 - **Peripheral conversion of T4 to T3:** T4 is converted to T3 in the peripheral tissues. ### Function of Thyroid Hormone - Brain maturation - Bone growth (synergism with GH) - β-adrenergic effects. β 1 receptors in heart - Basal metabolic rate ↑ - Blood sugar - Break down lipids - Stimulates surfactant synthesis in Babies ## Disorders of Thyroid Function - **Hypothyroidism** - Most common disorder of thyroid function - ↑ TSH ↓ T3 & T4 - **Hashimoto's Thyroiditis** - Most common cause of hypothyroidism in iodine-sufficient regions - Autoimmune disorder with antithyroid peroxidase (antimicrosomal) and antithyroglobulin antibodies - **Cretinism** - Hypothyroidism that begins at birth & results in developmental abnormalities and severe mental retardation. - **Myxedema** - Severe hypothyroidism - **Hyperthyroidism** - ↓ TSH ↑ T3 & T4 - **Grave's Disease** - Most common form of hyperthyroidism - Autoimmune disorder - TSH receptor stimulating antibodies - Hyperthyroidism manifestations + Grave's ophthalmology - **Thyroid storm** - Sudden acute exacerbation of all the symptoms of hyperthyroidism, presenting as a life-threatening syndrome. ## Comparison of Hypothyroidism and Hyperthyroidism | System | Hypothyroidism | Hyperthyroidism/Thyrotoxicosis | |-----------------|---------------------------------------------------------------------------------------|-------------------------------------------------------------------------------------------| | Metabolic | Cold intolerance, ↓ sweating, Weight gain, decrease basal metabolic rate (BMR) | Heat intolerance, ↑ sweating, weight loss, Increase BMR | | Skin/Hair | Dry, cool skin (↓ blood flow), puffy face and generalized nonpitting edema | Moist, warm skin (↑ blood flow), fine hair, onycholysis | | Ocular | Periorbital edema | Ophthalmology in Grave's disease | | GIT | Constipation (↓ motility), ↓ appetite | Hyper defecation (↑ motility), ↑ appetite | | Musculoskeletal | Muscle fatigue, carpal tunnel syndrome, decrease deep tendon reflex (DTR) | Muscle fatigue, osteoporosis, increased DTR, fine tremors | | Reproductive | Libido, Infertility, increased gonadal steroid metabolism | Libido, Infertility, decreased gonadal steroid metabolism | | Cardiovascular | Bradycardia | Tachycardia, arrythmia, palpitations | | Labs | ↑ TSH ↓ Free T3/T4 | ↓ TSH ↑ Free T3/T4 | ## Thyroid Preparations - **Dessicated Thyroid** - Not preferred treatment - Mixture of levothyroxine and liothyronine (2-5:1) - **Levothyroxine (T4)** - Preparation of choice for thyroid replacement and suppression - Stable, content uniformity, low cost, lack allergic foreign protein, longer t1/2 - Peripherally converted to T3 - **Liothyronine (T3)** - 3-4x more potent than T4 - Multiple doses, difficulty in monitoring - Greater risk for cardiotoxicity ## Antithyroid Agents - **Thioamides** - **Methimazole (MMI)** - 10X more potent (Children and adult) - **Propylthiouracil (PTU)** - Pregnancy - **Mechanism of Action (MoA):** - Inhibit thyroid peroxidase (TPO) enzyme - Inhibit coupling and organification - Inhibit peripheral conversion of T4 - **Use:** Hyperthyroidism - **Toxicity:** - GI distress, rash - Agranulocytosis - Aplasia cutis congenita - **Anion Inhibitors** (Perchlorate (ClO4-), Pertechnetate (TcO4-), Thiocyanate (SCN-): - **MoA:** Blocks iodide transport mechanism - **Uses:** Iodide-induced hyperthyroidism (Amiodarone induced hyperthyroidism) - **Iodides** (Lugol Solution (KISS), KI) - **MoA:** - Inhibit organification and hormone release - Decrease the size and vascularity of the thyroid gland - **Uses:** - Hyperthyroidism, Thyroid storm - Preparation for surgical thyroidectomy - **Toxicity:** - Iodism → acneiform rash, swollen salivary gland, mucus membrane ulceration - **Radioactive Iodine (I 131)** - **MoA:** Radioactive destruction of thyroid parenchyma - **Uses:** Hyperthyroidism - **Toxicity:** Sore throat, Sialitis, Hypothyroidism - **Beta-Blockers** (Metoprolol, Atenolol, Propranolol) - **MoA:** - (-) beta adrenoreceptors - (-) peripheral conversion (Propranolol) - **Uses:** - Thyroid storm - Adjunct to control tachycardia, hypertension, and arrythmia