Pharmacology Of Thyroid Hormone 2024-2025 PDF

# Pharmacology-2 ## Dietitian Program 2024-2025 ### Prof Dr Manar A Nader ## Pharmacology Of Thyroid hormone ### Diseases: **Image:** A detailed diagram relating to the metabolism of thyroid hormone. It shows the steps of iodine oxidation and coupling, the production of thyroxine and its releas...

# Pharmacology-2 ## Dietitian Program 2024-2025 ### Prof Dr Manar A Nader ## Pharmacology Of Thyroid hormone ### Diseases: **Image:** A detailed diagram relating to the metabolism of thyroid hormone. It shows the steps of iodine oxidation and coupling, the production of thyroxine and its release into the plasma. ### hypothyroidism * **hyposecretion of hormone (hypothyroidism)** * **Thyroid replacement therapy** * 2 thyroid hormone preparations: * **Levothyroxine sodium (thyroxin, T4)** - more effective in suppression of TSH than T3 * **liothyronine sodium (T3)** - rarely used. ### hyperthyroidism * **hypersecretion of hormone (hyperthyroidism)**. * **1. antithyroid drugs**, * **2. irradiation,** * **3. or surgical removal of the overactive tissue** ## THYROID HORMONE PREPARATIONS ### Levothyroxine and Liothyronine **Drugs/ Replacement therapy** * The synthetic thyroid hormone preparations include levothyroxine (T4), liothyronine (T3), and liotrix (a mixture containing T4 and T3 in a ratio of 4:1). * **Levothyroxine** - for thyroid hormone replacement in patients with hypothyroidism **drug of choice** **Pharmacokinetics** T4 & T3 - adequately absorbed following oral administration. **Half-life** T4 (one week) & T3 (2 days). **Adverse effects:** Elderly patients or have ischemic heart disease - given low initial dose with slow increase because angina or myocardial infarction can be precipitated. * Excess thyroid hormone - usual clinical features of thyrotoxicosis ## ANTITHYROID AGENTS * Antithyroid agents used in the treatment of hyperthyroidism include thioamide drugs [Thiourea anti-thyroid drugs], β-adrenoceptor antagonists, iodide salts, and RAI. ### 1. Thioamide drugs (Thiourea anti-thyroid drugs) **Include** Carbimazole & methimazole and propylthiouracil (PTU). * Propylthiouracil is the drug of choice in pregnancy and lactation **Use** In patients with Graves' disease, a thioamide drug can be used in an attempt to induce remission or as a means to control symptoms before surgery or RAI treatment. **Pharmacokinetics** * Given orally. * Carbimazole is hydrolyzed into methimazole. **Adverse effects:** * **Cross placenta - secreted in milk** * **1. Hypothyroidism & goiter enlargement** * **2. Agranulocytosis (neutrophiles-eosinophiles)→rare** - disappear on stopping therapy * **3. Cross placenta** * **4. Secreted in breast milk** ### II. β-Adrenoceptor Antagonists **Examples** Propranolol **Uses** * used to reduce cardiovascular stimulation associated with hyperthyroidism * used also in thyroid storm ### III. Iodide salts **Examples** * potassium iodide tablets and solutions, * saturated solution of potassium iodide * Lugol solution (elemental iodine and potassium iodide). * It has an immediate reducing effect on the release of thyroid hormones - so used in thyroid crisis. (acute thyrotoxicosis) **Uses** * Used for short term therapy. * Patient prepared for surgery * After RAI for inhibition the release of thyroid hormone. **Effect** Inhibit thyroid hormone formation, iodide trapping & reduces gland vascularity. **Duration** Maximum effect after 10-15 days, its effects then diminish because of loss of inhibitory effect on thyroid ### IV. Radioactive Iodine **It's** Colorless and tasteless solution of sodium iodide I-131 (1311). **Mechanism** Isotope is rapidly absorbed from the gut and concentrated by the thyroid gland. In the gland, it emits β-particles that destroy thyroid tissue **Uses** Definitive treatment for relapsed Graves' disease, toxic multinodular goiter & toxic solitary nodule. **Contraindication:** Pregnancy & lactation. **Kinetics** * Well, absorbed orally & given as a single dose. * Half-life 8 days **Duration** Its effect on the thyroid takes several weeks with maximal effect after two months. ## Bone disorder **Diagram:** A diagram shows the relationship between the thyroid gland, peripheral tissues and blood, and the movement of hormones and drugs. ## Drugs Affecting Calcium and Bone **Diagram:** A diagram shows the relationship between calcium, parathyroid hormone, calcitonin, cinacalcet, and bone. ## Bone Disorders * **Osteoporosis:** the most common bone disorder, characterized by a gradual reduction in bone mass that weakens bones and leads to the occurrence of fractures after minimal trauma, such as falls. * **Osteomalacia** - characterized by abnormal mineralization of new bone matrix. The condition has numerous causes, the most common of which include vitamin D deficiency, abnormal vitamin D metabolism, phosphate deficiency, and osteoblast dysfunction. **In children** Osteomalacia → results from vitamin D deficiency → rickets **In adults** This disorder is uncommon today because of vitamin D- supplemented foods and sun exposure factors such as aging - malabsorption - chronic renal impairment, use of phenytoin or other anticonvulsant drugs * Can interfere with vitamin D absorption, metabolism, or target organ response and result in Osteomalacia. ### Calcium and Vitamin D An adequate intake of calcium and vitamin D is essential for optimal bone formation in children and to prevent osteoporosis in adults. These recommendations can be met by ingesting calcium-rich foods, which are primarily dairy products, and by taking oral calcium and vitamin D supplements if dietary intake is inadequate. ## PHARMACOLOGIC AGENTS 1. **inhibit bone resorption by osteoclasts** - bisphosphonate drugs, calcitonin, estrogen and raloxifene, and denosumab 2. **stimulates bone formation by osteoblasts** - teriparatide 3. **dual mechanism** - Strontium inhibits bone resorption while increasing bone formation. Most of the drugs used in treating bone disorders. These agents include the. In contrast, ### I) Bisphosphonates * **The original bisphosphonate** - Etidronate * **Second-generation bisphosphonates** - such as alendronate, pamidronate, risedronate, and tiludronate * **third-generation** - ibandronate and zoledronic acid ### Uses **Generally used in** management of a variety of disorders - Paget disease of bone, hypercalcemia, osteolytic bone lesions of metastatic cancer reduced risk of developing breast cancer. * **Alendronate** - first bisphosphonate to be approved for the treatment of osteoporosis (All forms) * **Ibandronate and risedronate** - indicated for the prevention and treatment of osteoporosis in postmenopausal women. * **Pamidronate, Alendronate, risedronate, tiludronate** - approved for the treatment of Paget disease of bone * **pamidronate or zoledronic acid** - IV is the most effective treatment for hypercalcemia associated with cancer. * **In patients with bone cancer,** useful in the management of osteolytic bone disease and resulting hypercalcemia **Effects** * inhibits bone resorption * reduces the tumor burden in bone, * ↓bone pain, * the risk of fractures in patients whose cancer has metastasized to bone. ### II) Estrogen and Raloxifene * **Estrogen** * **Effect** - reduce the formation and activation of osteoclasts and thereby slow bone loss. * **Raloxifene** **Effect** increases bone density in postmenopausal women and decreases vertebral fractures in women with osteoporosis. ### III) Denosumab * Denosumab offers an entirely new approach to the treatment of osteoporosis through the inactivation of gene transcription required for osteoclast viability and function. * **route** - subcutaneous injection once every 6 months * **Use** - for the treatment of osteoporosis. ### IV) Calcitonin * **Forms** - not reliably absorbed from the gut and must be administered parenterally or by nasal inhalation * **Products** * 1. Salmon calcitonin has been available for a number of years * 2. recombinant human calcitonin is also available * Salmon calcitonin is 50 to 100 times more potent than human calcitonin. * **Clinical Uses** Because of its ability to inhibit osteoclast activity and decrease bone turnover, calcitonin is used to treat osteoporosis, Paget disease of bone, and hypercalcemia. ### V) Teriparatide * **It's** Newer type of drug available to treat osteoporosis. (In Hypocalcemia) * **Chemically** recombinant form of human PTH that consists of the 34 biologically active amino acids of the hormone ### VI) Strontium ranelate * Another treatment option for the prevention of osteoporosis. * After oral administration, strontium is laid down on the surface of newly formed bone where it decreases osteoclastic activity and reduces bone resorption. ### VII) Fluoride * **Sodium fluoride** - used to prevent tooth decay and dental caries * **Idea** * Fluoride is stored in bone and teeth where it replaces the hydroxyl group in calcium phosphate salts (hydroxyapatite) to form fluorapatite. * Fluorapatite deposited on the tooth surface is more resistant to erosion than is hydroxyapatite. ## Pharmacological Treatment of anemia/ **Types of Anemia** * ↓RBC production * Iron-deficiency anemia (IDA) * AI/ACD anemia * Anemia of inflammation and chronic disease