Thyroid Medicines & Calcium Homeostasis PDF

Thyroid Medicines & Calcium Homeostasis  It involves the study of therapeutic agents that regulate thyroid hormone levels and control calcium balance in the body. These medications are critical for managing conditions such as hypothyroidism, hyperthyroidism, and disorders related to ca...

Thyroid Medicines & Calcium Homeostasis  It involves the study of therapeutic agents that regulate thyroid hormone levels and control calcium balance in the body. These medications are critical for managing conditions such as hypothyroidism, hyperthyroidism, and disorders related to calcium metabolism, such as osteoporosis and hypocalcemia. 1. Thyroid Medicines Thyroid hormones play a significant role in regulating metabolism, growth, and development. The two primary thyroid hormones are thyroxine (T4) and triiodothyronine (T3). Thyroid Disorders 1.Hypothyroidism: A condition where the thyroid gland does not produce enough thyroid hormone, leading to symptoms like fatigue, weight gain, and cold intolerance. 2.Hyperthyroidism: Excessive production of thyroid hormones, causing symptoms like weight loss, heat intolerance, and rapid heartbeat. Medicinal Chemistry of Thyroid Drugs The key drugs used in treating thyroid disorders are either thyroid hormone replacements (for hypothyroidism) or thyroid inhibitors (for hyperthyroidism). Hypothyroidism Treatment Levothyroxine (T4): A synthetic form of thyroxine, levothyroxine is the drug of choice for hypothyroidism. It is a prodrug T4 that is converted into T3, the biologically active form, in peripheral tissues. Mechanism of Action (MOA): Levothyroxine mimics the natural T4 hormone, restoring normal thyroid hormone levels and metabolic activity. T3   Pharmacokinetics: It has a long half-life (approximately 7 days) and is typically administered once daily. Hyperthyroidism Treatment  Methimazole and Propylthiouracil (PTU): These are thioamide drugs that inhibit thyroid hormone synthesis by  blocking the enzyme This enzyme catalyzes thyroid peroxidase. the iodination of tyrosine residues on thyroglobulin, a critical step in thyroid hormone production. Methimazo Propylthiouracil le (PTU MOA: Methimazole and PTU prevent the synthesis of T3 and T4, thereby reducing the levels of thyroid hormones. SAR Considerations: The presence of a thiocarbamide group (- SC=NH) is crucial for the activity of these drugs. Modifications to this group can affect potency and toxicity. Clinical Use: Methimazole is preferred due to its longer half-life and lower hepatotoxicity compared to PTU, although PTU is used during pregnancy because of its safety profile in early pregnancy. Radioactive Iodine (I-131): Used to destroy overactive thyroid tissue in cases of hyperthyroidism or thyroid cancer. It selectively accumulates in the thyroid gland and emits beta radiation, leading to the destruction of thyroid cells. Beta-Blockers (e.g., Propranolol): While not directly acting on the thyroid, beta-blockers are used to manage the cardiovascular symptoms of hyperthyroidism, such as tachycardia.  Calcium Homeostasis and Related Medicines Calcium homeostasis is essential for bone health, muscle contraction, nerve function, and blood clotting. The key hormones regulating calcium levels are parathyroid hormone (PTH), calcitonin, and vitamin D. Calcium Homeostasis Disorders 1. Hypocalcemia: Low calcium levels in the blood, which can cause muscle cramps and tetany. 2. Hypercalcemia: Elevated blood calcium levels, leading to symptoms like nausea, vomiting, and arrhythmias. 3. Osteoporosis: A condition where bone density decreases, increasing the risk of fractures. Medicinal Chemistry of Drugs Regulating Calcium Homeostasis Vitamin D Analogs  Vitamin D is essential for calcium absorption in the intestines and for maintaining adequate serum calcium and phosphate levels. Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2): Both are precursors that are converted in the liver and kidneys to 1,25-dihydroxyvitamin D (calcitriol), the active form of vitamin D. Cholecalcife Calcitriol Ergocalcifer rol ol MOA: Vitamin D increases calcium and phosphate absorption in the intestines and reduces renal excretion of calcium. SAR: The D2 and D3 forms differ in their side chains, but both are hydroxylated to the active form. Structural modifications in synthetic analogs aim to improve bioavailability and reduce toxicity. Calcitriol: The most active form of vitamin D used in the treatment of hypocalcemia and metabolic bone diseases, including osteoporosis. Bisphosphonat es drugs are used to treat osteoporosis and hypercalcemia These by inhibiting bone resorption. Alendronate, Risedronate, Zoledronate: Bisphosphonates bind to hydroxyapatite in bone and inhibit osteoclast activity, preventing bone breakdown. Alendrona Risedrona Zoledrona te te te MOA: Bisphosphonates are analogs of pyrophosphate and inhibit the enzyme farnesyl pyrophosphate synthase, disrupting osteoclast function. SAR: The presence of two phosphonate groups is critical for binding to bone mineral, while nitrogen-containing bisphosphonates have increased potency compared to non- nitrogen bisphosphonates. Parathyroid Hormone (PTH) and Analogs  PTH increases blood calcium levels by promoting calcium release from bones, increasing calcium absorption in the intestines, and reducing calcium excretion in the kidneys. Teriparatide: A recombinant form of PTH, used to treat osteoporosis by stimulating bone formation. MOA: It promotes bone growth by activating osteoblasts more than osteoclasts when given intermittently. Calcitoni nCalcitonin lowers blood calcium levels by inhibiting osteoclast activity, which reduces bone resorption.  Synthetic Calcitonin: Used to treat osteoporosis and hypercalcemia. It has a similar structure to the endogenous hormone but is more stable and longer- lasting.  Calcium Supplements  Calcium Carbonate and Calcium Citrate: Commonly used to treat hypocalcemia and prevent bone loss in osteoporosis.  MOA: They provide a direct source of calcium to increase serum calcium levels. Therapeutic Uses in Calcium and Thyroid Disorders  Thyroid Drugs: Used to normalize thyroid hormone levels in hypothyroidism (levothyroxine) and to reduce excessive thyroid hormone production in hyperthyroidism  (methimazole, PTU). Calcium Homeostasis Drugs: Treat bone disorders such as osteoporosis, manage blood calcium levels in hypocalcemia and hypercalcemia, and ensure adequate calcium absorption (via vitamin D analogs, bisphosphonates, PTH analogs).