Pharmacology Of Thyroid Hormone & Bone PDF

# Pharmacology Of Thyroid hormone ## Diseases: - 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 u...

# Pharmacology Of Thyroid hormone ## Diseases: - 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. - hypersecretion of hormone (hyperthyroidism) - 1. antithyroid drugs - 2. irradiation, - 3. or surgical removal of the overactive tissue # Thyroid Hormone Preparations ## Drugs/Replacement therapy: - Levothyroxine and Liothyronine - 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 T& 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 RAL. ## I. 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. - Cross placenta - secreted in milk - 1. Hypothyroidism & goiter enlargement (neutrophiles-eosinophiles)→rare & disappear on stopping therapy - 2. Agranulocytosis - 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). - Uses It has an immediate reducing effect on release of thyroid hormones so used in thyroid crisis. (acute thyrotoxicosis) 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 (131). - 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 - Transport - Peroxidase - SCN, CIO,- - lodides, thioamides - Ipodate, B-blockers, corticosteroids - THYROID GLAND - Thyroglobulin - MIT-DIT-T, - lodides - Proteolysis - T, - PERIPHERAL TISSUES - TT - BLOOD - T, - Biosynthesis of thyroid hormones. The sites of action of various drugs that interfere with thyroid hormone biosynthesis are shown. # Drugs Affecting Calcium and Bone The diagram shows: - Cinacalcet activates the calcium-sensing receptor and decreases: a fall in the plasma calcium concentration - Calcitonin decreases: secretion of parathormone from the parathyroid which causes: conversion of calcifediol to calcitriol which causes: decreased excretion of calcium by the kidney which causes: increased calcium absorption in the intestine - Calcitonin decreases: a rise in the plasma calcium concentration which activates the calcium-sensing receptor on parathyroid cells which decreases: mobilization of calcium from bone # Drugs Affecting Calcium and Bone - Cinacalcet Activates the calcium-sensing receptor and decreases: A fall in the plasma calcium concentration causes: Decreased excretion of calcium by the kidney which causes: Increased calcium absorption in the intestine which causes: - Calcitonin Secretion of parathormone from the parathyroid which causes: Conversion of calcifediol to calcitriol which causes: Mobilisation of calcium from bone which causes: A rise in the plasma calcium concentration activates the calcium-sensing receptor on parathyroid cells which decreases: - Diet - Ca²+ - Vitamin D - Feces - Serum - Ca²+ - PTH - Urine - 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. T has numerous causes, the most common of which include vitamin D deficie vitamin D metabolism, phosphate deficiency, and osteoblast dysfunction. ## In children Osteomalacia results from vitamin D deficiency rickets 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. ## In adults # 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 teriparatide osteoblasts - 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, ## 1) Bisphosphonates - The original bisphosphonate - Second-generation bisphosphonates Etidronate 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. - Clinical uses: - 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 pamidronate or zoledronic acid approved for the treatment of Paget disease of bone - In patients with bone cancer. IV is the most effective treatment for hypercalcemia associated with 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 reduce the formation and activation of osteoclasts and thereby slow bone loss. - 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 - use - 1. Indicated for the treatment of postmenopausal women with osteoporosis who are at high risk for bone fracture - 2. Indicated to increase bone mass in hypogonadal men who are at high risk for fracture, such as those undergoing gonadotropin-releasing hormone therapy for prostate cancer. ## 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.