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Chapter 75

Chapter 75. Drugs Affecting Calcium Levels and Bone Mineralization. Calcium Physiology. Functions and daily requirements Critical to the function of the skeletal, nervous, muscular, and cardiovascular systems Body stores More than 98% stored in the bones Total serum calcium = 10 mg/dL

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Chapter 75

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  1. Chapter 75 Drugs Affecting Calcium Levels and Bone Mineralization

  2. Calcium Physiology • Functions and daily requirements • Critical to the function of the skeletal, nervous, muscular, and cardiovascular systems • Body stores • More than 98% stored in the bones • Total serum calcium = 10 mg/dL • Absorption • Absorption in the small intestine • Increased by parathyroid hormone and vitamin D • Glucocorticoids decrease absorption • Excretion • Calcitonin augments calcium elimination

  3. Calcium Physiology • Regulation of calcium levels • Absorption from the small intestine • Excretion by the kidney • Resorption in bone • Regulated by • Parathyroid hormone • Vitamin D • Calcitonin

  4. Hypercalcemia • Usually asymptomatic • If symptoms present: often involve the kidneys • Causes • Cancer • Hyperparathyroidism • Treatment • Promote urinary excretion • Decrease mobilization from bone • Decrease intestinal absorption • IV saline

  5. Hypercalcemia • Drugs • Furosemide (Lasix) • Glucocorticoids • Others: calcitonin, bisphosphonates, inorganic phosphates, gallium nitrate

  6. Hypocalcemia • Increases neuromuscular excitability • Clinical presentation • Tetany, convulsions, and spasm of the pharynx • Causes • Deficiency of parathyroid hormone (PTH), vitamin D, or calcium • Treatment • Calcium supplementation (calcium gluconate) • Vitamin D

  7. Other Disorders Involving Calcium • Rickets • Osteomalacia • Paget’s disease of bone • Hypoparathyroidism • Hyperparathyroidism • Primary • Secondary

  8. Drugs for Disorders Involving Calcium • Calcium salts • Vitamin D • Calcitonin-salmon (Calcimar, Miacalcin, Fortical) • Bisphosphonates • Alendronate, risedronate, ibandronate, tiludronate, etidronate, zoledronate, pamidronate

  9. Raloxifene (Evista) • Selective estrogen receptor modulator (SERM) • Structurally similar to estrogen and binds to estrogen receptors • Therapeutic uses • Osteoporosis and breast cancer • May decrease risk of cardiovascular events • Adverse effects • Venous thromboembolism, fetal harm, hot flashes

  10. Teriparatide (Forteo) • Form of parathyroid hormone (PTH) • Produced by recombinant DNA • Only drug that increases bone formation • Generally well tolerated • Nausea, headache, back pain, leg cramps

  11. Denosumab • Approved in 2010 • First-in-class RANKL inhibitor with two indications: • treatment of osteoporosis in postmenopausal women at high risk for fractures • prevention of skeletal-related events (see below) in patients with bone metastases from solid tumors

  12. Cinacalcet (Sensipar) • Calcimimetic drug • Approved for primary hyperparathyroidism and secondary hyperparathyroidism (caused by chronic kidney disease [CKD]) • Somehow increases the sensitivity of calcium-sensing receptors to activation by extracellular calcium • PTH secretion suppressed

  13. Drugs for Hypercalcemia • Furosemide • Glucocorticoids • Gallium nitrate • Bisphosphonates • Inorganic phosphates • Edetate disodium

  14. Osteoporosis • Most common disorder of calcium metabolism • Low bone mass and increased bone fragility • Primary prevention • Calcium, vitamin D, lifestyle • Diagnosis • Measuring bone mineral density (BMD) • Dual-energy x-ray absorptiometry (DEXA)

  15. Treating Osteoporosis in Women • Antiresorptive therapy:drugs that reduce bone resorption • Estrogen (Premarin) • Raloxifene (Evista) • Bisphosphonates • Alendronate (Fosamax) • Risedronate (Actonel) • Ibandronate (Boniva) • Calcitonin-salmon nasal spray (Miacalcin) • Drugs that promote bone formation • Teriparatide (Forteo)

  16. Treating Osteoporosis in Men • Antiresorptive therapy:drugs that reduce bone resorption • Not much research available on treatment of men • Four drugs approved • Bisphosphonates • Alendronate (Fosamax) • Risedronate (Actonel) • Teriparatide (Forteo) • Zoledronate (Reclast)

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