Drugs Affecting Calcium Levels and Bone Mineralization Calcium
Drugs Affecting Calcium Levels and Bone Mineralization
Calcium Physiology Functions and daily requirements Ø Body stores Ø Ø More than 98% stored in the bones Total serum calcium = 10 mg/d. L Absorption Ø Ø Ø Critical to the function of the skeletal, nervous, muscular, and cardiovascular systems Absorption in the small intestine Increased by parathyroid hormone and vitamin D Glucocorticoids decrease absorption Excretion Ø Calcitonin augments calcium elimination
Calcium Physiology Regulation of calcium levels Ø Ø Absorption from the small intestine Excretion by the kidney Resorption in bone Regulated by • Parathyroid hormone • Vitamin D • Calcitonin
Hypercalcemia Usually asymptomatic If symptoms present: often involve the kidneys Causes Ø Ø Cancer Hyperparathyroidism Treatment Ø Ø Promote urinary excretion Decrease mobilization from bone Decrease intestinal absorption IV saline
Hypercalcemia Drugs Ø Ø Ø Furosemide (Lasix) Glucocorticoids Others: calcitonin, bisphonates, inorganic phosphates, gallium nitrate
Hypocalcemia Increases neuromuscular excitability Clinical presentation Ø Causes Ø Tetany, convulsions, and spasm of the pharynx Deficiency of parathyroid hormone (PTH), vitamin D, or calcium Treatment Ø Ø Calcium supplementation (calcium gluconate) Vitamin D
Other Disorders Involving Calcium Rickets Osteomalacia Paget’s disease of bone Hypoparathyroidism Hyperparathyroidism Ø Ø Primary Secondary
Drugs for Disorders Involving Calcium salts Vitamin D Calcitonin-salmon (Calcimar, Miacalcin, Fortical) Bisphonates Ø Alendronate, risedronate, ibandronate, tiludronate, etidronate, zoledronate, pamidronate
Raloxifene (Evista) Selective estrogen receptor modulator (SERM) Structurally similar to estrogen and binds to estrogen receptors Ø Therapeutic uses • Osteoporosis and breast cancer • May decrease risk of cardiovascular events Ø Adverse effects • Venous thromboembolism, fetal harm, hot flashes Ø
Teriparatide (Forteo) Form of parathyroid hormone (PTH) Produced by recombinant DNA Only drug that increases bone formation Generally well tolerated Ø Nausea, headache, back pain, leg cramps
Denosumab Approved in 2010 First-in-class RANKL inhibitor with two indications: treatment of osteoporosis in postmenopausal women at high risk for fractures Ø prevention of skeletal-related events (see below) in patients with bone metastases from solid tumors Ø
Cinacalcet (Sensipar) Calcimimetic drug Approved for primary hyperparathyroidism and secondary hyperparathyroidism (caused by chronic kidney disease [CKD]) Somehow increases the sensitivity of calciumsensing receptors to activation by extracellular calcium PTH secretion suppressed
Drugs for Hypercalcemia Furosemide Glucocorticoids Gallium nitrate Bisphonates Inorganic phosphates Edetate disodium
Osteoporosis Most common disorder of calcium metabolism Low bone mass and increased bone fragility Primary prevention Ø Calcium, vitamin D, lifestyle Diagnosis Ø Ø Measuring bone mineral density (BMD) Dual-energy x-ray absorptiometry (DEXA)
Treating Osteoporosis in Women Antiresorptive therapy: drugs that reduce bone resorption Estrogen (Premarin) Raloxifene (Evista) Bisphonates • Alendronate (Fosamax) • Risedronate (Actonel) • Ibandronate (Boniva) Ø Calcitonin-salmon nasal spray (Miacalcin) Ø Ø Ø Drugs that promote bone formation Ø Teriparatide (Forteo)
Treating Osteoporosis in Men Antiresorptive therapy: drugs that reduce bone resorption Not much research available on treatment of men Four drugs approved Ø Bisphonates • Alendronate (Fosamax) • Risedronate (Actonel) • Teriparatide (Forteo) • Zoledronate (Reclast)
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