copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 75 drugs affecting calcium...

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.

Chapter 75

Drugs Affecting Calcium Levels and Bone Mineralization

Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc. 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


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


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


Hypercalcemia

Drugs Furosemide (Lasix) Glucocorticoids Others: calcitonin, bisphosphonates, inorganic

phosphates, gallium nitrate


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


Other Disorders Involving Calcium

Rickets Osteomalacia Paget’s disease of bone Hypoparathyroidism Hyperparathyroidism

Primary Secondary


Drugs for Disorders Involving Calcium

Calcium salts Vitamin D Calcitonin-salmon (Calcimar, Miacalcin,

Fortical) Bisphosphonates

Alendronate, risedronate, ibandronate, tiludronate, etidronate, zoledronate, pamidronate


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


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


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


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


Drugs for Hypercalcemia

Furosemide Glucocorticoids Gallium nitrate Bisphosphonates Inorganic phosphates Edetate disodium


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)


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)


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)

copyright © 2013, 2010 by saunders, an imprint of elsevier inc. chapter 75 drugs affecting calcium...

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