Download Chapter 16 Cholinesterase Inhibitors

Chapter 75
Drugs Affecting Calcium Levels
and Bone Mineralization
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
Calcium Physiology

Functions and daily requirements


Body stores



More than 98% stored in the bones
Total serum calcium = 10 mg/dL
Absorption




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

Calcitonin augments calcium elimination
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
2
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
3
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
4
Hypercalcemia

Drugs



Furosemide (Lasix)
Glucocorticoids
Others: calcitonin, bisphosphonates, inorganic
phosphates, gallium nitrate
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
5
Hypocalcemia


Increases neuromuscular excitability
Clinical presentation


Causes


Tetany, convulsions, and spasm of the pharynx
Deficiency of parathyroid hormone (PTH),
vitamin D, or calcium
Treatment


Calcium supplementation (calcium gluconate)
Vitamin D
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
6
Other Disorders Involving Calcium





Rickets
Osteomalacia
Paget’s disease of bone
Hypoparathyroidism
Hyperparathyroidism


Primary
Secondary
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
7
Drugs for Disorders
Involving Calcium




Calcium salts
Vitamin D
Calcitonin-salmon (Calcimar, Miacalcin,
Fortical)
Bisphosphonates

Alendronate, risedronate, ibandronate, tiludronate,
etidronate, zoledronate, pamidronate
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
8
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
9
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
10
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
11
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
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
12
Drugs for Hypercalcemia






Furosemide
Glucocorticoids
Gallium nitrate
Bisphosphonates
Inorganic phosphates
Edetate disodium
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
13
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)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
14
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)
Copyright © 2013, 2010 by Saunders, an imprint of Elsevier Inc.
15
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.
16