This chapter will be most useful after having a basic understanding of the material in Chapter 44, Agents Affecting Mineral Ion Homeostasis and Bone Turnover in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, 12th Edition. In addition to the material presented here, the 12th Edition contains:
A detailed discussion of the physiology of mineral ion homeostasis
A description of the hormonal regulation of calcium and phosphorous homeostasis
A discussion of bone physiology
A detailed discussion of the pharmacological treatment of disorders of mineral ion homeostasis and bone metabolism, including the therapeutic uses of vitamin D, calcitonin, bisphosphonates, parathyroid hormone (PTH), and calcium sensor mimetics
A description of an integrated approach to the prevention and treatment of osteoporosis
Understand calcium and phosphorous homeostasis.
Describe the roles of PTH, calcitonin, and vitamin D in calcium homeostasis.
Understand the concept of bone resorption and bone formation.
Describe the mechanism of action and untoward effects of bisphosphonates.
Describe the role of bisphosphonates in the prevention and treatment of osteoporosis.
Describe the pharmacological management of hypocalcemia and hypercalcemia.
DRUGS INCLUDED IN THIS CHAPTER
1α-hydroxycholecalciferol (1-OHD, alphacalcidol, ONE-ALPHA)
22-Oxacalcitrol (1,25-dihydroxy-22-oxavitamin D3, OCT, maxacalcitol, OXAROL)
Calcipotriene (DOVONEX, others)
Calcitonin (CALCIMAR, MIACALCIN)
Calcitriol (1,25-dihydroxycholecalciferol; CALCIJEX, ROCALTROL)
Dihydrotachysterol (DHT, ROXANE)
Doxercalciferol (1α-hydroxyvitamin D2, HECTOROL)
Ergocalciferol (calciferol, DRISDOL)
Etidronate sodium (DIDRONEL)
Lanthanum carbonate (FOSRENOL)
Paricalcitol (1,25-dihydroxy-19-norvitamin D2, ZEMPLAR)
Sevelamer hydrochloride (RENAGEL)
MECHANISMS OF ACTION OF DRUGS USED IN MINERAL HOMEOSTASIS AND BONE TURNOVER DISORDERS |Favorite Table|Download (.pdf) MECHANISMS OF ACTION OF DRUGS USED IN MINERAL HOMEOSTASIS AND BONE TURNOVER DISORDERS
|DRUG CLASS ||DRUGS ||MECHANISM OF ACTION |
|Hormones || |
Calcitonin actions are mediated by the calcitonin receptor (CTR), which is a member of the parathyroid PTH/secretin subfamily of GPCRs; the hypocalcemic and hypophosphatemic effects of calcitonin are caused by direct inhibition of osteoclastic bone resorption
Teriparatide is a synthetic PTH fragment (1-34); intermittant exposure to PTH promotes anabolic actions on bone and is the basis for teriparatide’s use in treating severe osteoporosis
|Vitamin D and Vitamin D Analogs || |
Calcitriol (biologically active metabolite of Vitamin D); (see Figure 31-1)
|Actions of vitamin D and analogs are mediated by the vitamin D receptor (VDR), a nuclear receptor; calcitriol and other drugs in this class act to maintain normal calcium and phosphate in plasma by facilitating their absorption in the small intestine, by interacting with PTH to enhance their mobilization from bone, and by decreasing their renal excretion |
|Phosphate Binders || |
Sevelamer is a nonabsorbable phosphate-binding polymer
Lanthanum is a poorly permeable trivalent cation that binds phosphate