Drugs Affecting Bone Mineral Homeostasis Flashcards
(35 cards)
Bone mineral homeostasis
Calcium and phosphorous
Regulated by Vitamin D, PTH
(also fibroblast growth factor 23 and calcitonin)
PTH and D
Stimulate preosteoblast proliferation and diffrentiation–> bone formation
Sitmulate differentiation and activation of osteoclast–> bone resorption
Calcium
Acts to clotting blood, muscle contraction, ossification of bone, release of endocrine hormones and neurotransmitters
Hypercalcemia
generalized muscular weakness and smooth muscle dysfunction
Hypocalcemia
skeletal, cardiac, smooth muscle spasms, tetany, generalized convulsions; paresthesias
Pharmacological uses of Ca
hypocalcemia, hypoparathyroidism, renal disease, hypocalcemic tetany, prophylaxis and tx of osteoporosis
toxicity- ectopic calcification
Calcium carbonate
oral
cheap
need to take with food
can cause gas, bloating, constipation
calcium citrate
oral
fewer GI problems
does not affect gastric pH
can take w/o food
IV calcium
calcium gluconate
for severe symptomatic hypocalcemia
least irritating to veins of IV Ca preparations
rapid infusion can cause arrythmias
Vitamin D
Formed in skin by UV irradiation, found in certain foods
D3 is intrinsic and dietary is D3 and D2 are inactive precursors that need to be converted to calcitriol (most active)
circulates bound to vitamin D binding protein
Primary function of Vitamin D
- regulation of Ca homeostasis
- bones increase bone formation and resorption (inc Ca mobilization)
- kidneys to increase tubular reabsorption (dec Ca excretion)
- small intestines to increase Ca and phosphate absorption
Normal range 30-70 ng/mL
Deficiency of vit D in children
Causes rickets resulting in abnormal and retarded bone growth
Vit D toxicities
hypercalcemia and hypercalciuria–> nausea, vomiting, decreased appetite, frequent urination, renal failure
relatively uncommon
Cholecalciferol
D3
hydroxylated by liver, and then kidney
longer 1/2 life- better for supplementation unless metabolism is compromised
otc
aminal source
Ergocalciferol
D2
made by plants
prescription
shorter 1/2 life
Calcitriol
1,25(OH)2D3
most active Vit D
Other Vit D analogs
Calcipotriene, doxercalciferol, paracalcitrol
Causes of Vit D def
inadequate dietary intake
inadequate exposure to sublight
renal dysfunction
administration of anticonvulsants (phenobarbital, phenytoin) that increase metabolism of 24(OH)D
Pharma uses of vit D
nutritional rickets
metabolic rickets (genetic defect in renal hydroxylase or renal failure)- use calcitriol
osteoporosis and osteomalacia
psoriasis- calcipotriene (topical)
hypoparathyroidism
secondary hyperparathyroidism in renal disease- doxercalciferol, paricalitol
bisphosphonates
Analogs of pyrophosphate
- suppress activity of osteoclasts by mechanism involving retardation of formation and dissolution of hydroxyapatite crystals within bone
- inhibit bone resorption and consequently bone formation
Use of bisphosphonate
osteoporosis in females and males
pagets disease of bone
hypercalcemia
bone mets
Bisphosphonates PK
less than 10% oral dose absorbed
oral reduced by food
take with full glass of water and remain upright for 30 min because it causes esophageal and gastric irritation
AE of bisphosphonates
gastric irritation (unless IV) adynamic bone osteonecrosis of jaw renal failure drug holiday recommended after 5 years of treatment
Oral bisphosphanates
Etidronate (daily), alendronate (daily or weekly), risedronate (daily, weekly, monthly)
