PHARMA calcium and bone homeostasis Flashcards
amt of calcium in averagediet
600-1000 mg
functions of bone
mineral reservoir
structural support
hematopoiesis
principal regulatoes
PTH
FGF 23
Steroid vitamin d
secondary regulators
calcitonin prolactin gh insulin
thyroid hormone, glucocorticoids, sex strroids
function of fgf 23
stimulates RENAL PO4 EXCRETION
what increases serum calcium and decrease serum phosphate
acts on bone and kidney
PTH
action of pth on bone
inc osteoclast activity by inducing RANK ligand (for bone REMODELING)
effect of low and intermittent PTH on bine
increase bone FORMATION
recombinant PTH 1-34
TERIPARATIDE
effect of pth on kidney
reabsorb calcium and magnesium
stimulate vit d production
forms of vit d
vit d3 cholecalciferol NATURAL
vit d2 ergocalciferol PLANT DERIVED
forms of vit d in liverr and kidney
liver 25OHD
kidney 1,25OH2D
kidney 24,24 OH 2D
calcifediol
calcitriol
secalcifediol
25 OH d3
1,25 oh 2D3
24,25 oh 2D3
give 3 vitamin d analogs
calcipotriene
doxercalciferol
paricalcitol
tx for psoriasis
CALCIPOTRIENE vit d analog
tx for 2ndary hyperparathyroidism
DOXERCALCIFEROL and PARACALCITOL vit d analogs
what inhibits and stimulates vit d metabolism
fgf23 inhibits
pth stimulates
which vit d is most potent and has low affinity
CALCITRIOL
calcifediol vs calcitriol
calcifediol more potent in stimulating renal reabsorption of ca and po4
pth regulated by feedback loops through?
calcium sensing receptors
directly inhibits PTH secretion
1,25(OH)2D
stimulates production of FGF23
1,25(OH)2D
inhibits 1,25(OH)2D production
FGF23
inhibit PTH secretion
Calcitriol analogs
mgmt of secondary hyperparathyroidism of CKD
Calcitriol analogs
Parafollicular cells of mammalian thyroid
Calcitonin
calcitonin half life
10mins
longer halflife, reduced metabolic clearance
salmon calcitonin
lowers Ca and PO4 reabsorption, dec GASTRIN secretion
calcitonin
potent stimulus for calcitonin secretion
Pentagastrin
block bone resorption and lower serum calcium
calcitonin
physiologic use of calcitonin
Paget’s disease, Hypercalcemia, Osteoporosis
Glucocorticoid use
stimulates renal calcium excretion
antagonizes vit D transport
blocks bone formation
hypercalcemia associated with inc production of 1,25(OH)2D
Granulomatous diseases - Sarcoidosis
Estrogen
prevent accelerated bone loss in post menopausal women
reduce bone resorption
inc 1,25(OH)2D
Selective estrogen receptor modulators
breast, uterus, cardiovascular system
newer therapies for osteoporosis
no risk of breast and endometrial ca
raloxifene
Bisphosphonates
osteoclast apoptosis
inhibition of cholesterol pathway
amino bisphosphonates
Alendronate and risedronate
block farnesyl pyrophosphate synthase
amino bisphosphonates
First generation bisphosphonates
MEDronate
ETIdronate
CLODronate
second generation bisphosphonates
ALEdronate
PAMidronate
3rd generation bisphosphonates
RISEdronate
ZolEDdronate
10,000x more potent than 1st gen
All current available bisphosphonate hav this complication
Gastric irritation (possible exception of ETIdronate)
main contraindication of bisphosphonates
dec renal dunction
esophageal motility disorders
peptic ulcer disease
physiologic use of bisphosphonates
hypercalcemia
paget’s disease
osteoporosis
bone metastasis
mineralization defect SE
ETIdronate
gastric and esophageal irritation SE
PAMidronate
high doses of ALEdronate