Medchem for Osteoporosis Flashcards
what are the names of the selective estrogen receptor modulators (SERMs)?
Lasoxifene and Raloxifene
what are the names of the Bisphosphonates?
Alendronate
Etidronate
Ibandronate
Pamidronate
Risedronate
Zoledronic Acid
Other agents for osteoporosis are calcitonin, cinacalcet, teriparatide, inorganic salts, denosumab, vitamin D, and romosozumab
which SERM has estrogen agonist activity in bone and CV system, and antagonistic activity in breast and uterus?
Raloxifene
Bisphosphonates are pyrophosphate analogues with a _____________ backbone. They bind to the __________ portion of the bone to inhibit ________ proliferation and activity, and decrease __________.
They are not ______ and are excreted unchanged
nonhydrolyzable
hydroxyapatite, osteoclast, bone resorption
metabolized
which bisphosphonate was the first approved and is 1,000 fold more potent than etidronate? what SE can it cause that is prevented by taking it with a glass of water and remaining upright for 30 min?
alendronate
esophagitis
Alendronate is used to treat?
osteoporosis and Paget’s disease
Etidronate is used to treat?
Paget’s disease, but not osteoporosis
Ibandronate is used to treat?
what is its bioavailability?
osteoporosis in postmenopausal women
0.6%
Pamidronate is used to treat?
hypercalcemia of malignancy
Risedronate is used to treat?
osteoporosis, Paget’s disease, and glucocorticoid-induced osteoporosis
Zoledronic Acid is used to treat?
hypercalcemia of malignancy
which drug is a peptide hormone consisting of 32 amino acids?
Calcitonin
Calcitonin is used to treat?
what formulation is best?
postmenopausal osteoporosis, hypercalcemia of malignancy, and Paget’s disease
calcitonin from salmon
which drug requires concomitant oral administration of calcium?
calcitonin
what is the MOA of Cinacalcet?
it is used to treat?
calcimimetic agent that increases binding of calcium to the calcium sensing receptor, this activates phospholipase C to inhibit PTH release
secondary hyperparathyroidism in pts with CKD on dialysis and hypercalcemia in pts with parathyroid cancer
what is the MOA of Teriparatide? it is recommended to be taken with?
it is used to treat?
enhances osteoblasts and osteoclasts to increase bone formation
calcium and vit D
postmenopausal osteoporosis with high fracture risk and increase bone mass of men with osteoporosis who have a high risk of fracture
what are the inorganic salts?
Calcium salts
gallium nitrate
sodium fluoride
strontium ranelate
why are calcium salts used?
improve absorption of calcium
why is gallium nitrate used?
treats hypercalcemia of malignancy. inhibits bone resorption
which organic salt is contraindicated in pts with severe renal impairment?
gallium nitrate
why is sodium fluoride used? why is it only combined with calcium?
promotes proliferation and activity of osteoblasts to treat osteoporosis
by itself, causes inferior bone tissue and can increase fracture risk
as a combo improves bone mass and decreases risk of vertebral fractures
when is strontium ranelate used?
when pts can’t tolerate bisphosphonates
Denosumab is used to treat?
MOA?
more or less potent than bisphosphonates?
how is it administered?
menopausal osteoporosis and bone metastases
inactivates RANKL which normally binds to RANK receptors and cause bone resorption, thus reducing bone resorption.
more potent
twice per year as a SC injection
which population benefits from vit D supplementation?
elderly because they often have reduced renal function
Romosozumab:
MoA?
binds and inactivates sclerostin to prevent inhibition of bone formation by allowing Wnt-B-catenin to bind to LPR 5/6
when Wnt binds to LPR 5/6 and the Frizzled family receptor, inhibition of the _______ destruction complex occurs and then accumulates to enter the nucleus, leading to transcription of ____________ and bone formation.
When sclerostin binds to LPR 5/6, the ________ destruction complex is assembled, and _______ is degraded, so ___________ are not activated, leading to increased bone resorption and decreased bone formation.
B-catenin, Wnt-responsive genes
B-catenin, B-catenin, Wnt-responsive genes
