Bone Mineral homeostasis drugs Flashcards
Intracellular calcium is where?
mitochondria/ER
Extracellular calcium is 40% albumin boundand 10% complexed to phosphate, citrate and 50% free ionized calcium
Parathyroid responds to the free ionized calcium
Denusomab
mAB to RANKL. It blocks osteoclasta ctivation by RANKL and thus inhibits osteoporosis. Also used to increase bone mass in patients with breast/prostate cancer
Calcitriol—in active Vit D.
Stimulates calcium and phosphate absorption in the GI. Induces Calbindin. Not a vitamin!!!
Calcipotriol
used in psoriasis
Cinacalcet
Binds allosterically to Calcium sensing receptors and makes the body think there is more calcium in the blood than there really is. Turns off PTH at lower calcium levels.
When would you use cinacalcet?
hyperparathyroidism and parathyroid carcinoma
What are bisphosphonates
non-hydrolyzable pyrophosphate analogs. They inhibit bone resorption. Effective in osteoporosis
How are bisphosphonates absorbed
Poorly in the gut. Must take them after overnight fast with water and no food for 30min. Now given in weekly dose form.
Big AE of bisphosphonates
Osteonecrosis of the Jaw…jaw bone exposure, swelling, loosening of teeth. Dentists make it worse as 80% of the instances of osteonecrosis follow dental work
Which type of bisphosphonates are most likely to cause osteonecrosis of the jaw?
The 3rd generation drugs that are used to treat ppl with cancer.
Why would you give a cancer pt bisphosphonates
Prevent bone loss caused by chemo
Which type of cancers are bisphosphonates receommended in?
Bone Mets, Breast, prostate
Ibandronate
2nd generation (10-100x potency)
Risedronate
3rd gen bisphosphonate (1k to 10k potency) . Cancer pts with bone mets. IV, may onlyneed one dose
WHat else can you give Risedronate for?
Paget’s disease
Raloxifene
Estrogen Receptor modulator
What is Raloxifene for?
Osteoporosis
Raloxifene mech
Inhibits osteoclasts without causing breast cancer.
What is a PTH analog
Activates adenylyl cyclase which raises cAMP levels. High cAMP can be measured in the urine for parathyroid function
PTH analogs used for
hypoparathyroidism
Teriparatide
PTH analog…only first 34 amino acids.
HOw does Teriparatide work?
Stimulates bone formation directly. We know that low doses of PTH activate osteoblasts without ativating osteoclasts…maybe thats whats going on.
When would you give Teriparatide?
after bisphosphonate therapy in women
Zoledronate?
the other 3rd gen bisphosphonate
When would you use Teriparatide?
In women post bisphosphonate…bisphosphonates like Ibandronate would prevent reabsorption and then you use the Teriparatide to kick start bone growth
Zoledronic acid
bisphosphonate…cancer pts with bone mets
