Agents for Bone Mineral Homeostasis Flashcards
What are the actions of Calcitriol?
1) Increased Serum Ca
2) Increased Serum Phos
What is calcitriol and how is it made?
It is active vitamin D3 and it it synthesized in skin and blood, activated in liver, then kidney (25 then 1)
How does Calcitriol increase Serum Ca?
Increases duodenal absorption of Ca (increased calbindin), increases renal reabsorption of Ca, and increases bone resorption
How are the PTH analogs mediated?
Gs mediated (activations of adenylyl cyclase to increase cAMP and the cAMP can be measured in urine to determine parathyroid function) Used in hypoparathyroidism; but it is more commonly treated with Vit D3 +- Ca supplements
What is Teriparatide? (specific)
It is a PTH analog; hrPTH 1-34 aa
What is the MOA of Teriparatide?
It stimulates bone formation directly because low doses of PTH activate osteoblasts without activating osteoclasts; may stimulate IGF-1
What is Teriparatide important in?
In women post bisphosphonate treatment
What is the MOA of Raloxifene?
Selective Estrogen Receptor Modulator (SERM); It inhibits osteoclasts without causing breast cancer
What is Raloxifene used for?
Osteoporosis
What is the MOA of Denosumab?
it is an mAB to RANKL that blocks osteoclast activation by RANKL
What is Denosumab used for?
Decrease osteoporosis and increase bone mass in patients with breast/prostate cancer; Biannual dose administration
What is the most important calcium regulating hormone and for therapeutics?
Calcitriol
What is Calcitriol used for?
Prophylaxis/Cure of rickets and osteomalacia; Treatment for hypoparathyroidism; Treatment for osteoporosis
What is a Calcipotriol and what is it used for?
Synthetic Calcitriol; Used for psoriasis and is more effective than glucocorticoids
What are bisphosphonates?
They are non-hydrolyzable analog of pyrophosphates that inhibit bone resorption. They are used in Paget’s and effective in osteoporosis.
Describe the absorption and administration of bisphosphonates?
Poorly absorbed in gut and taken after overnight fast w/ water and no food for 30 minutes, there is a weekly dose form, and effective if given IV 4-24 infusion at lowering serum Ca for several weeks
What is the big ADE of ALL of the Bisphosphonates?
Osteonecrosis of the Jaw! It is jaw bone exposure, swelling/loosening of teeth and dentists make it worse (80% follow dental work), it is complicated by infection and usually seen with 3rd generation drugs for cancer patients
What is beneficial about bisphosphonates when used in cancer patients?
They can prevent bone loss due to chemotherapy, recommended w/ bone mets, breast, and prostate dx; use shows a 1/3rd decrease in skeletal complications
What are Alendronate and Ibandronate?
The 2nd generation Bisphosphonates (10-100x more potent than 1st gen)
What disease is Alendronate specifically indicated for?
Paget’s
What are Risendronate and Zoledronate?
The 3rd generation Bisphosphonates (1k-10kx potent than 1st gen) Used in cancer patients with bone mets, given IV and may only need one dose
What disease is Risendronate specifically indicated for?
Paget’s
What is the MOA of Cincacalcet?
It allosterically binds to Ca sensing receptor and allows PTH suppression at lower blood Ca levels which will lower the circulating PTH
What is Cincacalcet approved to be used in?
Hyperparathyroidism from parathyroid carcinoma
