Ca therapeutics

Question 1

Primary osteoporosis can include what types?

Answer 1

-Post menopausal
- Senile

Question 2

What is calmodulin?

Answer 2

An intracellular Ca binding protein that assists with cell signaling

Question 3

Dysfunction of the intestine or kidney can disrupt

Answer 3

bone mineral homeostasis

Question 4

PTH is a polypeptide that ________ serum Ca levels through bone resorption, _______ renal calcium excretion, and increasing ______________

Answer 4

Increases; decreased; calcitriol synthesis

Question 5

PTH maintains constant concentration of _________ and ________ in ECF

Answer 5

Ca and phosphate

Question 6

Pulsatile exposure of PTH can promote

Answer 6

bone formation

Question 7

Dietary def of Vit D, Ca or phosphate will stimulate

Answer 7

1 alpha hydroxylase

Question 8

If Ca levels are high, then calcitriol will be deactivated through

Answer 8

24-hydroxylase

Question 9

PTH, low phosphate levels and low calcium can _______ calcitriol synthesis in the renal proximal cells

Answer 9

increase

Question 10

Chronic Kidney disease can also lead to significant bone loss called

Answer 10

renal osteodystrophy

Question 11

Renal failure or CKD will result in Vit D def or could lead to

Answer 11

hyperparathyroidism

Question 12

What are typical Tx for renal osteodystrophy

Answer 12

Vit D analogs (Calcitriol, Eldecalcitol, cinacalcet, denosumab)

Question 13

What are indications for calcitriol use?

Answer 13

• Secondary hyperparathyroidism, hypocalcemia in pts undergoing renal dialysis, CKD, osteoporosis
• Topical for psoriasis
• Vit D def or insufficiency

Question 14

What does calcitriol bind to?

Answer 14

Alpha globulin vitamin D binding protein

Question 15

What metabolizes calcitriol?

Answer 15

• 24 hydroxylase
• 23 and 26 hydroxylase in kidneys

Question 16

Calcitriol can undergo enterohepatic recylcing which will _______ the half life

Answer 16

increase

Question 17

What are adverse effects of calcitriol?

Answer 17

Ectopic calcification, cardiac arrhythmias, hypertension, hypercalcemia

Question 18

What is cinacalcet?

Answer 18

Calci-mimetic that suppresses PTH secretion

Question 19

What are indications for Cinacalcet?

Answer 19

• Secondary hyperparathyroidism in pts with CKD
• Hypercalcemia in pts with parathyroid carcinoma

Question 20

Cinacalcet will increase sensitivity of _________ to activation by extracellular Ca, which will inhibit _______ secretion

Answer 20

Ca sensing receptors; PTH

Question 21

How is Cinacalcet metabolized?

Answer 21

by CYPs

Question 22

What are adverse effects of cinacalcet?

Answer 22

• Don’t use in pts with liver impairment
• Can cause upset stomach, vomiting, weakness, chest pain

Question 23

What does Denosumab do?

Answer 23

Suppresses bone resorption in pts with metastatic bone cancer

Question 24

What are indications for Denosumab?

Answer 24

• Post menopausal with high risk fracture
• Breast cancer, nonmetastatic prostate cancer

Question 25

What is the MOA of denosumab?

Answer 25

Blocks RANKL from activating its receptor RANK on surface of osteoclasts. Blocks bone resorption and helpts increase bone mass and strength

Question 26

What are adverse effects of Denosumab?

Answer 26

Musculoskeletal pain, hypercholesterolemia, cystitis. Possible increased risk of infection. Pancreatitis

Question 27

What are treamtnets utilized to block osteoclast activity?

Answer 27

- Bisphosphonates - Calcitonin - Estrogen or testosterone

Question 28

Chronic use of glucocorticoids can lead to

Answer 28

osteoporosis and aseptic necrosis of the hip

Question 29

What secondary promblems can occur from Pagets?

Answer 29

Deafness, spinal cord compression, high output cardiac failure and pain

Question 30

What is tx for Pagets?

Answer 30

- Bisphosphonates or calcitonin NSAIDs also used in tx for pain

Question 31

What are bisphosphonates?

Answer 31

Analogs of pyrophosphate in which P-O-P bond has been replaced by P-C-P bond

Question 32

Bisphosophonates bind to what?

Answer 32

Hydroxyapatite crystals and reduces dissolution

Question 33

Bisphosphonates end in

Answer 33

"Dronate"

Question 34

What is Risedronic acid?

Answer 34

3rd gen bisphosphonate

Question 35

What are indications for Risedronic acid?

Answer 35

- Osteoporosis - pagets - Glucocorticoid induced osteoporosis

Question 36

What is the MOA of Risedronic acid?

Answer 36

Binds to bone hydroxyapartie and can induce apoptosis through inhibition of farnesyl pyrophosphate synthase

Question 37

What are adverse effects of Risedronic acid?

Answer 37

Back pain, arthralgia, abdominal pain, dyspeptis, esophagitis

Question 38

Should bisphosophonates be taken on empty or full stomach?

Answer 38

Empty

Question 39

Calcitonin tones down Ca levels in blood and opposes the fucntion of what?

Answer 39

PTH

Question 40

What are indications for recombinant calcitonin (elcatonin)?

Answer 40

Pagets or other diseases that induce hypercalcemia

Question 41

How does elcatonin, a recombinant calcitonin work?

Answer 41

Inhibits osteoclast mediated bone resorption

Question 42

What are adverse effects of elcatonin (Recombinant calcitonin)?

Answer 42

Hypocalcemia, do not give with Bisphosphonates. May increase rate of excretion of lithium

Question 43

Raloxifene has estrogenic activity in the bone, but does what in breast and endometrial tissue?

Answer 43

Antagonizes activity

Question 44

What are indications for raloxifene?

Answer 44

- Osteoporosis in post menopause - Glucocorticoid induced osteoporosis - Women with osteoporosis with high risk of invasive breast cancer

Question 45

What is the MOA of Raloxifene?

Answer 45

- Estrogenic effects on bone and lipid metabolsima dna anti-estrogenic effects on uterine endometrium and breast tissues. Stimulates osteoblasts and inhibits osteoclasts to increase bone density

Question 46

What are adverse effects of Raloxifene?

Answer 46

Leg cramps, hot flashes, dizziness (all from vasodilation). Possible venous thromboembolic events

Question 47

What are indications for calcium gluconate?

Answer 47

- Osteoporosis or rickets - Cardioprotective agent in high blood K - Antidote for magnesium sulfate toxicity

Question 48

With calcium gluconate, you must be careful to monitor blood pH, since it can induce

Answer 48

alkalosis

Question 49

Calcium gluconate can reduce absorption in patients with what?

Answer 49

Achlorhydria or hypochlorhydria

Question 50

What are adverse effects of calcium gluconate?

Answer 50

Bradycardia, hypotension, nausea, constipation, kidney stones

Question 51

What are indications for recombinant PTH (Teriparatide acetate, abaloparatide)?

Answer 51

- Post menopause with high risk fractures - Men with primary of hypogonadal osteoporosis with high risk fractures

Question 52

With recombinant PTH (Teriparatide), injections are daily since intermittent exposure can do what?

Answer 52

Activate osteoblasts which can help to stimulate new bone formation

Question 53

What are adverse effects of recombinant PTH (Teriparatide)?

Answer 53

Injection site reactions, nausea, headaches, elg cramps, dizziness

Question 54

Which drug should be given only for a Max of 2 years?

Answer 54

Recombinant PTH, Teriparatide acetate (since it can cause cancers)

Question 55

What is the most efficacious drug?

Answer 55

Teriparatide