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Flashcards in Calcium Metabolism Deck (43)
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1
Q

What interaction promotes osteoclast differentiation?

A

RANKL binding to RANK on an osteoclast precursor

2
Q

What is the function of calcitriol?

A

Increases calcium absorption

3
Q

What is the function of endogenous parathyroid hormone on Ca2+?

A

Promotes bone resorption

4
Q

What is the effect of exogenous parathyroid hormone on Ca2+?

A

Promotes bone deposition

5
Q

What are the effects of PTH?

A

 ↑ renal Ca2+ resorption
 ↑ renal phosphate excretion
 ↑ renal synthesis of calcitrol

6
Q

What regulates PTH?

A

Calcium Sensing Receptor - Ca2+ levels

7
Q

What are the functions of vitamin D?

A

‐ augments absorption of Ca2+ and phosphate from the small intestine
‐ decreases renal excretion of both calcium and phosphate
‐ Inhibits production of PTH

8
Q

What are the functions of calcitonin?

A

‐ secreted by the parafollicular cells of the parathyroid gland
‐ activity generally opposes the action of PTH
- secreted when Ca2+ levels are high

9
Q

What is the most common cause of hypercalcemia?

A

Primary Hyperparathyroidism

10
Q

What are common causes of hypocalcemia?

A

Hypoparathyroidism (PTH deficiency) and Vitamin D deficiency

11
Q

What are common causes of hyperphosphatemia?

A

Chronic kidney disease and secondary hyperparathyroidism

12
Q

What are the types of vitamin D used for supplementation?

A
  • Ergocholecalciferol (vitamin D2)

- Cholecalciferol (vitamin D3)

13
Q

What vitamin D has a rapidly acting effect within 24‐48hrs?

A

Calcitriol - 1,25 (OH)2 Vitamin D3

14
Q

What vitamin D requires only hepatic hydroxylation to be active?

A

Doxercalciferol 1‐OH Vitamin D2

15
Q

Vitamin D MOA

A

Agonists of VDR

  • ↑Ca2+/PO4 intestinal absorption
  • ↑Ca2+/PO4 renal absorption
  • ↓PTH expression
16
Q

Vitamin D SE

A

Hypercalcemia

17
Q

Vitamin D Indications

A
  • Nutritional Supplements
  • Rickets & Osteomalacia
  • Prevention of Osteoporosis
  • Hypoparathyroidism
  • Secondary Hyperparathyroidism
18
Q

Vitamin D Contraindications

A

Hyperphosphatemia

19
Q

What are these drugs: Alendronate, Pamidronate, Risendronate and Zoledronate?

A

Bisphosphonates

20
Q

Bisphosphonate MOA

A

Inhibit Farensyl Pyrophosphate Synthase
↓ Protein farnesylation
↓ Osteoclast activity
↓ Bone resorption

21
Q

What are bisphosphonates all analogs of?

A

All bisphosphonates are analogs of pyrophosphate

22
Q

What is protein farnesylation?

A

Protein farnesylation is important for the function of many signaling proteins especially small GTPases e.g. Rac/Rho/cdc42 that are involved in the regulation of the cytoskeleton and other signaling pathways

23
Q

Bisphosphonate Indications

A
  • Osteoporosis
  • Hypercalcemia
  • Paget’s Disease
24
Q

Bisphosphonate SE

A
  • Severe GI effects
  • Esophageal Irritation
  • Ocular side effects
  • Osteonecrosis of the Jaw
  • Renal impairment
25
Q

Bisphosphate Contraindications

A
  • Esophageal disease

- Chronic kidney disease

26
Q

Denosumab MOA

A

Anti‐RANKL mAb
RANKL antagonist
↓ Osteoclast bone resorption

27
Q

Denosumab Indications

A
  • Osteoporosis
  • Hypercalcemia
  • Giant Cell tumor of the bone
28
Q

Denosumab SE

A
  • Hypocalcemia

- Osteonecrosis of the Jaw

29
Q

Denosumab Contraindications

A

Hypocalcemia

30
Q

Teriparitide Indications

A

Osteoporosis

31
Q

Teriparitide MOA

A
  • PTH receptor agonist with intermittent activity as it is exogenous
  • Stimulates osteoblasts
  • Promotes bone growth
    ↑ Renal 1a‐hydroxylase activity
    ↑ Renal calcium reabsorption
32
Q

Teriparitide SE

A
  • Transient Hypercalcemia
  • Hyperuricemia
  • ↑ Risk of osteosarcoma
33
Q

Teriparitide Contraindications

A
  • History of gout
  • Risk of osteosarcoma
  • Active malignancy of the bone
  • Radiation therapy of the bone
34
Q

Raloxifene Indications

A

Osteoporosis (post menopausal women)

- This is a SERM drug

35
Q

Raloxifene MOA

A

SERM - ER agonist in bone Anti‐estrogen in breast & uterus
↓ Genes involved in osteoclast activation
↓ Osteoclast activity

36
Q

Raloxifene SE

A

↑ Risk venous thromboembolism

37
Q

Calcitonin Indications

A
  • Severe hypercalcemia
  • Paget’s Disease
  • Osteoporosis
38
Q

Calcitonin MOA

A

Calcitonin receptor agonist - opposes PTH actions

39
Q

Calcitonin SE

A
  • Nausea
  • Hand swelling
  • Intestinal cramping
40
Q

Cinacalcet Indications

A
  • CKD/secondary hyperparathyroidism
  • Hypercalcemia
  • Primary hyperparathyroidism
41
Q

Cinacalcet MOA

A

Calcimimetic - Allosterically enhances affinity of CaSR for Ca2+ so lower concentrations of calcium are sensed and PTH is more suppressed

42
Q

Cinacalcet SE

A
  • Hypocalcemia

- Seizure risk

43
Q

Cinacalcet Contraindications

A

Contraindicated with serum Ca2+ is below 8.4 mg/dL

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