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Exam 1 Pharm II > Calcium Homeostasis! > Flashcards

Calcium Homeostasis! Flashcards

1
Q

Where is majority of Ca++ stored?

A

In bone and teeth

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2
Q

Calcium is stored in bone as________

A

hydroxyapatite

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3
Q

Osteoblasts_____________ bone

A

Build

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4
Q

Osteoclasts_____________Bone

A

Resolve (Cut)

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5
Q

What factors released by osteocytes upregulate osteoblast/Clast activity?

A

Prostaglandins
Nitric Oxide
Dentin matrix protein

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6
Q

What factors released by osteocytes down-regulate osteoblast/Clast activity?

A

Sclerostin
Osteocalcin
MEPE

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7
Q

What is the role of PTH?

A

To maintain a constant Ca++ concentration in the ectracellular fluid (serum)

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8
Q

What receptors reabsorb Ca++ from the collecting tubules?

A

ECaC1/TrpV5

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9
Q

How does PTH regulate calcium?

A

Increaseding Ca++ reabsorption via TrpV5
Increased Bone resorption (Osteoclast)
Increased PO4 loss in urine
Increased 1,25 (OH)2 D3 prodution in kidney

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10
Q

What receptor in the parathyroid senses Ca levels?

A

a GPCR (CaR)

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11
Q

What are the steps and enzymes involved in Vit D synthesis?

A

7-dehydrocholestrol====>UV radiation====>Cholecalciferol(vit D3) ====>Liver (Vit D25-hydroxylase enzyme=====>25 hydroxyvitamin D3====> 1 alpha hydroxylase====> 1,25 Dihydroxy Vit D3 calcitriol.

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12
Q

What is the role of Vit D?

A

Increase Ca++ and PO4 absorption from the small intestine (via ECaC2/TrpV6)
Feedback inhibition of PTH via 1,25(OH)2D

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13
Q

What cellular transporters are upregulated by Vit D?

A

TryV6
Calbindin-D9k
Ca++ ATPase.

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14
Q

What is the role of the Ca++_ATPase?

A

To enable Ca++ absorption in the intestine

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15
Q

What is the function of Calbindin-D9K?

A

It binds Ca++ intracellularly after it has been absorbed.

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16
Q

What is the role of calcitonin? Where is it made?

A

It is a negative regulator of (extracellular Ca++) concentration.

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17
Q

What how does calcitonin regulate serum Ca++ conentration?

A

It inhibits bone resorption

Increases Ca++ and PO4 loss in urine

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18
Q

What stimulates Calcitonin?

A

High Ca++ concentration.

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19
Q

What is osteoporosis? What causes it?

A

Bone mass loss. It is caused by a decrease in estrogen (postmenopaural).(decreased osteoblast activity)

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20
Q

What are the risk factors for osteoporosis?

A

Physical inactivity
Age
Low Ca++ intake in early yrs
Long-term glucocorticoid therapy

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21
Q

Give two causes of hypercalcemia

A 
Hyperthyroidism-Increased bone resorption and decreased Ca++ excretion.
Malignant tumors (PTH activity)
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22
Q

What are the major manifestations of hypercalcemia?

A

CNS symptoms-Depression, coma

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23
Q

What are two causes of hypocalcemia?

A

Hypoparathyroidism

VitD deficiencies- Ricketts

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24
Q

How does Vit D work?

A

It increases absorption of Ca++ and PO4 from gut

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25
Q

What preparation is vitamin D supplement sold as?

A

Cholecalciferol (VitD3)

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26
Q

How is hypocalcemia and hypoparathyroidism treated?

A

Vit D+ Ca++

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27
Q

What are the consequences of a Vit D overdose?

A

Ca++ deposits in the kidney, soft tissues, Hypercalcemia=Coma, Death

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28
Q

What is Paget disease of bone?

A

Localized bone disorder characterized by increased osteoclast activity followed by increased osteoblast activity causing a “woven bone bone pattern”= More prone to fractures. Ca++ and phosphorus levels are normal!!! May have bone pain, deformity, loss of hearing

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29
Q

How is paget disease of bone (Osteitis deformans) treated?

A

Bisphosphonates

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30
Q

What do loop diuretics do to Ca++ levels?

A

Decrease them as they cause and increased secretion of Ca++

31
Q

What do thiazides do to Ca++ levels?

A

They cause a decreased secretion of Ca++ (can cause hypercalcemia)

32
Q

How do loop diuretics work?

A

They decrease the driving force of Ca++ uptake by inhibition Na+/K+/2Cl (May cause kidney stone)

33
Q

What do thiazides do to Ca++ levels?

A

Increase driving force for uptake by inhibiting Na/Cl transporter.

34
Q

What do PPIs and H2 antagonists do to Ca++ levels in the body?

A

They cause a decreased absorption of Ca++ by decreasing the acidity of the stomach.

35
Q

What drugs induce the VitD catabolic P450s?

A

Carbamezepine, Isoniazid, theophylline, rifampin

36
Q

How do bisphosphonates work?

A

Reduce formation and dissolution of hydroxyapatite crystals.

Disrupt cytoskeleton, induce apoptosis, inhibit farnesyl-PP synthesis of osteoclasts.

37
Q

What are some adverse effects of bisphosphonates?

A

Musculoskeletal pain, osteonecrosis of the jaw, atypical fractures of femur

38
Q

What bisphosphonates are used to treat osteoporosis(build bone mass)?

A 
Zole(dronate)
Alen(dronate)
Rise(dronate)
Iban(dronate)   
ZARI-Rise Allen b4 Iban ur Zole
39
Q

What bisphosphonates are used to reduce turnover of Ca++ (cancer and Paget’s?

A

Pamidronate
Tiludronate
Etidronate

40
Q

What enzyme is inhibited by bisphosphonates?

A

Farnesyl Pryophosphate Synthase.

41
Q

What is the first line treatment for osteoporosis?

A

Bisphosphonates

42
Q

What is the second line treatment for osteoporosis?

A

Estrogens and SERM’s (Selective estrogen modulator

Calcitonin, Recombinant PTH (Teriparatide)

43
Q

How do Estrogens and SERM’s treat osteoporosis?

A

Prevent menopausal bone resorption

Increase osteoblast activity and decrease osteoclast activity.

44
Q

What estrogens are used to treat osteoporosis?

A

Micronized estradiol

Raloxifene

45
Q

Name two calcitonin analogs used to treat osteoporosis?

A

Calcimar
Miacalcin
Cibacalcin

46
Q

How does calcitonin Tx for osteoporosis work?

A

Blocks renal absorption of PO4 and Ca++

47
Q

When is Tx with calcitonin indicated?

A

Paget’s disease
Hypercalcemia
Osteoporosis

48
Q

What are the side effects of calcitonin Tx?

A

Urticaria, hand swelling, nausea

49
Q

What is Teriparatide?

A

It is a recombinant PTH. Injected sub Q and given with Ca++ and Vit D.

50
Q

What does Teriparatide do at low concentrations vs high concentrations?

A 
Low= Stimulates osteoblast activity.
High= Stimilate Osteoclast activity.
51
Q

When is Teriparatide indicated?

A

Tx for osteoporosis in pts with high risk of fracture.

52
Q

Where is the PTH receptor found?

A

On osteoblasts and Kidney

53
Q

What is the function of RANKL?

A

It is released by osteoblasts to stimulate osteoclast precursors and enable their maturation/differentiation into .

54
Q

What is the function of Osteoprotegrin (OPG)?

A

OPG binds RANKL preventing it from binding to the osteoclast precursors.

55
Q

What is RANK?

A

RANK is a receptor activator of NFkB

56
Q

Continuous PTH infusion causes_______ increase and _________ decrease which causes a __________ in osteoclast activity.

A
  1. RANKL
  2. OPG
  3. Increase
57
Q

Intermittent infusion of PTH causes a___________ in osteoblast apoptosis and an increase in_______.

A
  1. Decrease

2. cbfa1

58
Q

What advantage does Teriparatide have over bisphosphonates?

A

More effective at preventing bone fractures as Teriparatide builds bone at a higher rate than bisphosphonates.

59
Q

What disadvantage does Teriparatide have over bisphosphonates?

A

Teriparatide has an increased risk for cancer (Osteosarcoma) and is injected daily. ALSO DO NOT USE FOR MORE THAN 2 yrs.

60
Q

What is Denosumab? How does it work

A

Humanized monoclonal Ab against RANKL. It prevents differentiation of osteoclasts. Take W/ Vit D

61
Q

When is Denosumab used?

A

For treatment of osteoporosis when bisphosphonates have failed. Used in PM women with fracture history and at a high risk for fractures.

62
Q

What is Cinacalcet?

A

Used to treat primary hyperparathyroisim (Parathyroid tumor) and secondary hyperparathyroidism in chronic kidney disease ( Loss of 1,25 (OH)2 Vit D3 production)

63
Q

What is the MOA of Cinacalcet?

A

It binds Calcium Sensing Receptor (CaR) - A GPCR on the PTH gland to inhibit release of PTH.

64
Q

How does Cinaclalcet bind to the CaR?

A

Allosterically to allow Ca++ to better binf to the CaR and stop PTH release. (Basically fixes a broken receptor)

65
Q

What effect does Cinaclcet have on serum PTH and Ca++ levels?

A

It decreases both PTH and Ca++ levels.

66
Q

Name two Vit D analogs

A

Zemplar

Hectrol

67
Q

How does Zamplar and Hectrol work?

A

Inhibit secretion of PTH with less effect on Serum Ca++ than 1,25(OH)2 Vit D3

68
Q

When are Zamplar and Hectrol used?

A

In treating secondary hyperparathyroidism

69
Q

What is not secreted in urine in chronic kidney disease?

A

Phosphate. This causes PO4 to combine with Ca++ and precipitate in tissues. causing calcific uremic Ateriopathy

70
Q

How do phosphate binders work?

A

Complex with phosphate in the gut preventing absorption.

71
Q

Name two Phosphate binders

A

Lanthanum

Sevelamer

72
Q

How is Lanthanum different from Sevelamer?

A

Lanthanum decreases serum PO4 and Ca++ levels. While Sevelamer decreases only serum PO4 levels selectively.

73
Q

What does serotonin do to osteoblasts?

A

Serotonin inhibits Osteoblast proliferation.

74
Q

What enzyme synthesizes serotonin in the gut?

A

Typtophan Hydroxylase 1 (TPH1)

Exam 1 Pharm II (8 decks)

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