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Pharmacology > Bone Minteral Homeostasis > Flashcards

Bone Minteral Homeostasis Flashcards

1
Q

what are the effects of PTH in the kidney?

A

decrease phosphate reabsorption
increase Ca reabsorption
increase 1,25-OH2-D3 formation

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2
Q

what is the effect of PTH on Ca and Phosphate?

A

Kidney:

  • decrease phosphate reabsorption -> decrease plasma phosphate
  • increase Ca reabsorption -> increase plasma Ca
  • increase 1,25-OH2-D3 formation -> increase intestinal Ca absorption
    • > increase plasma Ca
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3
Q

what is the effect on calcium and phosphate in the presence of calcitonin?

A

Kidney:
decrease phosphate reabsorption -> decrease plasma phosphate
decrease Ca reabsorption -> decrease plasma Ca

Bone:
decrease bone resorption -> decrease plasma Ca

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4
Q

What is the role of Mg in PTH secretion?

A
  1. moderate decline in Mg -> enhance in PTH secretion

2. severe decline in Mg -> decrease PTH secretion

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5
Q

what are the common causes of decreased Mg?

A

chronic diarrhea
diuretics
EtOH abuse
Chronic PPI and aminoglycoside use.

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6
Q

what are the sources of Vit D?

A

sunlight and dietary intake.

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7
Q

what is the active form of vit d?

what is the pathway?

A
  1. calcitriol (1,25 dihydroxy cholecalciferol)
  2. 7-dehydrocholeseterol -[sunlight]-> cholecalciferol (vit D3) -[25-hydroxylase]-> 25-hydroxyvitD3 -[1alpha-hydroylase]-> 1,25 dihydroxyvitD3
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8
Q

what is Ergocalciferol?

A

dietary intake of VitD2 and VitD3.

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9
Q

what are the effects of 1,25-dihydroxycholecalciferol?

A

kidneys:

  • increase phosphate reabsorption -> increase plasma phosphate
  • increase Ca reabsorption -> increase plasma Ca

Intestine:

  • increase phosphate absorption -> increase plasma phosphate
  • increase Ca absorption -> increase plasma Ca

bone:
promote PTH action -> increase Ca plasma

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10
Q

what are the hormonal regulators of bone mineral homeostasis?

A 
PTH
VitD
calcitonin
estrogen
glucocorticoids
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11
Q

what are the non-hormonal regulators of bone mineral homeostasis?

A

bisphosphonates
fluoride
calcimimetics

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12
Q

actions of PTH?

A
  • increase both osteoclasts and osteoblasts in bone via RANKL and TNF cytokine.
  • couples Gs receptors to increase cAMP in bone and renal tubular cells.
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13
Q

WHat is a recombinant PTH?

A

Teriparatide

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14
Q

Teriparatide

PD?

A

pulsatile doses: stimulate bone formation

high doses: bone resorption

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15
Q

Teriparatide

clinical applications?

A

osteoporosis

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16
Q

Teriparatide

A.E?

A

hypercalcemia

hypercalciuria

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17
Q

what is a RANKL inhibitor?

A

Denosumab

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18
Q

Denosumab

MOA?

A

binds c RANKL and prevents stimulating osteoclast differentiation and function.
inhibit bone resportion

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19
Q

Denosumab

clinical applications?

A

osteoporosis

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20
Q

Denosumab

A.E?

A

risks of infxn

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21
Q

Vit D

MOA?

A

activate steroidal nuclear receptor

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22
Q

What are the two types of VitD dependent rickets?

A

type I - defect 1alpha hydroxylase enzyme -> decrease calcitriol -> decrease Ca and P

Type II - defective receptor for vitD

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23
Q

What is used to treat secondary hyperparathyroidism in pts c chronic renal disease and liver disease?

A

calcitriol

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24
Q

What is used for the tx of psoriasis (topical application)?

A

Calcipotriol

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25
Q

what are vitD supplements used for?

A

osteoporosis
chronic renal failure
nutritional rickets d/t inadequate intake
chronic liver disease

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26
Q

vit D

ADR?

A

chronic over dose = hypercalcemia and hyperphosphatemia

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27
Q

what is the level of Ca and PTH in primary hyperparathyroidism?

A

high PTH

high Ca

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28
Q

what is the level of Ca and PTH in seconday hyperparathyroidism?

A

high PTH

low or normal Ca

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29
Q

what causes secondary hyperparathyroidism?

A

Vit D deficiency

Chronic renal failure.

30
Q

what is vitD3 generic name?

A

cholecalciferol

31
Q

what is vitD2 generic name?

A

ergocalciferol

32
Q

what is 1,25-dihydroxyvitD3 generic name?

A

calcitriol

33
Q

what is 1alpha-hydroxyvitD2 generic name?

A

doxercalciferol

34
Q

what is 19-nor-1,25dihydroxyvitD2 generic name?

A

paricalcitol

35
Q

what is calcipotriene generic name?

A

calcipotriol

36
Q

what is a phosphate binding drug?

A

sevelamer

37
Q

Sevelamer

clinical applications?

A

prev hyperphosphatemia in pts c chronic renal failure.

38
Q

sevelamer

MOA?

A

binds to P and prev absorption in GI

39
Q

What are some Ca oral preps?

A

Ca carbonate
Ca citrate
Ca lactate

40
Q

what are some Ca IV preps and tx?

A

Clacium gluconate

tx:
hypocalcemic tetany
counteract overdose of Mg sulfate used in eclampsia

41
Q

calcium preps

A.E?

A 
IM = necrosis and abscess formation
IV = thrombophlebitis
42
Q

Calcitonin

clinical applications?

A

osteoporosis

increase bone mass and reduce spine fractures

43
Q

Salmon Calcitonin

PK?

A

longer half life and greater potency

Injxn and nasal spray

44
Q

Estrogens

clinical applications?

A

prev bone loss
osteoporosis in post menopausal women
given as hormonal replacement therapy

45
Q

estrogens

A.E?

A

thromboembolism
migraine
increase risk of breast and endometrial cancer

46
Q

tamoxifen

MOA?

A

estrogen antagonist in breast

agonist in bone and uterus

47
Q

tamoxifen

clinical applications?

A

breast cancer

beneficial effect on bone

48
Q

tamoxifen

ADR?

A

increased risk of endometrial cancer
thromboembolism
hot flushes

49
Q

Raloxifene

MOA?

A

estrogen antagonistic on breast

agonist on bone

50
Q

raloxifene

clinical applications?

A

osteoporosis in post-menopausal women

51
Q

raloxifene

ADR?

A

thromboembolism

hot flushes

52
Q

what are some Bisphosphates?

A
  1. Etidronate (not for long term use)
  2. Alendronate
  3. Pamidronate (i.v)
  4. Risedronate
53
Q
  1. Etidronate
  2. Alendronate
  3. Pamidronate
  4. Risedronate

MOA?

A

inhibit osteoclastic activity via decrease farnesyl pyrophosphate syn by disrupting mevalonate pathway decrease osteoclast H ATPas.

reduce resorption
helps formation of hydroxyapatite

54
Q

what drug results in bone malformation decrease osteoblastic activity if long term use?

A

etidronate

55
Q
  1. Etidronate
  2. Alendronate
  3. Pamidronate
  4. Risedronate

clinical applications?

A

osteoporosis
malig assoc hypercalcemia
Paget’s disease of bone

56
Q

what is Paget’s disease?

A

increased turnover c extreme bone resorption and excessive bone formation.

presentation: aching bone and joint pain or fractures

57
Q
  1. Etidronate
  2. Alendronate
  3. Pamidronate
  4. Risedronate

A.E?

A

erosive esophagitis d/t direct irritation

  • prev by upright position after taking rx
  • increase fluid intake
58
Q

which bisphosphonates is assoc c osteomalacia, osteonecrosis of jaw and fractures?

A

etidronate

59
Q

Cinacalcet

MOA?

A

activates Ca-sensing receptors in parathyroid cells, leading to decrease in PTH syn and release

60
Q

cinacalcet

clinical applications?

A

secondary hyperparathyroidism in chronic renal disease

hyperparathyroidism in pts c parathyroid cacinoma

61
Q

cinacalcet

A.E?

A

nausea

hypocalcemia

62
Q

Fluoride (rx affecting calcium homeostasis)

A.E?

A

new bone synthesis which is denser but brittle.

63
Q

gallium nitrate (rx affecting calcium homeostasis)

MOA?
clinical applications?
A.E?

A
  1. inhibits bone resorption
  2. tx: cancer related hypercalcemia
  3. Nephrotoxicity
64
Q

plicamycin (mithracin) - (rx affecting calcium homeostasis)

MOA?
clinical applications?
ADR?

A
  1. cytotoxic anticancer rx
  2. cancer-related hypercalcemia
  3. thrombocytopenia, hepatic and renal toxicity
65
Q

what are the drugs causing osteoporosis?

A 
corticosteroids
heparin
lithium
anastrozole
alcohol
66
Q

what are the drugs causing osteomalacia?

A

phenytoin

etidronate (>12mos use)

67
Q

what are drugs prev Ca excretion?

what is it used for?

what is the clinical application of the drug?

A

thiazide diuretics - increasing reabsorption

prev renal stone formation

tx: htn in osteoporosis pt

68
Q

what are the tx’s for hypercalcemia?

A

furosemide & saline infusion
bisphosphonates
Calcitonin
Parathyroidectomy

69
Q

tx of osteoporosis?

A 
stop smoking, EtOH abuse, and corticosteroid
HRT - in sx perimenopausal period
Ca & vitD suppl.
bisphosphonates
SERMs
teriparatide
70
Q

what is the remodeling cycle for bones?

A

Osteoclast activity = resorption

Osteoblast activity = deposit new bone to restore integrity

Pharmacology (13 decks)

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