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Pharmacology > Calcium and Bone > Flashcards

Calcium and Bone Flashcards

1
Q

What is the entry, storage, exit and control site of Ca2+

A
  1. Entry: Intestines/gut
  2. Storage: bone
  3. Exit: kidney
  4. Control: PT gland
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2
Q

Describe the effects of 1,25(OH2)D3 (Vit. D) on Ca2+ and phosphate homeostasis?

A
  1. Stimulates intestinal absorption of Ca and P
  2. Promotes bone formation AND resorption by stimulating OB and OC
  3. Enhance reabsorption of C at kidney
  4. Enhance P retention at kidney
  5. Inhibit (so does Ca2+) PTH synthesis and release from parathyroid gland
  6. Induce RANKL in OBs–> role in bone mineralization

NET effect: increase Ca2+ and P

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3
Q

Describe the effects of PTH on Ca2+ and phosphate homeostasis?

A
  1. Promote bone formation and resorption by stimulating OB and OC
  2. Enhance reabsorption of Ca2+ at kidneys
  3. Renal excretion of P
  4. Renal production of active Vit. D synthesis stimulation
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4
Q

in pharmacologic concentrations, calcitonin can ____ by ___

A

reduce serum Ca2+ and P by inhibiting bone resorption

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5
Q

What stimulates and inhibits PTH

A

Stimulates: hypocalcemia

2. Vit. D and high Ca inhibit PTH

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6
Q

PTH increases the number and activity of OC via actions on OB to induce ___

A

RANKL (which acts on OC to increase their activity and increase bone remodeling)

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7
Q

Net effect of excess PTH is to ____ BUT low and intermittent doses of PTH _____

A

increase bone resorption

stimulate formation w/o first increasing bone resorption

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8
Q

Describe the metabolism of Vit. D

A
  1. 7-dehydrocholesterol converted to D3 via UV light and heat
  2. D3 (diet) is converted to 25(OH)D3 in liver
  3. 25(OH)D3 is converted to active D3 1,25(OH)2 D3 in kidney
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9
Q 
Which of the following drugs is routinely added to calcium supplements and milk for the purpose of preventing rickets in children and osteomalacia in adults? 
A.  Cholecalciferol 
B.  Calcitriol 
C.  Calcitonin 
D.  Dihydrotachysterol 
E.  Fluoride
A

A.  Cholecalciferol

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10
Q

What is cholecalciferol and its use?

A

Vit. D3 supplement

*preferred over other metabolites due to modest cost

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11
Q

What is ergocalciferol and its use?

A

Vit. D2 (from plants)

-LESS efficient that D3

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12
Q

What is calcitriol and its use?

A

1,25(OH)2 D3 (ACTIVE D3)

Uses:
In those w/ decreased synthesis of calcitriol
1. CKD
2. Type 1 (vit. d dependent) rickets

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13
Q

Adverse reaction of calcitriol

A
  1. hypercalcemia
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14
Q

What is calcifediol and its use?

A

24(OH)2 D3

*use in liver dz bc does not require hepatic 25-hydroxylation

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15
Q

what is dihydrotachysterol use?

A

alternative for use in disorders that calcitriol is used

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16
Q

A 67-year-old man with chronic kidney disease was found to have an elevated serum PTH concentration and a low serum concentration of 25-hydroxy vitamin D. He was
successfully treated with ergocalciferol. Unfortunately, his kidney disease progressed so that he required dialysis and his serum PTH concentration became markedly elevated. Which of the following drugs is most likely to lower this patient’s serum PTH concentration?
A.  Cholecalciferol
B.  Alendronate
C.  Teriparatide
D.  Raloxifene
E.  Calcitriol

A

E.  Calcitriol

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17
Q 
Side effects associated with the use of calcitriol in the treatment of hyperparathyroidism include: 
A.  Erosive esophagitis 
B.  Thromboembolic disorders 
C.  Hypercalcemia 
D.  Endometrial cancer 
E.  Kidney stones
A

C.  Hypercalcemia**

E.  Kidney stones

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18
Q

The active metabolites of vitamin D act through a nuclear receptor to produce which of the following effects?
A.  Decrease the absorption of calcium from bone
B.  Decrease PTH formation
C.  Increase renal production of erythropoietin
D.  Increase the absorption of calcium from the GI tract
E.  Lower the serum phosphate concentration

A

B.  Decrease PTH formation

D.  Increase the absorption of calcium from the GI tract

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19
Q

Which of the following statements concerning vitamin V3 and its metabolites is FALSE?
A.  One of the gene products resulting from the action of vitamin D is a calcium binding protein.
B.  Glucocorticoids can antagonize the actions of vitamin D on both intestine and bone.
C.  The most potent and rapid acting vitamin D metabolite (calcitriol) is synthesized in the liver.
D.  The conversion of 7-dehydrocholesterol to vitamin D3 occurs in the skin and requires UV radiation.
E.  Vitamin D is necessary for both bone resorption and bone mineralization.

A

C.  The most potent and rapid acting vitamin D metabolite (calcitriol) is synthesized in the liver.

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20
Q

What stimulates calcitonin release

A

Hypercalcemia

*it TONES DOWN Ca2+

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21
Q

What effect does calcitonin have on Ca2+ and P levels

A
  1. Increase OC bone resorption (decrease C and P)
  2. reduce reabsorption/increase excretion of Ca and P

NET: decrease Ca and P

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22
Q

What are estrogens actions on bone?

A
  • Positive effect on bone mass–> agonist at ERalpha receptors on OBs and OCs
    1. decrease OC number and activity
    2. Increase OB production of OPG**–> binds RANKL–> decrease OC activity
    3. Increase OC apoptosis
    4. Anti-reasorptive agent* (use in osteoporosis)
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23
Q

What is OPG

A

produced by OBs and it is a decoy receptor that binds RANKL and prevents OC activation

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24
Q

What 4 things lead to increase bone fraction in postmenopause due to decrease in estrogen?

A
  1. Increased production of cytokines–> activate OCs
  2. Longer lifespan of OCs (decrease apoptosis)
  3. Shorter lifespan of OBs (increase apoptosis)
  4. Short lifespan of osteocytes (increase apoptosis)
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25
Q

How do GC affect bone denisty

A

decrease bone density

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26
Q

GCs action on bone

A
  1. lower serum Ca2+–> increase PTH–> stimulate OC activity
  2. Increase RANKL production by OBs and decrease OPG–> increase OC activation–>
  3. Increase bone resorption
  4. Suppressive effects on OBs
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27
Q

What thing increase OC (bone resportion)

A
  1. increased RANKL
  2. Decreased OPG
  3. high OC
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28
Q

What things increase OB (bone formation)

A
  1. high PTH
  2. High activated D3
  3. low sclerostin Ab
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29
Q

Osteoporosis is defined as bone mineral density:
A.  2.5 or more standard deviations below the mean value at the spine, femoral neck,, or total hip in young adults
B.  1 standard deviation below the mean value at the spine, femoral neck, or total hip in young adults
C.  1 standard deviation below the mean value at the spine, femoral neck, or total hip in adults of the same age
D.  Lower than the mean value in adults of the same age

A

A.  2.5 or more standard deviations below the mean value at the spine, femoral neck,, or total hip in young adults

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30
Q

Pharmacologic treatment for postmenopausal osteoporosis should be considered for women with:
A.  A hip or spine fracture
B.  A T-score of -2.5 or below at the spine, femoral neck, or total hip
C.  A T-score between -1.0and -2.5 and a 10-year FRAX risk of ≥ 3% for hip fracture or ≥ 20% for humerus, forearm, or clinical vertebral fracture
D.  All of the above

A

D.  All of the above

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31
Q

What is Denosumab?

A

RANKL Ab hat binds RANKL and prevent the RANK-RANKL interaction
**Anti-resorptive agent used in osteoporosis

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32
Q

What drugs decrease OC activity

A
  1. Bisphosphates
  2. Cacitonin

*inhibit bone resorption by OC

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33
Q

Examples of Bisphosphates

A
  1. Alendronate
  2. Risedronate
  3. ibandronate
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34
Q

What SERM is used for osteoporosis

35
Q 
A 58-year-old postmenopausal woman was sent for dual-energy x-ray absorptiometry to evaluate bone mineral density of her lumbar spine, femoral neck, and total. Test results revealed low bone density in all sites. Chronic use of which of the following is most likely to have contributed to this woman’s osteoporosis? 
A.  Atorvastatin 
B.  Metformin
C.  Fludrocortisone 
D.  Dexamethasone 
E.  Methimazole 
F.   Cabergoline 
G.  Somatropin 
H.  Prednisone
A

D.  Dexamethasone

H.  Prednisone

36
Q 
OP is a 65-year-old female who has been diagnosed with postmenopausal osteoporosis. She has no history of fractures and no other pertinent medical conditions. Which of the following would be most appropriate for management of her osteoporosis? 
A.  Calcitonin
B.  Denosumab 
C.  Ibandronate 
D.  Raloxifene
E.  Teriparatide 
F.   Alendronate
A

C.  Ibandronate

F.   Alendronate

37
Q 
Multiple pharmacotherapeutic options are available for the treatment and / or prevention of osteoporosis, including all of the agents listed below.  Which of these agents is associated with an increase in bone formation rather than a decrease in bone resorption? 
A.  Alendronate
B.  Calcitonin 
C.  Estrogen 
D.  Raloxifene 
E.  Teriparatide
A

E.  Teriparatide (PTH analog)

38
Q

Describe the MOA of bisphosphates

A
  1. bind to active sites of bone remodeling–> direct inhibitiory effects on OC:
  2. induce OC apoptosis
  3. Inhibits prenylation of proteins necessary for OC fxn
  4. Buried in bone, recycled when resorptive site undergoes remodeling
39
Q

pyrophosphate analong w/ high affinity for bone at Ca-P interface

A

bisphosphate

40
Q

Describe the PK of bisphosphates including absorption, formulations/adminstration, t1/2, and excretion

A

1-10% absorbed orally–> half to bone, half excreted

Q week- alendronate/risedronate
Q month/Q3 months- ibandronate

t1/2 YEARS!

Renally excreted

41
Q

Adverse reactions of bisphophates

A
  1. GI irritation
  2. esophagitis (avoid w/ special administration)
  3. bone, joint, and muscle pain
  4. osteonecrosis of the jaw
42
Q

What is the most effective drug for the treatment AND prevention of osteoporosis

A

Bisphosphates

43
Q

What administration technique can avoid esophagitis w/ BPs

A

taken first thing in morning on an empty stomach, follow w/ water, stay upright for 30-60 min

44
Q

Which of the following is correct regarding the pharmacokinetics of the bisphosphonates?
A.  Bisphosphonates are well absorbed after oral administration
B.  Food or other medications greatly impair absorption of bisphosphonates
C.  Bisphosphonates are mainly metabolized by the CYP450 system
D.  Elimination half-life of bisphosphonates ranges from 4-6hours

A

B.  Food or other medications greatly impair absorption of bisphosphonates

45
Q 
A patient has begun therapy with risedronate (Actonel ®), a bisphosphonate, and was advised to drink large quantities of water with the tablets and remain in an upright position for at least 30 minutes and until eating the first meal of the day.  These instructions are given to reduce the risk of:
A.  Osteonecrosis of the jaw
B.  Diarrhea
C.  Constipation
D.  Erosive esophagitis
E.  Duodenal ulcers
A

D.  Erosive esophagitis

46
Q

Describes SERMs use for bone

A

option for prevention AND treatment of osteoporosis if pt cannot tolerate any BP OR if they are at increased risk for invasive breast CA

47
Q

SE of SERMS relative to estrogen

A
  1. worsening hot flashes
  2. leg cramps
  3. VTE
48
Q

Use of estrogen for bone

A

NO longer 1st line tx!

*MHT for osteoporosis prevention only in women w/ significant hot flashes and have no risk for heart disease

49
Q

Describe the PK administration and elimination of Denosumab

A

Subcutaneous q 6 months

*not cleared by kidneys so not dose adjustment w/ CKD

50
Q

Clinical use of Denosumab

A
  • Decrease RANKL and therefore OC activity

1. tx of pts at HIGH RISK for fractures- intolerant or non-responsive to other therapies

51
Q

Adverse reactions of Denosumab

A
  1. Hypocalcemia

2. flu-like sx

52
Q

Describe the PK of calcitonin including form

A

SC or nasal spray

53
Q

Clinical use of Calcitonin

A 
Treatment ONLY (not prevention) of osteoporosis 
*useful if back pain is a problem
54
Q

Adverse reactions of calcitonin

A
  1. Nausea
  2. Hand swelling
  3. Urticaria
  4. Rhinitis and epistaxis w/ nasal formulation
  5. Increase malignancies
55
Q 
Which of the following agents used in the treatment of osteoporosis will promote bone deposition at low intermittent levels but increase bone resorption at higher sustained levels? 
A.  Alendronate 
B.  Calcitonin 
C.  Calcitriol 
D.  Calcium salts 
E.  Estrogen 
F.   Teriparatid
A

F.   Teriparatid

56
Q

What is the only agent available for treatment of osteoporosis that STIMULATES bone formation

A

Teriparatide

57
Q

Describe the effects of CONTINUOUS HIGH levels and INTERMITTENT administration of Teriparatide

A

Continuous–> bone demineralization and osteopenia

Intermittent: increase OB activity and bone formation

58
Q

describe the PK of Teriparatide including the form, and peak/duration of action

A

Daily SC dose

peak: 30 min then decline to undetectable w/in 3 hrs

59
Q

Clinical use of Teriparatide

A

Treatment of severe osteoporosis in postmenopausal women and me at HIGH RISK for fracture

60
Q

Adverse SE of Teriparatide

A
  1. Nausea
  2. HA
  3. Dizziness
  4. Severe muscle pain
  5. hypercalcemia
61
Q 
Which of the following agents is a partial estrogen receptor agonist that is used to reduce bone loss associated with postmenopausal osteoporosis? 
A.  Calcitonin 
B.  Clomiphene 
C.  Ethinyl estradiol 
D.  Raloxifene 
E.  Tamoxifen 
F.   Alendronate
A

D.  Raloxifene

likely test question

62
Q 
Oral bisphosphonates should be taken: 
A.  On a full stomach 
B.  With 6-8 ounces of water 
C.  For at least 10 years 
D.  All of the above
A

B.  With 6-8 ounces of water

63
Q 
Denosumab: 
A.  Stimulates bone formation 
B.  Can be taken orally 
C.  Remains effective for up to 5 years after treatment is stopped 
D.  May cause hypocalcemia
A

D.  May cause hypocalcemia

*goes back after you stop it, SC

64
Q 
Which of the following drugs increases BMD by stimulating bone formation? 
A.  Alendronate 
B.  Ibandronate 
C.  Raloxifene 
D.  Teriparatide
A

D.  Teriparatide

65
Q

Raloxifene:
A.  Has been shown to decrease the risk of nonvertebral fractures
B.  Has estrogen-like effects on bone and antiestrogen effects on uterus and breast
C.  Should be taken once every 6 months for treatment of postmenopausal osteoporosis
D.  Has been associated with an increased incidence of esophageal cancer

A

B.  Has estrogen-like effects on bone and antiestrogen

66
Q

What effect do thiazide diuretics have on Ca2+

A
  1. reduce urinary Ca2+ excretion (and decrease hypercalciuria and kidney stones)
  2. increase serum Ca2+

*use in hypercalciuria
Acts in DCT

67
Q

What effects to loop diuretics have on Ca2+

A
  1. Decrease Plasma Ca2+
  2. Increase urinary Ca2+ excretion

*use in hypercalcemia
Acts in TAL

68
Q

What meds can be used to tx hypercalcemia

A
  1. Saline diuresis + furosemide– loop diuretic)
  2. BP (Zoledronate, Pamidronate)
  3. Calcitonin
  4. +/- Phosphates
  5. Glucocorticoids
69
Q

in the tx of hypercalcemia, ___ increases Ca++ excretion + counter volume expansion if renal insufficiency or heart failure

A

Saline diuresis (+ furosemide)

70
Q

preferred tx in hypercalcemia of malignancy, response within 2d, lasting weeks

A

BP

Zoledronate
Pamidronate IV

71
Q

What treatment is useful in chronic hypercalcemia (granulomatous in origin –> sarcoidosis, lymphoma, or increased Vit D)

A

Glucocorticorids (usually HD prednisone)

72
Q

tx for short-term hypercalcemic control

A

oral phosphates (pre-surgery for HPT)

OR IV route if pt is hypophosphatemic

73
Q

Adverse reactions ofIV sodium phosphate quickly reducing serum Ca2+

A
  1. sudden hypocalcemia
  2. ectopic calcification
  3. renal failure
74
Q

SX of hypocalcemia

A
  1. Tetany
  2. paresthesias
  3. muscle cramps
  4. convulsions
75
Q

what meds can treat acute hypocalcemia

A
  1. Calcium gluconate** (TX of choice) - IV
  2. Calcium chloride
  3. Calcium gluceptate (IM)
  4. Oral calium salts
  5. Normalize serum Mg++
76
Q

A 55-year-old woman being treated with a bisphosphonate for postmenopausal osteoporosis asks if she should take a supplement that contains calcium and vitamin D. You should tell her that:
A.  Supplements are only recommended for women > 65 years-old
B.  Women being treated with a bisphosphonate usually will need to take a supplement
C.  She does not need to take a supplement
D.  Supplements are not recommended for women who are also taking a bisphosphate

A

B.  Women being treated with a bisphosphonate usually will need to take a supplement

77
Q

Meds used to treat chronic hypocalcemia

A
  1. Ca supplementation (Carbonate, citrate)

2. Vitamin D supplement

78
Q 
Elemental calcium differes among Ca2+ salts: 
Carbonate \_\_
Chloride \_\_
Phosphate \_\_
Citrate \_\_
Lactate \_\_
Gluconate \_\_\_
A 
Carbonate 40%
Chloride 27%
Phosphate 25%
Citrate 21%
Lactate 13%
Gluconate 9%
79
Q

What medication should be used if someone has chronic hypocalcemia and is on a PPI or H2 antagonist

A

Cirate Ca2+ supplement

80
Q

Adverse effects of Ca2+ supplementation for chronic hypocalcemia

A
  • usually well tolerated
    1. Constipation
    2. GI bloating– esp. CaCO3
    3. Urinary stones– less w/ citrate
81
Q

Adverse effects of Vit. D supplements in Chronic hypocalcemia

A
  1. hypercalciuria (kidney stones)
  2. hypercalcemia (lethargy and weakness)

*first signs

82
Q

What is the tx for chronic renal failure–> renal osteodystrophy

A
  1. Vit D (calcitriol)
  2. Ca supplementation
  3. Phosphate restriction
  4. Phosphate binders
83
Q

Tx of Vit. D RESISTANT ricketts vs Vit. D DEPENDENT ricketts

A

Resistant: Phosphate supp., Vit D2 or D3

Dependent: D3 (calcitriol), and calcium supplment

Pharmacology (31 decks)

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