Calcium Homeostasis (Welch) Flashcards

1
Q

What is a SERM?

A

Selective Estrogen Receptor Modulation

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2
Q

What are 3 common SERMs?

A
  1. Tamoxifen
  2. Raloxifene
  3. Clomiphene
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3
Q

Tamoxifen, Raloxifene, and Clomiphene exert their effects how?

A

Competetive partial agonist inhibitor of estradiol at the estrogen receptor

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4
Q

What are 2 indications for Tamoxifen (a SERM)?

A

“Palliative treatment of breast cancer in post menopausal women”

“Chemoprevention of breast cancer in high risk women”

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5
Q

Of the SERMs Tamoxifen, Raloxifene, and Clomiphene, which ones increase bone density?

A
  1. Tamoxifene

2. Raloxifene

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6
Q

Of the SERMs Tamoxifen, Raloxifene , and Clomiphene, which ones increase ovulation?

A
  1. Clomiphene

2. Tamoxifene

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7
Q

Of the SERMs Tamoxifen, Raloxifene , and Clomiphene, which ones have an effect on mammary cell proliferation?

A

None

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8
Q

Of the SERMs Tamoxifen, Raloxifene , and Clomiphene, which ones increase uterine cell proliferation?

A

Tamoxifene

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9
Q

What is the only thing that Raloxifene (a SERM) stimulates in women?

A

Bone density

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10
Q

What is the only thing that Clomiphene (a SERM) stimulates in women(?

A

Ovulation

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11
Q

What are the three things Tamoxifen (a SERM) stimulates in women?

A
  1. Ovulation
  2. Uterine cell proliferation
  3. Bone density
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12
Q

What is the one thing that Tamoxifen (a SERM) interrupts in women?

A

Mammary cell proliferation

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13
Q

What are the 3 things Raloxifene (a SERM) interrupts in women?

A
  1. Ovulation
  2. Mammary cell proliferation
  3. Uterine cell proliferation
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14
Q

Why is Clomiphene (a SERM) both estrogenic and anti-estrogenic?

A

it is estrogenic because it stimulates pituitary release of LH and FSH that increase ovulation

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15
Q

Evista is the brand name for what SERM?

A

Raloxifene

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16
Q

Raloxifene protects against what fractures related to osteoporosis?

A
  1. Spine fractures

2. Not protective against hip fractures

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17
Q

What is an increased risk when taking Raloxifene?

A

Thrombophlebitis

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18
Q

What are 2 osteoporosis drugs that do prevent both spine and hip fractures?

A
  1. Bisphosphonates

2. Teriparatide

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19
Q

What are 2 physiologic functions of Parathyroid hormone (PTH)?

A
  1. Maintains calcium levels in extracellular fluid

2. Maintains integrity of parathyroid gland

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20
Q

If PTH maintains extracellular Calcium levels, by default what is it also maintaining?

A

Intracellular calcium levels

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21
Q

If the level of extracellular Calcium decreases, what is released by what?

A

PTH released by parathyroid gland to increase extracellular calcium

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22
Q

What hormone opposes PTH?

A

Calcitonin from the C-cells of the thyroid

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23
Q

What is the major source for PTH to harvest Calcium to increase the extracellular calcium levels?

A

Bone

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24
Q

What 2 things are released when PTH acts on bone?

A
  1. Calcium ions (Ca++)

2. Phosphate (PO4)

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25
Q

What are Primary, Secondary, and Tertiary sources for PTH to increase Calcium?

A
Primary = bone 
Secondary = intestine 
Tertiary = kidney
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26
Q

How does PTH get calcium from the kidney?

A

Resorb calcium and excrete Phosphate

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27
Q

What will result if pt has excess PTH with respect to the kidney?

A

Patient will no longer excrete phosphate (PO4) and calcium will not be resorbed causing a calcium phosphate kidney stone

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28
Q

What is a lab value to check for a patient with kidney stones?

A

PTH level

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29
Q

What are 2 causes of Hypoparathyroidism?

A
  1. Iatrogenic (surgery, most common)

2. Parathyroid gland disease

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30
Q

A person having tetany, muscle spasms, generalized convulsions, possible respiratory failure causing death could have what condition and why?

A

Hypoparathyroidism, no enough Calcium to control muscle contractions

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31
Q

Can PTH be given directly to treat hypoparathyroidism?

A

No, it is a peptide and very expensive

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32
Q

What is the treatment for hypoparathyroidism?

A

Vitamin D and Calcium supplement of the diet

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33
Q

What is the synthetic form of human PTH?

A

Forteo. Recombinant human PTH 1,34 (teriparatide)

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34
Q

When would Forteo (rhPTH 1,34) be indicated?

A

Hyperparathyroidism

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35
Q

What do chronically high levels of PTH cause?

A

increased osteoclast activity

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36
Q

What would intermittent administration of rhPTH1,34 do?

A

Stimulate osteoblastic activity when given intermittently. The key is the intermittent administration of rhPTH 1,34.

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37
Q

What are 2 causes of primary hyperparathyroidism?

A
  1. Parathyroid hyperplasia

2. Adenoma

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38
Q

Hypercalcemia caused by hyperparathyroidism produces what symptoms?

A
  1. Muscle weakness

2. Smooth m. dysfunction causing constipation, flatulence, anorexia, nausea, vomiting

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39
Q

What are 2 renal symptoms associated with Primary hyperparathyroidism?

A
  1. Hypercalciuria
  2. Hyperphosphaturia
    (Both lead to kidney stones and calcified nephrons)
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40
Q

What is the treatment for Primary Hyperparathyroidism?

A

Surgery

41
Q

A patient with kidney stones, calcified nephrons, and profound osteoporosis would likely have?

A

Primary hyperparathyroidism

42
Q

A malabsorption syndrome or renal disease, either one causing low plasma calcium that leads to an increased secretion of PTH is what?

A

Secondary hyperparathyroidism

43
Q

What will be the only clinical symptom of secondary hyperparathyroidism?

A

Decalcification of bone

44
Q

What clinical symtoms differ primary hyperparathyroidism from secondary hyperparathyroidism?

A

Secondary has no hypercalciuria or hypercalcemia

45
Q

What is the treatment for secondary hyperparathyroidism?

A

Treat underlying renal or malabsorption disorder

46
Q

What hormone is secreted by the parafollicular C- cells of the thyroid and has the physiologic function of lowering plasma Calcium ion levels (antagonist of PTH)?

A

Calcitonin

47
Q

What stimulates release of Calcitonin?

A

High plasma calcium levels (PTH would be inhibited)

48
Q

What inhibits release of calcitonin?

A

Low calcium levels (PTH would be released)

49
Q

What is the mechanism of action of calcitonin?

A

Inhibits bone resorption by opposing action of PTH

50
Q

What are 3 therapeutic uses for calcitonin?

A
  1. Lower hypercalcemia in hyperparathyroidism, idiopathic hypercalcemia, and Vitamin D intoxation
  2. Postmenopausal osteoporosis
  3. Paget’s disease
51
Q

What are 2 major uses for calcitonin in the U.S.?

A
  1. Paget’s disease

2. Osteoporosis

52
Q

What are 3 preparations of Calcitonin for the treatment of hypercalcemia, postmenopausal osteoporosis, or Paget’s disease?

A
  1. Miacalcin
  2. Calcimar
  3. Cibacalcin
53
Q

What are 3 side effects of Calcitonin treatment?

A
  1. Nausea
  2. Inflammation at injection site
  3. Flushing
54
Q

Where are the majority of osteoporosis related fractures?

A

Vertebral fractures

55
Q

What are 8 drugs associated with the development of osteoporosis?

A
  1. Corticosteroids
  2. Thyroid hormone
  3. Anticonvulsant
  4. Aluminum antacids
  5. Heparin
  6. Cancer chemotherapy
  7. Tetracycline
  8. Isoniazid (Tb antibiotic)
56
Q

What are 10 diseases that can predispose to osteoporosis?

A
  1. Hyperthyroidism
  2. Hyperparathyroidism
  3. Paralysis
    4, Chronic obstructive lung disease
  4. Intestinal malabsorption
  5. Renal dysfunction
  6. Malignancy
  7. Diabetes mellitus
  8. Pregnancy
  9. Rheumatoid arthritis
57
Q

What are 3 strategies for management of osteoporosis?

A
  1. Prevent it
  2. Detect it and treat early to decrease progression
  3. Limit disability and provide rehab
58
Q

What are 3 treatment modalities for Osteoporosis?

A
  1. Calcium supplementation
  2. Salmon calcitonin
  3. Estrogens
59
Q

What is required for calcium absorption and bone mineralization?

A

Vitamin D

60
Q

What is the starting point for Vit D in the body?

A

7-dehydrocholesterol conversion to cholecalciferol by UV light on the skin

61
Q

What is an Inactive form of Vit D?

A

Cholecalciferol

62
Q

What is the active form of Vitamin D?

A

1,25 dihydroxycholecalciferol

63
Q

Where does cholecalciferol get hydroxylized to its active form?

A
  1. C-25 hydroxylized in liver
  2. C-1 hydroxylized in kidney
  3. Kidney hydroxylization is final step
64
Q

What therapy is FDA approved for the prevention of osteoporosis, but the woman must be informed of the inherent risk of using it?

A

Estrogen therapy

65
Q

What ist he mechanism of action for estrogen therapy to prevent osteoporosis?

A

Decrease osteoclast activity

66
Q

Does estrogen just decrease fracture risk of osteoporosis?

A

No, also increases bone density by 1-5%

67
Q

What is a disadvantage of estrogen therapy?

A

Discontinuing will accelerate bone loss

68
Q

What is a Selective Estrogen Receptor Modulator (SERM) that is used to treat and prevent osteoporosis?

A

Raloxifene (Evista)

69
Q

What effects does Raloxifene (Evista, a SERM) have on bone?

A

Estrogenic effect on bone (decrease osteoclastic activity)

70
Q

What effect does Raloxifene (Evista, a SERM) have on breasts and endometrium?

A

Antiestrogenic effect

71
Q

By how much does Raloxifene (Evista, a SERM) increase bone density?

A

2%

72
Q

Raloxifene (Evista, a SERM) decreases the risk of what fracture type?

A

Vertebral fracture (by 30-40%)

73
Q

Can Raloxifene (Evista, a SERM) be used to treat or prevent osteoporosis in men?

A

No

74
Q

What is an osteoporosis treatment that works by mimicking a normal structural component of the bone and get into Osteoclast DNA and cause osteoclast apoptosis?

A

Bisphosphonates

75
Q

What is the risk associated with bisphosphonates?

A

Stay in bone for a long time because they mimic bone components

76
Q

What are 2 approved bisphosphonates?

A
  1. Alendronate (Fosamax)

2. Ridedronate (Actonel)

77
Q

What are 3 indications for bisphosphonate use?

A
  1. Prevention and treatment of osteoporosis
  2. Steroid induced osteoporosis treatment
  3. Paget’s disease treatment
78
Q

Risendronate (Actonel) is also approved for what?

A

Increase bone mass in men

79
Q

Where do bisphosphonates bind to inhibiti osteoclast function?

A

Bind to hydroxyapatite at sites of active bone resorption

80
Q

What is increased with increased duration of taking a bisphosphonate?

A

BONJ

81
Q

What are 4 bisphosphonates Dr Welch listed?

A
  1. Alendronate (can treat men, women, glucocorticoid-induced, and Paget’s)
  2. Risendronate (can treat women, glucocorticoid- induced, and Paget’s)
  3. Pamidronate
  4. Zoledronic acid
82
Q

What would chronic application of rhPTH 1,34 (Forteo PTH pen) do?

A

Activate osteoclasts and break down bone

83
Q

What would intermittent application of rhPTH 1,34 (Forteo PTH pen) do?

A

Stimulate osteoblasts and build bone

84
Q

Forteo (rhPTH 1,34) can be used to treat what pt types?

A
  1. Postmenopause osteoporosis
  2. Men w/idiopathic or hypogonadal osteoporosis 3. Men who can’t tolerate other osteoporosis therapy Pt w/ low bone density(T-score <3)
  3. Patient w/ fractures and on other osteoporosis therapy
  4. Patient who cannot tolerate oral bisphosphonate therapy
85
Q

Who should not be given Forteo?

A
  1. Patient w/ Paget’s disease (their PTH is already high)
  2. Patient w/ open epiphyses (puberty/adolescents)
  3. History of irradiation of the skeleton
  4. Undefined increase in bone alkaline phosphotase
86
Q

What is the result of the abnormal Growth hormone of Paget’s causing increased bone growth potential as well as PTH breaking down bone while Calcitonin building bone up?

A

Poorly formed bones

87
Q

What is the demographic of Paget’s disease?

A

Patient over 40 years old

88
Q

What causes the bone lesions of Paget’s disease?

A

Increased bone resorption followed by a period of increased bone formation

89
Q

What are 3 treatments for Paget’s disease?

A
  1. Antibiotic
  2. Calcitonin
  3. Palmidronate (bisphosphonate = inhibit bone resorption)
90
Q

A patient with the following symptoms would have what disease: headache, hearing loss, increased head size, bowing of limbs, curvature of spine, hip pain?

A

Paget’s disease

91
Q

What are 3 things that can be used to diagnose Paget’s disease?

A
  1. Serum alkaline phosphatase
  2. X-rays
  3. Bone scans
92
Q

What is the drug of choice for Paget’s disease treatment?

A

Bisphosphonates

93
Q

Because Paget’s and osteoporosis can be treated with bisphosphonates are they dosed the same and treated for the same duration?

A

No. Paget’s is done 4/day for 6 months (increased dose for shorter duration). Osteoporosis is 1/week for 2 years (lower dose for longer duration)

94
Q

What is an alternate therapy for Paget’s should the bisphosphonate not be tolerated ?

A

Calcitonin

95
Q

What drug is contraindicated in Paget’s disease?

A

rhPTH 1,34 (Fortea)

96
Q

What are hearing loss and headaches common in Paget’s?

A

Elongated skull stretches nerves

97
Q

What are 7 complications of Paget’s disease?

A
  1. Neural compression
  2. Fractures
  3. Sarcoma
  4. Gout
  5. Hypercalcuria
  6. Kidney stones
  7. Heart failure
98
Q

Of the complications of Paget’s Disease, which two are due to increased PTH?

A
  1. Hyperalcuria

2. Kidney stones