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Fall 2021: Therapeutics III > Bone Modifying Agents (Weddle) > Flashcards

Bone Modifying Agents (Weddle) Flashcards

1
Q

Hypercalcemia of malignancy (HCM) occurs most frequently in which two tumor types?

A

lung and breast

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2
Q

List the five components of HCM pathophysiology.

A
  • Increased PTHrP
  • Increased calcitriol
  • Increased resorption
  • Decreased elimination
  • Bony metastases
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3
Q

80% of HCM cases are ___________.

A

humoral

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4
Q

What compound is responsible for humoral HCM?

A

PTHrP

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5
Q

20% of HCM cases are _______________.

A

local osteolytic hypercalcemia

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6
Q

What compounds are responsible for causing local osteolytic hypercalcemia?

A

cytokines and PTHrP

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7
Q

What renal symptoms are associated with mild HCM?

A

polyuria and polydipsia

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8
Q

What GI symptoms are associated with mild HCM?

A

constipation and anorexia

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9
Q

What neurologic symptoms are associated with mild HCM?

A

fatigue

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10
Q

What cardiac symptoms are associated with mild HCM?

A

none

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11
Q

What renal symptoms are associated with moderate HCM?

A

dehydration

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12
Q

What GI symptoms are associated with moderate HCM?

A

nausea and vomiting

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13
Q

What neurologic symptoms are associated with moderate HCM?

A
  • Lethargy/confusion
  • Muscle weakness
  • Loss of deep tendon reflexes
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14
Q

What cardiac symptoms are associated with moderate HCM?

A

shortened QT and widened T wave

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15
Q

What renal symptoms are associated with severe HCM?

A

decreased GFR and nephrocalcinosis

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16
Q

What GI symptoms are associated with severe HCM?

A

none

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17
Q

What neurologic symptoms are associated with severe HCM?

A

seizures, stupor, coma

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18
Q

What cardiac symptoms are associated with severe HCM?

A

heart block, arrhythmias, asystole

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19
Q

What is the corrected calcium equation?

A

serum calcium + 0.8 (4 - serum albumin)

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20
Q

What is the normal range for calcium?

A

8.5-10 mg/dL

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21
Q

What’s the corrected calcium range for mild hypercalcemia?

A

10-12 mg/dL

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22
Q

What’s the corrected calcium range for moderate hypercalcemia?

A

12-14 mg/dL

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23
Q

What’s the corrected calcium range for severe hypercalcemia?

A

> 14 mg/dL

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24
Q

A patient states they are experiencing some polyuria and fatigue. Their labs come back, with a corrected calcium of 11 mg/dL. What treatment would you recommend?

A

counsel to drink 3 L/day, and repeat calcium level in 4 weeks

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25
A patient arrives to your clinic complaining of lethargy and dehydration. Upon further investigation, their EKG shows shortened QT and a calcium level of 11.6 mg/dL. What course of treatment would you recommend?
hydration and/or bisphosphonate
26
What corrected calcium level would warrant admission to an inpatient setting?
\> 14 mg/dL
27
A patient arrives to the ER with a corrected calcium of 13.2 mg/dL. What course of treatment would you recommend?
1. 0.9% NS IV 2. zoledronic acid or pamidronate
28
A patient presents to the ER with seizures and general stupor. Upon further investigation, it is revealed that their corrected calcium is 16 mg/dL. What course of treatment would you recommend?
1. 0.9% NS IV 2. zoledronic acid or pamidronate 3. probably calcitonin
29
IV bisphosphonates inhibit ________ activity.
osteoclast
30
What is pamidronate FDA-approved for?
* SRE prevention for breast cancer & MM bony mets * HCM
31
What is zoledronic acid FDA-approved for?
* Bony mets in all solid tumors & MM * HCM
32
In what situation do bisphosphonates NOT need to be renally dose adjusted?
almost all HCM cases
33
Which reduces calcium faster: hyperhydration or bisphosphonates?
hyperhydration
34
Which bisphosphonate has been shown to be superior for the treatment of moderate to severe hypercalcemia?
zoledronic acid
35
What complication can occur when administering calcitonin for severe hypercalcemia?
tachyphylaxis after 48 hours
36
When would you use calcitonin for hypercalcemia?
severe symptoms or very high calcium or after bisphosphonate
37
Which should be administered first: calcitonin or zoledronic acid?
zoledronic acid; calcitonin can be administered before, but barely reduces calcium
38
What treatment options are available for refractory HCM?
* Phosphates * Denosumab * Gallium nitrate (not really used anymore)
39
What drugs can be used for chronic HCM?
monthly zoledronic acid or pamidronate
40
In normal bone, _________ are in balance with \_\_\_\_\_\_\_\_\_\_.
osteoclasts; osteoblasts
41
Increased osteoclasts lead to increased bone \_\_\_\_\_\_\_\_\_\_\_\_\_\_.
resorption
42
List some cancers that have an affinity for bone.
* Breast * Prostate * Myeloma * Lung * Kidney
43
What symptom is most associated with SREs?
bone pain or tenderness
44
What scan is best for diagnosing SREs?
radionuclide bone scan
45
Give some fracture risk factors for women with breast cancer.
* Bone mineral density score \< -2.5 * AI treatment * \> 65 YO * Corticosteroid use \> 6 months * BMI \< 20 * Family hx of hip fractures * Hx of fracture before age 50 * Smoking
46
Give some fracture risk factors for men with prostate cancer.
* Androgen deprivation therapy * \> 65 YO * Corticosteroid use \> 6 months * BMI \< 20 * Family hx of hip fractures * Hx of fracture before age 50 * Smoking
47
What is the overall goal for treatment of bone metastases?
palliation of symptoms
48
What are the three treatment options for bone metastases?
* Chemo * IV bone modifying agents * Radioisotopes
49
What drug class is considered 1st line for SRE?
IV bisphosphonates
50
What radioisotope can be used for treatment of bone metastases from thyroid cancer?
131-iodine
51
What radioisotope has shown overall survival improvements in prostate cancer?
radium-223
52
What radioisotopes have been used for metastatic breast and prostate cancers?
strontium and samarium
53
What toxicity is associated with radioisotopes?
myelosuppression
54
What patient factor must be considered before dosing IV bisphosphonates for SRE?
renal function
55
Which IV bisphosphonate should NOT be used for SREs if CrCl \< 30?
zoledronic acid
56
What should be supplemented with IV zoledronic acid?
calcium and vitamin D
57
Even though IV pamidronate is much cheaper than zoledronic acid, what is a drawback of it?
longer infusion time
58
Does denosumab work directly on osteoclasts?
no
59
What is a beneficial consequence of denosumab lacking affinity for hydroxyapatite?
spreads more evenly throughout bone
60
What can occur if a patient who poorly responded to bisphosphonates in the past initiates denosumab?
residual osteoclast function may be suppressed
61
What is *Xgeva* used for?
bone metastases from solid tumors
62
What is *Prolia* used for?
osteopenia from breast cancer
63
What is the *Xgeva* dosing for bone metastases from solid tumors?
120 mg SQ every 4 weeks
64
What is the *Prolia* dosing for osteopenia from breast cancer?
60 mg SQ every 6 months
65
What should be corrected prior to initiating denosumab?
hypocalcemia
66
Which agent is more likely to cause hypocalcemia: densoumab or bisphosphonates?
denosumab
67
Should denosumab be renally dose adjusted?
nah
68
What are some risk factors for osteonecrosis of the jaw (ONJ)?
* Invasive dental procedures * Poor oral hygiene * Use of dental appliances * Oral infection * Monthly bone modifying agent * IV bone modifying agents
69
What drugs are most associated with ONJ?
zoledronic acid, denosumab
70
What should happen to help prevent ONJ?
baseline dental evaluation/intervention before starting bisphosphonates and denosumab
71
What are the two proposed mechanisms for ONJ?
* angiogenesis suppression * osteocyte depletion leading to avascular necrosis
72
What are the possible treatment options for ONJ?
* palliative * pain control * chlorhexidine and/or antibiotics * conservative surgeries * \*\*discontinuing bone modifying agents may be associated with slow improvement, but may not return to normal\*\*
73
Rank the bone modifying agents from most to least likely to cause renal dysfunction.
1. zoledronic acid 2. pamidronate 3. denosumab
74
Does denosumab need to be renally dose adjusted? Hepatically dose adjusted?
no and no
75
Beyond ONJ and renal dysfunction, what are some other common adverse effects of bone modifying agents?
* hypocalcemia (especially with denosumab) * bone pain * nausea * diarrhea * fatigue
76
What is the extended dosing interval generally for bone modifying agents?
monthly for 1 year, then every 3 months
77
What are the standard screening guidelines for prostate cancer?
none exist

Fall 2021: Therapeutics III (25 decks)

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