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PHRM 864 > Exam 2: Bone modifying Agents > Flashcards

Exam 2: Bone modifying Agents Flashcards

1
Q

Epidemiology of Hypercalcemia of Malignancy (HCM)

A

increased bisphosphonate use

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2
Q

What does absorption =

A

elimination of calcium in the blood

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3
Q

Pathophysiology of HCM

A
  • increased PTH
  • increased calcitriol
  • increased resorption
  • decreased elimination
  • bone mets
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4
Q

Humoral HCM

A
  • caused by PTHrP
  • stimulated osteoclasts in bone marrow and renal calcium retention
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5
Q

Local osteolytic hypercalcemia

A

caused by cytokines and PTHrP

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6
Q

Renal HCM etiology

A
  • increased calcium reabsorption
  • decreased phos reabsorption
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7
Q

symptoms of hypercalcemia

A
  • lethargy
  • confusion
  • weakness
  • shortened QT
  • widened T wave
  • heart block
  • arrhythmias
  • a systole
  • seizures
  • stupors
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8
Q

Corrected Calcium

A

Serum calcium + 0.8(4-serum albumin)

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9
Q

Mild HCM Asymptomatic or Mild Symptoms

A
  • 10-12 mg/dL
  • encourage hydration
  • d/c medications that increase serum calcium or decrease renal flow
  • repeat calcium in 4 weeks
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10
Q

Mild HCM Moderate Symptoms

A
  • 10/12 mg/dL
  • Hydration (normal saline)

Bisphosphonate
- zolendronic acid IV OR
- Pamidonate IV
- can be repeated after 7 days if needed

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11
Q

Moderate HCM

A
  • 12-14 mg/dL
  • hydration reduces calcium more quickly than bisphosphonate
  • Zolendronic acid
  • repeat 7 days if needed
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12
Q

Severe HCM

A
  • > 14 mg/dL
  • Hydration 200 mL/hr
  • Zolendronic acid
  • Calcitonin (tachyphylaxis after 48 hour, used for severe symptoms or very high calcium or after bisphosphonate)
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13
Q

Refractory HCM Treatment

A
  • phosphates
  • gallium nitrates
  • denosumab
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14
Q

Chronic HCM Management

A
  • Zolendronic acid
  • pamidronate
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15
Q

0.9% NS in HCM

A
  • dilutes calcium and improves renal elimination
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16
Q

Loop diuretics in HCM

A
  • increases urinary calcium excretion
17
Q

Bisphosphonates in HCM

A
  • blocks bone resorption
18
Q

Calcitonin in HCM

A

blocks bone resorption and increases calcium excretion

19
Q

IV bisphosphonates MOA

A
  • affinity for hydroxyapatite
  • inhibit osteoclast activity by inducing direct osteoclast apoptosis and inhibiting differentiation and maturation
  • decreases bone resorption
  • increasing mineralization
  • concentrate at active bone remodeling sites
20
Q

Bone in cancer patients

A
  • tumor cells secrete cytokines and growth factors
  • increased production of receptor activate or nuclear factor kappa B ligand (RANK-L)
  • increased osteoclasts leads to increased bone resorption
21
Q

Cancers with bone affinity

A
  • breast
  • prostate
  • myeloma
  • lung
  • kidney
22
Q

Skeletal Related Events (SRE) Definition

A
  • pathologic fracture
  • need for bone radiation
  • need for bone surgery
  • spinal cord compression
  • hypercalcemia
23
Q

Diagnosis of SRE’s

A
  • bon pain or tenderness
  • radiograph
  • CT can show bony destruction
  • MRIs in patient with normal X-rays and positive bone scans
  • PET
24
Q

Risk Factors for Fractures in Women

A
  • bone mineral densit <-2.5
  • on AI
  • age > 65
  • corticosteroid use > 6 months
  • BMI < 20 kg/m2
  • family history of hip fractures
  • history of fracture before age of 50
  • smoking
25
Q

Risk Factors for Fractures Men with Prostate Cancer

A
  • androgen deprivation therapy
  • smoking
26
Q

Treatment of Bone Mets Overview

A
  • goal is palliative
  • radiation
  • chemo
  • IV bone modifying agents
  • Radioisotopes
27
Q

Radiation Therapy for bony mets

A
  • pain relief within 1-2 weeks
  • radioisotops
28
Q

IV Bisphosphonate for SRE’s prevention

A
  • pamidronate
  • zoledronic acid (more expensive)
  • renal adjustment dosing needed
  • do not use <30 mL/min
  • no adjustments are warrented if these are used for HCM
29
Q

Other considerations for bisphosphonates

A
  • supplement with calcium and vitamin D
30
Q

Denosumab MOA

A

RANK-L

31
Q

Denosumab considerations

A
  • rapidly reduces bone turnover
  • lack of affinity for hydroxyapatite and more evenly spreads throughout the bone
  • may suppress residual osteoclast function in patients who poorly responds to bisphosphonates
32
Q

Denosumab brand name

A
  • Xgeva for bony mets
  • Prolia for osteopenia
33
Q

Dose adjust for denosumab?

A
  • No renal
  • supplement with calcium and vitamin D as it causes hypocalcemia
34
Q

Adverse effects of bone modifying therapies

A

osteonecrosis of jaw

35
Q

Renal dysfunction

A

Zoledronic acid > pamidronate > denosemab in terms increased renal dysfunction

36
Q

Which medication is safe in renal dysfunction

A

denosumab

37
Q

Which medication causes the most hypocalcemia

A

denosumab

PHRM 864 (10 decks)

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