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Pharmacology Test 3 > Drugs for Bone Disorders > Flashcards

Drugs for Bone Disorders Flashcards

1
Q

Osteoclast

A

dissolve/break down

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2
Q

osteoblast

A

build up

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3
Q

Remodeling

A
  • bone resorption by osteoclasts
  • bone formation by osteoblasts
  • mineralization (hardening)
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4
Q

osteocyte

A

buried inside bone

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5
Q 
Parathyroid Hormone (PTH)/Calcitonin
(regulation of bone formation)
A
  • low Ca stimulates parathyroid hormone to make PTH
  • PTH raises Ca levels from BONE, KIDNEY, and INTESTINE
  • high Ca levels induce CALCITONIN from thyroid glands
  • calcitonin stimulates Ca deposition into bone
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6
Q

Vitamin D is the principal regulator of

A

intestinal calcium and phosphate absorption

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7
Q

Stimulate bone formation and resorption

A
  • PTH and D
  • stimulate pre-osteoblast proliferation and differentiation into osteoblasts
  • PTH and D stimulate the expression of RANKL by the osteoblast
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8
Q

RANKL

blocked by

A
  • OPG

^inhibited by PTH and D

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9
Q

Intestine

A

increases absorption of Ca and P

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10
Q

Bone

A

increases bone mineralization

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11
Q

Cholecalciferol

A

from skin after exposure to sunlight

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12
Q

Rickets & Osteomalacia

A
  • soft and weak bones

- can stunt growth of children

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13
Q

Osteoporosis

A
  • asymptomatic to severe bane

- bone density T SCORE: = -2.5

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14
Q

Osteopenia

A

T score between -1.5 to -2.4

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15
Q

Causes of Osteoporosis

A
  • menopause
  • old age
  • glucocorticoids
  • alcohol and smoking
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16
Q

Paget’s Disease of Bone

A
  • chronic enlarged and deformed bones
  • marked increase in alkaline phosphatase (ALP)
  • – ALP increases if there is active bone formation occurring (osteoblast activity)
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17
Q

Osteolytic Bone Metastases

A
  • resorbed bone releases factors that stimulate tumor growth forming a VICIOUS CYCLE
  • complications can include hypercalcemia
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18
Q

Calcium Side Effects & Safety

A
  • SAFE for most people, but avoid taking too much
  • ** Ca can interfere with thyroid hormone replacement treatment and others **
  • separate Ca and other medications by atleast 4 hours
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19
Q

Calcifediol / Calcitriol

A

Calcifediol (inactive; becomes active)

Calcitriol = active

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20
Q

Vitamin D2/D3

A

Ergocalciferol/Cholecalciferol

  • given orally to prevent Vitamin D deficiency
  • treat familial hypophosphatemia, hypoparathyroidism, and hereditary Vitamin D-resistant rickets
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21
Q

Calcitriol

A
  • water soluble

- may be given orally or intravenously

22
Q

Calcitriol-induced hypercalcemia

A
  • resolves quickly once calcitriol is stopped
23
Q

Ergocalciferol

A

D2

24
Q

Cholecalciferol

A

D3

25
Q

Most important agent for treating osteoporosis

A

Bisphosphonate

26
Q

Bisphosphonates

name them

A

-dronate

  • Alendronate
  • Ibandronate
  • Risedronate
  • Zoledronate
27
Q

Bisphosphonates

A
  • analogs of pyrophosphate with a P-C-P bond
  • non-hydrolyzable & binds to calcium
  • – bind irreversibly (covalently) to Ca
  • accumulate at bone & prevent bone dissolution
28
Q

Mechanism of Bisphosphonates

A
  • incorporated into bone & inhibits osteoclast activity
  • BIND CA, accumulate at remodeling sites, incorporated into bone matrix
  • PREVENT DIFFERENTIATION OF MACROPHAGES into osteoclasts; endocytosed by osteoclasts and inhibit osteoclast activity and cause apoptosis
  • nitrogen-containing BPs inhibit FARNESYL PYROPHOSPHATE (FPP) SYNTHASE, inhibiting osteoclast activity
29
Q

Bisphosphonates inhibit

A

farnesyl pyrophosphate (FPP) synthase, inhibiting osteoclast activity

30
Q

Alendronate Indications

A
  • osteoporosis

- paget’s disease of bone

31
Q

Risedronate Indications

A
  • osteoporosis

- paget’s disease of bone

32
Q

Ibandronate Indications

A
  • osteoporosis
33
Q

Zoledronate Indications

A
  • multiple myeloma
  • skeletal mestastases
  • hypercalcemia of malignancy
34
Q

Pamidronate Indications

A
  • multiple myeloma
  • skeletal metastases
  • hypercalcemia of malignancy
  • paget’s disease of bone
35
Q

Most potent bisphosphonate

A
  • zoledronic acid
36
Q

Bisphosphonate Absorption

A
  • poorly absorbed from the GI tract; food reduces absorption even further
37
Q

Bisphosphonate t1/2

A

10-12 years

- very stable once absorbed

38
Q

Osteonecrosis of the Jaw

A

RARE

- seen mostly in patients with cancer receiving bisphosphonate doses 6-10x higher than used to treat osteoporosis

39
Q

Calcitonin (CT)

A
  • less critical in Ca homeostasis
  • promote bone deposition
  • stimulate renal excretion
  • produced by the thyroid gland
  • ** inhibits bone resorption by DIRECTLY BLOCKING OSTEOCLAST ***
  • salmon
40
Q

Summary of Calcitonin

A
  • increases bone density, decreases fractures
  • REDUCES ACUTE PAIN due to fractures or metastases
  • DESTORYED QUICKLY IN THE GI TRACT
  • can worsen postmenopausal symptoms like HOT FLASHES
  • TOLERANCE is common
41
Q

How is Calcitonin Given?

A

nasal spray or injections; destroyed quickly in GI tract

42
Q

Injection Calcitonin also for

A

symptomatic Paget’s disease of bone

43
Q

Teriparatide Indication

A
  • indicated for postmenopausal, and glucocorticoid-induced osteoporosis
  • reserved for patients at HIGH RISK FOR FRACTURES
44
Q

What can you NOT use Teriparatide for?

A

Paget’s disease of bone

- already have increased bone remodeling

45
Q

Mechanism of Teriparatide

A

Double edged sword

  • chronic increase in PTH causes decrease in BMD (hyperthryoidism)
  • intermittent dosing of PTH once a day increased BMD
  • binds on osteoblasts STIMULATING OSTEOBLAST PROLIFERATION
  • increase the number of REMODELING UNITS
46
Q

Summary Teriparatide

adverse effects; contraindications

A
  • in combination with calcium and vitamin D, can decrease fractures by ~65%

Adverse Effects:
** increased risk of OSTEOSARCOMA, osteoblastoma, osteoma **

Contraindications:
- osteosarcoma, metabolic diseases of bone, bone cancer, Paget’s, pediatric populations, hypercalcemia, pregnancy

47
Q

Abaloparatide

A
  • parathyroid hormone related polypeptide; same sequence as natural with some changes
  • PTH-RELATED PROTEIN; analog
  • ANABOLIC agent
  • INJECTION
  • increases BMD, decreases bone fracture
48
Q

Abaloparatide Contraindications

A

ONLY BUILD BONE, follow with BP to decrease bone loss
- osteosarcoma, limit 2 years use

  • after discontinue can have rebound bone loss -> intermittent treatment followed by BP to prevent rebound
49
Q

RANK-RANKL

A
  • promotes maturation of osteoclasts
50
Q

Denosumab (Dmab)

A
  • mab AGAINST RANKL; make RANKL unavailable
  • decreases maturation of osteoclasts
  • antiresorptive agent
  • prevent skeletal events in patients with BONE METASTASES
51
Q

Warning against Denosumab

A

CANT JUST DISCONTINUE - will have multiple fractures

- need to transition to another antiresorptive agent

52
Q

Romosozumab

A
  • antibody against sclerostin
  • cause increase in bone formation, moderate reduction in bone resorption
  • minimal risk of side effects because sclerostin is only found in SKELETAL TISSUE
  • POTENTIAL RISK OF CARDIOVASCULAR ADVERSE EVENTS
  • can only be used for a limited time

Pharmacology Test 3 (9 decks)

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