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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

24
Q

Cholecalciferol

25
Most important agent for treating osteoporosis
Bisphosphonate
26
Bisphosphonates | name them
-dronate - Alendronate - Ibandronate - Risedronate - Zoledronate
27
Bisphosphonates
- 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
Mechanism of Bisphosphonates
- 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
Bisphosphonates inhibit
farnesyl pyrophosphate (FPP) synthase, inhibiting osteoclast activity
30
Alendronate Indications
- osteoporosis | - paget's disease of bone
31
Risedronate Indications
- osteoporosis | - paget's disease of bone
32
Ibandronate Indications
- osteoporosis
33
Zoledronate Indications
- multiple myeloma - skeletal mestastases - hypercalcemia of malignancy
34
Pamidronate Indications
- multiple myeloma - skeletal metastases - hypercalcemia of malignancy - paget's disease of bone
35
Most potent bisphosphonate
- zoledronic acid
36
Bisphosphonate Absorption
- poorly absorbed from the GI tract; food reduces absorption even further
37
Bisphosphonate t1/2
10-12 years | - very stable once absorbed
38
Osteonecrosis of the Jaw
RARE | - seen mostly in patients with cancer receiving bisphosphonate doses 6-10x higher than used to treat osteoporosis
39
Calcitonin (CT)
- 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
Summary of Calcitonin
- 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
How is Calcitonin Given?
nasal spray or injections; destroyed quickly in GI tract
42
Injection Calcitonin also for
symptomatic Paget's disease of bone
43
Teriparatide Indication
- indicated for postmenopausal, and glucocorticoid-induced osteoporosis - reserved for patients at HIGH RISK FOR FRACTURES
44
What can you NOT use Teriparatide for?
Paget's disease of bone | - already have increased bone remodeling
45
Mechanism of Teriparatide
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
Summary Teriparatide | adverse effects; contraindications
- 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
Abaloparatide
- parathyroid hormone related polypeptide; same sequence as natural with some changes - PTH-RELATED PROTEIN; analog - ANABOLIC agent - INJECTION - increases BMD, decreases bone fracture
48
Abaloparatide Contraindications
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
RANK-RANKL
- promotes maturation of osteoclasts
50
Denosumab (Dmab)
- mab AGAINST RANKL; make RANKL unavailable - decreases maturation of osteoclasts - antiresorptive agent - prevent skeletal events in patients with BONE METASTASES
51
Warning against Denosumab
CANT JUST DISCONTINUE - will have multiple fractures | - need to transition to another antiresorptive agent
52
Romosozumab
- 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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