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OD2 - Applied Clinical Training & Research Studies in Vision and Optometry > PHARM - Drugs Used to Treat Bone Disorders - Week 8 > Flashcards

PHARM - Drugs Used to Treat Bone Disorders - Week 8 Flashcards

1
Q

Name three mechanical functions of bone.

A

Provides structural support
Protects organs
Sites of attachment for muscles

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2
Q

Name two metabolic functions for bone.

A

Reservoir of calcium (~99%) and phosphate (85%)

Acid-base balance

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3
Q

Name one synthesis function of bone.

A

Production of white and red blood cells

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4
Q

Are bones metabolically active?

A

Yesd

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5
Q

Describe the bone strucutr in terms of percentages.

A

80% cortical bone

20% trabecular bone

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6
Q

What percentage of total bone is remodelled every year in adults?

A

10%

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7
Q

What four factors affect bone remodelling.

A

Ageing
Physical factors (exercise/loading)
Hormones (oestrogen)
Drugs (corticosteroids)

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8
Q

Which type of bone do processes affecting bone remodelling preferentially affect? Name two specific bones that are affected.

A

Trabecular bone

-femoral neck and vertebral bodies

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9
Q

Give three reasons why is bone remodelled (5).

A 
Bone growth during skeletal development
Response to mechanical stress
-mechanical loading
-stress related micro-fractures
Regulation of calcium in the ECM
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10
Q

Name the three constituent cells of bone.

A

Osteoblasts
Osteocytes
Osteoclasts

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11
Q

What two components form the bone ECM?

A

Osteoid

Hydroxyapatite

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12
Q

What is calcium phosphate?

A

Hydroxyapatite

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13
Q

Name 5 components of the osteoid.

A 
Unmineralised bone matrix
Collagen I
Proteoglycans
Osteocalcin
Osteonectin
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14
Q

Name the 5 phases of bone remodelling.

A 
Activation
Resorption
Reversal
Formation
Quiescence
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15
Q

In what phase of bone remodelling does oesteoclastogenesis occur?

A

Activation

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16
Q

What initiates osteoclastogenesis?

A

Upstream pro-resorptive cytokines

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17
Q

The balance between the action of what two cells determines bone mineral density?

A

Modelling osteoblasts and remodelling osteoclasts

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18
Q

What three factors regulate bone mineral homeostasis?

A

Parathyroid hormone PTH
Vitamin D
Calcitonin

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19
Q

Where are the thyroid and parathyroid glands found?

A

Found inferior to the larynx, a wing-shaped organ with the lobes on either side of the trachea.
On the posterior surface are four nodes where the parathyroid glands sit, which is small and circular, found at each superior and inferior end of the lobes.
The region of the thyroid connecting the two lobes is called the isthmus.

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20
Q

What hormone is released in response to low blood Ca2+ levels?

A

Parathyroid hormone

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21
Q

What effects does parathyroid hormone have on the kidney and bones (2)?

A

Increases Ca2+ uptake in kidneys

Stimulates Ca2+ release from bones

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22
Q

Consider parathyroid hormone’s effect on the kindey. What does it result in the increased synthesis of, what effect does this have, and where?

A

Increased calcitriol (vitamin D) synthesis which indirectly increases calcium uptake in the GI tract.

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23
Q

What hormone is released in response to high blood Ca2+ levels and by what?

A

Thyroid gland releases calcitonin

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24
Q

What two effects does calcitonin have on the kidney and bones?

A

Stimulates Ca2+ deposition in bones

Reduces Ca2+ uptake in kidneys

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25
Q

Calcitonin decreases the activity of which bone cell?

A

Osteoclast

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26
Q

What is ergocalciferol, where does it come from, and what happens to it once it is uptaken (3)?

A

It is vitamin D2 - or vitamin D sourced from plants.

It is modified first in the liver and then again in the kidney into the active form of vitamin D3.

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27
Q

What is the active form of vitamin D3?

A

Calcitriol

28
Q

What is cholecalciferol, where does it come from (2), and what happens to it when it is uptaken (4)?

A

It is vitamin D3 - or vitamin D sourced from eggs, fish, and cheese. It is also made by the skin.
It is modified first by UVB light in the skin, then again in the liver, and a final time in the kidney, into the active form of vitamin D3.

29
Q

What are precursors of vitamin D converted to in the liver?

A

Calcifediol

30
Q

In what three ways does calcitriol increase plasma calcium?

A

Increased intenstinal absorption
Decreased renal excretion
Increased osteoclast activity in bones

31
Q

Define osteoporosis.

A

Reduction in bone mass more than 2.5 standard deviations below the normal for healhy 30 year old women

32
Q

What happens to the trabeculae with osteoporosis (2)?

A

Loss and thinning

33
Q

In what three circumstances can osteoporosis occur?

A

Post-menopausal
With ageing
Following glucocorticoid therapy

34
Q

How do glucocorticoids induce osteoporosis?

A

They upregulate osteoclast activity, inducing bone resorption

35
Q

Name five anti-resporptive drug classes to treat bone disorders.

A 
Bisphosphonates
Selective oestrogen receptor modulators (SERMs)
RANK ligand inhibitors
Calcitonin
Calcimimetics
36
Q

Name five anabolic drug classes to treat bone disorders.

A

Parathyroid hormone
Oral calcium
Oral vitamin D analogues

37
Q

What drug class is the first line of treatment for post-menopausal women at risk of fractures?

A

Bisphosphonates

38
Q

Briefly describe the mechanism of bisphosphonates (3).

A

It has a high affinity for bone mineral as it binds to hydroxyapatite.
It is incorporated into the bone matrix and remains for long periods.
When ingested by osteoclasts, apoptosis occurs.

39
Q

Name and describe the three generations of bisphosphonates and briefly mention their action.

A

Non-nitrogen containing - 1st generation
-metabolised to a cytotoxic ATP analogue
Nitrogen containing - 2nd and 3rd generation
-impaired osteoclast attachment, formation of a ruffled border

40
Q

Name four modalities by which bisphosphonates can exert their effect.

A
  • Cytotoxic or metabolic injury of mature osteoclasts
  • Inhibition of osteoclast attachment to bone
  • Inhibition of osteoclast differentiation or recruitment
  • Interference with osteoclast structural features necessary for bone resorption
41
Q

What three conditions are bisphosphonates indicated for, how is it administered (2), and its bioavailability (including percentage).

A 
Osteoporosis
Paget's disease
Hypercalcaemia
Given orally or IV once yearly
Poorly absorbed orally - 1-2%
42
Q

Name 5 side effects of bisphosphonates.

A 
Nausea
Discomfort
Vomiting
Diarrhoea
Headache
43
Q

What effect does oestrogen have on bone?

A

Protective effect from PTH induced bone resorption

44
Q

Why is there a greater risk of osteoporosis in women post-menopause?

A

Descreased oestrogen production

45
Q

Name a treatment therapy for women post-menopause who have osteoporosis and whether it increases or maintains bone mass.
Name two risks associated with this.

A

Hormone replacement therapy, which maintains mass and slows bone loss.
Increased risk of cardiovascular disease and breast cancer.

46
Q

What therapy has replaced hormone replacement therapy for treating osteoporosis?

A

Selective oestrogen receptor modulators (SERMs)

47
Q

What are SERMs (6)?

A

Agonist at oestrogen receptors in bone and cardiovascular tissue
Antagonist at oestrogen receptors in mammary tissue and the uterus

48
Q

What is the preferred treatment for osteoporosis in women who have breast cancer or a family history of breast cancer?

A

SERMs

49
Q

How are SERMs administered and what is its bioavailability?

A

Once daily orally with 2% bioavailability

50
Q

Name 7 side effects of SERMs.

A 
Hot flushes
Sweating
Leg cramps
Oedema
Sleep disorders
Increased risk of DVT and pulmonary embolism
51
Q

Describe how RANK ligand inhibitors work.

A

Human monoclonal antibodies that bind to RANK ligands, inhibiting them.

52
Q

Name three outcomes of RANK ligand inhibitors.

A

Reduces osteoclast differentation, survival, and activity.

53
Q

Name two side effects of RANK ligand inhibitors.

A

Eczema

Hypercholesterolaemia

54
Q

Describe how pharmacologically administered calcitonin works, name 4 outcomes, and what two diseases it is used for.

A

Binds to calcitonin receptors on osteoclasts
Decreases osteoclastic resorption and mobilisation of calcium from bone
Increases urinary excretion of calcium and phosphate
It is used in Paget’s disease and hypercalcaemia associated with neoplasia

55
Q

Is pharmacologically administered calcitonin a 1st line therapy for oesteoporosis?

A

No

56
Q

How is calcitonin administered (3)?

A

Subcutaneous injection
Intramuscular injection
Nasal spray

57
Q

Name four side effects of calcitonin.

A

Flushing
Nausea
Vomiting
Diarrhoea

58
Q

Briefly describe how calcimimetics work.

A

Allosteric modulators of the calcium sensing receptor on the parathyroid cells, increasing its sensitivity to blood Ca2+, and suppressing PTH.

59
Q

What two diseases are calcimimetics indicated for?

A

Hypercalcaemia in parathyroid carcinoma

Primary hyerthyroidism when parathyroidectomy isnt an option

60
Q

Name 9 side effects of calcimimetics.

A 
Hypocalcaemia
Nausea
Vomiting
Anorexia
Dizziness
Parasthaesia
Weakness
Myalgia
Rash
61
Q

What must patients taking calcimimetics be monitored for?

A

Hypocalcaemia

62
Q

What is given for severe osteoporosis (an alternatives are unsuitable)?

A

Bone anabolic agents

63
Q

Give an example of a pharmaceutical bone anabolic agent and name 5 side effects.

A 
Teriparatide
Nausea
Headaches
Dizziness
Cramping
Joint pain
64
Q

What kind of onset and duration of action does orally administered cholecalciferol have? Is there a risk of hypercalcaemia?

A 
Slow onset (4-8 weeks) and prolonged duration of action (8-16 weeks)
No risk of hypercalcaemia at physiological doses
65
Q

What kind of onset and duration of action does orally administered calcitriol have? Is there a risk of hypercalcaemia?

A 
Rapid onset (1-3 days) and short duration of action (<1 week)
Higher risk of hypercalcaemia
66
Q

Is calcitriol used for osteoporosis? Can it be taken with calcium like cholecalciferol can?

A

Calcitriol is rarely used.

Shouldnt be taken with calcium supplements due to the risk of hypercalcaemia.

OD2 - Applied Clinical Training & Research Studies in Vision and Optometry (174 decks)

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