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Flashcards in Drugs affecting bone metabolism Deck (45):
1

Describe calcium homeostasis

1 for PTH release from parathyroid glands in response to low plasma Ca2+ levels
3 for 3 effects of circulating PTH (bone - promote osteoclast activity), intestine and kidney absorb Ca2+)
1 for negative feedback (calcitonin)

2

How do PTH and osteoclast precursors interact?

PTH stimulates recruitment of osteoclast precursors, and differentiation into osteoclasts

3

How might cytokines such as ILs interact with osteoclast precursors?

Stimulate recruitment of osteoclast precursors, and differentiation into osteoclasts

4

How might a cytokine such as IGF-1 interact with osteoblast precursors?

Promotes differentiation into osteoblasts

5

Where might IGF-1 be found?

Circulating in the bloodstream or stored in osteoids

6

What is RANKL? Describe how it can change blood Ca2+ levels?

RANKL is an activating factor that stimulates transcription, pushing osteoblasts to osteoclasts. RANKL interacts with RANK receptors on osteoclast precursors. These then form multinucleated osteoclasts that resorb bone.

7

Provide 3 examples that stimulate RANKL pathway and 1 example that inhibits RANKL pathway

Calcitriol, PTH and ILs stimulate, osteoprotogerin inhibits by being a decoy for RANKL - by not allowing interaction with RANK receptors, it inhibits osteoclast activity

8

3 diseases bisphosphonates are used for?

Osteoporosis, Paget's disease, hypercalcaemia (due to malignancies)

9

What are bisphosphonates?

Analogues of pyrophosphate

10

What do bisphosphonates do and how? (3)

Inhibit bone breakdown and resorption
Taken up by osteoclasts in matrix - inhibit recruitment and promote apoptosis
Indirectly stimulate osteoblasts

11

2 examples of bisphosphonates?

alendronate and risedronate

12

Can bisphosphonates be taken orally?

Poorly absorbed orally, can be taken with lots of water to prevent gastro-oesophageal irritation

13

Common adverse effects of bisphosphonates?

GI upset, musculoskeletal pain, headache

14

Rare adverse effects to bisphosphonates?

Osteonecrosis of the mandible; risk increased by recent dental work or jaw trauma

15

When are SERMS used?

selective oestrogen receptor modulators used in post-menopausal osteoporosis; a decline in oestrogen leads to a loss in bone-protective effect

16

Agonist and antagonistic properties of SERMS?

agonist: bone and cardiovascular system (tibolone - vagina, and prosteogenic effect on breasts, common ADRs are headache, dizziness and vaginal bleeding)
antagonist: breast and uterus

17

Side effects of SERMS?

hot flushes, thromboembolism, dizziness, GI upset, leg cramps

18

When is Vitamin D used?

treatment in deficiency states, rickets and osteomalacia, hypocalcaemia due to hypoparathyroidism

19

What is the common clinical form of Vitamin D3 used in treatment?

calcitriol/ 1,25-dihydroxycholecalciferol - most biologically active form of Vitamin D

20

How might vitamin D be administered?

oral preparations and injectable calciferol

21

What is Vitamin D's distribution?

Lipid soluble - can be transported to fat stores and remain there for months

22

A common ADR of vitamin D

hypercalcaemia

23

Examples of calcium salts and routes of administration

oral: gluconate, carbonate or lactate salts
intravenous: gluconate preferred or chloride

24

Disadvantage of carbonates?

poorly absorbed and binds to phosphates

25

Routes of administration of calcium salts to avoid

SC or IM injections are severely irritant

26

When to use calcium salts?

deficiency states, hypocalcaemia in hypoparathyroidism, prevention and treatment of osteoporosis

27

Common ADRs of calcium salts

GI disturbances, especially in oral form

28

What is teriparatide and significance of its structure?

peptide with human parathyroid hormone sequence
- given SC intermittently, stimulates osteoblasts
- given in postmenopausal women in terms of fracture rates and bone density

29

Side effects of teriparatide

nausea, dizziness, injection site reactions, joint pain
- risk of osteosarcoma limits duration of therapy

30

In what diseases is it good to use calcitonin?

Paget's disease and osteoporosis

31

What does calcitonin do?

stimulates calcium uptake into bone and inhibits bone resorption

32

Duration of effect of calcitonin (relative)?

Rapid, short acting

33

Types of calcitonin

Porcine (pig) calcitonin or synthetic (salmon) form

34

How is calcitonin administered?

Injected subcutaneously because it is a peptide

35

What is cincalcet?

calcium mimetic agent

36

When is cincalcet used?

in PTH-induced hypercalcaemia, to decrease PTH secretion, lower Ca2+ plasma levels
(works in same way as having high Ca2+ levels)

37

mechanism of cincalcet?

increase sensitivity of calcium ion sensing receptor on PTH cells

38

common ADRs of cincalcet?

- nausea and vomiting
- also need to monitor for hypocalcaemia, and calcium and phosphate levels
- drug interactions

39

What is denosumab, what is it directed at?

a monoclonal antibody
directed to RANKL and its receptor RANK

40

mechanism of action of denosumab?

decreases osteoclast activity, and consequently bone resorption

41

common ADRs of denosumab?

hypocalcaemia, hypercholesterolaemia, eczema, osteonecrosis rarely

42

How is denosumab administered?

SC

43

What else needs to be taken with denosumab?

concomitant vitamin D and calcium supplementation

44

What is the significance of bisphosphonates being taken up into the bone?

bisphosphonates can be incorporated into the bone matrix, taken up by osteoclasts causing apoptosis

45

Effect of glucocorticoids on osteoblasts and osteoclasts?

- inhibit differentiation pathway to form osteoblasts
- can inhibit osteoclasts and IGF
- tend to lose Ca2+ from the bone when using potent anti-inflammatory agents