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Bisphosphonates Flashcards

1
Q

LO
* Explain the pharmacological action of bisphosphonates in
the treatment of osteoporosis, hypercalcaemia and bone
pain related to malignancy
* Explain how the pharmacist can advise on treatment of,
and prevention of consequences of osteoporosis
* Provide appropriate advice for patients prescribed
bisphosphonates

A
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2
Q

bisphos: 1st line tretament for __ and are effective at reducing age related decline in BMD by promoting apoptosis of osteoclasts

A

osteoporosis

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3
Q

the long chain of bisphos determines what?

A

MOA and strength

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4
Q

the short side chain of bisphos determines what?

A

PK

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5
Q

What are the 2 classes of bisphosphonates?

A

Nitrogen containing and non-nitrogen containing

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6
Q

What are the non-nitrogen containing bisphosphonates?

A
  • etidronate
  • clodronate
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7
Q

What are the nitrogen containing bisphosphonates?

A

pamidronate

alendronate

ibandronate

Risendronate

Zoledronic acid

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8
Q

How do bisphosphonates work?

A
  • bind strongly to pre-formed hydroxyapatite in bone for up to 10 yrs
  • attenuate osteoclast activity
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9
Q

How does etidronate work?

A

inhibits formation + dissolution of hydroxyapatite crystals, w potential to interfere w bone mineralisation

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10
Q

Which of the bisphosphonate classes are more potent?

A

nitrogen containing

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11
Q

What is the difference in activity between non-nitrogen and nitrogen-containing BPs?

A
  • non-nitrogen: mimic pyrophosphate, accumulating in osteoclasts to cause apoptosis
  • nitrogen containing: inhibit certain metabolic pathways
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12
Q

What metabolic pathways do nitrogen containing BPs affect?

A
  • inhibit mevalonate biosynthesis
  • target farnesyl pyrophosphate synthase (FPPS) important in production of signalling proteins for osteoclast activity
    [stop likelihood of bone breaking down]
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13
Q

What is the oral absorption of bisphosphonates like? Give examples.

A

Poor:

  • alendronate & risedronate F= 0.7%
  • etidronate F = 2.5%
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14
Q

What affects the oral absorption of bisphosphonates?

A

food/drink containing calcium or polyvalent cations reduces it

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15
Q

Where is the majority (50%) of the bisphosphonate dose sequestered?

A

in the bone, as high affinity

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16
Q

How are bisphosphonates excreted?

A

unchanged in urine

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17
Q

why must you take bisphos on empty stomach?

A

as less absorbed the closer you take it to food

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18
Q

What are the clinical indications for bisphosphonates? 4

A
  • prevention/treatment of osteoporosis
  • hypercalcaemia of malignancy
  • bone damage due to metastatic cancer or bone pain
  • Paget’s disease
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19
Q

What are the aims of bisphosphonate treatment in OA?

A
  • increase BMD
  • reduce fracture risk (vertebral, non-vertebral, hip)
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20
Q

Which bisphosphonates are used for osteoporosis- (prevention of fragility fractures)?

A
  • alendronic acid
  • ibandronic acid (for menopausal OP)
  • risedronate
  • zoledronic acid
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21
Q

What is first choice for osteoporosis?

A

alendronic acid tablets

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22
Q

What is second choice for osteoporosis?

A

risedronate

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23
Q

What characteristics must be fulfilled by the patient to be given oral bisphosphonates?

A
  • px eligible for NICE guidance risk assessment
  • 10 year probability of osteoporotic fracture is at least 1%
  • bisphosphonate treatment appropriate
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24
Q

What tools can be used to measure fracture risk? 3

A
  • DXA (measures BMD)
  • FRAX score
  • QFracture score
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25
What is the corrected serum concentration of calcium that's defined as hypercalcaemia?
>2.6mmol/L
26
What are the groups of symptoms of hypercalcaemia?
- skeletal - neuromuscular and psychiatric - GI - renal - cardiovascular
27
common 4 symptoms of hypercalcaemia?
confusion dorwsy thirst constipated
28
What are the skeletal symptoms of hypercalcaemia?
- pain - fracture
29
What are the neuromuscular and psychiatric symptoms of hypercalcaemia?
- drowsiness - muscle weakness - impaired concentration/memory
30
What are the GI symptoms of hypercalcaemia?
- nausea - anorexia - constipation
31
What are the renal symptoms of hypercalcaemia?
- renal colic - thirst
32
What are the cardiovascular symptoms of hypercalcaemia?
- arrhythmia - shortened QT interval
33
How is hypercalcaemia of malignancy treated?
- zoledronic acid IV or - pamidronate IV - together w IV fluids (hydration) - treatment within 48hrs, max effect 5-7 days
34
What monitoring must be done for hypercalcaemia treatment?
- renal function (as excreted renally) - calcium at 5-7 days
35
What are the treatment options for bone pain in malignancy?
- ibandronic acid - pamidronate IV - sodium clodronate - zoledronic acid IV
36
What dose of ibandronic acid is licensed for bone pain in malignancy? (decreased bone damage in metastatic cancer)
- 50mg daily PO - 6mg IV infusion every 3-4 weeks
37
What dose of pamidronate is licensed for bone pain in malignancy?
90mg IV infusion every 4 weeks
38
What dose of sodium clodronate is licensed for bone pain in malignancy?
orally 1.6-3.2g daily
39
What dose of zoledronic acid is licensed for bone pain in malignancy?
IV infusion 4mg every 3-4 weeks
40
For IV administration of bisphosphonates, what must the dose be adjusted for?
renal impairment (reduction)
41
For IV administration of bisphosphonates, what must the dose be related to?
serum Ca levels see SPC
42
SE in px also on aminoglycoside antibiotics ?
severe hypocalcaemia
43
What is a key interaction of bisphosphonates?
- aminoglycosides + other nephrotoxic drugs -> severe hypocalcaemia + aminoglycoside toxicity
44
what 3 things elevated in Paget's disease of bone? what does this result in?
Oc bone repsorption vascularity of bone Ob activity --> abnormal bone architechture w redcued strength
45
Paget's disease of bone can present with ?
bone pain, deformity, deafness or asymptomaic, diagnosed on basis of X-ray/ blood tests
46
What are the main adverse effects of bisphosphonates?
- osteonecrosis of jaw (ONJ) or external auditory canal - oesophageal ulceration - atypical femoral fractures
47
What are the risk factors for ONJ with bisphosphonates?
- IV: zoledronate, pamidronate - higher potency bisphosphonates: zoledronate - history of dental disease/treatment
48
What lowers the risk of ONJ? w bisphos
- oral use for osteoporosis of Paget's disease - good oral hygiene
49
What patient advice should be provided to prevent ONJ?
- good oral hygiene - report any oral symptoms: pain, swelling, dnetal mobility - dental check-up before initiating !!
50
When does osteonecrosis of external auditory canal typically occur?
- long-term bisphosphonates >2yrs - very rare <1 in 10,000
51
When do atypical femoral fractures typically occur and when should they be reported?
- long-term osteoporosis treatment - after minimal or no trauma - patients should report thigh/hip/groin pain
52
What drug class can induce osteoporosis?
steroids - first 3-6 months of use
53
why may steroids induce OP?
increase bone loss + risk of bone fractures
54
What is first-line for steroid-induced osteoporosis?
oral alendronate or risedronate
55
What treatment is available for steroid induced osteoporosis?
- 1st line: oral alendronate or risedronate - optimise calcium + vit D intake - continue bisphosphonates w long-term steroid
56
When should bisphosphonates for steroid-induced osteoporosis be reviewed?
when steroid is stopped
57
What advice should be provided to minimise oesophageal risk w bisphosphonates?
- swallow whole/ full oral soln dose, w at least 200ml water on empty stomach in morning - stay upright for 30 mins-1 hr and avoid other food/drink - avoid foods reducing absorption: aluminium, calcium, iron magnesium, antacids, mineral supplements, osmotic laxatives
58
why take bisphosphonates w plenty of water?
to minime oesophageal risk wash down tabs so dont get stuck to oesaphageal wall
59
What are the warning signs for oesophageal ulcers? and must stop taking tabs and seek advice
- difficulty swallowing - chest pain - new/worsening heartburn - existing oesophageal conditions
60
When should alendronic acid, risedronate sodium and ibandronic acid be reviewed?
after 5 years
61
When should zoledronic acid be reviewed?
after 3 years
62
What patients should have their bisphosphonates reviewed? 4
- over 75 yrs - previous hip/fracture - fragility fractures - long-term glucocorticoid therapy

Health 31 (16 decks)

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