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Health 31 > Bisphosphonates > Flashcards

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
Q

What is the corrected serum concentration of calcium that’s defined as hypercalcaemia?

A

> 2.6mmol/L

26
Q

What are the groups of symptoms of hypercalcaemia?

A
  • skeletal
  • neuromuscular and psychiatric
  • GI
  • renal
  • cardiovascular
27
Q

common 4 symptoms of hypercalcaemia?

A

confusion
dorwsy
thirst
constipated

28
Q

What are the skeletal symptoms of hypercalcaemia?

A
  • pain
  • fracture
29
Q

What are the neuromuscular and psychiatric symptoms of hypercalcaemia?

A
  • drowsiness
  • muscle weakness
  • impaired concentration/memory
30
Q

What are the GI symptoms of hypercalcaemia?

A
  • nausea
  • anorexia
  • constipation
31
Q

What are the renal symptoms of hypercalcaemia?

A
  • renal colic
  • thirst
32
Q

What are the cardiovascular symptoms of hypercalcaemia?

A
  • arrhythmia
  • shortened QT interval
33
Q

How is hypercalcaemia of malignancy treated?

A
  • zoledronic acid IV or
  • pamidronate IV
  • together w IV fluids (hydration)
  • treatment within 48hrs, max effect 5-7 days
34
Q

What monitoring must be done for hypercalcaemia treatment?

A
  • renal function (as excreted renally)
  • calcium at 5-7 days
35
Q

What are the treatment options for bone pain in malignancy?

A
  • ibandronic acid
  • pamidronate IV
  • sodium clodronate
  • zoledronic acid IV
36
Q

What dose of ibandronic acid is licensed for bone pain in malignancy?
(decreased bone damage in metastatic cancer)

A
  • 50mg daily PO
  • 6mg IV infusion every 3-4 weeks
37
Q

What dose of pamidronate is licensed for bone pain in malignancy?

A

90mg IV infusion every 4 weeks

38
Q

What dose of sodium clodronate is licensed for bone pain in malignancy?

A

orally 1.6-3.2g daily

39
Q

What dose of zoledronic acid is licensed for bone pain in malignancy?

A

IV infusion 4mg every 3-4 weeks

40
Q

For IV administration of bisphosphonates, what must the dose be adjusted for?

A

renal impairment (reduction)

41
Q

For IV administration of bisphosphonates, what must the dose be related to?

A

serum Ca levels see SPC

42
Q

SE in px also on aminoglycoside antibiotics ?

A

severe hypocalcaemia

43
Q

What is a key interaction of bisphosphonates?

A
  • aminoglycosides + other nephrotoxic drugs

-> severe hypocalcaemia + aminoglycoside toxicity

44
Q

what 3 things elevated in Paget’s disease of bone?

what does this result in?

A

Oc bone repsorption
vascularity of bone
Ob activity

–> abnormal bone architechture w redcued strength

45
Q

Paget’s disease of bone can present with ?

A

bone pain, deformity, deafness

or asymptomaic, diagnosed on basis of X-ray/ blood tests

46
Q

What are the main adverse effects of bisphosphonates?

A
  • osteonecrosis of jaw (ONJ) or external auditory canal
  • oesophageal ulceration
  • atypical femoral fractures
47
Q

What are the risk factors for ONJ with bisphosphonates?

A
  • IV: zoledronate, pamidronate
  • higher potency bisphosphonates: zoledronate
  • history of dental disease/treatment
48
Q

What lowers the risk of ONJ? w bisphos

A
  • oral use for osteoporosis of Paget’s disease
  • good oral hygiene
49
Q

What patient advice should be provided to prevent ONJ?

A
  • good oral hygiene
  • report any oral symptoms: pain, swelling, dnetal mobility
  • dental check-up before initiating !!
50
Q

When does osteonecrosis of external auditory canal typically occur?

A
  • long-term bisphosphonates >2yrs
  • very rare <1 in 10,000
51
Q

When do atypical femoral fractures typically occur and when should they be reported?

A
  • long-term osteoporosis treatment
  • after minimal or no trauma
  • patients should report thigh/hip/groin pain
52
Q

What drug class can induce osteoporosis?

A

steroids - first 3-6 months of use

53
Q

why may steroids induce OP?

A

increase bone loss + risk of bone fractures

54
Q

What is first-line for steroid-induced osteoporosis?

A

oral alendronate or risedronate

55
Q

What treatment is available for steroid induced osteoporosis?

A
  • 1st line: oral alendronate or risedronate
  • optimise calcium + vit D intake
  • continue bisphosphonates w long-term steroid
56
Q

When should bisphosphonates for steroid-induced osteoporosis be reviewed?

A

when steroid is stopped

57
Q

What advice should be provided to minimise oesophageal risk w bisphosphonates?

A
  • 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
Q

why take bisphosphonates w plenty of water?

A

to minime oesophageal risk
wash down tabs so dont get stuck to oesaphageal wall

59
Q

What are the warning signs for oesophageal ulcers?

and must stop taking tabs and seek advice

A
  • difficulty swallowing
  • chest pain
  • new/worsening heartburn
  • existing oesophageal conditions
60
Q

When should alendronic acid, risedronate sodium and ibandronic acid be reviewed?

A

after 5 years

61
Q

When should zoledronic acid be reviewed?

A

after 3 years

62
Q

What patients should have their bisphosphonates reviewed? 4

A
  • over 75 yrs
  • previous hip/fracture
  • fragility fractures
  • long-term glucocorticoid therapy

Health 31 (16 decks)

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