Bisphosphonates Flashcards
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
bisphos: 1st line tretament for __ and are effective at reducing age related decline in BMD by promoting apoptosis of osteoclasts
osteoporosis
the long chain of bisphos determines what?
MOA and strength
the short side chain of bisphos determines what?
PK
What are the 2 classes of bisphosphonates?
Nitrogen containing and non-nitrogen containing
What are the non-nitrogen containing bisphosphonates?
- etidronate
- clodronate
What are the nitrogen containing bisphosphonates?
pamidronate
alendronate
ibandronate
Risendronate
Zoledronic acid
How do bisphosphonates work?
- bind strongly to pre-formed hydroxyapatite in bone for up to 10 yrs
- attenuate osteoclast activity
How does etidronate work?
inhibits formation + dissolution of hydroxyapatite crystals, w potential to interfere w bone mineralisation
Which of the bisphosphonate classes are more potent?
nitrogen containing
What is the difference in activity between non-nitrogen and nitrogen-containing BPs?
- non-nitrogen: mimic pyrophosphate, accumulating in osteoclasts to cause apoptosis
- nitrogen containing: inhibit certain metabolic pathways
What metabolic pathways do nitrogen containing BPs affect?
- inhibit mevalonate biosynthesis
- target farnesyl pyrophosphate synthase (FPPS) important in production of signalling proteins for osteoclast activity
[stop likelihood of bone breaking down]
What is the oral absorption of bisphosphonates like? Give examples.
Poor:
- alendronate & risedronate F= 0.7%
- etidronate F = 2.5%
What affects the oral absorption of bisphosphonates?
food/drink containing calcium or polyvalent cations reduces it
Where is the majority (50%) of the bisphosphonate dose sequestered?
in the bone, as high affinity
How are bisphosphonates excreted?
unchanged in urine
why must you take bisphos on empty stomach?
as less absorbed the closer you take it to food
What are the clinical indications for bisphosphonates? 4
- prevention/treatment of osteoporosis
- hypercalcaemia of malignancy
- bone damage due to metastatic cancer or bone pain
- Paget’s disease
What are the aims of bisphosphonate treatment in OA?
- increase BMD
- reduce fracture risk (vertebral, non-vertebral, hip)
Which bisphosphonates are used for osteoporosis- (prevention of fragility fractures)?
- alendronic acid
- ibandronic acid (for menopausal OP)
- risedronate
- zoledronic acid
What is first choice for osteoporosis?
alendronic acid tablets
What is second choice for osteoporosis?
risedronate
What characteristics must be fulfilled by the patient to be given oral bisphosphonates?
- px eligible for NICE guidance risk assessment
- 10 year probability of osteoporotic fracture is at least 1%
- bisphosphonate treatment appropriate
What tools can be used to measure fracture risk? 3
- DXA (measures BMD)
- FRAX score
- QFracture score
What is the corrected serum concentration of calcium that’s defined as hypercalcaemia?
> 2.6mmol/L
What are the groups of symptoms of hypercalcaemia?
- skeletal
- neuromuscular and psychiatric
- GI
- renal
- cardiovascular
common 4 symptoms of hypercalcaemia?
confusion
dorwsy
thirst
constipated
What are the skeletal symptoms of hypercalcaemia?
- pain
- fracture
What are the neuromuscular and psychiatric symptoms of hypercalcaemia?
- drowsiness
- muscle weakness
- impaired concentration/memory
What are the GI symptoms of hypercalcaemia?
- nausea
- anorexia
- constipation
What are the renal symptoms of hypercalcaemia?
- renal colic
- thirst
What are the cardiovascular symptoms of hypercalcaemia?
- arrhythmia
- shortened QT interval
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
What monitoring must be done for hypercalcaemia treatment?
- renal function (as excreted renally)
- calcium at 5-7 days
What are the treatment options for bone pain in malignancy?
- ibandronic acid
- pamidronate IV
- sodium clodronate
- zoledronic acid IV
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
What dose of pamidronate is licensed for bone pain in malignancy?
90mg IV infusion every 4 weeks
What dose of sodium clodronate is licensed for bone pain in malignancy?
orally 1.6-3.2g daily
What dose of zoledronic acid is licensed for bone pain in malignancy?
IV infusion 4mg every 3-4 weeks
For IV administration of bisphosphonates, what must the dose be adjusted for?
renal impairment (reduction)
For IV administration of bisphosphonates, what must the dose be related to?
serum Ca levels see SPC
SE in px also on aminoglycoside antibiotics ?
severe hypocalcaemia
What is a key interaction of bisphosphonates?
- aminoglycosides + other nephrotoxic drugs
-> severe hypocalcaemia + aminoglycoside toxicity
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
Paget’s disease of bone can present with ?
bone pain, deformity, deafness
or asymptomaic, diagnosed on basis of X-ray/ blood tests
What are the main adverse effects of bisphosphonates?
- osteonecrosis of jaw (ONJ) or external auditory canal
- oesophageal ulceration
- atypical femoral fractures
What are the risk factors for ONJ with bisphosphonates?
- IV: zoledronate, pamidronate
- higher potency bisphosphonates: zoledronate
- history of dental disease/treatment
What lowers the risk of ONJ? w bisphos
- oral use for osteoporosis of Paget’s disease
- good oral hygiene
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 !!
When does osteonecrosis of external auditory canal typically occur?
- long-term bisphosphonates >2yrs
- very rare <1 in 10,000
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
What drug class can induce osteoporosis?
steroids - first 3-6 months of use
why may steroids induce OP?
increase bone loss + risk of bone fractures
What is first-line for steroid-induced osteoporosis?
oral alendronate or risedronate
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
When should bisphosphonates for steroid-induced osteoporosis be reviewed?
when steroid is stopped
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
why take bisphosphonates w plenty of water?
to minime oesophageal risk
wash down tabs so dont get stuck to oesaphageal wall
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
When should alendronic acid, risedronate sodium and ibandronic acid be reviewed?
after 5 years
When should zoledronic acid be reviewed?
after 3 years
What patients should have their bisphosphonates reviewed? 4
- over 75 yrs
- previous hip/fracture
- fragility fractures
- long-term glucocorticoid therapy
