Bisphosphonates Flashcards
what are the two types of bisphosphonates?
- non nitrogen containing
- nitrogen containing
name some non-nitrogen containing and nitrogen containing bisphosphonates?
describe the two classifications of bisphosphonates
what are the mechanism of action for bisphosphonates
inhibit HMG-CoA
inhibiting osteoclasts = inhibiting bone resorption
=bind strongly onto the bone (up to 10 years)
they also inhibit formation and dissolution of hydroxyapatite crystals = potential to interfere with bone mineralisation
compare the activity of two types of bisphosphonates?
- Non-nitrogen BP (etidronate, clodronate)
* Mimic pyrophosphate
* Accumulate in osteoclasts to cause cell death - Nitrogen containing BP – more potent antiresorptive
* Interfere with specific metabolic reactions
* Inhibit mevalonate biosynthesis pathway,
* Main target farnesyl pyrophosphate synthase (FPPS) important in production
of signalling proteins for osteoclast activity
describe the PK of BP’s?
Poor oral absorption
* Alendronate, risedronate F= 0.7%
* Etidronate F=6%
* Oral absorption reduced
- Excreted unchanged in urine = no metabolism
why do BP’s have a reduced oral absorption?
this is due to food increasing gastric emptying
particularly calcium containing products or polyvalent cations = decrease the efficacy of BP’s
what are the clinical indications for BP’s?
- Prevention and treatment of osteoporosis
- Hypercalcaemia of malignancy
- Bone damage due to metastatic cancer and bone pain 4. Paget’s disease
what are the overall aims of BP’s?
increase bone mineral density
= reduce fracture risk
-vetebral/non-veterbral/hip fractures
what are the conditions you must meet as a patient to take BP’s for osteoporosis?
- eligible under NICE recommended guidance for osteoporosis
- fracture score is at least 1%
- determined by FRAX score/ BMD with DXA/ Fracture score
what are symptoms of malignancy?
Skeletal (pain, fracture)
Neuromuscular and psychiatric (drowsiness, muscle weakness, impaired concentration/ memory) Gastrointestinal (nausea, anorexia, constipation)
Renal (renal colic, thirst)
Cardiovascular – (arrhythmia, shortened QT interval)
how does malignancy cause hypercalcemia?
malignancy = increase bone turnover = increase calcium release
what are symptoms of hypercalcemia?
confusion
nausea
Anorexia
impaired concentration
what BPs are licensed to treat hypercalemia?
IV zoledronic
IV pamidronate
with IV fluids
effective within 24 hrs
what monitoring is required for BPs to treat hypercalemia?
Check renal function (adjust dose if necessary),
- renally excreted
* Check calcium at 5 to 7 days be careful of hypocalcemia
HYPOCALCEMIA with those with amino glycoside antibiotics toxicity
what is Paget disease?
