Your SlideShare is downloading. ×
0
Powerpoint Templates
Page 1
Bisphosphonates
Powerpoint Templates
Page 2
Bisphosphonates are
pyrophosphate
analogues inwhich
the oxygen in p–o–p
has been replaced by
a...
Powerpoint Templates
Page 3
Bisphosphonates have two side chains:
R1 affects binding affinity tobone;
R2 affects antiresor...
Powerpoint Templates
Page 4
.
Powerpoint Templates
Page 5
Generations of Bisphosphonates
• With each successive generation, there has been
increased pot...
Powerpoint Templates
Page 6
Mechanism of action
• Nitrogenous bisphosphonates act on bone
metabolism by binding and blocki...
Powerpoint Templates
Page 7
Powerpoint Templates
Page 8
• Disruption of the HMG coa-reductase
pathway at the level of FPPS prevents the
formation of t...
Powerpoint Templates
Page 9
• While inhibition proteins can affect
osteoclastogenesis, cell survival, and
cytoskeletal dyn...
Powerpoint Templates
Page 10
Non-N-containing bisphosphonates
• Etidronate ,Clodronate ,Tiludronate
• The non-nitrogenous ...
Powerpoint Templates
Page 11
Pharmacokinetics
• Oral bisphosphonates have a very low
bioavailability and poor gastrointest...
Powerpoint Templates
Page 12
Indications for Use
• Indications for bisphosphonates include such conditions
1. Postmenopaus...
Powerpoint Templates
Page 13
Powerpoint Templates
Page 14
Fracture Intervention Trial
• Here 658 osteoporotic women with either
vertebral fracture or o...
Powerpoint Templates
Page 15
• An oral daily dose of risedronate (5 mg)
resulted in BMD increases after 6 months
of therap...
Powerpoint Templates
Page 16
• Thirteen patients who received 30 mg of
pamidronate intravenously over 3 months
had an incr...
Powerpoint Templates
Page 17
Bisphosphonates in Metastatic disease
1. They control hypercalcemia,
2. Reduce bone pain,
3. ...
Powerpoint Templates
Page 18
• Intrvenous zolendronate and
palmindronate are the ones most useful
and should be combined w...
Powerpoint Templates
Page 19
• Studies suggest the use of bisphosphonates
As oral and local adjuvants in total joint
arthr...
Powerpoint Templates
Page 20
Drug Interactions
• Bisphosphonates generally should not be taken
with antacids that contain ...
Powerpoint Templates
Page 21
Adverse effects
• Oral bisphosphonates causes
Gastrointestinal complications such as
gastriti...
Powerpoint Templates
Page 22
BISPHOSPHONATE-RELATED
OSTEONECROSIS OF THE JAW
• AKA Phossy jaw
• American Academy of Oral a...
Powerpoint Templates
Page 23
• It has been postulated that reduced bone
remodeling associated with bisphosphonate
use may ...
Powerpoint Templates
Page 24
STAGES
• stage 1-were patients with asymptomatic
necrotic bone
• stage 2-accompanied by infec...
Powerpoint Templates
Page 25
ATYPICAL SUBTROCHANTERIC AND
DIAPHYSEAL FRACTURES
• bisphosphonate may alter the biomechanica...
Powerpoint Templates
Page 26
Powerpoint Templates
Page 27
Upcoming SlideShare
Loading in...5
×

Bisphosphonates

1,989

Published on

Published in: Health & Medicine
0 Comments
5 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total Views
1,989
On Slideshare
0
From Embeds
0
Number of Embeds
0
Actions
Shares
0
Downloads
116
Comments
0
Likes
5
Embeds 0
No embeds

No notes for slide

Transcript of "Bisphosphonates"

  1. 1. Powerpoint Templates Page 1 Bisphosphonates
  2. 2. Powerpoint Templates Page 2 Bisphosphonates are pyrophosphate analogues inwhich the oxygen in p–o–p has been replaced by a carbon, resulting in a metabolically stable p–c–p structure Resistant to enzymatic destruction
  3. 3. Powerpoint Templates Page 3 Bisphosphonates have two side chains: R1 affects binding affinity tobone; R2 affects antiresorptive capacity and, possibly, Side-effect profile. Bisphosphonates vary in potency Based on these specific side chains.
  4. 4. Powerpoint Templates Page 4 .
  5. 5. Powerpoint Templates Page 5 Generations of Bisphosphonates • With each successive generation, there has been increased potency, with more selectivity for inhibition of resorption and less inhibition of bone formation. • First-generation bisphosphonates, such as etidronate and clodronate, inhibit bone formation and bone resorption equally. • Second-generation bisphosphonates include pamidronate and alendronate • The third generation includes the highly potent risedronate and zolendronate.
  6. 6. Powerpoint Templates Page 6 Mechanism of action • Nitrogenous bisphosphonates act on bone metabolism by binding and blocking the enzyme farnesyl diphosphate synthase (FPPS) in the HMG-coa reductase pathway (also known as the mevalonate pathway)
  7. 7. Powerpoint Templates Page 7
  8. 8. Powerpoint Templates Page 8 • Disruption of the HMG coa-reductase pathway at the level of FPPS prevents the formation of two metabolites (farnesol and geranylgeraniol) that are essential for connecting some small proteins to the cell membrane. This phenomenon is known as prenylation, and is important for proper sub-cellular protein trafficking
  9. 9. Powerpoint Templates Page 9 • While inhibition proteins can affect osteoclastogenesis, cell survival, and cytoskeletal dynamics. In particular, the cytoskeleton is vital for maintaining the "ruffled border" that is required for contact between a resorbing osteoclast and a bone surface.
  10. 10. Powerpoint Templates Page 10 Non-N-containing bisphosphonates • Etidronate ,Clodronate ,Tiludronate • The non-nitrogenous bisphosphonates (disphosphonates) are metabolised in the cell to compounds that replace the terminal pyrophosphate of ATP, forming a nonfunctional molecule that competes with ATP in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone
  11. 11. Powerpoint Templates Page 11 Pharmacokinetics • Oral bisphosphonates have a very low bioavailability and poor gastrointestinal absorption rates (from <0.7% alendronate and risedronate to 6% for etidronate). • Oral absorption can be diminished in the presence of mineral water, other liquids,or food in the stomach. • Absorbed bisphosphonate remains in the skeleton for prolonged periods(half-lives of 1.5 to 10 years), whereas nonincorporated drug is excreted in the urine
  12. 12. Powerpoint Templates Page 12 Indications for Use • Indications for bisphosphonates include such conditions 1. Postmenopausal 2. Glucocorticoid-induced osteoporosis, 3. Paget’s disease, 4. Osteolytic and osteoblastic bone metastases, 5. Fibrous dysplasia, 6. Heterotopic ossification, 7. Myositis ossificans. 8. Other bisphosphonates, medronate (R1, R2 = H) and oxidronate (R1 = H, R2 = OH) are mixed with radioactive technetium and are injected for imaging bone and detecting bone disease
  13. 13. Powerpoint Templates Page 13
  14. 14. Powerpoint Templates Page 14 Fracture Intervention Trial • Here 658 osteoporotic women with either vertebral fracture or osteoporosis at femoral neck were treated with alendronate for 3 to 4 Years. • There was decreased risk of fracture, with relative risks of 0.47 for hip fracture , 0.52 for radiographic vertebral fracture, 0.55 for clinical vertebral fracture, and 0.70 for all clinical fractures
  15. 15. Powerpoint Templates Page 15 • An oral daily dose of risedronate (5 mg) resulted in BMD increases after 6 months of therapy. • At 24 months, lumbar spine BMD increased from baseline by 4%, with increases of 1.3% and 2.7% in the femoral neck and femoral trochanter, respectively • A single weekly dose is as clinically effective as daily dosage but with lower incidences of dyspepsia,Esophagitis, and gastroesophageal reflux disease (GERD)
  16. 16. Powerpoint Templates Page 16 • Thirteen patients who received 30 mg of pamidronate intravenously over 3 months had an increased BMD of 6.2% in the lumbar spine and 4.7% in the hip. • Parenteral zolendronate administered at annual intervals showed 4.3% to 5.1% increase in BMD in the treatment group for spine than in the placebo group
  17. 17. Powerpoint Templates Page 17 Bisphosphonates in Metastatic disease 1. They control hypercalcemia, 2. Reduce bone pain, 3. Delay skeletally related events (sres), 4. Reduce the number of pathologic fractures, 5. Prolong survival.
  18. 18. Powerpoint Templates Page 18 • Intrvenous zolendronate and palmindronate are the ones most useful and should be combined with either chemotherapy or hormonal therapy in women with metastatic bone disease. • Zolendronate is the first bisphosphonate shown to be effective in both lytic and blastic metastatic disease
  19. 19. Powerpoint Templates Page 19 • Studies suggest the use of bisphosphonates As oral and local adjuvants in total joint arthroplasties increase periimplant bone density or reduce implant migration • The effect of soaking morselized allograft in bisphosphonate before impacting it around an experimental implant has been described
  20. 20. Powerpoint Templates Page 20 Drug Interactions • Bisphosphonates generally should not be taken with antacids that contain aluminum or magnesium, bottled water containing minerals, or calcium supplements because these agents decrease bisphosphonate absorption. • Food renders bisphosphonates ineffective; • A 2-hour interval between meals drug is recommended. • Aminoglycosides taken with bisphosphonates may cause severe hypocalcemia.
  21. 21. Powerpoint Templates Page 21 Adverse effects • Oral bisphosphonates causes Gastrointestinal complications such as gastritis or esophagitis, abdominal pain, nausea, vomiting, diarrhea, and constipation. • To minimize gastrointestinal inflammation • And ulcer, patients should remain upright (sitting or standing) for at least 30 minutes after taking the medication
  22. 22. Powerpoint Templates Page 22 BISPHOSPHONATE-RELATED OSTEONECROSIS OF THE JAW • AKA Phossy jaw • American Academy of Oral and Maxillofacial Surgeons (AAOMS) proposed a definition for bisphosphonate-related ONJ that requires the satisfaction of the following criteria: • (1) Current or prior use of bisphosphonate • (2) An area of exposed bone within the maxillofacial region without healing for more than 8 weeks • (3) Absence of history of radiation to the jaws
  23. 23. Powerpoint Templates Page 23 • It has been postulated that reduced bone remodeling associated with bisphosphonate use may lead to an increased risk of developing bone necrosis in select patients. • The antiangiogenic effects of bisphosphonates may result in a reduction in the blood supply to the region and contribute to poor wound healing. • Infection has also been implicated in the pathogenesis of ONJ
  24. 24. Powerpoint Templates Page 24 STAGES • stage 1-were patients with asymptomatic necrotic bone • stage 2-accompanied by infection with or without purulent drainage • stage 3- patients with necrotic bone accompanied by infection, pain, and at least one of the conditions, including pathologic fractures, extraoral fistula, or osteolysis extending to the inferior border
  25. 25. Powerpoint Templates Page 25 ATYPICAL SUBTROCHANTERIC AND DIAPHYSEAL FRACTURES • bisphosphonate may alter the biomechanical properties of bone matrix via its effect on bone collagen and bone mineralization density distribution, resulting in brittle and stiff bones that could fracture with littletrauma. • Reduced bone remodeling, coupled with the antiangiogenic effect of bisphosphonates, may further impair the healing of stress fractures, which eventually develop into a complete fracture.
  26. 26. Powerpoint Templates Page 26
  27. 27. Powerpoint Templates Page 27
  1. A particular slide catching your eye?

    Clipping is a handy way to collect important slides you want to go back to later.

×