NR566 Week 1 Study Outline
Chapter 21: Drugs Affecting the Endocrine System
Bisphosphonates
• Drugs: etidronate (Didronel), pamidronate (Aredia),
... [Show More] risedronate (Actonel) alendronate (Fosamax), tiludronate (Skelid), zoledronic acid (Zometa), ibandronate (Boniva)
• Used for bone support, most commonly used
• Pharmacodynamics
Adhere to bone, inhibit osteoclastic activity, potent inhibitors of both normal and abnormal bone resorption
o Etidronate (Didronel): reduces both bone resorption and bone formation because formation is coupled with resorption
o Pamidronate (Aredia) (available as IV only)
o and risedronate (Actonel): inhibit bone resorption with out inhibiting bone formation and mineralization
o Alendronate (Fosamax): highly selective inhibitor of bone resorption 1
100 to 500 time more potent than the other drugs
Does not interfere with osteoclastic recruitment or attachment but does inhibit osteoclastic activity
o Tiludronate (Skelid): inhibits protein-tyrosine-phosphatease, results in detachment of osteoclasts from the bone surface
Inhibits the osteoclastic proton pump
o Zoledronic acid (Zometa): inhibits osteoclastic activity and induces osteoclast apoptosis
Also inhibits the increased osteoclastic activity and skeletal calcium release induced by various stimulatory factors release by tumors
Only available as IV formulation
o Ibandronate (Boniva): inhibits osteoclast activity and reduces bone resorption and turnover based on its affinity for hydroxyapatite (part of the bone matrix)
• All drugs in this class reduce vertebral fracture however,
o Only alendronate, risedronate, and zoledronic acid have demonstrated nonvertebral fracture reduction
o Pamidronate and zoledronic acid: only for parenteral use
• Pharmacotherapeutics
o Contraindication: uncorrected hypocalcemia, documented Barrett’s esophagus, and renal insufficiency
o Caution: patient with GI disorders
o R/F severe esophageal adverse reactions is greater in patients who lie down after taking these drugs or fail to take with a full glass of water
o Etidronate has been withheld from patients with enterocolitis r/t diarrhea particularly at high doses
Associated with fracture in patients with Paget’s disease when given high doses or when therapy lasted longer than 6 months
• Monitor with x-rays and lab work to assess for lesions
• Rare femur fracture in non-Paget’s patients using bisphosphonates
o IV formulations associated with higher renal toxicity risk especially with rapid infusion
Check crt prior to every dose is required, force fluids before and after infusion
• Clinical Use (Page 546 Dosing Chart)
o Osteoporosis
Prevention and treatment of osteoporosis and its risk for fracture in men and postmenopausal women (especially vertebral fractures)
First line drugs: Alendronate, risedronate, and zolendronic acid with hip fracture reductions, FDA approved for this indication
Second-line drug: Ibandronate
Ibandronate and zoledronic acid come in IV form
Alendronate PO solution (Binosto) and PO tablets
Zoledronic acid: only alternative form that shows evidence of hip fracture reduction
Prophylactic use in patients with early osteopenia r/t long term use of medications that contribute to bone loss
• Includes (thyroid hormone, aromatase inhibitors, and glucocorticoids, PPIs, SSRIs)
It is recommended that all adults taking more than 7.5 mg of prednisone or its equivalent for more than 3 weeks be given alendronate or risedrone
In very high risk patients, maximum 2-year use of teriparatide (Forteo) (bone mass benefit disappears after d/c) a parathyroid hormone, may be more efficacious
• Bisphosphonates: bone mass benefit does not decline for 5 years
Alendronate and risedronate initial doses for prevention of bone loss: 5mg/day or 35mg/week
For existing osteoporosis: alendronate 10mg/day or 70mg/week
Risedronate: 75mg for 2 days or 150mg once a month
o Paget’s Disease (Osteitis Deformans)
All bisphosphonates are used to treat Paget’s disease when the alkaline phosphatase is at least twice the upper limit of normal
Asymptomatic or at risk for future complications from their disease
Symptomatic Paget’s best treated with etidronate
Etidronate slows accelerated bone turnover in pagetic lesions and to a lesser extend in normal bone
Reduced turnover causes symptomatic improvement: less bone pain and decreased fractures
5-10 mg/kg daily for up to 6 months or 11 to 20 mg/kg daily for 3 months
For all drugs indications for retreatment are evidence of active disease or failure to normalize alkaline phosphatase levels
Supplemental calcium and vitamin D if dietary intake is not adequate
Space calcium supplements and bisphosphonates to prevent reduced bioavailability
o Heterotopic Ossification
Complications of THR
Etidronate: first line
Heterotopic ossification r/t spinal cord injury
Use as soon as possible after injury
• Drug Interactions
o Adverse GI reactions, interact with drugs that affect the GI tract
Histamine 2 blocking agents double alendronate bioavailability but the impact with unknow
o Calcium supplements and antacids interfere with bisphosphonate absorption when taken within 1 hr
o R/F GI bleeding is increased when ASA and NSAIDs are concomitantly taken
o ASA may decrease the bioavailability of tiludronate by up to 50% when taken 2 hrs after the tiludronate
o Indomethacin increases the bioavailability of tiludronate by 2- to 4- fold
Diclofenac does not significantly alter bioavailability therefore each NSAID must be evaluated individually
o Concurrent use of bisphosphonates and other drugs known to build bone density (estrogens and SERMs) have additive bone density however fracture reduction potential is unknown
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