NR566 Week 1 Study Outline
Chapter 21: Drugs Affecting the Endocrine System
Bisphosphonates Drugs: etidronate (Didronel), pamidronate (Aredia), 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 oEtidronate (Didronel): reduces both bone resorption and bone formation because formation is coupled with resorption oPamidronate (Aredia) (available as IV only) oand risedronate (Actonel): inhibit bone resorption with out inhibiting bone formation and mineralization
oAlendronate (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 oTiludronate (Skelid): inhibits protein-tyrosine-phosphatease, results in detachment of osteoclasts from the bone surface Inhibits the osteoclastic proton pump oZoledronic 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 oIbandronate (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, oOnly alendronate, risedronate, and zoledronic acid have demonstrated nonvertebral fracture reduction
oPamidronate and zoledronic acid: only for parenteral use
Pharmacotherapeutics oContraindication: uncorrected hypocalcemia, documented Barrett’s esophagus, and renal insufficiency
oCaution: patient with GI disorders
oR/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 oEtidronate 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 oIV 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 1 / 3
Clinical Use (Page 546 Dosing Chart) oOsteoporosis 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
oPaget’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 oHeterotopic Ossification Complications of THR
Etidronate: first line
Heterotopic ossification r/t spinal cord injury Use as soon as possible after injury Drug Interactions oAdverse GI reactions, interact with drugs that affect the GI tract Histamine 2 blocking agents double alendronate bioavailability but the impact with unknow oCalcium supplements and antacids interfere with bisphosphonate absorption when taken within 1 hr oR/F GI bleeding is increased when ASA and NSAIDs are concomitantly taken oASA may decrease the bioavailability of tiludronate by up to 50% when taken 2 hrs after the tiludronate 2 / 3
oIndomethacin increases the bioavailability of tiludronate by 2- to 4- fold Diclofenac does not significantly alter bioavailability therefore each NSAID must be evaluated individually oConcurrent use of bisphosphonates and other drugs known to build bone density (estrogens and SERMs) have additive bone density however fracture reduction potential is unknown ADRs
oAll bisphosphonates: musculoskeletal pain
More common in Paget’s disease More common in those taking risedronate High doses of etidronate Rare reports of osteonecrosis of the jaw in active dental disease, invasive procedure, especially in CA patients Can occur without dental issues in those receiving frequent high IV doses R/F A-fib Bioavailability of bisphosphonate drugs and appropriate patient education oAbsorption and bioavailability of oral doses are significantly reduced by the presence of food in the gut or other preparations containing divalent cations oTo enhance absorption take with 8 oz of water, no other food or drink and remain upright for at least half an hr (1 hour with ibandronate) oHistamine 2 blocking agents double alendronate bioavailability but the impact with unknow oASA may decrease the bioavailability of tiludronate by up to 50% when taken 2 hrs after the tiludronate oIndomethacin increases the bioavailability of tiludronate by 2- to 4- fold Diclofenac does not significantly alter bioavailability therefore each NSAID must be evaluated individually oPatient education: Take oral drugs first thing in the morning at least 30 minutes prior to other medications, beverages, or food (60 minutes for ibandronate) oEtidronate and tiludronate take 2 hours before food oAlendronate, ibandronate, risedronate, and tiludronate should be taken with 8 oz of plain water oMineral water, coffee, OJ, and other drinks greatly reduce absorption oSupplemental calcium or antacids take the bisphosphonate at least 1 hr before these drugs oSkip missed daily doses and resume the next morning oSit up for at least 30 mins after taking to decrease risk of esophageal irritation (1hr for ibandronate) Adverse effects associated with long-term use oEtidronate: Fractures in patients with Paget’s disease when given high doses or when therapy lasted longer than 6 months oOral drugs in this class: rare osteonecrosis of the jaw after 3 years of use (higher risk in IV drugs) Growth hormones Drugs: somatropin (Nutropin and Nutropin AQ, Gentropin, Humatrope, Norditropin, Nutropin, Accretropi9n, Saizen, Serostim) and somatrem (Protropin) Dosage of the various forms of somatropin varies by manufacturer Pharmacodynamics oGHRH secreted by hypothalamus in response to decreased serum glucose oGHRH then binds to receptors in the anterior pituitary, secrets GH (somatotropin) oPasses through cell membrane, fosters proteins synthesis, fat breakdown, and tissue growth
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