NR566 Week 1 Study Guide

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 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