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NR566 Week 1 Study Outline Chapter 21: Drugs Affecting the Endocrine System
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NR566 Week 1 Study OutlineChapter 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
▪ 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
• ADRs
o All 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
o Absorption and bioavailability of oral doses are significantly reduced by the presence of food in the
gut or other preparations containing divalent cations
o To 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)
o Histamine 2 blocking agents double alendronate bioavailability but the impact with unknow
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 Patient education: Take oral drugs first thing in the morning at least 30 minutes prior to other
medications, beverages, or food (60 minutes for ibandronate)
o Etidronate and tiludronate take 2 hours before food
o Alendronate, ibandronate, risedronate, and tiludronate should be taken with 8 oz of plain water
o Mineral water, coffee, OJ, and other drinks greatly reduce absorption
o Supplemental calcium or antacids take the bisphosphonate at least 1 hr before these drugs
o Skip missed daily doses and resume the next morning
o Sit up for at least 30 mins after taking to decrease risk of esophageal irritation (1hr for ibandronate)
• Adverse effects associated with long-term use
o Etidronate: Fractures in patients with Paget’s disease when given high doses or when therapy lasted
longer than 6 months
o Oral 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
o GHRH secreted by hypothalamus in response to decreased serum glucose
o GHRH then binds to receptors in the anterior pituitary, secrets GH (somatotropin)
o Passes through cell membrane, fosters proteins synthesis, fat breakdown, and tissue growth
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