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
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
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
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
