Exam 2 Drugs: Bone Flashcards
1
Q
Estrogen + Progestin
A
- anti-resorptive agent
- Hormone Replacement Therapy
- used for osteoporosis prevention and treatment
- Est acts to reduce bone resorption
- suppresses transcription of genes coding for cytokine IL-6 (normally induces osteoclast prolif, differentiation, and activation)
- promotes apoptosis of osteoCLASTS
- inhibits the apoptosis of osteoBLASTS and osteoCYTES
- administered with progestational agent to reduce risk of endometrial cancer
- adverse: increased risk of deep vein thrombosis, BC (small but significant risk), also vaginal bleeding and breast tenderness
- may reduce symptoms of menopause like hot flashes and vaginal dryness
- concluded that increased risk outweighs potential benefits of HRTs
2
Q
Raloxifene
A
- anti-resorptive agent
- SERM
- Antagonist at breast and endometrial tissue, agonist at bone
- prevention and treatment of postmenopausal osteoporosis
- preferred therapy for women with BC, with past history or family history of BC or endometrial cancer, women who wish to avoid adverse effects of HRT
- not associated with breast or endometrial cancer (may lower risk of BC)
- lowers LDL cholesterol levels (may prevent heart disease)
- does still increase risk of venous thromboembolism
- contra: pregnancy, history or presence of blood clotting
3
Q
Alendronate
A
- anti-resorptive agent
- currently available bisphosphate, contains amino moiety in one of the side chains which enhances activity
- analogue of pyrophosphate
- decreases solubility of hydroxyapatite; more resistant to osteoclastic resorption
- inhibits a step in mevalonate pathway (localized to osteoclasts) which leads to loss of some osteoclastic functions like H+/ATPase activity
- ultimately causes osteoclastic apoptosis
- Uses: osteoporosis prevention and treatment, Paget’s disease
- taken orally 1x/week, with lots of water, and patient to remain upright for 30 minutes
- adverse: still concern over long term use, esophageal pain and erosion, esophagitis, jaw osteonecrosis
4
Q
Ibandronate
A
- Anti-resorptive agent
- bisphosphate, contains amino moiety
- analogue of pyrophosphate
- decreases solubility of hydroxyapatite; more resistant to osteoclastic resorption
- inhibits step in mevalonate pathway (localized to osteoclasts) which leads to loss of some osteoclastic functions like H+/ATPase activity
- ultimately causes osteoclastic apoptosis
- Uses: osteoporosis prevention and treatment, Paget’s disease
- taken orally 1x/MONTH, with lots of water, patient to remain upright for 30 minutes
- adverse: still concern for long-term use, esophageal pain and erosion, esophagitis, jaw osteonecrosis
5
Q
Pamidronate
A
- Anti-resorptive agent
- bisphosphate, contains amino moiety
- analogue of pyrophosphate
- decreases solubility of hydroxyapatite; more resistant to osteoclastic resorption
- inhibits step in mevalonate pathway (localized to osteoclasts) which leads to loss of some osteoclastic functions like H+/ATPase activity
- ultimately causes osteoclastic apoptosis
- Uses: osteoporosis prevention and treatment, Paget’s disease, hypercalcemia of malignancy (tumors that produce PTHrP)
- given via IV
- adverse: long-term effects still unknown, osteonecrosis
6
Q
Risedronate
A
- Anti-resorptive agent
- bisphosphate, contains amino moiety
- analogue of pyrophosphate
- decreases solubility of hydroxyapatite; more resistant to osteoclastic resorption
- inhibits step in mevalonate pathway (localized to osteoclasts) which leads to loss of some osteoclastic functions like H+/ATPase activity
- ultimately causes osteoclastic apoptosis
- uses: prevention and treatment of osteoporosis, Paget’s disease
- given orally 1x/week
- adverse: not sure about long-term effects, esophageal pain and erosion, esophagitis, jaw osteonecrosis
7
Q
Zoledronic Acid
A
- anti-resorptive agent
- bisphosphate, contains IMIDAZOLE side chain
- analogue of pyrophosphate
- decreases solubility of hydroxyapatite; more resistant to osteoclastic resorption
- inhibits step in mevalonate pathway (localized to osteoclasts) which leads to loss of some osteoclastic functions like H+/ATPase activity
- ultimately causes osteoclastic apoptosis
- uses: prevention and treatment of osteoporosis, Paget’s disease, hypercalcemia of malignancy (tumors that secret PTHrP)
- given IV only
- adverse: not sure about long term effects, osteonecrosis
8
Q
Salmon Calcitonin
A
- anti-resorptive agent
- binds and activates a GPCR on osteoCLASTS which decreases resorptive activity
- uses: osteoporosis, Paget’s disease, hypercalcemia
- higher affinity for the human calcitonin receptor
- longer half life than human calcitonin
- administered sub-cu or nasal spray
- can get tachyphylaxis from long term use
- weak analgesic properties
- adverse: flushing, nausea, diarrhea, anorexia
- Plicamycin may enhance HYPOcalcemia effect
9
Q
PTH(1-34) (teriparatide)
A
- bone anabolic agents
- increase bone mass
- more effective than fluoride
- intermittent stim of bone cells increases bone remodeling, more new bone formed than old bone resorbed
- uses: severe osteoporosis in post-menopausal women and men
- sub cu injection, self administered
- adverse: hypotension, syncope, arthralgia
- induces osteosarcoma in long-term rat studies
10
Q
Fluoride
A
- bone anabolic agent
- effectiveness remains uncertain
- use to treat osteoporosis
- stims production of osteoblasts
- increases trabecular bone mass
- conversion of hydroxyapatite to fluoroapatite
- fluoroapatite is denser but more brittle
11
Q
Strontium Ranelate
A
- bone anabolic agent
- investigational
- use to treat osteoporosis
12
Q
Aluminum Hydroxide
A
- Oral phosphate binder
- treats hyperphosphatemia with CKD
- ppts with phosphate in the GI tract to form non-absorbable complexes
- significant long-term risk of aluminum toxicity
- because of this, rarely used
- adverse with chronic: neurotoxicity, osteomalacia, chronic anemia
13
Q
Calcium Carbonate (oral phosphate binder)
A
- oral phosphate binder
- Oral prep given with meals
- uses: CKD, osteoporosis, hypocalcemia, antacid
- binds to dietary phos and inhibits its absorption
- requires high doses
- may increase risk of vascular calcifications
- can cause iatrogenic hypercalcemia
- requires acidic environment
- adverse: milk-alkali syndrome
14
Q
Calcium Acetate
A
- oral phos binder
- oral prep given with meals
- uses: CKD, osteoporosis, hypocalcemia, antacid
- binds to dietary phos and inhibits its absorption
- requires high doses
- can cause iatrogenic hypercalcemia
- can be used in acidic or alkaline enviro
- may increase risk of vascular calcifications
- adverse: milk-alkali syndrome
15
Q
Sevelamer
A
- oral phosphate binder
- uses: CKD
- Nonabsorbable cationic ion-exchange resin that binds intestinal phosphate
- also binds bile acids and lowers serum cholesterol levels
- adverse: thrombosis
