KG - Pharm 2 Exam 3, Osteoporosis Flashcards
which cells are responsible for bone resorption?
osteoclasts
which cells are responsible for bone formation?
osteoblasts
what is key to osteoporosis tx and why?
DECREASING BONE RESORPTION
- 3 wks to dig resorption pit, but 3-4 months to complete new bone unit
- bone remodeling = RESORPTION DOMINANT
gen info PTH?
- stim when blood Ca2+ low
increases Ca2+ by:
- increases osteoclast activity & # (RANK LIGAND)
- increase renal ability to reabsorb Ca2+ (decr Ca2+ excretion, incr PO4 excretion)
- stim production Vit D
gen info Vit D?
increases Ca2+ by:
- stim collagen synthesis in osteoblasts
- stim osteoclast activity via RANK LIGAND
- incr intestinal absorption
- decr renal excretion
*works w/ PTH
gen info Calcitonin
- secreted when Ca2+ too high
- DECREASE Ca2+ by inhibiting osteoclasts to decrease resorption
- maintain bone in pregnancy/lactation (stim by estrogen)
gen info osteoporosis?
- AMT BONE DECREASED
- STRUCTURAL INTEGRITY TRABECULAR BONE IMPAIRED
- CORTICAL BONE BECOMES POROUS, THINNER
- makes bone WEAKER, MORE LIKELY TO FRACTURE
osteoporosis - complications
- hip fractures (14% DEATH RATE)
- spinal compression fractures (60% don’t realize it)
osteoporosis - risk factors
- POSTMENOPAUSAL WOMEN
- LONG TERM GLUCOCORTICOID USE
- THYROTOXICOSIS
- ALCOHOLISM
- MALABSORPTION SYNDROME
osteoporosis - tx options?
- Ca2+, vit D (ALWAYS)
- HRT (estrogen, SERMS)
- Ca2+ regulating hormones (PTH, Calcitonin)
- bisphosphonates = DOC
DOC for osteoporosis?
BISPHOSPHONATES
why use Calcium and Vit D to treat osteoporosis?
- can’t prevent or treat osteoporosis alone bc CALCIUM AND VIT D ALWAYS NEEDED FOR OTHER Txs TO WORK!
- Calcium chewables work best
- VITAMIN D MUST BE ADEQUATE FOR OPTIMAL CALCIUM ABSORPTION
calcitonin - gen info?
- DECREASES BONE RESORPTION of Ca2+
- ANTAGONIST OF PTH
- decrease bone pain/loss
- increase bone density
- decrease fractures
calcitonin - pharmacokinetics?
- NASAL SPRAY
- INJECTION
calcitonin - adverse effects?
- allergic rxns (esp FISH)
- nasal RHINITIS/SINUSITIS (nasal spray)
- NAUSEA/VOMITING (injection)
calcitonin - indications
- osteoporosis (not 1st line)
- Paget’s dz
Teriparatide - info?
RECOMBINANT PTH
- INTERMITTENT ADMIN produces bone GROWTH
- -> protects weight bearing bones, decr new fractures, incr bone mass/strength
- actions diminish w/ time
- ANABOLIC
Teriparatide - indications?
- osteoporosis
- hypoPTH
Teriparatide - pharmokinetics?
SC injection
- INTERMITTENT (1-2 x weekly)
Teriparatide - adverse effects?
- hyperCa2+
- hypercalciuria
- injection site rxns
- dizziness, cramps
Teriparatide - contraindications/precautions?
- DO NOT USE w/ OSTEOSARCOMA (or those susceptible to osteosarcoma)
Denosumab - info?
- antibody against RANK ligand
- DENsity, OSteo, hUman, Monoclonal AntiBody
Denosumab - MOA?
- inhibits bone resorption
- ANTIBODY TO RANK LIGAND (FACTOR MADE BY OSTEOBLASTS THAT IS NECESSARY FOR FORMATION OF OSTEOCLASTS)
Denosumab - indications/therapeutic effects?
- SEVERE OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN & MEN AT HIGH FRACTURE RISK
- INCREASE BONE MASS & STRENGTH IN BOTH CORTICAL AND TRABECULAR BONE
Denosumab - pharmacokinetics?
- SC injection, once/q 6 months
Denosumab - adverse effects?
- OSTEONECROSIS of jaw in cancer studies
Denosumab - contraindications, absolute?
- HYPOCALCEMIA - fix this first
- pregnancy
Denosumab - contraindications, relative?
- chronic kidney dz
- pts at risk for infection
bisphosphonates - FDA approved?
- Alendronate
- Risedronate
- Ibandronate
- Zoledronic Acid
bisphosphonates - off label use?
- Etidronate
- Pamidronate
bisphosphonates - oral only?
- Risedronate
- Alendronate
bisphosphonates - IV only?
- Pamidronate (slow IV)
- Zoledronate
bisphosphonates - IV and oral?
- Ibandronate
- Etidronate
bisphosphonates - info?
- SUBSTITUTES for PO4 in Ca2+ BINDING
- INCORPORATES INTO BONE
- INHIBITS BONE RESORPTION
- reduce incidence fractures
bisphosphonates - MOA?
- inhibit osteoclast activity & bone resorption
- strengthen bone
- mechanism unclear
bisphosphonates - indications?
- DOC FIRST LINE POST MENOPAUSAL OSTEOPOROSIS
- paget’s dz
bisphosphonates - pharmacokinetics
- ORAL prep absorption VERY POOR
- TAKE ON EMPTY STOMACH
- 1/2 GLASS WATER & STAY UPRIGHT 30 MIN
- ALSO IV
bisphosphonates - adverse effects, oral?
- ABD PAIN
- UPPER GI IRRITATION
- ESOPHAGEAL ULCERATION
- CONSTIPATION
- DIARRHEA
- FLATULENCE
bisphosphonates - adverse effects, IV?
- RENAL TOXICITY IF GIVEN TOO FAST
bisphosphonates - adverse effects (all)?
- NAUSEA, VOMITING
- mild hypoCa2+
- possible Afib
- incr incidence OSTEONECROSIS OF JAW after dental work
