KG - Pharm 2 Exam 3, Osteoporosis

Question 1

which cells are responsible for bone resorption?

Answer 1

osteoclasts

Question 2

which cells are responsible for bone formation?

Answer 2

osteoblasts

Question 3

what is key to osteoporosis tx and why?

Answer 3

DECREASING BONE RESORPTION

• 3 wks to dig resorption pit, but 3-4 months to complete new bone unit
• bone remodeling = RESORPTION DOMINANT

Question 4

gen info PTH?

Answer 4

• 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

Question 5

gen info Vit D?

Answer 5

increases Ca2+ by:

• stim collagen synthesis in osteoblasts
• stim osteoclast activity via RANK LIGAND
• incr intestinal absorption
• decr renal excretion

*works w/ PTH

Question 6

gen info Calcitonin

Answer 6

• secreted when Ca2+ too high
• DECREASE Ca2+ by inhibiting osteoclasts to decrease resorption
• maintain bone in pregnancy/lactation (stim by estrogen)

Question 7

gen info osteoporosis?

Answer 7

• AMT BONE DECREASED
• STRUCTURAL INTEGRITY TRABECULAR BONE IMPAIRED
• CORTICAL BONE BECOMES POROUS, THINNER
• makes bone WEAKER, MORE LIKELY TO FRACTURE

Question 8

osteoporosis - complications

Answer 8

• hip fractures (14% DEATH RATE)

- spinal compression fractures (60% don’t realize it)

Question 9

osteoporosis - risk factors

Answer 9

• POSTMENOPAUSAL WOMEN
• LONG TERM GLUCOCORTICOID USE
• THYROTOXICOSIS
• ALCOHOLISM
• MALABSORPTION SYNDROME

Question 10

osteoporosis - tx options?

Answer 10

• Ca2+, vit D (ALWAYS)
• HRT (estrogen, SERMS)
• Ca2+ regulating hormones (PTH, Calcitonin)
• bisphosphonates = DOC

Question 11

DOC for osteoporosis?

Answer 11

BISPHOSPHONATES

Question 12

why use Calcium and Vit D to treat osteoporosis?

Answer 12

• 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

Question 13

calcitonin - gen info?

Answer 13

• DECREASES BONE RESORPTION of Ca2+
• ANTAGONIST OF PTH
• decrease bone pain/loss
• increase bone density
• decrease fractures

Question 14

calcitonin - pharmacokinetics?

Answer 14

• NASAL SPRAY

- INJECTION

Question 15

calcitonin - adverse effects?

Answer 15

• allergic rxns (esp FISH)
• nasal RHINITIS/SINUSITIS (nasal spray)
• NAUSEA/VOMITING (injection)

Question 16

calcitonin - indications

Answer 16

• osteoporosis (not 1st line)

- Paget’s dz

Question 17

Teriparatide - info?

Answer 17

RECOMBINANT PTH

• INTERMITTENT ADMIN produces bone GROWTH
• -> protects weight bearing bones, decr new fractures, incr bone mass/strength
• actions diminish w/ time
• ANABOLIC

Question 18

Teriparatide - indications?

Answer 18

• osteoporosis

- hypoPTH

Question 19

Teriparatide - pharmokinetics?

Answer 19

SC injection

- INTERMITTENT (1-2 x weekly)

Question 20

Teriparatide - adverse effects?

Answer 20

• hyperCa2+
• hypercalciuria
• injection site rxns
• dizziness, cramps

Question 21

Teriparatide - contraindications/precautions?

Answer 21

• DO NOT USE w/ OSTEOSARCOMA (or those susceptible to osteosarcoma)

Question 22

Denosumab - info?

Answer 22

• antibody against RANK ligand

- DENsity, OSteo, hUman, Monoclonal AntiBody

Question 23

Denosumab - MOA?

Answer 23

• inhibits bone resorption

- ANTIBODY TO RANK LIGAND (FACTOR MADE BY OSTEOBLASTS THAT IS NECESSARY FOR FORMATION OF OSTEOCLASTS)

Question 24

Denosumab - indications/therapeutic effects?

Answer 24

• SEVERE OSTEOPOROSIS IN POSTMENOPAUSAL WOMEN & MEN AT HIGH FRACTURE RISK
• INCREASE BONE MASS & STRENGTH IN BOTH CORTICAL AND TRABECULAR BONE

Question 25

Denosumab - pharmacokinetics?

Answer 25

- SC injection, once/q 6 months

Question 26

Denosumab - adverse effects?

Answer 26

- OSTEONECROSIS of jaw in cancer studies

Question 27

Denosumab - contraindications, absolute?

Answer 27

- HYPOCALCEMIA - fix this first | - pregnancy

Question 28

Denosumab - contraindications, relative?

Answer 28

- chronic kidney dz | - pts at risk for infection

Question 29

bisphosphonates - FDA approved?

Answer 29

- Alendronate - Risedronate - Ibandronate - Zoledronic Acid

Question 30

bisphosphonates - off label use?

Answer 30

- Etidronate | - Pamidronate

Question 31

bisphosphonates - oral only?

Answer 31

- Risedronate | - Alendronate

Question 32

bisphosphonates - IV only?

Answer 32

- Pamidronate (slow IV) | - Zoledronate

Question 33

bisphosphonates - IV and oral?

Answer 33

- Ibandronate | - Etidronate

Question 34

bisphosphonates - info?

Answer 34

- SUBSTITUTES for PO4 in Ca2+ BINDING - INCORPORATES INTO BONE - INHIBITS BONE RESORPTION - reduce incidence fractures

Question 35

bisphosphonates - MOA?

Answer 35

- inhibit osteoclast activity & bone resorption - strengthen bone - mechanism unclear

Question 36

bisphosphonates - indications?

Answer 36

- DOC FIRST LINE POST MENOPAUSAL OSTEOPOROSIS | - paget's dz

Question 37

bisphosphonates - pharmacokinetics

Answer 37

- ORAL prep absorption VERY POOR - TAKE ON EMPTY STOMACH - 1/2 GLASS WATER & STAY UPRIGHT 30 MIN - ALSO IV

Question 38

bisphosphonates - adverse effects, oral?

Answer 38

- ABD PAIN - UPPER GI IRRITATION - ESOPHAGEAL ULCERATION - CONSTIPATION - DIARRHEA - FLATULENCE

Question 39

bisphosphonates - adverse effects, IV?

Answer 39

- RENAL TOXICITY IF GIVEN TOO FAST

Question 40

bisphosphonates - adverse effects (all)?

Answer 40

- NAUSEA, VOMITING - mild hypoCa2+ - possible Afib - incr incidence OSTEONECROSIS OF JAW after dental work