Ex 4. L6: Ca+ Homeostasis (40)

Question 1

1st line drug to treat osteoporosis

Answer 1

Bisphosphonates/Denosumab

Question 2

Drugs to treat osteoporosis - High fracture risk:

Answer 2

Teriparatide/abaloparatide
Romosozumab

Question 3

Vitamin D and osteoporosis

Answer 3

Vitamin D (800-1000 IU) + Ca2++ (>1200mg) daily can reduce fracture risk (slightly)
Also: supplementation of osteoporosis therapy

Question 4

Vitamin D and Hypocalcemia/hypoparathyroidism

Answer 4

Vitamin D + Ca2+ (+ rPTH (100micrograms/day))

Question 5

Vitamin D and Hyperparathyroidism 2° to CKD

Answer 5

Vitamin D analogs suppress PTH

Question 6

Vitamin D overdose

Answer 6

Ca2+ deposits in kidney, soft tissues
Hypercalcemia - Coma, death

Question 7

First line of therapy for osteoporosis

Answer 7

Bisphosphonates

Question 8

Bisphosphonates:

Answer 8

Inhibit bone resorption
-Reduce formation and dissolution of hydroxyapatite crystals (Accumulation in bone as part of matrix) -50% of absorbed dose ends up in bone
Disrupt cytoskeleton, induce apoptosis, inhibit farensyl-PP synthesis of osteoclasts

Question 9

Dosing precautions with Bisphosphonates

Answer 9

10% absorbed orally; taken with H2O 30 min before breakfast problems:
1. May lead to hypocalcemia - supplement w/Ca2+ + Vit D
2. Esophagitis, nausea and heart burn
3. Necrosis of the jaw, atypical femur fractures

Question 10

Alendronate bone loss in OVX rats -

Answer 10

-

Question 11

Bisphosphonates: Pamidronate, Etidronate

Answer 11

Approved for Paget’s and cancer
Not approved for osteoporosis

Question 12

Bisphophonates: Zoledronate (Reclast); Alendronate (Fosamax); Risedndronate (Actonel); Ibandronate (Boniva)

Answer 12

Build bone mass
approved for osteoporosis

Question 13

Zolendronate dosing

Answer 13

IV infusion once every year

Question 14

Ibandronate dosing:

Answer 14

IV infusion, or Oral
Does not prevent hip fractures

Question 15

Alendronate and Risedronate dosing:

Answer 15

Oral only

Question 16

MOA of Bisphosphonates

Question 17

Ternary complex of risedronate, IPP, and FPPS

Answer 17

-

Question 18

Teriparatide (Forteo)

Answer 18

Amino acids 1-34 of PTH produced in E.Coli

Question 19

Abaloparatide (Thymlos)

Answer 19

Amino acids 1-34 of PTHrP produced synthetically

Question 20

Teriparatide and Abaloparatide dosing and MOA

Answer 20

Injected sub Q daily (20/80 micro grams) w/ oral Ca2+ and vitamin D
Preferentially stimulates osteoblast activity with this pattern of admin
-Indicated for tx of osteoporosis in patients w/ high risk of fracture
Potential for hypercalcemia

Question 21

Interaction of Teriparatide w/ the PTH1 Receptor:

Answer 21

Receptor is a GPCR
Activates Gs/Adenylyl cyclase
Activates Gq/PLC
Expressed on osteoblasts and kidney cells

Question 22

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