Block 9 Drugs - Calcium & Bone

Question 1

Ergocalciferol (Vitamin D2)

Answer 1

MOA: Once metabolized/converted to 1, 25-OH Vitamin D, it regulates gene transcription via Vitamin D receptor

­­­↑dietary absorption of both Ca²⁺ & (PO₄)^3-

↑bone resorption of both Ca²⁺ & (PO₄)^3-

USE: Vitamin D deficiency

S/E: Hypercalcemia

Hyperphosphatemia

Hypercalciuria

Unique: Obtained from plants

Requires metabolism in liver & kjidney to active forms of Vitamin D

Converted to:

25-OH Vitamin D in liver

1,25-OH Vitamin D in kidney

Question 2

Calcifediol

(25-OH Vitamin D3)

Answer 2

MOA: Once metabolized/converted to 1,25-OH Vitamin D, it regulates gene transcription via the Vitamin D receptor

↑absorption of both Ca2+ & (PO4)3-

↑bone resorption of both Ca2+ & (PO4)3-

USE: Vitamin D deficiency

S/E: Hypercalcemia

Hyperphosphatemia

Hypercalciuria

Unique: Requires metabolism in kidney to 1,25-OH Vitamin D in the active form of Vitamin D

Question 3

Calcitriol

(1,25-OH Vitamin D3)

Answer 3

MOA: Active form of Vitamin D

Does not require metabolism to be active

↑absorption of both Ca2+ & (PO4)3-

↑bone resorption of both Ca2+ & (PO4)3-

USE: management of secondary hyperparathyroidism in patients w/ chronic kidney disease

Management of hypocalcemia in patients with hypoparathyroidism

S/E: Hypercalcemia

Hyperphosphatemia

Hypercalciuria

Unique: ↑ 1,25 OH Vitamin D results in feedback inhibition to limit its production

Question 4

Teriparatide

Forteo®

Answer 4

MOA: PTH receptor agonist (GPCR)

↑bone resorption of both Ca²⁺ & (PO₄)^3-

↑kidney reabsorption of Ca²⁺

↓kidney reabsorption of (PO₄)^3-

↑1,25-OH Vitamin D production in kidney

USE: Osteoporosis

S/E: Hypercalcemia

Hypercalciuria

Osteosarcoma in experimental animals

CI: Children or young adults with open epiphysis

Hypercalcemia

Active Paget’s disease of bone

Skeletal metastases or malignant conditions: risk of osteosarcoma

History of radiation to the skeleton: risk of osteosarcoma

Pregnancy and lactation

Unique: Although both bone resorption and bone formation are enhanced by PTH, the net effect is an increase in bone formation

Question 5

Alendronate

Fosamax®

Answer 5

MOA: Inhibits farnesyl diphosphate synthase (FPPS) to block protein prenylation (farneslyation and geranylgeranylation)

Supresses the activity of osteoclasts and inhibits bone resorption

Aminobiphosphonates

USE: Osteoporosis

Padget’s disease of bone

Bone metastases

S/E: Esophageal irritation (esophagitis including Barrett’s esophagitis)

Osteonecrosis of the jaw

Musculoskeletal pain

Nausea, diarrhea

CI: Avoid in patients with renal dysfunction (GFR<30)

Unique: Binds and coordinates with Ca²⁺

Since bone is largest store of Ca²⁺ in the body, biphosphonates are preferentially targeted to bone; internalized by osteoclasts

Question 6

Ibandronate

Answer 6

MOA: (Same as alendronate) Inhibits farnesyl diphosphate synthase (FPPS) to block protein prenylation (farneslyation and geranylgeranylation)

Supresses the activity of osteoclasts and inhibits bone resorption

Aminobiphosphonates

USE: (Same as alendronate)

Osteoporosis

Padget’s disease of bone

Bone metastases

S/E: (Same as alendronate)

Esophageal irritation (esophagitis including Barrett’s esophagitis)

Osteonecrosis of the jaw

Musculoskeletal pain

Nausea, diarrhea

Unique: (Same as alendronate)

Binds and coordinates with Ca2+

Since bone is largest store of Ca2+ in the body, biphosphonates are preferentially targeted to bone; internalized by osteoclasts

Question 7

Risedronate

Answer 7

MOA: (Same as alendronate) Inhibits farnesyl diphosphate synthase (FPPS) to block protein prenylation (farneslyation and geranylgeranylation)

Supresses the activity of osteoclasts and inhibits bone resorption

Aminobiphosphonates

USE: (Same as alendronate)

Osteoporosis

Padget’s disease of bone

Bone metastases

S/E: (Same as alendronate)

Esophageal irritation (esophagitis including Barrett’s esophagitis)

Osteonecrosis of the jaw

Musculoskeletal pain

Nausea, diarrhea

Question 8

Zoledronate

Answer 8

MOA: (Same as alendronate) Inhibits farnesyl diphosphate synthase (FPPS) to block protein prenylation (farneslyation and geranylgeranylation)

Supresses the activity of osteoclasts and inhibits bone resorption

Aminobiphosphonates

USE: (Same as alendronate)

Osteoporosis

Padget’s disease of bone

Bone metastases

S/E: (Same as alendronate)

Esophageal irritation (esophagitis including Barrett’s esophagitis)

Osteonecrosis of the jaw

Musculoskeletal pain

Nausea, diarrhea

Question 9

Etidronate

Answer 9

MOA: metabolized to compounds that replace the terminal pyrophosphate moiety of ATP in osteoclasts

Competes with ATP ultimately leading to osteoclast apoptosis → ↓bone resorption

Unique: Binds and coordinates with Ca²⁺

Since bone is the largest store of Ca²⁺ in body, bisphosphonates are preferentially targeted to bone; internalized by osteoclasts

Question 10

Clodronate

Answer 10

MOA: (Same as Etidronate) metabolized to compounds that replace the terminal pyrophosphate moiety of ATP in osteoclasts

Competes with ATP ultimately leading to osteoclast apoptosis → ↓bone resorption