Drugs That Affect Bone Mineral Homeostasis

Front 1

Action of PTH intracellularly?

Back 1

↑ cAMP in bone and renal tubular cells.

Front 2

Function of PTH in the kidney?

Back 2

• inhibit calcium excretion
• promotes phosphate excretion
• stimulates production of vitamin D

Front 3

Function of PTH in the bone?

Back 3

Stimulation of osteoblast and osteoclasts.

Front 4

Is the stimulation of PTH on the osteoclasts a direct effect?

Back 4

No, stimulation on the osteoclasts is NOT a direct effect. Instead it acts through osteoblast formation of a RANK-ligand.

Front 5

Low intermittent doses of PTH produce a net increase in bone formation; this is the basis of use of what drug?

Back 5

teriparatide

(a recombinant truncated form of PTH)

Front 6

Teriparatide is used for what?

Back 6

osteoporosis

Front 7

Route of administration of teriparatide?

Back 7

parenteral

Front 8

Where do you inject teriparatide?

Back 8

SC

Front 9

The synthesis and secretion of PTH is regulated by what?

Back 9

free ionized calcium

(low calcium will stimulate release of PTH and high calcium will inhibited release)

Front 10

Where are the active metabolites of vitamin D formed?

Back 10

liver + kidney

Front 11

Renal synthesis of active vitamin D is stimulated by what?

Back 11

• PTH
• fibroblast GF 23

Front 12

What cells produce fibroblast GF 23?

Back 12

• osteoblasts
• osteroclasts

Front 13

Active vitamin D metabolites causes what?

Back 13

Increase in calcium and phosphates by increasing intestinal absorption and bone resorption and decreasing renal excretion.

Front 14

Topical formulations of vitamin D is used in what disease?

Back 14

psoriasis

Front 15

Name the 2 non-active forms of vitamin D?

Back 15

• cholecalciferol (vitamin D3)
• ergocalciferol (vitamin D2)

Front 16

How does the human body get cholecaliferol and ergocalciferol?

Back 16

Cholecalciferol through sunlight when UV-light forms cholecaliferol from 7-dehydrocholesterol.

Ergocalciferol is not a compound of the human body and can only be gained orally (vegetables).

Front 17

Route of administration of cholecalciferol and ergocacliferol?

Back 17

They are both available as oral supplements.

Front 18

In patients with conditions that impair vitamin D activation, an activated form of vitamin D is needed. What is the active form of vitamin D?

Back 18

calcitriol

Front 19

What is the function of the active vitamin D metabolite calcitonin?

Back 19

Decrease serum calcium and phosphate by inhibiting bone resorption.

Front 20

Clinical application of calcitonin?

Back 20

• Paget’s disease
• hypercalcemia

(Paget's disease is a chronic disorder that can result in enlarged and misshapen bones. The excessive breakdown and formation of bone tissue causes affected bone to weaken, resulting in pain, misshapen bones, fractures, and arthritis in the joints near the affected bones.)

Front 21

Although human calcitonin is available, salmon calcitonin is most selected. Why?

Back 21

Longer half-life and greater potency.

Front 22

Route of administration of calcitonin?

Back 22

• SC injection
• intranasal
(both calcitonin and teriparatide are injection SC)

Front 23

What does SERM stand for?

Back 23

Selective estrogen receptor modulator

Front 24

What SERM can prevent or delay bone loss in postmenopausal women?

Back 24

raloxifen

Front 25

Name the suffix of the bisphosphonates!

Back 25

-dronate

(dronate = dronic acid)

(alendronate, etidronate, ibandronate, pamidronate, risedronate, tiludronate, zoledronate)

Front 26

What is the function of the bisphosphonates?

Back 26

Reduce both resorption and formation of bone by an action on the basic hydroxyapatite crystal structure.

Front 27

When are bisphosphonates used?

Back 27

• hypercalcemia
• Paget’s disease

(Both bisphosphonates and calcitonin are used against hypercalcemia and Paget’s disease.)

Front 28

Normal route of administration of bisphosphonates?

Back 28

oral

Front 29

All bisphosphonates are taken orally except for 3 that can be taken parenteral. Name them!

Back 29

• Pamidronate
• Etidronate
• Zoledronate

Front 30

Oral bioavailability of bisphosphonates is high or low?

Back 30

low (<10%)

Front 31

What is the effect of eating food while taking bisphosphonates orally?

Back 31

Food will impair absorption.

Front 32

What is the primary toxicity of the oral bisphosphonates?

Back 32

Gastric and esophageal irritation.

Front 33

To reduce these problems, patients are advised to take the oral bisphonates in what way?

Back 33

Take drug with large quantities of water.

Front 34

What is the mechanism of action of cinacalcet?

Back 34

Activates the calcium-sensing receptor in parathyroid gland.

Front 35

Effect of cinacalcet?

Back 35

lowers PTH

Front 36

Route of administration of cinacalcet?

Back 36

oral

Front 37

Clinical application of cincalcet used to treat what patients?

Back 37

Patients with secondary hyperparathyroidism.

Front 38

Appropriate concentrations of fluoride ion in drinking water have well-documented ability to reduce what?

Back 38

dental caries

Front 39

What is strontium?

Back 39

A metallic compound.

Front 40

What is the function of the drug strontium ranelate?

Back 40

Promotes osteoclast apoptosis.

Front 41

215. What is the mechanism of action of gallium nitrate?

Back 41

Inhibits bone resorption.

Front 42

Clinical application of gallium nitrate?

Back 42

• hypercalcemia
• Paget’s disease

Front 43

What can be a serious adverse effect when taking gallium nitrate?

Back 43

nephrotoxicity

Front 44

To prevent the nephrotoxicity when taking gallium nitrate the patient has to consider what?

Back 44

It’s important to be well hydrated and have high renal output.

Front 45

The antibiotic plicamycin has been used in what?

Back 45

• Paget’s disease
• hypercalcemia

Front 46

Why has plicamycin been restricted to short-term treatment of serious hypercalcemia?

Back 46

Because of serious toxicity:

• thrombocytopenia
• hemorrhage
• hepatic damage
• renal damage

Front 47

What diuretics can affect urinary calcium levels?

Back 47

Diuretics, most notable:

• loopdiuretic (furosemide)
• thiazide diuretics (hydrochlorothiazide).