Drugs Affecting Bone Mineralization (online)

Question 1

What is the key molecule that causes formation, activation and maintenance of osteoclasts and is highly regulated by multiple systems in the body

Answer 1

NF-kB ligand RANKL is

Question 2

what is the purpose of RANK ligand would inhibition of RANK ligand would do to overall bone balance?

Answer 2

since RANK ligand stimulates bone resorption, inhibition of RANK ligand would favor overall bone building as osteoclast activity would be less than osteoblast activity.

Question 3

What are the three MAJOR regulators of calcium homeostasis?

Answer 3

PTH, vitamin D and FGF-23.

Question 4

What effects does PTH have on the kidneys?

Answer 4

increase calcium reabsorption and decreases phosphorous reabsorption

Question 5

What effect does PTH have in the gut?

Answer 5

increases BOTH calcium and phosphorous to reabsorption.

Question 6

Net effect of PTH on serum calcium and Phosphorus levels

Answer 6

increase Calcium, decrease phosphorus

Question 7

what is Teriparatide (Forteo)?

Answer 7

a subunit of amino acids 1-34 of human PTH

Question 8

What is the MOA of Teriparatide?

Answer 8

stimulator of bone formation

Question 9

What does intermittent PTH treatment do to bones?

Answer 9

stimulates osteoblastic bone formation with

Question 10

Side effects of teriparatide include (6)

Answer 10

nausea, dizziness, headache, joint pain, mild hypercalcaemia, and orthostatic hypotension.

Question 11

Teriparatide currently a drug of choice for treating? Why? .

Answer 11

osteoporosis and this is because it is currently the only drug with a primary mechanism of action of increasing bone formation.

Question 12

Teriparatide is also used in the prevention and treatment of ?

Answer 12

pathological fractures

Question 13

Where is Vitamin D first hydroxylated? to form? (aka)

Answer 13

in the liver to form 25-hydroxyvitamin D which is also called calcifediol calcidiol

Question 14

After the liver, what organ converts vitamin D metabolites to what? (aka)

Answer 14

in kidney, 25-hydroxyvitamin D is further converted to 1,25-hydroxyvitamin D (aka calcitrol) = the activated form of vitamin D

Question 15

PTH has what effect on Vit D mtb

Answer 15

PTH stimulates the production of 1,25-hydroxyvitamin D = calcitrol

Question 16

what enzyme in the kidney converts 25-hydroxyvitamin D into 1,25-hydroxyvitamin D?

Answer 16

1-a hydroxylase

Question 17

Three activities of vitamin D and their locations ***

Answer 17

1. bone mineralization (via increased Ca and P)
2. facilitates calcium absorption in the small intestine.
3. helps to decrease calcium excretion in the kidneys.

Question 18

viramin D is used to treat what 4 diseases

Answer 18

rickets and osteomalacia, hypocalcemia. and hypoparathyroidism

Question 19

How does Vitamin D increase serum Ca levels? what is the implication for it’s administration?

Answer 19

stimulates intestinal calcium absorption–> so it is often given with calcium supplements

Question 20

analogues of Vitamin D that are nonhypercalcemic are used in what case?

Answer 20

used in secondary hyperparathyroidism

Question 21

What is the MOA of the (2) vitamin D analogues and what are they called?

Answer 21

Both paricalcitol and doxercalciferol may lower plasma PTH levels without significantly raising plasma calcium levels

Question 22

What is the side effect condition of vitamin D toxicity and it’s sx? (7)

Answer 22

hypercalcemia

constipation, depression, weakness, fatigue, kidney stones, or even renal failure

Question 23

What is the main role of FGF-23? (acting where?)

Answer 23

The main role of FGF-23 is to inhibit 1,25 hydroxy vitamin D formation in the kidney.

Question 24

What is another function of FGF-23

Answer 24

also inhibits phosphate reabsorption in the kidney.

Question 25

What is a common hereditary form of FGF-23/phosphatonin excess in humans?

Answer 25

X-linked hypophosphatemic rickets (XLH)

Question 26

What is X-linked hypophosphatemic rickets (XLH) caused by?

Answer 26

caused by mutations in the endopeptidase PHEX.

Question 27

What metabolic influence increases serum calcium and phosphate? Vit D PTH Calcitonin Cortisol

Answer 27

Vitamin D

Question 28

how does intermittent vs continuous PTH affect bone modeling?

Answer 28

Intermittent - PTH stimulates bone formation | Continuous - PTH stimulates bone resorption

Question 29

What is the primary mechanism of action of Teriparatide?

Answer 29

stimulates osteblastic bone formation

Question 30

Calcitonin effects on kidney (1) and bone (2)

Answer 30

kidney- prevents reabsorption of calcium Bone- 1. stimulates osteoblasts 2. inhibits osteoclast

Question 31

Net effect of calcitonin

Answer 31

decrease serum calcium.

Question 32

What are the two forms of clacitonin and which is stronger?

Answer 32

salmon calcitonin (salcatonin) human recombinant calcitonin. Salmon calcitonin is 50 to 100 times more potent than human calcitonin

Question 33

what does "calcitonin escape" refer to, and what is the implication********************************

Answer 33

It limits the use of calcitonin to lower plasma calcium and phosphorous concentrations in patients with hypercalcemia due to decreased bone resorption. It refers to downregulation of receptors

Question 34

Calcitonin is also effective in what 2 disorders of increased skeletal remodeling

Answer 34

Paget's disease and osteoporosis.

Question 35

Salmon calcitonin available in what form to treat what? **********************************************

Answer 35

as nasal spray is indicated for postmenopausal osteoporosis.

Question 36

the nasal form of calcitonin is ineffective for what? why?

Answer 36

ineffective for the indication of hypercalcemia due to its limited bioavailability.

Question 37

What is the most common ADE to calcitonin?

Answer 37

is local inflammation at injection site

Question 38

What is GH effect on minerals and where? (2 locations)

Answer 38

GH increases intestinal calcium absorption and renal phosphate resorption.

Question 39

Patients who are GH deficient are prone to what as kids and what as adults?

Answer 39

decreased bone mineral density in childhood and osteoporosis as adults

Question 40

What is thyroid hormone function in bone?

Answer 40

It has direct effects on osteoblasts to stimulate bone formation.

Question 41

Hypothyroidism, or an underactive thyroid, leads to ?

Answer 41

decreased bone growth

Question 42

hyperthyroidism can lead to? (4)

Answer 42

increased bone loss, suppression of PTH, decreased vitamin D metabolism, and decreased calcium absorption leading to osteoporosis

Question 43

What is the treatment goal of hyperthyroidism?

Answer 43

to normalize thyroid hormone levels to prevent decreased bone mineral density

Question 44

What effect do excess glucocorticoid levels have? (3)

Answer 44

decrease renal calcium reabsorption decrease intestinal calcium absorption stimulate PTH secretion.

Question 45

glucocorticoid excess effect on GH

Answer 45

lowers GH

Question 46

net result of excessive glucocorticoids?

Answer 46

bone loss and osteoporosis.

Question 47

In what 5 ways does estrogen reduce bone resorption?

Answer 47

1. inhibits production of bone cell cytokines 2. inhibits secretion of osteoclast-stimulating factors by osteoblasts 3. inhibits PTH 4. increases calcitonin levels 5. 1,25(OH)2D which is calcitriol, increases in the blood

Question 48

What is net effect of estrogen on bone? why?

Answer 48

The net effect of this action is bone formation is favored since osteoclast activity is inhibited by calcitonin

Question 49

Why do postmenopausal women suffer from osteoporosis?

Answer 49

they have less estrogen

Question 50

What is The principal therapeutic application for estrogen?

Answer 50

is in the treatment and/or prevention of postmenopausal osteoporosis.

Question 51

what type of drug is Raloxifene?

Answer 51

SERM

Question 52

What effect does Raloxifene have? (4)

Answer 52

stimulates bone estrogen receptors inhibits breast and uterine estrogen receptors. Raloxifene also increases bone mineral density by inhibiting bone resorption.

Question 53

The primary indication for raloxifene?

Answer 53

is in the treatment of postmenopausal osteoporosis

Question 54

most important ADEs of raloxifene (3)*************************************

Answer 54

raloxifene increases the risk of stroke, pulmonary emboli, and deep vein thrombosis

Question 55

What effect does thyroxine have on bone?*****************************

Answer 55

stimulates osteoclast function

Question 56

which is only homo that inhibits osteoblasts********************************

Answer 56

Glucocorticoids

Question 57

which 2 homos inhibit osteoclast activity***********************************

Answer 57

estrogen | calcitonin

Question 58

How does raloxifiene cause hot flashes******************************

Answer 58

antagonistic action on some tissues sometimes intensifies hot flashes

Question 59

What do homos Est, Androgens, and GH have in common with regard to bone mineralization?*****************

Answer 59

They all stimulate osteoblast activity