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Endocrinology > Agents affecting bone mineral homeostasis > Flashcards

Agents affecting bone mineral homeostasis Flashcards

1
Q

Ca is controlled by 3 calcitropic hormones. What are they?

A

PTH, calcitonin, calcitriol (active Vd)

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2
Q

What are the 3 major sites of action for blood calcium regulation?

A

Bone, GI tract, Kidneys

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3
Q

What are the 3 major actions of PTH?

A

increase bone resorption, increase kidney reabsorption, increase active form of VD

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4
Q

PTH is released when concentration of Ca is _____ in the blood.

A

low

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5
Q

Activation of calcium sensor has what 2 main transducing effect?

A

Activation of Phospholipase C and inhibition of adenylyl cyclase

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6
Q

Where are PTH and Calcitonin secreting cells found?

A

parathyroid, and parafollicular cells in thyroid

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7
Q

Other than pT and thyroid, where else is the calcium sensor expressed?

A

kidney, osteoblasts, hematopoietic cells, Gi mucosa

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8
Q

Calcitonin functions to _____ plasma Ca.

A

decrease

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9
Q

3 major actions of calcitonin

A

decrease bone resorption, decrease kidney resorption, decrease active form of vitamin D.

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10
Q

In general, calcitonin _____ PTH actions.

A

opposes

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11
Q

Calcitriol acts to ____ plasma Ca.

A

increase

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12
Q

Where is calcitriol synthesized

A

skin and blood

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13
Q

What are the most important physiological actions of calcitriol?

A

increase calcium uptake from GI, increase kidney reabsoprtion, increase bone reabsoprtion

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14
Q

What can cause loss of Ca homeostasis?

A

estrogen deficiency, GC excess, GH deficiency, insulin deficiency, primary hypoparathydoidism, cancer

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15
Q

Response to low Ca

A

detected by PT–> release of PTH–> increase absorption at kidney, increased synthesis of calcitriol, increased resoprtion of bone, more calcitriol results in increased GI absorption

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16
Q

Response to high Ca

A

Detected by parafollicular cells causing release of calcitonin–> decreased synthesis of PTH, decreased resoprtion of bone, shift to inactive VD, decreased PTH causes increase excretion of calcium

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17
Q

PTH MOA

A

binds plasma membrane receptor, activates adenylyl cyclase, increase cAMP–> activates PK–> increased urine cAMP

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18
Q

What is the treatment for hypoparathyroidism?

A

bioengineered PTH, injectible daily form

19
Q

MOA of teriparatide

A

HRpth1-34 directly stimulates bone formation without stimulating resorption. IMportant for women after bisphosphonate, may stimulate IGF-1

20
Q

Uses of raloxifene

A

first SERM to be approved for osteoporosis. Has beneficial effects of estrogen without stimulating breast cancer.

21
Q

____ is a monoclonal antibody to RANKK

A

denosumab

22
Q

MOA of denosumab

A

blocks stimulation of osteocyte formation by RANKL and decreases osteoporosis. Increases bone mass in pt with breast or prostate cancer

23
Q

What does FGF23 do?

A

inhibits formation of VD, opposes PTH in the kidney, produced by osteoblasts and clasts

24
Q

MOA of calcitonin

A

binds to plasma membrane receptor, decreases ruffled border surface area on osteoclasts, not a global inhibitor of PTH, has direct renal effects

25
Q

What is calcitonin used in tx for?

A

Hypercalcemia- short term treatment, effective for short term tx, antibodies may develop
Pagets
Osteoporosis

26
Q

Calcitriol MOA

A

stimulates Ca and phosphate absoprtion in small intestine, induces synthesis of calbindin, binds to transcription factor to increase mRNA, protein synthesis, has additional effects to increase uptake of Ca from intestine

27
Q

Major uses of calcitriol in therapeutics

A

prophylaxis and cure of nutritional rickets, treatment of metabolic rickets and osteomalacia, treatment of hypoparathyroidism, prevention and treatment of osteoporosis

28
Q

Analogs of calcitriol

A

calcipotriol, dihydrotachysterol, paricalcitol, 22-oxacalcitriol

29
Q

Uses of calcipotriol

A

used in psoriasis

30
Q

What does paricalcitol do to PTH secretion? oxacalcitriol?

A

Both reduce

31
Q

What are bisphosphonates?

A

nonhydrolyzable analogs of inorganic pyrophosphate, inhibitors of bone resoprtion

32
Q

Which bisphosphonates are used in Pagets?

A

alendronate, risedronate

33
Q

What are bisphosphonates used for? Which are not effective orally in the management of hypercalciemia?

A

first used in pagets, effective in osteoporosis, etidronate, pamidronate

34
Q

Which bisphosphonates are used in osteoporosis?

A

alendronate

35
Q

What are the 2 3rd generation bisphosphonates?

A

risedronate, zoledronate (super potent)

36
Q

Describe absorption of bisphosphonates

A

all are poorly absorbed from intestine. Must be taken after overnight fast with full glass of water and no food for 30 minutes

37
Q

ADE of bisphosphonate

A

osteonecrosis of jaw- exposed bone under teeth, swelling and lose of teeth, may follow dental extraction, more common with 3rd generation drugs

38
Q

What does gc do to Ca uptake in intestine

A

antagonize

39
Q

Is estrogen effective in preventing osteoporosis

A

yes

40
Q

MOA of cinacalcet

A

calcimimetic that binds allosterically to CaSR and allows PTH suppression at lower Ca. Lowers PTH.

41
Q

Therapeutic use of cinacalcet

A

hyperparathyroidism in pt with parathyroid carcinoma

42
Q

Describe the use of fluoride

A

long used in cavity prevention, binds calcium and can be used to prevent clotting, potential agent in preventing osteoporosis. ADE: osteosclerosis, mottled enamel

43
Q

What are the 2 second generation bisphosphonates?

A

alendronate, ibandronate

44
Q

Role of prednisone in calcium therapuetics

A

Tx of hypercalcemia

Endocrinology (31 decks)

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