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Exam 4 (MHT/ Thyroid/ Osteoporosis) P1 Therapeutics > Calcium (Hockerman) > Flashcards

Calcium (Hockerman) Flashcards

1
Q

what is the term fr moving both phosphorus and Ca2+ in and out of bone?

A

continuous balance

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2
Q

what ARE OSTEOBLASTS?

A

bone forming cells

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3
Q

what are osteoclasts?

A

bone reabsorption cells

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4
Q

what inc. BMD?

A
  1. osteonectin
  2. nitric oxide
  3. denin matrix protein 1
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5
Q

what dec. BMD?

A
  1. sclerostin
  2. DKK-1
  3. RANKL
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6
Q

what does a deletion of aa in the PTH do?

A

deletion aa 1&2 eliminates activity

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7
Q

what does PTH do?

A
  1. increase calcium in extracellular fluid
  2. inc. Ca2+ reabsorption from ECaC1 7 TrpV5
  3. inc. Ca2+ resorption from bone (inc. osetoclast # & activity)
  4. increased PO4 loss in urine
  5. inc. 1,25 (OH2) D3 production by kidney
  6. PTH secretion triggered by low serum Ca++ levels and GPCR that binds Ca2+ (CSR)
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8
Q

how can vitamin D (cholecalciferol) be obtained?

A

in the diet or via exposure to sun light

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9
Q

what does increased Ca2+ and PO43- absorption from small intestine do?

A

direct (rapid) effect on brush border of intestinal mucosal cells

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10
Q

what cells are there a indirect slow effect?

A
  1. calbindins
  2. vitamin D binding protein
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11
Q

what vitamin D deals with feedback inhibition of PTH?

A

1,25(OH)2D3

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12
Q

what does the fibroblast growth factor 23 do?

A
  1. auto/paracrine effect on osteocytes inhibits bone mineralization
  2. high levels of FGF23 correlate with poor prognosis in patients with CKD on dialysis
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13
Q

what do high Ca2+, 1,25(OH2) vit D3, and FGF23 inhibit?

A

PTH secretion

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14
Q

what does low Ca2+ do?

A

stimulates PTH secretion

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15
Q

what does a negative regulator of serum (extracellular) Ca2+ do?

A
  1. inhibit osteoclastic bone resorption
  2. increase Ca2+ and PO4 loss in urine
  3. stimulated by high serum calcium levels
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16
Q

what are some side effects of Padgetts disease?

A
  1. bone remodeling
  2. bone deformities
  3. loss of hearing, hypercalcemia
  4. may be caused by slowly acting virus
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17
Q

what are some risk factors for osteoporosis?

A
  1. physical inactivity
  2. age
  3. low Ca2+ intake in early years
  4. long term glucocorticoid therapy
18
Q

what is hyperparathyroidism?

A
  1. inc. bone resorption and decreased Ca2+ excretion
19
Q

what care some reasons for malignant tumors?

A

some produce a peptide with PTH activity

20
Q

what are osme causes of CNS symtpoms?

A

depression and coma

21
Q

what is a first line treatment for osteoporosis?

A

bisphosphates/ denosumab

22
Q

what drugs for osteoporosis cause a high fracture risk?

A

teriparatide abaloparatide, romosozumab

23
Q

what is a regimen for Vitamin D in osteoporosis?

A
  1. Vitamin D (800-1000 IU) + Ca2+ (>1200mg) daily can reduce fracture risk
  2. also supplement for osteoporosis therapy
24
Q

what are the characteristics of bisphosphates?

A
  1. inhibit bone resorption
  2. 50% absorbed dose ends up in bone
  3. may lead to hypocalemia so we need to supplement with Ca2+ + Vit D
25
Q

what bisphosphates are approved for padget’s and cancer but not for osteoporosis?

A
  1. pamidronate
  2. etidronate
26
Q

what bisphosphates are approved for osteoporosis and build bone mass?

A
  1. zoledronate
  2. alendronate
  3. risendronate
  4. ibandronate
27
Q

what is the mechanism of action of bisphosphates?

A

it disrupts prenylation of proteins in osteoclasts

28
Q

what is teriparatide?

A

amino acid 1-34 of PTH produced in E.coli

29
Q

what is abaloparatide?

A

amino acids 1-34 of PTHrP produced synthetically

30
Q

where are PTH1 receptors expressed?

A

on osteoblasts and kidney cells

31
Q

what does intermittent PTH do?

A

increase bone mass and strength

32
Q

what does continuous PTH do?

A

increase bone resorption

33
Q

what are the pros of teriparatide to bisphosphates?

A

build bone mass at higher rate than bisphosphonates

34
Q

what are the cons of teriparatide to bisphosphates?

A

black box warning required by FDA for risk of bone cancer
–> reserved for severe cases of osteoporosis

35
Q

tell me about prolia (denosumab)?

A

approved in June 2010 for postmenopausal osteoporosis
1. hypocalcemia risk- take calcium daily
2. increased risk of fracture upon discontinuation

36
Q

tell me about romosozumab?

A
  1. MAB against sclerostin
  2. osteocyte secretion increased
  3. sclerostoin decreases osteoblasts and increases osteoclasts
  4. ADRs–> MACE (hypersensitivity, hypocalcemia, osteonecrosis, atypical fractures)
37
Q

what is calcitonin and its characteristics?

A
  1. decreased osteoclast activity, blocks renal reabsorption of PO4 and Ca2+
  2. rapid loss of efficacy in treatment of hypercalcemia
  3. not the drug of choice in most causes for treatment of osteoporosis
38
Q

what is the mechanism cinacalcet?

A
  1. CKD with dialysis the CSR become less responsive to Ca 2+
  2. cinacalcet is a PAM
  3. when cinacalcet is bound its more responsive to Ca2+
39
Q

what are the characteristics for the second line treatment for hyperparathyroidism?

A
  1. Zemplar
    –> stage 2&4 or dialysis
    –> 1-4ug 3x per week IV or oral
  2. Hectorol
    –> dialysis
    –> 4ug 3x per week IV or oral
    –> prodrug- 25 hydroxylation by CYP 27 in live
    » inhibit secretion of PTH with less effect on serum Ca2+ than 1,25(OH)2 Vit D3
40
Q

what is the treatment of hyperphosphatemia in CKD with dialysis?

A
  1. calcification –> calcific uremic arteriolopathy
  2. phosphate binders are complex with dietary phosphate and prevent absorption from GI
  3. Sevelamer dec. serum PO43- levels selectively
  4. Lanthanum Carbonate dec. serum PO43- AND Ca2+ levels
41
Q

what does calcium receptor sensitization do?

A

—decrease both serum PTH and Ca2+ levels and can help in
—many treatments such as chronic kidney disease with dialysis

42
Q

what are third line treatments for osteoporosis?

A

estrogens/ SERMs
–> inc. osteoblasts and dec. osteoclasts
–> risk of blood clots
–> raloxifene& bazedoxifene
—–> antagonist: in breast/ uterus/ brain
——> agonist: in bone/liver

Exam 4 (MHT/ Thyroid/ Osteoporosis) P1 Therapeutics (5 decks)

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