13 - Vitamin D Flashcards

1
Q

What are the most important forms of vitamin D?

A
  • Cholecalciferol (D3)

- Ergocalciferol (D2)

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2
Q

What is osteomalcia? What is another name for it?

A
  • AKA rickets

- Softening of the bone caused by defective bone mineralization due to inadequate amount of phosphorus and calcium

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3
Q

Which vitamins does vitamin D enhance the intestinal absorption of?

A

Calcium, iron, magnesium, phosphorus, and zinc

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4
Q

What are some causes of vitamin D deficiency?

A
  • Sunscreen, melanin, winter
  • Medications and supplements (antiseizure drugs, glucocorticoids, rifampin, St John’s wort)
  • Malabsorption (Crohn’s disease, Whipple’s disease, cystic fibrosis, celiac disease, liver disease)
  • Hepatic or renal failure; nephrotic syndrome, obesity
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5
Q

What are some consequences of vitamin D deficiency?

A
  • Infections (tuberculosis, influenza, upper respiratory tract infections)
  • Schizophrenia, depression
  • Lung disease
  • Autoimmune diseases (type 1 diabetes, MS, Crohn’s disease, RA)
  • Cancer (breast, colon, prostate, pancreatic)
  • Muscle weakness, osteoporosis, osteoarthritis, rickets
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6
Q

What are the 3 types of pericyclic reactions?

A

1) Electrocyclic reactions - intramolecular reaction in which a pi bond is converted to sigma bond
2) Cycloaddition reaction - intermolecular reaction in which two pi-bond-containing molecules react to form a new cycle
3) Sigmatropic rearrangement - intramolecular reaction in which a sigma bond is broken, a new sigma bond is formed and pi bond is rearranged

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7
Q

How is vitamin D3 synthesized?

A

7-dehydrocholesterol (provitamin D3) is converted into previtamin D3 in the skin epidermis by sunlight 290-310 nm, which is then converted to cholecalciferol (vitamin D3) by heat (body temperature)

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8
Q

Blocking which UV rays would prevent the conversion of provitamin D3/D2 to previtamin D3/D2?

A

UVB

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9
Q

How is vitamin D3 activated?

A
  • Cholecalciferol -> calcidiol -> 24,25-OH-vitamin D3 -> calcitetiol
  • OR Cholecalciferol -> calcidiol -> calcitriol -> calcitetiol
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10
Q

What is significant about calcitriol?

A

Active form of vitamin D3 that binds to its nuclear receptor and triggers genomic effects

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11
Q

What are the effects of calcitriol binding to its receptor?

A
  • Increased production of certain calcium transport proteins, insulin, parathyroid and thyroid hormones
  • Decreased production of interleukin
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12
Q

When do calcitriol and parathyroid hormone work in concert?

A

To reduce urinary excretion of calcium and increase bone resorption

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13
Q

What is the overall goal of calcitriol?

A

Increase plasma Ca2+ levels

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14
Q

What can a long period of high calcitriol cause?

A
  • Hypercalcemia
  • Stones, bones, groans, thrones, chest tones, and psychiatric overtones (kidney and biliary stones; bone pain; groans from abdominal pain and N/V; increased urination and polyuria; cardiac rhythm; psychiatric disorders like depression)
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15
Q

How is vitamin D2 synthesized?

A
  • Ergosterol (provitamin D2) from plants is converted to previtamin D2 in skin epidermis from sunlight 290-310 nm
  • Previtamin D2 is converted to vitamin D2 (ergocalciferol) by heat
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16
Q

How is vitamin D2 activated?

A

Vitamin D2 -> 1,25-diOH-vitamin D2 by 25-hydroxylase in liver and 1 alpha-hydroxylase in kidney

17
Q

What is the principle counterion of serum Ca2+?

A

HPO4-

18
Q

What is the major reservoir of calcium in the body?

A

Bone crystal lattice – Ca10(PO4)6(OH)2

19
Q

What regulates the unbound ions in serum?

A

Vitamin D, calcitonin, and parathyroid hormone

20
Q

What is the homeostasis of calcium essential for?

A
  • Bone growth and remodeling
  • Muscle contraction
  • Cardiac rhythm
  • Neurotransmission
21
Q

What do osteoblasts do?

A
  • Stimulate bone formation by producing products required to form bone matrix and mineralization
  • Mediated by cytokines, hormones, and growth factors
22
Q

What do osteoclasts do?

A
  • Stimulate bone resorption (destruction) by acidifying and dissolving bone minerals, and digesting bone collagen matrix
  • Activated by cytokines, parathyroid hormone, and calcitriol
23
Q

Where are osteocytes found? What are they activated by and what do they do?

A
  • Found deep in bone matrix
  • Activated by parathyroid hormone
  • Mobilize calcium to bone surface
24
Q

When is calcitonin secreted? What does it do?

A
  • Secreted when serum calcium > 9 mg/dL
  • Serves to oppose the effects of parathyroid hormone
  • Inhibits osteoclast activity, leading to reduced bone resorption
  • Stimulates urinary excretion of HPO4- and Ca2+ and stops intestinal absorption of Ca2+
25
Q

When is parathyroid hormone secreted? What does it do?

A
  • Secreted when serum Ca2+ < 9 mg/dL
  • Activates production of calcitriol in kidneys, which helps regulate parathyroid hormone levels
  • Works in concert w/ calcitriol to promote osteoclast activity, leading to bone resorption
  • Decreases urinary excretion of Ca2+ and indirectly stimulates intestinal absorption of Ca2+
26
Q

Are low or high levels of PTH preferred? Why?

A

Low levels seem to help achieve a balanced bone remodeling process

27
Q

What are the therapeutic options for osteoporosis?

A
  • Calcium
  • Calcitonin and PTH
  • Vitamin D
  • Estrogen
  • Biphosphonates
  • Fluoride
  • Cathepsin K inhibitors
  • Exercise
28
Q

How does estrogen inhibit bone loss?

A
  • Activation of estrogen-specific receptors on osteoclasts may shorten their life span by blocking production of certain cytokines (thus reduces bone resorption)
  • Promotes calcitonin production
  • Enhances intestinal calcium uptake
29
Q

What is the action of bisphosphonates?

A

Replaces pyrophosphate of hydroxyapatite in forming an interaction w/ Ca2+

30
Q

What is the effect of bisphosphonates on osteoclasts?

A
  • Inhibit osteoclast proliferation
  • Decrease osteoclasts activity
  • Reduce osteoclast life span
  • Decrease # of sites along the bone surface where bone resorption occurs, reducing bone loss
31
Q

Which drugs are bisphosphonates?

A
  • Zoledronate
  • Alendronate
  • Risedronate
  • Ibandronate
32
Q

Bisphosphonates have selective uptake in areas of bone that ____

A

Are actively undergoing remodeling

33
Q

How should bisphosphonates be taken?

A

In an upright position, on an empty stomach w/ a minimum amount of water

34
Q

What is an adverse effect of oral bisphosphonates?

A

Inflammation and erosions of esophagus, leading to esophageal cancer

35
Q

What is cathepsin K?

A
  • Lysosomal cysteine protease involved in bone remodeling and resorption
  • Expressed predominantly in osteoclasts
  • Catabolizes bone and cartilage
36
Q

Which drug is a cathepsin K inhibitor? How is it dosed?

A

Odanacatib; dosed once weekly

37
Q

What is teriparatide used for?

A

To assist bone remodeling via activating osteoblasts more than osteoclasts

38
Q

What is abaloparatide?

A

Parathyroid hormone-related protein

39
Q

What is romosozumab used for?

A
  • Humanized monoclonal antibody that targets sclerostin for tx of osteoporosis
  • Sclerostin = glycoprotein produced by osteocytes and inhibits bone formation