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Endocrine > 187. Calcium/Parathyroid/Bone Pharmacology/Basic Science > Flashcards

187. Calcium/Parathyroid/Bone Pharmacology/Basic Science Flashcards

1
Q

Pharmacokinetics:

  • poor oral absorption (need w/o food)
  • retained in bone
  • renal excretion
  • dosed once a week

Adverse effects:

  • heartburn, esophageal irritation, esophagitis
  • abdominal pain, diarrhea
  • Osteonecrosis of the jaw and atypical femoral fractures are rare but serious side effects
A

Bisphosphanates

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2
Q

Functions of __:

  • regulation of excitable tissues
  • secretion
  • coagulation
  • enzymatic activity
  • signal transduction
  • formation and maintenance of the skeleton (structural role)
A

Calcium

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3
Q

Important for the maintenance of bone

Decreased __ at menopause accelerates bone loss

__ is antiresorptive and anabolic:

  • inhibits production of RANKL and IL-6
  • Increases production of osteoprotegerin
  • causes apoptosis of osteoclasts
  • decreases sclerostin, promoting bone formation
A

Estrogen

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4
Q

An __ pool provides buffering, acid-base balance

  • minute-to-minute calcium that the body may need
  • > 1% of calcium in bone
A

Exchangeable

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5
Q

Thin, cortex, largely trabecular, highly connected bony plates

Contain more marrow and fat

Trabecular bone has the highest activity

  • turnover
  • more likely for bone loss
A

Axial bones

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6
Q

251 AA protein produced by osteoblasts and osteocytes
- synthesis increased by calcitriol and phosphate

Inhibits renal calcitriol synthesis, phosphate reabsorption

Tumoral calcinosis results from mutations that inhibit __ secretion

Hypophosphatemic rickets results from mutations in a cleavage site require for __ inactivation

A

FGF-23

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7
Q

Normal serum calcium levels

A

8.5-10.4

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8
Q

Acts on the same receptor as PTH

Etiologic factor in the hypercalcemia of malignancy and in the osteolytic metastases of breast cancer

Effects on mammary glands, placenta, smooth muscle

Anabolic action on bone

A

PTHrP

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9
Q

Products used as markers of osteoblastic activity (3 of them)

A

Osteocalcin
Alk phos
Collagen peptide cleaved off during synthesis

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10
Q

Secrete H+ and proteolytic enzymes to eat away at old bone

Have a monocyte lineage

Stimulated by RANKL

A

Osteoclasts

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11
Q

Short term glucocorticoid treatment can reduce __ because glucocorticoids:

  • decrease intestinal calcium absorption
  • increase renal calcium excretion
A

Hypercalcemia

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12
Q

What accompanies calcium when being absorbed in the gut due to Vit D activity?

A

Phosphate

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13
Q

Human monoclonal antibody against RANKL

Inhibits osteoclast fusion, function, and survival
- antiresorptive

Increases bone mineral density and decreases fractures

Use:

  • osteoporosis
  • bone metastases from solid tumors

Adverse effects:

  • hypocalcemia
  • rashes
  • osteonecrosis of the jaw
  • risk of infections in individuals with weak immune systems
A

Denosumab

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14
Q

Type of SERM - selective estrogen response modulator

Interact with estrogen receptors in a tissue-specific manner

  • largely antiresorptive
  • anti-estrogenic effects on the mammary gland

Uses:

  • prevent and treat postmenopausal osteoporosis
  • reduces risk of breast cancer

Adverse effects:

  • thromboses
  • hot flashes
  • don’t use if pregnant or wanna be
A

Raloxifene

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15
Q

Anabolic agent for the treatment of osteoporosis
- used the first 34 AAs of PTH

Administered by subcutaneous injection once daily
- get pulsatile effect of PTH

A

Teriparatide

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16
Q

32 AA peptide secreted by the C-cells of the thyroid gland
- secretion is stimulated by calcium

Acts on mature osteoclasts through GPCRs to inhibit bone resorption

A

Calcitonin

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17
Q

BP medication that actually decreases calcium excretion

- can be used to treat hypocalcemia

A

Thiazide diuretics

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18
Q

Calcium __ in the kidney is increased by:

  • dietary protein
  • glucocorticoids
A

Excretion

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19
Q

Major site of calcium storage in the body

A

Bone

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20
Q

Used to treat __:

  • Loop diuretics
  • Bisphosphonates
  • Calcitonin
  • Glucocorticoids
A

Hypercalcemia

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21
Q

Factors promoting osteoblast differentiation and activity:

  • Wnt signaling
  • What other 2 factors?
A

IGF-1 and BMP (bone morphogenic proteins)

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22
Q

Increases calcium absorption in the distal nephron

- 99% calcium reabsorbed

A

PTH

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23
Q

Major director of calcium absorption in the gut

A

Activated Vit D (1,25-(OH)2 Vit D)

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24
Q

Secrete Type I collagen, other matrix proteins, growth factors, and cytokines (including RANKL)

  • osteocalcin
  • Alk phos

Derived from pluripotent precursors that can also give rise to adipocytes, chondrocytes, and myocytes

A

Osteoblasts

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25
Q

Effects are produced through nuclear receptors

Stimulates intestinal calcium and phosphate absorption, resulting in bone mineralization

Suppresses PTH secretion

In excess, can cause hypercalcemia through

  • excess calcium and phosphate intestinal absorption
  • direct actions on osteoblasts to increase RANKL
A

Calcitriol

26
Q

PTH action on bone:

  • bone resorption results from __ exposure
  • -> resorption is largely due to increased RANKL
  • -> PTH increases RANKL
A

Continuous

27
Q

Actions on kidney:

  • increase calcium absorption
  • decrease phosphate reabsorption
  • stimulate 1alpha-hydroxylation of 25-OH Vit D to form 1,25-(OH)2 Vit D

Actions on intestine:
- indirectly mediated through the increase of 1,25-(OH)2 Vit D

A

PTH

28
Q

3 major sites at which calcium is regulated

A

Intestine
Kidney
Bone

29
Q

50% of calcium in the blood is __

  • active states
  • mediates biological responses
A

Ionized

30
Q

Use is related to its effects on calcium and phosphate absorption

Treatment of nutritional rickets

In patients with osteoporosis, adequate __ is an important adjunct to other therapy

A

Vitamin D

31
Q

Decreased calcium leads to..

A

Increased PTH secretion

32
Q

Chronic glucocorticoid treatment can cause __ because glucocorticoids:

  • decrease intestinal calcium absorption
  • increase renal calcium excretion
  • increase PTH secretion
  • decrease gonadal steroids
  • decrease protein synthesis in bone
A

Osteoporosis

33
Q

Systemic condition in which osteoblastic activity cannot keep pace with accelerated osteoclastic activity, resulting in loss of mineral and matrix and increased susceptibility to fracture
- d/t menopause or estrogen loss in most cases

A

Osteoporosis

34
Q

Largely compact cortical bone, with some trabecular regions

Long bones

A

Appendicular bones

35
Q

Disorder in which local increased osteoclastic activity is followed by increased osteoblastic activity, resulting in abnormal bone

A

Paget’s Disease of Bone

36
Q

As bone forms around osteoblasts, they become __

Comprise 90% of the cells of the bone

Sensors of mechanical load

A

Osteocytes

37
Q

PTH action on bone:

  • bone formation results from __ exposure
  • -> decreased osteoblast apoptosis
  • -> increased osteoblast differentiation
  • -> suppression of sclerostin production
A

Intermittent

38
Q

Used to treat __:

  • Vitamin D
  • Calcitriol
  • Alphacalcidol
  • Thiazide diuretics

All supplemented with calcium

A

Hypocalcemia

39
Q

RANKL antagonist secreted by osteoblasts

A

Osteoprotegerin

40
Q

Vitamin D analog that does not require 1-hydroxylation

Useful when 1-hydroxylase is deficiency

  • renal disease
  • VDRR
A

Alphacalcidol

41
Q

What two factors increase phosphate excretion in the kidney?

A

FGF-23

PTH

42
Q

Vitamin D analog that suppresses parathyroid hormone

Minimal effects on intestine

Useful for secondary hyperparathyroidism
- seen in renal disease

A

Paracalcitol

43
Q

40% of calcium is protein bound

- of that, ~90% is bound with __

A

Albumin

44
Q

Calcium __ through the intestine can result from:

  • glucocorticoids which decrease calcium absorption
  • mucosal and biliary secretion
  • steatorrhea, diarrhea, and malabsorption syndromes
A

Loss

45
Q

Osteocytes produce __ that inhibits Wnt signaling and osteoblast differentiation and maturation

Antagonists increase bone formation

A

Sclerostin

46
Q

The final activation step of Vit D, 1-hydroxylation, occurs in the __

  • stimulated by PTH
  • stimulated by low serum phosphate
  • tightly feedback regulated
A

Kidney

47
Q

GPCR found in the parathyroids that is the site of negative feedback control from calcium levels in the blood
- increased calcium in blood is going to decrease PTH levels through this receptor

A

CaSR

48
Q

A __ pool is regulated by cellular activity, affected by hormones, cytokines, growth factors, and drugs
- 99% of calcium in bone

A

Stable

49
Q

Membrane-associated cytokine produced by osteoblasts and other cells

Acts on a receptor on osteoclasts and osteoclast precursors

Promotes fusion, differentiation, activity, and survival of osteoclasts

A

RANKL

50
Q

In times of __calcemia there is dehydrations, renal stones, pain, weakness, confusion, and cardiac arrythmias

A

Hyper

51
Q

Makes up 90% of the protein of the bone matrix (osteoid)

- osteoid + hydroxyapatite = mineralized matrix

A

Collagen

52
Q

Analogs of pyrophosphate
- alendronate, risedronate, zoledronic acid, ibandronate

Accumulate in bone at sites of active resorption

Taken up by osteoclasts, inhibit their activity and survival
- antiresorptive

Prevent and treat osteoporosis
- ~50% decrease in fracture risk

Treatment of:

  • bone metastases from breast and prostate cancer
  • hypercalcemia
  • Paget’s disease
A

Bisphosphonates

53
Q

BP medication that increases calcium excretion

- can be used to treat hypercalcemia

A

Loop diuretics

54
Q

Tight homeostatic control of calcium is a consequence of the feedback regulation between calcium and __

A

PTH

55
Q

Site of hematopoiesis

Provides bone cell precursors
- formation of bone and remodeling

Cells produce cytokines that affect bone

A

Bone marrow

56
Q

Calcimimetic that acts as an allosteric activator of the CaSR
- enhances the activity of the CaSR –> lowers the calcium concentration at which the parathyroid is suppressed
=> Decreased PTH secretion

Used to suppress excess PTH in hyperparathryoidism, parathyroid carcinoma

Orally effective, metabolized by CYPs, renally excreted

Side effects:

  • hypocalcemia
  • adynamic bone disease (if PTH is too low)
A

Cinacalcet

57
Q

In times of __calcemia there is increased neuromuscular excitability
- experience tetany seizures, parasthesias

A

Hypo

58
Q

Intestinal calcium __ is promoted by:

  • facilitated diffusion throughout the small intestine
  • Vit D-dependent transport of calcium and phosphate (major pathway)
A

Absorption

59
Q

Metabolic roles of bone

A

Calcium homeostasis

Buffering

60
Q

Teriparatide and Abaloparatide are examples of __ therapies used to treat osteoporosis

A

Anabolic

61
Q

Vitamin D is converted to 25-OH Vit D in the __

A

Liver

Endocrine (26 decks)

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